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Dos Santos DM, Penteado JO, Nader MM, Basso RP, da Silva NMO, Quiche LCP, Borges MP, Gehres LFS, Hoffmann T, Rodrigues LF, da Silva Júnior FMR. Analysis of noninvasive methods in chronic hepatitis/human immunodeficiency virus mono- and co-infected patients with advanced fibrosis. Eur J Gastroenterol Hepatol 2025; 37:638-643. [PMID: 39976004 DOI: 10.1097/meg.0000000000002936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
OBJECTIVES The aim of this study was to evaluate the degree of advanced fibrosis (F3/F4) using noninvasive methods [elastography, Fibrosis-4 (FIB4), and aspartate aminotransferase to platelet ratio index (APRI)] before and after treatment with new direct-acting antiviral agents (DAAs) in patients with hepatitis C virus (HCV), both in cases of co-infection (HCV/HIV) and single infection (HCV). METHODS This is a longitudinal study involving patients with HCV who are co-infected with HIV, who initiated HCV treatment between a positive anti-HCV test for more than 6 months and detectable HCV RNA. The control group consisted of patients with HCV infection without HIV co-infection, who received treatment during the same period as the co-infected patients. RESULTS A total of 75 co-infected and 87 mono-infected HCV patients were eligible. Before treatment, elastography and FIB4 methods showed a strong agreement (0.73), while after treatment, the agreement was moderate (0.58). Between elastography and APRI, a strong agreement was observed before treatment (0.66) and fair/weak agreement after treatment (0.30). Both FIB4 and APRI showed perfect agreement at both time points with values above 0.9 (0.97 for pretreatment and 0.92 for posttreatment). The use of DAAs was associated with high rates of sustained virological response and reduction in fibrosis degrees in the posttreatment period, as assessed through biomarkers and hepatic elastography. CONCLUSION The utilization of biomarkers in clinical practice for assessing hepatic fibrosis is an essential tool. Thus, for an accurate evaluation of hepatic fibrosis, particularly after HCV treatment, the use of elastography, rather than biomarkers alone, is more appropriate.
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Affiliation(s)
| | - Júlia Oliveira Penteado
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
| | - Maiba Mikhael Nader
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Rossana Patrícia Basso
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | | | | | | | | | - Tchurle Hoffmann
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
| | - Leandro Farias Rodrigues
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Flavio Manoel Rodrigues da Silva Júnior
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
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Nagaoki Y, Yamaoka K, Fujii Y, Uchikawa S, Fujino H, Ono A, Murakami E, Kawaoka T, Miki D, Aikata H, Hayes CN, Tsuge M, Oka S. Impact of viral eradication by direct-acting antivirals on clinical outcomes after curative treatment for hepatitis C virus-associated hepatocellular carcinoma. Therap Adv Gastroenterol 2025; 18:17562848251324094. [PMID: 40078327 PMCID: PMC11898033 DOI: 10.1177/17562848251324094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Background It is not clear that antiviral therapy for hepatitis C virus (HCV) after recovery from curative treatment for hepatocellular carcinoma (HCC) has an effect on suppressing recurrence or improving survival rates. Objectives We analyzed the impact of eradication by interferon (IFN)-free direct-acting antiviral (DAA) therapy on clinical outcomes of patients with HCV-associated HCC who underwent curative treatment. Design This was a retrospective study. Methods We retrospectively reviewed 109 consecutive patients with sustained virologic response with DAA therapy after HCC treatment and analyzed HCC recurrence and overall survival (OS). Among these patients are those with a history of HCC recurrence and curative HCC treatments administered as definitive HCC treatments prior to initiation of DAA therapy. Results Among 109 patients, 64 received DAA therapy after curative treatment for HCC; the remaining 45 received ⩾2 subsequent treatments for HCC. Cumulative HCC recurrence rates at 1, 3, and 5 years were 23%, 47%, and 56%, respectively. Multivariate analysis identified predictive factors for suppression of HCC recurrence as tumor number (hazard ratio (HR) 2.293 for multiple; p = 0.006) and number of HCC treatments before DAA therapy (HR 2.928 for ⩾2; p = 0.001). Among 64 patients who received curative treatment for HCC, cumulative first HCC recurrence rates at 1, 3, and 5 years were 12%, 34%, and 44%, respectively, second recurrence rates were 11%, 28%, and 39%, and third recurrence rates were 0%, 22%, and 53%, respectively; recurrence tended to be suppressed until 3 years. Cumulative OS rates at 3 and 5 years were 87% and 75%, respectively. On multivariate analysis, tumor number (HR 2.452 for single; p = 0.026) was the only independent predictor of OS. Conclusion DAA therapy after curative treatment for HCC suppresses HCC recurrence in the long term, but recurrence was higher in patients with a history of many HCC treatments.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology, Mazda Hospital, Mazda Motor Corporation, 2-15 Aosakiminami, Fuchu-cho, Aki-gun, Hiroshima 735-8585, Japan
| | - Kenji Yamaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan Liver Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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Iwamoto T, Nozaki Y, Inoue T, Suda T, Mizumoto R, Arimoto Y, Ohta T, Yamaguchi S, Ito Y, Sudo Y, Yoshimura M, Kai M, Sasaki Y, Tahata Y, Hikita H, Takehara T, Hagiwara H. Histological improvement of fibrosis in patients with hepatitis C who achieved a 5-year sustained virological response to treatment with direct-acting antivirals. J Gastroenterol 2025; 60:197-209. [PMID: 39585387 PMCID: PMC11794422 DOI: 10.1007/s00535-024-02165-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND The histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA. METHODS This retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2 binding protein glycosylation isomer, autotaxin, and Fibrosis-4 index) were assessed before and 5 years after treatment. Transient elastography using the FibroScan® device was performed 5 years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively. RESULTS Histological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75 kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment. CONCLUSIONS Long-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.
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Affiliation(s)
- Takayuki Iwamoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yasutoshi Nozaki
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takanori Inoue
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takahiro Suda
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Rui Mizumoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yuki Arimoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takashi Ohta
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Shinjiro Yamaguchi
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yoshiki Ito
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yoshiko Sudo
- Department of Diagnostic Pathology, Kansai Rosai Hospital, Hyogo, Japan
| | - Michiko Yoshimura
- Department of Diagnostic Pathology, Kansai Rosai Hospital, Hyogo, Japan
| | - Machiko Kai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoichi Sasaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hideki Hagiwara
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan.
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Zhang Y, Xia H, Fan L, Jiang L, Yang B, Wang F. Five-Year Prospective Follow-Up of Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antiviral Agents. Infect Drug Resist 2025; 18:455-471. [PMID: 39877380 PMCID: PMC11774102 DOI: 10.2147/idr.s487414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/11/2025] [Indexed: 01/31/2025] Open
Abstract
Purpose The research intended to present prospective data on the long-term prognosis of individuals with hepatitis C virus (HCV) infection who received direct-acting antiviral agent (DAA) treatment. Patients and Methods Patients who received DAA treatment at Tianjin Third Central Hospital and Tianjin Second People's Hospital were prospectively enrolled and subsequently underwent a longitudinal follow-up. This research monitored occurrences of virological relapse, hepatocellular carcinoma (HCC), mortality, and liver disease progression. The annualized incidence rates (AIRs), cumulative incidence rates of adverse events and risk factors were investigated. Changes in liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, as well as the albumin-bilirubin (ALBI) scores were also documented. Results A total of 862 individuals were followed up for 4.86 (P25, P75; 4.48, 5.48) years. The proportion of all participants with undetectable HCV-RNA exceeded 98% at all follow-up time points. Patients experienced virological relapse, HCC, death and disease progression with a cumulative AIRs of 1.03% (95% confidence interval [CI] 0.6-1.5), 1.76% (95% CI 1.2-2.3), 1.51% (95% CI 1.0-2.0), and 5.81% (95% CI 4.8-6.8), respectively. Cirrhotic patients were at a heightened risk of virological relapse (adjusted hazard ratio [aHR] 3.20, 95% CI 1.59-9.75; p = 0.016), HCC (aHR 6.57, 95% CI 2.66-16.28; p < 0.0001), and unfavorable prognosis (aHR 6.93, 95% CI 2.56-18.74; p < 0.0001). Additionally, patients with diabetes faced an elevated risk of HCC (aHR 2.33, 95% CI 1.05-5.15; p = 0.038) and poor prognosis (aHR 2.72, 95% CI 1.13-6.55; p = 0.026). Furthermore, liver stiffness measurement (LSM) exhibited a significant decrease compared to baseline. Additionally, patients in the cirrhosis group showed reductions in APRI score, FIB-4 index and ALBI score to different degrees. Conclusion Cirrhotic patients exhibited increased susceptibility to virological relapse, HCC, unfavorable prognosis, and liver disease progression following DAA treatment. Consequently, it is imperative to implement a rigorous monitoring protocol for all cirrhotic patients after DAA treatment.
