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Ismail MH. Beyond genotype-4: Direct-acting antiviral agents in patients with chronic hepatitis C infection from the Eastern Province of Saudi Arabia. Health Sci Rep 2024; 7:e1795. [PMID: 38186940 PMCID: PMC10767762 DOI: 10.1002/hsr2.1795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 11/14/2023] [Accepted: 12/17/2023] [Indexed: 01/09/2024] Open
Abstract
Background and Aims Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting. Methods This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0. Results Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects. Conclusions Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.
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Affiliation(s)
- Mona H. Ismail
- College of Medicine at Imam Abdulrahman bin Faisal UniversityDammamSaudi Arabia
- Department of Internal Medicine, Division of GastroenterologyKing Fahd Hospital of the UniversityAl KhobarSaudi Arabia
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Chandran V, Rajandran A, Loo KF, Bate J, Wigg A, Chinnaratha MA. Hepatocellular carcinoma (HCC) is changing its face: analysis of the temporal trends in aetiology and clinical patterns of HCC in South Australia. Intern Med J 2023; 53:1131-1136. [PMID: 36040722 DOI: 10.1111/imj.15689] [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: 09/04/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The epidemiology of chronic liver disease is changing with the introduction of potent antiviral therapies for chronic hepatitis C virus (HCV) and the increasing prevalence of non-alcoholic steatohepatitis (NASH). AIM To establish the impact of this change on the rates and clinical patterns of hepatocellular carcinoma (HCC) in South Australia (SA). METHODS Newly diagnosed HCC patients from January 2014 until December 2019 from four tertiary centres in SA were included. The overall age-standardised incidence rates (ASIR) of HCC were calculated using 2016 SA population as the standard. To assess the trends, Join-Point regression models were used to calculate the average annual percentage change (AAPC). Forecasting of overall and aetiology-specific HCC from 2020 to 2024 was performed using linear regression. RESULTS There were 626 new cases of HCC in SA (males 80%; median age 64 years) during the study period. There was a significant increase in NASH-related HCC (AAPC: +7.0%; P < 0.05) from 2014 to 2019. However, there were no significant differences in the ASIR for overall HCC (AAPC: -4.1%), HCV-related HCC (AAPC: -8.0%) and stage of HCC diagnosis (AAPC: +3.0%; P > 0.05). Forecasting analysis projected the decline and increase in the incidence of HCV and NASH-related HCC, respectively, over the next few years. CONCLUSION Overall ASIR of HCC has plateaued in SA. However, NASH-related HCC has increased significantly and is expected to continue to increase in the near future. Further research and intervention is required to reduce NASH-related HCC, a major contributor to the current and future burden of HCC.
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Affiliation(s)
- Vidhyaleha Chandran
- Department of Gastroenterology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
| | - Arvinf Rajandran
- Department of Gastroenterology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
| | - Kee Fong Loo
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - John Bate
- Department of Gastroenterology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
- Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Alan Wigg
- Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Mohamed A Chinnaratha
- Department of Gastroenterology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
- School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
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Liu SY, Li C, Sun LY, Guan MC, Gu LH, Yin DX, Yao LQ, Liang L, Wang MD, Xing H, Zhu H, Pawlik TM, Lau WY, Shen F, Tong XM, Yang T. ASAP Score versus GALAD Score for detection of hepatitis C-related hepatocellular carcinoma: A multicenter case-control analysis. Front Oncol 2022; 12:1018396. [PMID: 36263214 PMCID: PMC9576185 DOI: 10.3389/fonc.2022.1018396] [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: 08/13/2022] [Accepted: 08/31/2022] [Indexed: 11/15/2022] Open
Abstract
Background The GALAD and ASAP scores are two well-recognized algorithms to estimate the risk of hepatocellular carcinoma (HCC) based on gender, age, alpha-fetoprotein (AFP), protein induced by vitamin K absence or Antagonist-II (PIVKA-II) and AFP-L3 (included in the GALAD score but not in the ASAP score). The current study sought to compare the diagnostic performance of each score to detect HCC among patients infected with hepatitis C virus (HCV). Methods A multicenter case-control study was undertaken in which blood samples were collected from HCVinfected patients with and without HCC. Using the area under the receiver operating characteristic curve (AUROC), ASAP and GALAD scores were compared relative to diagnostic performance to detect any stage HCV-HCC and early-stage HCV-HCC. Results The analytic cohort included 168 HCV-HCC patients and a control group of 193 HCV-infected patients. The ASAP score had a higher AUROC to detect any stage HCV-HCC versus the GALAD score, both in the overall group (0.917 vs. 0.894, P=0.057) and in the cirrhosis subgroup (0.909 vs. 0.889, P=0.132). Similar results were noted relative to the detection of early-stage HCV-HCC, whether defined by BCLC staging (stage 0-A: 0.898 vs. 0.860, P=0.026) or 8th TNM staging (stage I: 0.899 vs. 0.870, P=0.070). In subgroup analysis to