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Affiliation(s)
- Yaping Zhang
- The Third Central Clinical College of Tianjin Medical University, Tianjin Medical University, Tianjin, 300170, People’s Republic of China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Central Hospital, Tianjin, 300072, People’s Republic of China
| | - Huan Xia
- Department of Infectious Diseases, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Luchang Fan
- The Third Central Clinical College of Tianjin Medical University, Tianjin Medical University, Tianjin, 300170, People’s Republic of China
| | - Lu Jiang
- Department of Hepatology and Gastroenterology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China
| | - Bin Yang
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Central Hospital, Tianjin, 300072, People’s Republic of China
| | - Fengmei Wang
- Department of Hepatology and Gastroenterology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer, Tianjin First Central Hospitial, Tianjin, 300192, People’s Republic of China
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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Cheng HH, Ho MW, Chi CY, Kao JT. Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024; 57:840-853. [PMID: 39216998 DOI: 10.1016/j.jmii.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 07/15/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND/PURPOSE There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. METHODS From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. RESULTS Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). CONCLUSION For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.
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Affiliation(s)
- Ming-Han Hsieh
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ting-Hui Hsieh
- Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chi Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsing-Hung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Yu Chi
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Hassan AM, Orabi HH, Abdel-Gawad M, Mohamed O, Sawy SS, Abdelmeguid MM, Bashir MA, Abdelrazzak E, Ead K, Haridy MA. Changes in Vascular Endothelial Growth Factor and Development of Hepatocellular Carcinoma in Direct-Acting Antiviral Drugs (DAAs)-Treated Hepatitis C Virus (HCV) Patients. Cureus 2024; 16:e75982. [PMID: 39830567 PMCID: PMC11742266 DOI: 10.7759/cureus.75982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/22/2025] Open
Abstract
Background There is ongoing debate regarding the impact of direct-acting antiviral drugs (DAAs) on the occurrence of de novo hepatocellular carcinoma (HCC). Vascular endothelial growth factor (VEGF) plays a crucial role in the development and angiogenesis of HCC. Aim This study aims to evaluate dynamic changes in vascular endothelial growth factor (VEGF) levels at different point times during and after treatment of HCV to evaluate the risk of de novo HCC in DAAs-treated HCV patients. Methods This prospective cohort study was conducted on 60 HCV-infected patients; 30 patients had early fibrosis (F1-F2) and 30 patients had advanced fibrosis (F3-F4). HCV-RNA, aspartate aminotransferase (AST) to platelet ratio index (APRI), and fibrosis-4 index scores, liver function tests, serum VEGF, alpha-fetoprotein (AFP), and abdominal ultrasound were done at baseline, 4 weeks after starting treatment, at the end of treatment, and 12 weeks after treatment. Results VEGF was significantly decreased after completion of treatment (78.94± 10.03) compared to its baseline level (103.17 ± 33.89 pg/ml). Conclusion No de-novo hepatic focal lesion was detected during and up to 12 weeks after completion of treatment. The treatment of HCV by DAAs was associated with a significant decrease in VEGF and AFP levels and an improvement in liver enzymes and fibrosis scores.
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Affiliation(s)
- Amro M Hassan
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Heba H Orabi
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Muhammad Abdel-Gawad
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Omran Mohamed
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Safwat S Sawy
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | | | - Mohamed A Bashir
- Department of Clinical Pathology, Al-Azhar University, Assiut, EGY
| | - Emad Abdelrazzak
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Khalid Ead
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Mustafa A Haridy
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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Huiban L, Stanciu C, Muzica CM, Girleanu I, Avram R, Damian I, Nastasa R, Stratina E, Zenovia S, Minea H, Stafie R, Rotaru A, Singeap AM, Chiriac S, Balmus IM, Trifan A. Impact of Treatment with Direct Antivirals on Coagulation Parameters in Patients with Hepatitis C Virus-Related Liver Cirrhosis and Sustained Virological Response. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1539. [PMID: 39336579 PMCID: PMC11434478 DOI: 10.3390/medicina60091539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/15/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024]
Abstract
Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.
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Affiliation(s)
- Laura Huiban
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Raluca Avram
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Ioana Damian
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Horia Minea
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
| | - Ioana-Miruna Balmus
- CENEMED Platform for Interdisciplinary Research, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Exact Sciences and Natural Sciences, Institute of Interdisciplinary Research, "Alexandru Ioan Cuza" University of Iasi, 700057 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
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Koppandi O, Iovănescu D, Miuțescu B, Motofelea AC, Jigău OM, Papoi AI, Burciu C, Gadour E, Vuletici D, Miuțescu E. Prospective Assessment of Serum Lipid Alterations in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals: Insights Six Months Post Sustained Virological Response. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1295. [PMID: 39202576 PMCID: PMC11355975 DOI: 10.3390/medicina60081295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 07/29/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Chronic hepatitis C virus (HCV) infection is intricately linked with dysregulation of lipid metabolism. In particular, cholesterol plays a crucial role in HCV replication. Direct-acting antiviral agents (DAAs) therapy has revolutionized the hepatitis C treatment landscape, achieving high rates of sustained virological response (SVR). However, viral clearance comes with some alterations in lipid-related markers. This prospective study aimed to evaluate the impact of HCV clearance on lipid homeostasis and non-invasive liver fibrosis markers in hepatitis C patients treated with DAAs. Material and Methods: Fifty-two patients with varying degrees of fibrosis treated with DAAs therapy were evaluated at baseline and 24 weeks post-SVR. Lipid profiles and non-invasive liver fibrosis markers were assessed. Results: Our findings revealed an increase in total cholesterol, triglyceride, and LDLc (low-density lipoprotein cholesterol) levels at 24 weeks post-SVR, alongside an improvement in serum liver enzymes. Although improvements in liver stiffness were observed in non-invasive tests, there was an increase in lipid-related markers post-SVR. Conclusions: This suggests a potential increased cardiovascular risk despite improvements in liver function and fibrosis, highlighting the necessity for statin therapy in some cases and extended follow-ups for these patients. These findings underscore the importance of closely monitoring lipid profiles in chronic hepatitis C patients post-SVR, as well as the potential need for statin therapy to mitigate cardiovascular risk. Additionally, extended follow-up is essential to assess long-term outcomes and ensure the optimal management of these patients.
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Affiliation(s)
- Oana Koppandi
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
- Multidisciplinary Doctoral School, Western University “Vasile Goldiș” of Arad, 310025 Arad, Romania
| | - Dana Iovănescu
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
| | - Bogdan Miuțescu
- Department of Gastroenterology and Hepatology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041 Timișoara, Romania; (B.M.); (D.V.)
- Advanced Regional Research Center in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Alexandru Cătălin Motofelea
- Department of Internal Medicine, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timișoara, Romania;
| | - Oana Maria Jigău
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
- Multidisciplinary Doctoral School, Western University “Vasile Goldiș” of Arad, 310025 Arad, Romania
| | - Andreea Iulia Papoi
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
- Multidisciplinary Doctoral School, Western University “Vasile Goldiș” of Arad, 310025 Arad, Romania
| | - Călin Burciu
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
- Department of Gastroenterology and Hepatology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041 Timișoara, Romania; (B.M.); (D.V.)
- Advanced Regional Research Center in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Eyad Gadour
- Department of Gastroenterology and Hepatology, King Abdulaziz Hospital-National Guard, Ahsa 31982, Saudi Arabia;
- Department of Internal Medicine, Faculty of Medicine, Zamzam University College, Khartoum 11113, Sudan
| | - Deiana Vuletici
- Department of Gastroenterology and Hepatology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041 Timișoara, Romania; (B.M.); (D.V.)
- Advanced Regional Research Center in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Eftimie Miuțescu
- Department of Gastroenterology, Faculty of Medicine, Western University “Vasile Goldiș” of Arad, Revoluţiei Boulevard 94, 310025 Arad, Romania; (O.K.); (O.M.J.); (A.I.P.); (C.B.); (E.M.)
- Multidisciplinary Doctoral School, Western University “Vasile Goldiș” of Arad, 310025 Arad, Romania
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10
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Park Y, Na SK, Yoon JH, Kim SE, Park JW, Kim GA, Lee HY, Lee YS, Kim JH. Prognosis Following Sustained Virologic Response in Korean Chronic Hepatitis C Patients Treated with Sofosbuvir-Based Treatment: Data from a Multicenter Prospective Observational Study up to 7 Years. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1132. [PMID: 39064561 PMCID: PMC11279039 DOI: 10.3390/medicina60071132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/08/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child-Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.
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Affiliation(s)
- Yewan Park
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea; (Y.P.); (G.-A.K.)
| | - Seong-Kyun Na
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea; (S.-K.N.); (H.-Y.L.)
| | - Jae-Hyun Yoon
- Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea;
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Ji-Won Park
- Department of Internal Medicine, Hallym University College of Medicine, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Gi-Ae Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea; (Y.P.); (G.-A.K.)
| | - Hyo-Young Lee
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea; (S.-K.N.); (H.-Y.L.)
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University Medical Center, Seoul 08308, Republic of Korea;
| | - Jeong-Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, Republic of Korea
- Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05029, Republic of Korea
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11
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Collazos J, Asensi V. Noninvasive Liver Fibrosis Markers in the Evaluation of Fibrosis Regression After Direct-Acting Antiviral Therapy. J Infect Dis 2024; 229:1926-1927. [PMID: 38394618 DOI: 10.1093/infdis/jiae095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 02/25/2024] Open
Affiliation(s)
- Julio Collazos
- Infectious Diseases Unit, Hospital de Galdácano-Usansolo, Galdácano, Spain
| | - Víctor Asensi
- Infectious Diseases-HIV Unit, Hospital Universitario Central de Asturias, Microbiology and Infectious Diseases Group, FINBA-ISPA, Oviedo, Spain
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12
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Ragazzo TG, Zitelli PMY, Mazo DF, Oliveira CP, Carrilho FJ, Pessoa MG. Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients? Clinics (Sao Paulo) 2024; 79:100381. [PMID: 38733689 PMCID: PMC11103362 DOI: 10.1016/j.clinsp.2024.100381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 03/20/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVES The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.
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Affiliation(s)
- Taisa Grotta Ragazzo
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil
| | - Patricia Momoyo Yoshimura Zitelli
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil
| | - Daniel F Mazo
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil; Divisão de Gastroenterologia (Gastrocentro), Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
| | - Claudia P Oliveira
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil
| | - Flait José Carrilho
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil
| | - Mário Guimarães Pessoa
- Divisão de Gastroenterologia e Hepatologia Clínica, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo ((HCFMUSP), São Paulo, SP, Brazil.
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13
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Sirinawasatien A, Supawan P. Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment. Medicine (Baltimore) 2024; 103:e38096. [PMID: 38728473 PMCID: PMC11081621 DOI: 10.1097/md.0000000000038096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.
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Affiliation(s)
- Apichet Sirinawasatien
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Paweenuch Supawan
- Division of Gastroenterology, Department of Medicine, Buriram hospital, Medical Education Center, Suranaree University, Buriram, Thailand
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14
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Xu S, Qiu L, Xu L, Liu Y, Zhang J. Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. Infect Agent Cancer 2024; 19:17. [PMID: 38664813 PMCID: PMC11046761 DOI: 10.1186/s13027-024-00578-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. METHOD Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. RESULTS During the median follow-up period of 61.00 (57.00-66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02-1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10-5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86-1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01-1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram's 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80-0.88), 0.83 (95% CI 0.79-0.87), and 0.81 (95% CI 0.77-0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). CONCLUSIONS Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
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Affiliation(s)
- Shanshan Xu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Lixia Qiu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Liang Xu
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People's Republic of China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
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15
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Lai JCT, Liang LY, Wong GLH. Noninvasive tests for liver fibrosis in 2024: are there different scales for different diseases? Gastroenterol Rep (Oxf) 2024; 12:goae024. [PMID: 38605932 PMCID: PMC11009030 DOI: 10.1093/gastro/goae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/25/2024] [Accepted: 03/11/2024] [Indexed: 04/13/2024] Open
Abstract
Liver fibrosis is the common pathway from various chronic liver diseases and its progression leads to cirrhosis which carries a significant risk for the development of portal hypertension-related complications and hepatocellular carcinoma. It is crucial to identify and halt the worsening of liver fibrosis given its important prognostic implication. Liver biopsy is the gold standard for assessing the degree of liver fibrosis but is limited due to its invasiveness and impracticality for serial monitoring. Many noninvasive tests have been developed over the years trying to assess liver fibrosis in a practical and accurate way. The tests are mainly laboratory- or imaging-based, or in combination. Laboratory-based tests can be derived from simply routine blood tests to patented laboratory parameters. Imaging modalities include ultrasound and magnetic resonance elastography, in which vibration-controlled transient elastography is the most widely validated and adopted whereas magnetic resonance elastography has been proven the most accurate liver fibrosis assessment tool. Nonetheless, noninvasive tests do not always apply to all liver diseases, nor does a common cut-off value of a test mean the same degree of liver fibrosis in different scenarios. In this review, we discuss the diagnostic and prognostic performance, as well as the confounders and limitations, of different noninvasive tests on liver fibrosis assessment in various liver diseases.
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Affiliation(s)
- Jimmy Che-To Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
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Furuta A, Oura S, Shintani H, Kataoka N, Tanaka H, Takamatsu S, Ono W. Focal coagulative necrosis of the liver in a patient with sustained virologic response to anti-hepatitis C virus therapy. Radiol Case Rep 2024; 19:1514-1518. [PMID: 38304350 PMCID: PMC10830427 DOI: 10.1016/j.radcr.2024.01.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/08/2024] [Accepted: 01/10/2024] [Indexed: 02/03/2024] Open
Abstract
A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.
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Affiliation(s)
- Akito Furuta
- Department of Gastroenterology, Kishiwada Tokushukai Hospital, Kishiwada-city, Osaka, Japan
| | - Shoji Oura
- Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada-city, Osaka, 596-8522, Japan
| | - Hiroshi Shintani
- Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada-city, Osaka, 596-8522, Japan
| | - Naoki Kataoka
- Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada-city, Osaka, 596-8522, Japan
| | - Hiroto Tanaka
- Department of Gastroenterology, Kishiwada Tokushukai Hospital, Kishiwada-city, Osaka, Japan
| | - Seigo Takamatsu
- Department of Gastroenterology, Kishiwada Tokushukai Hospital, Kishiwada-city, Osaka, Japan
| | - Wataru Ono
- Department of Gastroenterology, Kishiwada Tokushukai Hospital, Kishiwada-city, Osaka, Japan
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Collazos J, Pérez-Is L, de la Fuente B, Morano L, Rivas-Carmenado M, Rodriguez M, Romero-Favela A, de Jesús Fonseca-González G, Melón S, Diaz-Arias J, Valle-Garay E, Asensi V. No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients. Sci Rep 2024; 14:7534. [PMID: 38553507 PMCID: PMC10980728 DOI: 10.1038/s41598-024-57845-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/22/2024] [Indexed: 04/02/2024] Open
Abstract
Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.
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Affiliation(s)
- Julio Collazos
- Infectious Diseases Unit, Hospital of Galdakao-Usansolo, Galdácano Vizcaya, Spain
| | - Laura Pérez-Is
- Biochemistry and Molecular Biology, University of Oviedo Medical School, Oviedo, Spain
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | - Luis Morano
- Infectious Diseases Unit, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain
| | - Maria Rivas-Carmenado
- Infectious Diseases-HIV Unit, Hospital Universitario Central de Asturias, University of Oviedo Medical School, Oviedo, Spain
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Manuel Rodriguez
- Gastroenterology and Hepatology Service, Hospital Universitario Central de Asturias, University of Oviedo Medical School, Oviedo, Spain
| | | | | | - Santiago Melón
- Virology Division, Hospital Universitario Central de Asturias, University of Oviedo Medical School, Oviedo, Spain
| | - Javier Diaz-Arias
- Biochemistry and Molecular Biology, University of Oviedo Medical School, Oviedo, Spain
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Eulalia Valle-Garay
- Biochemistry and Molecular Biology, University of Oviedo Medical School, Oviedo, Spain
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Víctor Asensi
- Infectious Diseases-HIV Unit, Hospital Universitario Central de Asturias, University of Oviedo Medical School, Oviedo, Spain.
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
- Infectious Diseases-HIV Unit, Hospital Universitario Central de Asturias, Avenida de Roma S/N, 33011, Oviedo, Spain.
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18
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Hildenbrand FF, Illi B, von Felten S, Bachofner J, Gawinecka J, von Eckardstein A, Müllhaupt B, Mertens JC, Blümel S. Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis. BMC Gastroenterol 2024; 24:54. [PMID: 38291388 PMCID: PMC10825988 DOI: 10.1186/s12876-023-03116-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND & AIMS With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. METHODS 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman's correlation and AUROC analyses. RESULTS Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman's rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65-0.83), and 0.67(95%CI 0.56-0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. CONCLUSIONS sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.
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Affiliation(s)
- Florian F Hildenbrand
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Stadtspital Zurich, Zurich, Switzerland
| | - Barbara Illi
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Stefanie von Felten
- Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Jacqueline Bachofner
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Joanna Gawinecka
- Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Arnold von Eckardstein
- Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Beat Müllhaupt
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | | | - Sena Blümel
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
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19
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Zhou J, Wang FD, Li LQ, Li JY, Chen EQ. Decreased Efficacy of Sofosbuvir/Velpatasvir in HIV Patients Coinfected with HCV Genotype 3b. Future Virol 2024; 19:33-45. [DOI: 10.2217/fvl-2023-0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 01/29/2024] [Indexed: 01/13/2025]
Affiliation(s)
- Jing Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Fa-Da Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lan-Qing Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing-Yu Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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20
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Mondelli MU, Ottolini S, Oliviero B, Mantovani S, Cerino A, Mele D, Varchetta S. Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity. Int J Mol Sci 2023; 25:268. [PMID: 38203436 PMCID: PMC10779088 DOI: 10.3390/ijms25010268] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatitis C virus (HCV) has spread worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of the host's immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct-acting antivirals (DAA) has created hope for the progressive elimination of chronic HCV infections; however, this approach requires a monumental global effort. HCV elicits a prompt innate immune response in the host, characterized by a robust production of interferon-α (IFN-α), although interference in IFN-α signaling by HCV proteins may curb this effect. The late appearance of largely ineffective neutralizing antibodies and the progressive exhaustion of T cells, particularly CD8 T cells, result in the inability to eradicate the virus in most infected patients. Moreover, an HCV cure resulting from DAA treatment does not completely restore the normal immunologic homeostasis. Here, we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.
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Affiliation(s)
- Mario U. Mondelli
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Sabrina Ottolini
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Barbara Oliviero
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Stefania Mantovani
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Antonella Cerino
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Dalila Mele
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Stefania Varchetta
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
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21
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Herlihy T, Moran M, Heeney A, Okhai H, De Franceso D, Cronin C, Feeney E, Houlihan D, Stewart S, Cotter AG. A comparison of transient elastography with acoustic radiation force impulse elastography for the assessment of liver health in patients with chronic hepatitis C: Baseline results from the TRACER study. ULTRASOUND (LEEDS, ENGLAND) 2023; 31:244-253. [PMID: 37929249 PMCID: PMC10621485 DOI: 10.1177/1742271x221139181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 10/18/2022] [Indexed: 11/07/2023]
Abstract
Background Liver stiffness measurements can be used to assess liver fibrosis and can be acquired by transient elastography using FibroScan® and with Acoustic Radiation Force Impulse imaging. The study aimed to establish liver stiffness measurement scores using FibroScan® and Acoustic Radiation Force Impulse in a chronic hepatitis C cohort and to explore the correlation and agreement between the scores and the factors influencing agreement. Methods Patients had liver stiffness measurements acquired with FibroScan® (right lobe of liver) and Acoustic Radiation Force Impulse (right and left lobe of liver). We used Spearman's correlation to explore the relationship between FibroScan® and Acoustic Radiation Force Impulse scores. A Bland-Altman plot was used to evaluate bias between the mean percentage differences of FibroScan® and Acoustic Radiation Force Impulse scores. Univariable and multivariable analyses were used to assess how factors such as body mass index, age and gender influenced the agreement between liver stiffness measurements. Results Bland-Altman showed the average (95% CI) percentage difference between FibroScan® and Acoustic Radiation Force Impulse scores was 27.5% (17.8, 37.2), p < 0.001. There was a negative correlation between the average and percentage difference of the FibroScan® and Acoustic Radiation Force Impulse scores ( r (95% CI) = -0.41 (-0.57, -0.21), p < 0.001), thus showing that percentage difference gets smaller for greater FibroScan® and Acoustic Radiation Force Impulse scores. Body mass index was the biggest influencing factor on differences between FibroScan® and Acoustic Radiation Force Impulse (r = 0.12 (0.01, 0.23), p = 0.05). Acoustic Radiation Force Impulse scores at segment 5/8 and the left lobe showed good correlation (r (95% CI) = 0.83 (0.75, 0.89), p < 0.001). Conclusion FibroScan® and Acoustic Radiation Force Impulse had similar predictive values for the assessment of liver stiffness in patients with chronic hepatitis C infection; however, the level of agreement varied across lower and higher scores.
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Affiliation(s)
- Therese Herlihy
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
| | - Mary Moran
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Aoife Heeney
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Hajra Okhai
- Institute for Global Health, University College London, London, UK
| | | | - Carmel Cronin
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Eoin Feeney
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
- St. Vincent’s University Hospital, Dublin, Ireland
| | | | - Stephen Stewart
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Aoife G Cotter
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
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22
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Bojanic K, Bogojevic MS, Vukadin S, Sikora R, Ivanac G, Lucic NR, Smolic M, Tabll AA, Wu GY, Smolic R. Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update. J Clin Transl Hepatol 2023; 11:1228-1238. [PMID: 37577224 PMCID: PMC10412701 DOI: 10.14218/jcth.2022.00365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/04/2022] [Accepted: 02/27/2023] [Indexed: 07/03/2023] Open
Abstract
Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.
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Affiliation(s)
- Kristina Bojanic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | | | - Sonja Vukadin
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Renata Sikora
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | - Gordana Ivanac
- University Hospital Dubrava, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Nikola Raguz Lucic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Martina Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt
| | - George Y. Wu
- University of Connecticut Health Center, Farmington, CT, USA
| | - Robert Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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23
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Elbahrawy A, Atalla H, Mahmoud AA, Eliwa A, Alsawak A, Alboraie M, Madian A, Alashker A, Mostafa S, Alwassief A, Aly HH. Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents. FRONTIERS IN VIROLOGY 2023; 3. [DOI: 10.3389/fviro.2023.1227317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
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24
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Thi Thu PN, Hoang Van D, Ngo Thi Quynh M, Tran Thi N, Pham Minh K, Pham Van L. Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study. PLoS One 2023; 18:e0290235. [PMID: 37656689 PMCID: PMC10473482 DOI: 10.1371/journal.pone.0290235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/05/2023] [Indexed: 09/03/2023] Open
Abstract
The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.
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Affiliation(s)
- Phuong Nguyen Thi Thu
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | | | | | - Ngan Tran Thi
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Khue Pham Minh
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Linh Pham Van
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
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25
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Rinaldi L, Giorgione C, Mormone A, Esposito F, Rinaldi M, Berretta M, Marfella R, Romano C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023; 15:1730. [PMID: 37632072 PMCID: PMC10459581 DOI: 10.3390/v15081730] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Andrea Mormone
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Francesca Esposito
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Michele Rinaldi
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, 80131 Naples, Italy;
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
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Watanabe T, Tokumoto Y, Joko K, Michitaka K, Horiike N, Tanaka Y, Hiraoka A, Tada F, Ochi H, Kisaka Y, Nakanishi S, Yagi S, Yamauchi K, Higashino M, Hirooka K, Morita M, Okazaki Y, Yukimoto A, Hirooka M, Abe M, Hiasa Y. Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals. Sci Rep 2023; 13:8992. [PMID: 37268672 DOI: 10.1038/s41598-023-36052-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/28/2023] [Indexed: 06/04/2023] Open
Abstract
The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.
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Affiliation(s)
- Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Norio Horiike
- Department of Gastroenterology, Saiseikai Imabari Hospital, 7-1-6 Kitamura, Imabari, Ehime, 799-1502, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, 2-6-5 Ootemachi, Matsuyama, Ehime, 790-0067, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, 83 Kasugamachi, Matsuyama, Ehime, 790-0024, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, 1 Bunkyocho, Matsuyama, Ehime, 790-8524, Japan
| | - Yoshiyasu Kisaka
- Department of Gastroenterology, Uwajima City Hospital, 1-1 Gotenmachi, Uwajima, Ehime, 798-8510, Japan
| | - Seiji Nakanishi
- Department of Gastroenterology, Ehime Prefectural Imabari Hospital, 4-5-5 Ishiicho, Imabari, Ehime, 794-0006, Japan
| | - Sen Yagi
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Kazuhiko Yamauchi
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Makoto Higashino
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, 880-2 Yamanishicho, Matsuyama, Ehime, 791-8026, Japan
| | - Kana Hirooka
- Department of Gastroenterology, National Hospital Organization Ehime Medical Center, 366 Yokogawara, Toon, Ehime, 791-0203, Japan
| | - Makoto Morita
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yuki Okazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Atsushi Yukimoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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Tahata Y, Sakamori R, Yamada R, Kodama T, Hikita H, Hagiwara H, Oshita M, Imai Y, Hiramatsu N, Mita E, Kaneko A, Miyazaki M, Ohkawa K, Hijioka T, Fukui H, Ito T, Yamamoto K, Doi Y, Yoshida Y, Yamada Y, Yakushijin T, Tatsumi T, Takehara T. Improved Liver Function After Sustained Virologic Response Enhanced Prognosis in Hepatitis C with Compensated Advanced Liver Fibrosis. Dig Dis Sci 2023; 68:2115-2122. [PMID: 36526814 DOI: 10.1007/s10620-022-07629-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 07/16/2022] [Indexed: 04/27/2023]
Abstract
BACKGROUND AND AIM Liver function can be improved in patients with chronic hepatitis C virus (HCV) infection who achieved sustained virologic response (SVR) with direct-acting antiviral (DAA) treatment. However, to our knowledge, the impact of liver function improvement after SVR on prognosis has not been investigated. METHODS A total of 716 patients with chronic HCV infection and compensated advanced liver fibrosis who began receiving DAA treatment between September 2014 and August 2018 in 25 Japanese hospitals and achieved SVR were enrolled. RESULTS The median age was 73 years, and 336 (47%) and 380 (53%) patients had albumin-bilirubin (ALBI) grade 1 and grade 2, respectively. Improvement to ALBI grade 1 at 1 year after the end of treatment (EOT) was observed in 76% of the patients with baseline ALBI grade 2. Among 380 patients with baseline ALBI grade 2, alanine aminotransferase (ALT) levels ≥ 40 U/L (p < 0.001) and modified ALBI (mALBI) grade 2a (p < 0.001) were significantly associated with improvement to ALBI grade 1 at 1 year after EOT in multivariate analysis. During the median observation period of 51.8 months, 4 and 10 patients with baseline ALBI grade 1 and 2, respectively, died. In patients with baseline ALBI grade 2, only the absence of improvement to ALBI grade 1 at 1 year after EOT was significantly associated with all-cause mortality in univariate analysis. CONCLUSIONS Baseline ALT levels and mALBI grade were significantly associated with improvement in liver function after SVR. Patients whose liver function improved after SVR could have better prognosis.
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Affiliation(s)
- Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | | | | | | | | | - Eiji Mita
- National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan
| | | | | | | | - Taizo Hijioka
- National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan
| | | | - Toshifumi Ito
- Japan Community Healthcare Organization Osaka Hospital, Osaka, Osaka, Japan
| | - Keiji Yamamoto
- National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
| | | | | | | | | | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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Matsumoto K, Kikuchi K, Namura Y, Watanabe A, Tsunashima H, Doi S. Histological improvement in chronic hepatitis C-autoimmune hepatitis overlap syndrome by glecaprevir and pibrentasvir. Clin J Gastroenterol 2023:10.1007/s12328-023-01809-7. [PMID: 37118643 DOI: 10.1007/s12328-023-01809-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 04/18/2023] [Indexed: 04/30/2023]
Abstract
A 60-year-old man with type-2 diabetes and chronic hepatitis C (HCV) was diagnosed with single hepatocellular carcinoma (HCC) of 67 mm in the hepatic posterior right lobe. Lenvatinib 8 mg was initiated but discontinued because of grade 3 liver injury. The patient continued to have prolonged liver injury and persistently high immunoglobulin G levels. Antinuclear antibody titer increased from 1:40 to 1:320. Histopathological examination of a liver biopsy specimen revealed interface hepatitis with lymphocyte and plasma cell infiltration, rosette formation, and emperipolesis, suggesting the possibility of autoimmune hepatitis (AIH). First, treatment with prednisolone was initiated; however, the response was poor. After starting glecaprevir/pibrentasvir (GLE/PIB) as direct-acting antivirals (DAA), HCV RNA rapidly disappeared, and serological liver function improved. After confirmation of sustained virological response 24, HCC recurrence was observed, and partial hepatectomy was performed. Background liver findings showed that liver parenchymal inflammation improved compared with that before DAA treatment. This is the first case of HCV-AIH overlap syndrome treated with DAA using GLE/PIB. Liver function improved within a short treatment period of 8 weeks, as confirmed using serology and histology.
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Affiliation(s)
- Kotaro Matsumoto
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, 213-8507, Japan.
| | - Kentaro Kikuchi
- Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan
| | - Yuta Namura
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, 213-8507, Japan
| | - Ayako Watanabe
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, 213-8507, Japan
| | - Hiromichi Tsunashima
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, 213-8507, Japan
| | - Shinpei Doi
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, 213-8507, Japan
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Niu B, Zang W, Zhou H, Mi Y, Lu C, Li P. Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment. BMC Gastroenterol 2023; 23:102. [PMID: 37013471 PMCID: PMC10069046 DOI: 10.1186/s12876-023-02732-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 03/20/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.
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Affiliation(s)
- Bin Niu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Wenqian Zang
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Hui Zhou
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Chengzhen Lu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China.
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30
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Rasmy HS, Elmalatawy MAE, ElKarmoty KZ, Abdelwarth EY, Isaac A. Serum retinol-binding protein 4 as a predictor of fibrosis regression and response to direct-acting antiviral drugs in chronic hepatitis C virus patients. EGYPTIAN LIVER JOURNAL 2023. [DOI: 10.1186/s43066-023-00251-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
Abstract
Abstract
Background
Hepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents.
Methods
This study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis.
Results
Baseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%.
Conclusion
Serum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis.
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31
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Passos-Castilho AM, Udhesister STP, Fontaine G, Jeong D, Dickie M, Lund C, Russell R, Kronfli N. The 11th Canadian Symposium on Hepatitis C Virus: 'Getting back on track towards hepatitis C elimination'. CANADIAN LIVER JOURNAL 2023; 6:56-69. [PMID: 36908576 PMCID: PMC9997521 DOI: 10.3138/canlivj-2022-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 08/20/2022] [Indexed: 11/05/2022]
Abstract
Hepatitis C virus (HCV) affects approximately 204,000 Canadians. Safe and effective direct-acting antiviral therapies have contributed to decreased rates of chronic HCV infection and increased treatment uptake in Canada, but major challenges for HCV elimination remain. The 11th Canadian Symposium on Hepatitis C Virus took place in Ottawa, Ontario on May 13, 2022 as a hybrid conference themed 'Getting back on track towards hepatitis C elimination.' It brought together research scientists, clinicians, community health workers, patient advocates, community members, and public health officials to discuss priorities for HCV elimination in the wake of the COVID-19 pandemic, which had devastating effects on HCV care in Canada, particularly on priority populations. Plenary sessions showcased topical research from prominent international and national researchers, complemented by select abstract presentations. This event was hosted by the Canadian Network on Hepatitis C (CanHepC), with support from the Public Health Agency of Canada and the Canadian Institutes of Health Research and in partnership with the Canadian Liver Meeting. CanHepC has an established record in HCV research and in advocacy activities to address improved diagnosis and treatment, and immediate and long-term needs of those affected by HCV infection. The Symposium addressed the remaining challenges and barriers to HCV elimination in priority populations and principles for meaningful engagement of Indigenous communities and individuals with living and lived experience in HCV research. It emphasized the need for disaggregated data and simplified pathways for creating and monitoring interventions for equitably achieving elimination targets.
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Affiliation(s)
- Ana Maria Passos-Castilho
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.,Department of Medicine, McGill University, Montreal, Quebec, Canada
| | - Sasha Tejna Persaud Udhesister
- Faculté de Médecine, Université de Montréal, Centre de Recherche du Centre hospitalier de l'Université de Montré (CRCHUM), Montréal, Québec, Canada
| | - Guillaume Fontaine
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Dahn Jeong
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Melisa Dickie
- Community Health Programming, CATIE, Toronto, Ontario, Canada
| | | | - Rodney Russell
- Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada
| | - Nadine Kronfli
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.,Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
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32
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Sato T, Head KZ, Li J, Dolin CE, Wilkey D, Skirtich N, Smith K, McCreary DD, Liu S, Beier JI, Singhi AD, McEnaney RM, Merchant ML, Arteel GE. Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2. Matrix Biol Plus 2023; 17:100127. [PMID: 36632559 PMCID: PMC9826883 DOI: 10.1016/j.mbplus.2022.100127] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 12/05/2022] [Accepted: 12/25/2022] [Indexed: 12/29/2022] Open
Abstract
Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was twofold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the "degradome") in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl4) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl4. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new "theragnostic" targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.
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Affiliation(s)
- Toshifumi Sato
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, United States
| | - Kimberly Z. Head
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Jiang Li
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, United States
| | - Christine E. Dolin
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States
| | - Daniel Wilkey
- Department of Medicine, Division of Nephrology and Hypertension, University of Louisville, Louisville, KY 40292, United States
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40292, United States
| | - Nolan Skirtich
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Katelyn Smith
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Dylan D. McCreary
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Sylvia Liu
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, United States
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Juliane I. Beier
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, United States
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Aatur D. Singhi
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, United States
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Ryan M. McEnaney
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States
| | - Michael L. Merchant
- Department of Medicine, Division of Nephrology and Hypertension, University of Louisville, Louisville, KY 40292, United States
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40292, United States
| | - Gavin E. Arteel
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, United States
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States
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33
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Kozuka R, Tamori A, Enomoto M, Muto-Yukawa Y, Odagiri N, Kotani K, Motoyama H, Kawamura E, Hagihara A, Fujii H, Uchida-Kobayashi S, Kawada N. Risk factors for liver-related and non-liver-related mortality following a sustained virological response after direct-acting antiviral treatment for hepatitis C virus infection in a real-world cohort. J Viral Hepat 2022; 30:374-385. [PMID: 36583600 DOI: 10.1111/jvh.13795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 12/15/2022] [Accepted: 12/17/2022] [Indexed: 12/31/2022]
Abstract
A direct-acting antiviral (DAA)-induced sustained virological response (SVR) reduces the risk of mortality. However, the risk factors associated with liver-related and non-liver-related mortality following a SVR after DAA treatment are unclear. We assessed the incidence and risk factors of liver-related and non-liver-related mortality in 1180 patients who achieved a SVR after DAA treatment. During the follow-up period after DAA treatment (median duration, 1099 [range: 84-2345] days), 53 (4.5%) patients died: 15 due to liver-related mortality, 25 due to non-liver-related mortality and 13 due to unknown causes. The all-cause, liver-related and non-liver-related mortality rates were 14.9, 4.2 and 7.0/1000 person-years, respectively. In a multivariate analysis, the development of hepatocellular carcinoma (HCC) after DAA treatment (p = .009; hazard ratio [HR], 31.484), an estimated glomerular filtration rate (eGFR) at baseline ≤61.68 ml/min/1.73 m2 (p = .015; HR, 6.607), and an α-fetoprotein level post-treatment ≥7.6 ng/ml (p = .041; HR, 18.490) were significantly associated with liver-related mortality. Furthermore, eGFR ≤67.94 ml/min/1.73 m2 at baseline (p = .012; HR, 3.407) and albumin-bilirubin (ALBI) grade ≥ 2 at SVR (p = .024; HR, 3.449) were significantly associated with non-liver-related mortality. Early diagnosis and therapeutic interventions for HCC development after DAA treatment are important to reduce liver-related mortality. The ALBI grade, which reflects the hepatic functional reserve, is a useful predictor of non-liver-related mortality after a SVR induced by DAA treatment. Furthermore, the renal dysfunction caused by metabolic syndrome may affect prognosis even after eliminating hepatitis C virus.
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Affiliation(s)
- Ritsuzo Kozuka
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Kashiwara Municipal Hospital, Osaka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yoshimi Muto-Yukawa
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Naoshi Odagiri
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Kohei Kotani
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Hiroyuki Motoyama
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Etsushi Kawamura
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Sawako Uchida-Kobayashi
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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Takehara T, Izumi N, Mochida S, Genda T, Fujiyama S, Notsumata K, Tamori A, Suzuki F, Suri V, Mercier RC, Matsuda T, Matsuda K, Kato N, Chayama K, Kumada H. Sofosbuvir-velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan. Hepatol Res 2022; 52:833-840. [PMID: 35802063 DOI: 10.1111/hepr.13810] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/28/2022] [Accepted: 07/06/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND & PURPOSE Protease-free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir-velpatasvir in participants with HCV and compensated cirrhosis in Japan. METHODS This was a Phase 3, multi-center, open-label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir-velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment-naïve or treatment-experienced with interferon-based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance-associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on-treatment breakthrough or relapse occurred. Sofosbuvir-velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia. CONCLUSION Sofosbuvir-velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single-tablet regimen offers a highly effective, protease-inhibitor free regimen for treating HCV. CLINICALTRIALS gov Identifier: NCT04112303.
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Affiliation(s)
- Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Shigetoshi Fujiyama
- Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto, Japan
| | - Kazuo Notsumata
- Department of Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital Kajigaya, Kanagawa, Japan
| | - Vithika Suri
- Gilead Sciences, Inc, Foster City, California, USA
| | | | | | | | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis. J Pers Med 2022; 12:jpm12091517. [PMID: 36143302 PMCID: PMC9506163 DOI: 10.3390/jpm12091517] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/30/2022] Open
Abstract
DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83–88%), the development of HCC 7% (95% CI 5–9%), and mortality 6% (95% CI 4–8%). Improvement in liver function was observed in 51% (95% CI 44–58%) of patients, and 16% (95% CI 5–40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.
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Choi GH, Jang ES, Kim YS, Lee YJ, Kim IH, Cho SB, Lee HC, Jang JW, Ki M, Choi HY, Baik D, Jeong SH. Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study. World J Gastroenterol 2022; 28:4182-4200. [PMID: 36157119 PMCID: PMC9403421 DOI: 10.3748/wjg.v28.i30.4182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/24/2022] [Accepted: 07/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries.
AIM To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR.
METHODS This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results.
RESULTS During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis.
CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.
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Affiliation(s)
- Gwang Hyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, South Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 47392, South Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju 54907, Jeonbuk, South Korea
| | - Sung Bum Cho
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, South Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Moran Ki
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Hwa Young Choi
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Dahye Baik
- Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea
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Armandi A, Rosso C, Troshina G, Pérez Diaz Del Campo N, Marinoni C, Nicolosi A, Caviglia GP, Saracco GM, Bugianesi E, Ciancio A. Changes in Liver Stiffness and Markers of Liver Synthesis and Portal Hypertension following Hepatitis C Virus Eradication in Cirrhotic Individuals. BIOLOGY 2022; 11:1160. [PMID: 36009789 PMCID: PMC9404889 DOI: 10.3390/biology11081160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 11/16/2022]
Abstract
The advent of direct antiviral agents (DAAs) has radically changed the natural history of hepatitis C virus (HCV) chronic liver disease. Even patients with cirrhosis may display improvements in liver function or features of portal hypertension following viral eradication. The aim of this study was to assess whether a HCV cure would lead to improvements in cirrhotic patients using simple, readily available tools in clinical practice, together with liver stiffness (LS) measurement. This is a retrospective study of cirrhotic patients with cured HCV infection, with or without previous decompensation. Clinical and biochemical parameters as well as LS measurements were collected before antiviral treatment with DAAs and after 6 months following sustained virological response. Hepatic synthesis was assessed by serum albumin levels. Portal hypertension was indirectly assessed by platelet count. Liver function was determined by the CHILD score. A total of 373 cirrhotic patients with successful HCV eradication were retrospectively included. After 6 months of follow-up, a significantly higher proportion of patients showed improved liver function, shifting from the CHILD B/C to CHILD A group, (71.4%, p < 0.001). Similarly, LS improved from a median of 19.3 kPa (14.7−27) at the baseline vs. a median of 11.6 (7.7−16.8 kPa) at follow-up (p < 0.001). The proportion of patients who showed improved hepatic synthesis was 66.0%, which was statistically different when compared to that of patients who had a worsened condition (0.3%) (p < 0.001). Moreover, when classifying the cohort according to the RESIST-HCV score, we found that a significant proportion of patients shifted into the “low risk” group following DAA treatment (52% baseline vs. 45.6% at follow-up, p = 0.004). Even in the decompensated patients, LS improved from 1.6 to 2-fold from the baseline. Antiviral treatment is effective in improving indirect signs of hepatic synthesis and portal hypertension. Similarly, the LS values displayed significant improvements, even in decompensated patients.
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Affiliation(s)
- Angelo Armandi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany
| | - Chiara Rosso
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Giulia Troshina
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Nuria Pérez Diaz Del Campo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Chiara Marinoni
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Aurora Nicolosi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Gian Paolo Caviglia
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
| | - Giorgio Maria Saracco
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
- Division of Gastroenterology, Città Della Salute e Della Scienza University-Hospital, 10100 Turin, Italy
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
- Division of Gastroenterology, Città Della Salute e Della Scienza University-Hospital, 10100 Turin, Italy
| | - Alessia Ciancio
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.T.); (N.P.D.D.C.); (C.M.); (A.N.); (G.P.C.); (G.M.S.); (E.B.); (A.C.)
- Division of Gastroenterology, Città Della Salute e Della Scienza University-Hospital, 10100 Turin, Italy
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Kaneko S, Kurosaki M, Kurisu A, Akita T, Tanaka J, Kanto T. Impact of antiviral therapy for disease progression and non-invasive liver fibrosis index in patients with chronic hepatitis C: Markov chain model analysis. Hepatol Res 2022; 52:665-676. [PMID: 35591759 DOI: 10.1111/hepr.13794] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/19/2022] [Accepted: 05/13/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND/AIM Antiviral therapy advancements resulted in an era in which eradication of hepatitis C has become a goal, however, there are few reports on the long-term course of liver disease progression with antiviral therapy. The aim of this study was to use the Markov model to analyze disease progression and non-invasive liver fibrosis index in hepatitis C Patients. METHODS Patients with chronic hepatitis C (n = 1432) were diagnosed between January 2012 and May 2021 in the Musashino Red Cross Hospital. Patients with other hepatitis virus co-infection, chronic liver disease, and hepatocellular carcinoma (HCC) at the beginning of the study were excluded. A total of 618 patients with a 1-year or longer observation period were studied. The liver disease state was defined as chronic hepatitis (CH), compensated liver cirrhosis (CLC), decompensated liver cirrhosis (DLC), and HCC. RESULTS Cirrhosis and high FIB-4 index (≥3.61) were 42 cases (6.8%) and 208 cases (33.6%), respectively at the start of the study. The 40 years estimated transition analysis of 40-year-old CH low FIB-4 level (<3.61) revealed that the proportion of CH low/high, CLC low/high, DLC low/high, and HCC were 10.83%/10.86%, 0.35%/2.64%, 0%/3.21% 72.11% in untreated unit and 47.83%/9.21%, 6.69%/1.32%, 0.70%/0.99%, 33.27% in treated unit, respectively. Antiviral therapy suppressed liver fibrosis, disease progression, and HCC development significantly. CONCLUSION Markov model analysis of hepatitis C virus patients showed the impact of antiviral therapy on the suppression of disease progression in the order of CH, CLC, and DLC.
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Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tatsuya Kanto
- Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan
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Dai YK, Zhao ZM, Liu C. Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis. Front Pharmacol 2022; 13:942841. [PMID: 35903335 PMCID: PMC9315937 DOI: 10.3389/fphar.2022.942841] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 06/13/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives: To analyze the research hotspots, evolution, and trends of the treatment of liver fibrosis in the recent 20 years, bibliometric and knowledge-map analysis were used. Methods: Publications associated with the treatment of liver fibrosis were retrieved from the Web of Science Core Collection on 16 April 2022. CiteSpace 5.8.R3 and VOSviewer 1.6.18 were calculated to perform bibliometric and knowledge-map analysis. Results: A total of 72,686 authors from 200 institutions in 134 countries/regions published 15,237 studies in different academic journals. United States was the most productive country, and Shanghai Jiao Tong University was the most published institution. Trauner Michael had the most published articles, whereas Scott L. Friedman was the most frequently co-cited author. Moreover, there was frequent inter-institution cooperation between countries in the years 2015 and after, but the before years showed rare inter-institution cooperation. The journal HEPATOLOGY was both the most published publication and the most frequently co-cited one in this field. Screened keywords, such as virus infection, inflammation, oxidative stress, activation of hepatic stellate cell (HSC), and hepatocellular apoptosis, could be both therapeutic targets and pathological mechanisms in terms of liver fibrosis. Furthermore, long-term suppression of hepatitis B virus replication and the activation of HSC were the latest hotspots and topics related to the treatment of liver fibrosis. Besides, the treatments of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis were also involved in the treatment of liver fibrosis, which were both emerging topics and rapidly developing hot fields. Conclusion: This bibliometric analysis conducted a full overview of the treatment of liver fibrosis, which provided important clues and ideas for scholars focusing on this field. Not only that, the field is still in a stage of rapid development and will continue to be a research hotspot in the future.
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Affiliation(s)
- Yun-Kai Dai
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhi-Min Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- *Correspondence: Chenghai Liu, ; Zhi-Min Zhao,
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai, China
- *Correspondence: Chenghai Liu, ; Zhi-Min Zhao,
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Lockart I, Yeo MGH, Hajarizadeh B, Dore G, Danta M, Abe K, Carrat F, Lusivika‐Nzinga C, Degasperi E, Di Marco V, Hou J, Howell J, Janjua NZ, Wong S, Kumada T, Lleo A, Persico M, Lok AS, Wei L, Yang M, Nabatchikova E, Nguyen MH, Antonio Pineda J, Reig M, Shiha G, Yu M, Tsai P. HCC incidence after hepatitis C cure among patients with advanced fibrosis or cirrhosis: A meta-analysis. Hepatology 2022; 76:139-154. [PMID: 35030279 PMCID: PMC9303770 DOI: 10.1002/hep.32341] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/28/2021] [Accepted: 01/04/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS HCV cure reduces but does not eliminate the risk of HCC. HCC surveillance is recommended in populations where the incidence exceeds 1.5% per year. In cirrhosis, HCC surveillance should continue after HCV cure, although it is uncertain if this should be indefinite. For patients with advanced fibrosis (F3), guidelines are inconsistent in their recommendations. We evaluated the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. APPROACH AND RESULTS This systematic review and meta-analysis identified 44 studies (107,548 person-years of follow-up) assessing the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. The incidence of HCC was 2.1 per 100 person-years (95% CI, 1.9-2.4) among patients with cirrhosis and 0.5 per 100 person-years (95% CI, 0.3-0.7) among patients with F3 fibrosis. In a meta-regression analysis among patients with cirrhosis, older age (adjusted rate ratio [aRR] per 10-year increase in mean/median age, 1.32; 95% CI, 1.00-1.73) and prior decompensation (aRR per 10% increase in the proportion of patients with prior decompensation, 1.06; 95% CI, 1.01-1.12) were associated with an increased incidence of HCC. Longer follow-up after HCV cure was associated with a decreased incidence of HCC (aRR per year increase in mean/median follow-up, 0.87; 95% CI, 0.79-0.96). CONCLUSIONS Among patients with cirrhosis, the incidence of HCC decreases over time after HCV cure and is lowest in patients with younger age and compensated cirrhosis. The substantially lower incidence in F3 fibrosis is below the recommended threshold for cost-effective screening. The results should encourage the development of validated predictive models that better identify at-risk individuals, especially among patients with F3 fibrosis.
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Affiliation(s)
- Ian Lockart
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia,St. Vincent’s HospitalSydneyNew South WalesAustralia
| | - Malcolm G. H. Yeo
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
| | - Behzad Hajarizadeh
- The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Gregory J. Dore
- St. Vincent’s HospitalSydneyNew South WalesAustralia,The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Mark Danta
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia,St. Vincent’s HospitalSydneyNew South WalesAustralia
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Elsharkawy A, Samir R, El-Kassas M. Fibrosis regression following hepatitis C antiviral therapy. World J Hepatol 2022; 14:1120-1130. [PMID: 35978676 PMCID: PMC9258254 DOI: 10.4254/wjh.v14.i6.1120] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/16/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Reham Samir
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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Mezina A, Krishnan A, Woreta TA, Rubenstein KB, Watson E, Chen PH, Rodriguez-Watson C. Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis C patients. World J Clin Cases 2022; 10:5566-5576. [PMID: 35979107 PMCID: PMC9258363 DOI: 10.12998/wjcc.v10.i17.5566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 12/16/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases. Fibrosis progression varies markedly in patients with hepatitis C virus (HCV). Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV. AIM To investigate changes in liver stiffness measured by transient elastography (TE) in a large, racially diverse cohort of United States patients with chronic hepatitis C (CHC). METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral (DAA) therapy and untreated patients. Patients had ≥ 2 TE measurements and no prior DAA exposure. We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment, controlling for age, sex, race, diabetes, smoking status, human immunodeficiency virus status, baseline alanine aminotransferase, and baseline liver stiffness. Separate regression models analyzed the change in liver stiffness as measured by kPa, stratified by cirrhosis status. RESULTS Of 813 patients, 419 (52%) initiated DAA treatment. Baseline liver stiffness was 12 kPa in 127 (16%). Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients, respectively. There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment (0.016 kPa/month; CI: -0.051, 0.084) or in the untreated group (0.001 kPa/mo; CI: -0.090, 0.092), controlling for covariates. A higher baseline kPa score was independently associated with decreased liver stiffness. CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.
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Affiliation(s)
- Anya Mezina
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Kevin B Rubenstein
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Eric Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Carla Rodriguez-Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, United States
- Innovation in Medical Evidence Development and Surveillance (IMEDS) Program, Reagan-Udall Foundation for the FDA, Washington, 20036, United States
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Rau M, Buggisch P, Mauss S, Boeker KHW, Klinker H, Müller T, Stoehr A, Schattenberg JM, Geier A. Prognostic impact of steatosis in the clinical course of chronic HCV infection—Results from the German Hepatitis C-Registry. PLoS One 2022; 17:e0264741. [PMID: 35709466 PMCID: PMC9203066 DOI: 10.1371/journal.pone.0264741] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/15/2022] [Indexed: 11/29/2022] Open
Abstract
Background Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients. Methods The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores. Results At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4–24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m2) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT. Conclusion Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors.
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Affiliation(s)
- Monika Rau
- Medizinische Klinik II, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Peter Buggisch
- ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Gernamny
| | | | - Hartwig Klinker
- Medizinische Klinik II, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Tobias Müller
- Charité Campus Virchow-Klinikum (CVK), Berlin, Gernamny
| | - Albrecht Stoehr
- ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | - Jörn M. Schattenberg
- Metabolic Liver Research Program, University Medical Centre Mainz, Mainz, Germany
| | - Andreas Geier
- Medizinische Klinik II, Universitätsklinikum Würzburg, Würzburg, Germany
- * E-mail:
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Morgan JR, Marsh E, Savinkina A, Shilton S, Shadaker S, Tsertsvadze T, Kamkamidze G, Alkhazashvili M, Morgan T, Belperio P, Backus L, Doss W, Esmat G, Hassany M, Elsharkawy A, Elakel W, Mehrez M, Foster GR, Wose Kinge C, Chew KW, Chasela CS, Sanne IM, Thanung YM, Loarec A, Aslam K, Balkan S, Easterbrook PJ, Linas BP. Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set. J Viral Hepat 2022; 29:474-486. [PMID: 35278339 PMCID: PMC9248016 DOI: 10.1111/jvh.13672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/15/2022] [Indexed: 12/09/2022]
Abstract
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.
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Affiliation(s)
- Jake R. Morgan
- Department of Health Law, Policy, and ManagementBoston University School of Public HealthBostonMassachusettsUSA
| | - Elizabeth Marsh
- Department of MedicineSection of Infectious DiseasesBoston Medical CenterBostonMassachusettsUSA
| | - Alexandra Savinkina
- Department of MedicineSection of Infectious DiseasesBoston Medical CenterBostonMassachusettsUSA
| | | | - Shaun Shadaker
- Division of Viral HepatitisNational Center for HIV/AIDSViral HepatitisSTD and TB PreventionCDCAtlantaGeorgiaUSA
| | - Tengiz Tsertsvadze
- Infectious Diseases, AIDS and Clinical Immunology Research CenterTbilisiGeorgia
| | | | | | - Timothy Morgan
- United States Department of Veteran’s AffairsLong BeachCaliforniaUSA
| | - Pam Belperio
- United States Department of Veteran’s AffairsLong BeachCaliforniaUSA
| | - Lisa Backus
- United States Department of Veteran’s AffairsLong BeachCaliforniaUSA
| | - Waheed Doss
- National Committee for Control of Viral Hepatitis NCCVHCairoEgypt
| | - Gamal Esmat
- Endemic Medicine and Hepatogastroentrology Department, Cairo UniversityCairoEgypt
| | - Mohamed Hassany
- Tropical Medicine and Hepatology DepartmentNational Hepatology and Tropical Medicine Research InstituteCairoEgypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatogastroentrology Department, Cairo UniversityCairoEgypt
| | - Wafaa Elakel
- Endemic Medicine and Hepatogastroentrology Department, Cairo UniversityCairoEgypt
| | - Mai Mehrez
- Tropical Medicine and Hepatology DepartmentNational Hepatology and Tropical Medicine Research InstituteCairoEgypt
| | | | | | - Kara W. Chew
- Department of MedicineDivision of Infectious DiseasesDavid Geffen School of Medicine at University of California Los AngelesLos AngelesCaliforniaUSA
| | - Charles S. Chasela
- Implementation Science UnitRight to CareCenturion. South AfricaDepartment of Epidemiology and BiostatisticsSchool of Public HealthFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
| | - Ian M. Sanne
- Right to CareCenturion. South Africa, and Clinical HIV Research UnitSchool of Clinical MedicineFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
| | | | | | | | | | - Philippa J. Easterbrook
- Department of Global HIV, Hepatitis and STI ProgrammesWorld Health OrganizationGenevaSwitzerland
| | - Benjamin P. Linas
- Department of MedicineSection of Infectious DiseasesBoston Medical CenterBostonMassachusettsUSA
- Department of EpidemiologyBoston University School of Public HealthBostonMassachusettsUSA
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Gulumsek E, Sumbul HE, Buyuksimsek M, Demir K, Koc AS, Tas A, Bulut Y, Kara B. Liver Stiffness Is Markedly Decreased After Chronic Hepatitis C Treatment. Ultrasound Q 2022; 38:142-148. [PMID: 35678480 DOI: 10.1097/ruq.0000000000000572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
AIM The aim of the study was to demonstrate the liver stiffness (LS) change in chronic hepatitis C (CHC) patients obtained by elastography point quantification technique in before and after antiviral treatment (AVT). MATERIAL AND METHODS This prospective study included 84 patients diagnosed with CHC who had not previously received treatment for CHC and who had an indication for using direct-acting AVT. Necessary measurements were recorded with noninvasive liver fibrosis (LF) examinations. Posttreatment control of patients was carried out (ombitasvir + paritaprevir + ritonavir) + 3 months after the start of treatment for those treated with dasabuvir and 6 months after the start of treatment for patients treated with sofosbuvir + ribavirin. Liver stiffness changed after AVT is accepted as (Δ-LS), LS before AVT-LS after AVT. RESULTS Basal LS was found to decrease significantly after AVT (8.00 ± 2.56 kPa vs 6.95 ± 2.86 kPa, P < 0.05). Similar aspartate aminotransferase-to-platelet ratio index and platelet number fibrosis 4 indices were observed before and after AVT (P > 0.05). It was observed that Δ-LS value after AVT was lower in patients with Child-Pugh class A cirrhosis than patients without cirrhosis (P < 0.05). In the comparison between Δ-LS value after AVT and LF score determined by liver biopsy, it was seen that the greatest Δ-LS value was in patients with fibrosis score of 3. An independent relationship was found between Δ-LS after AVT and LF score determined by biopsy (P < 0.05). CONCLUSIONS The LS value determined by the elastography point quantification technique is more effective than other noninvasive laboratory methods in demonstrating the CHC treatment response in clinical practice.
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Affiliation(s)
| | | | | | | | - Ayse Selcan Koc
- Radiology, University of Health Sciences-Adana Health Practice and Research Center
| | | | - Yurdaer Bulut
- Department of Intensive Care, Cukurova University Faculty of Medicine, Adana, Turkey
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Hsu CE, Liu YC, Cheng YT, Jeng WJ, Chien RN, Lin CY, Tai DI, Sheen IS. Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals. Viruses 2022; 14:786. [PMID: 35458516 PMCID: PMC9024676 DOI: 10.3390/v14040786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/03/2022] [Accepted: 04/06/2022] [Indexed: 02/07/2023] Open
Abstract
Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.
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Affiliation(s)
- Cheng-Er Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Yen-Chun Liu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ya-Ting Cheng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Dar-In Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan; (C.-E.H.); (Y.-C.L.); (Y.-T.C.); (R.-N.C.); (C.-Y.L.); (D.-I.T.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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Aydın NN, Köksal İ. An Evaluation of Chronic Hepatitis C Patients’ Responses to Direct-Acting Antivirals According to Transient Elastography and Serum Biomarkers. Egypt J Immunol 2022. [DOI: 10.4274/vhd.galenos.2022.2021-8-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Nakajima T, Karino Y, Hige S, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Toyota J. Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection. Ann Hepatol 2022; 27:100566. [PMID: 34688887 DOI: 10.1016/j.aohep.2021.100566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 09/18/2021] [Accepted: 09/27/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.
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Affiliation(s)
- Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan; Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan.
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | | | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Joji Toyota
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
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24-month decline of non-invasive liver fibrosis markers in HCV-mono and HCV/HIV coinfection after direct-acting antiviral therapy. Sci Rep 2022; 12:3828. [PMID: 35264591 PMCID: PMC8907337 DOI: 10.1038/s41598-022-07548-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 02/17/2022] [Indexed: 11/08/2022] Open
Abstract
Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair. Their plasma levels might assess long-term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients. TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.
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Kumar A, Saraswat V, Pande G, Kumar R. Does Treatment of Erectile Dysfunction With PDE 5 Inhibitor Tadalafil Improve Quality of Life in Male Patients With Compensated Chronic Liver Disease? A Prospective Pilot Study. J Clin Exp Hepatol 2022; 12:1083-1090. [PMID: 35814506 PMCID: PMC9257884 DOI: 10.1016/j.jceh.2022.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Erectile dysfunction (ED) is common in patients with compensated cirrhosis but its impact on the quality of life (QOL) is usually overlooked. This study aimed at determining the frequency of ED in male patients with compensated chronic liver disease (CLD), assessing their QOL and the response to treatment with tadalafil. A secondary aim was to assess the effect of the tadalafil therapy on liver fibrosis, if any. METHODS Consecutive patients with compensated CLD and advanced liver fibrosis were screened at the baseline with the International Index of Erectile Function-5 (IIEF-5), QOL questionnaire (WHOQOL-BREF), liver stiffness measurements (LSM) made with Fibroscan™ (Echosens, France), and fibrosis index based on 4 factors (FIB-4) scores. Patients with ED meeting eligibility criteria were prescribed PDE5 inhibitor tadalafil 20 mg on alternate days. During the follow-up, IIEF-5, LSM, and FIB-4 were monitored after 3 and 6 months while the WHOQOL-BREF questionnaire was administered at the baseline and at 6 months. RESULTS Among 89 patients with CLD and advanced liver fibrosis, ED was present in 43 (48%) and tadalafil was prescribed to 34 patients (38%) meeting exclusion and inclusion criteria. At 3 months follow-up, the mean IIEF 5 score increased from 15.57 ± 4 to 20.78 ± 3.6, (P = 0.0001) and the improvement persisted at 6 months (IIEF-5 score 21.87 ± 2.2; P = 0.12). The physical, social relationships, and environment domains in the WHOQOL-BREF questionnaire showed significant improvement at six months (P < 0.05) but not the psychological domain (P = ns). From a baseline value of 12.69 ± 3.1 kPa, the mean LSM decreased to 11.37 ± 3.9 kPa, (P = 0.02) after 3 months on tadalafil. After 6 months, the LSM further decreased from 11 ± 0.9 to 8.2 ± 3.2 kPa (P = 0.034). FIB-4 values showed a decline from the baseline at 3 months, from 1.52 ± 0.58 to 1.32 ± 0.55, P < 0.05 and at 6 months, from 1.25 ± 0.53 to 0.97 ± 0.36, P > 0.05. The CAP values did not show any significant change. There was an insignificant decline in the SGOT and SGPT levels (P > 0.05) with no significant change in CTP or MELD scores. CONCLUSIONS In the short term, tadalafil improves ED and QOL in patients with CLD and advanced liver fibrosis. It may also reduce liver fibrosis in them. Further studies that include liver histology are needed to confirm this preliminary observation of a possible antifibrotic effect.
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Key Words
- ALD, alcoholic liver disease
- CLD, chronic liver disease
- ED, Erectile dysfunction
- FIB-4
- FIB-4, fibrosis index based on 4 factors
- HRQOL, health-related quality of life
- IIEF-5
- IIEF-5, the International Index of Erectile Function-5
- LC, liver cirrhosis
- LSM, liver stiffness measurement
- MAP, mean arterial pressure
- PDE-5 I
- PDE5-I, phosphodiesterase inhibitors
- PDEs, phosphodiesterases
- PPH, porto-pulmonary hypertension
- QOL, quality of life
- SMT, standard medical therapy
- TAA, thioacetamide
- TE, transient elastography
- WHOQOL-BREF
- cAMP, cyclic adenosine monophosphate
- cGMP, cyclic guanosine monophosphate
- erectile dysfunction
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Affiliation(s)
- Alok Kumar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India
| | - Vivek Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India,Address for correspondence: Vivek A. Saraswat, Head, Department of Hepatology, Pancreatobiliary Sciences and Liver Transplantation Mahatma Gandhi Medical College and Hospital, Jaipur, 302022, Rajasthan, India
| | - Gaurav Pande
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India
| | - Rajesh Kumar
- Department of Community Medicine, Rajendra Institute of Medical Sciences, Ranchi, JH, India
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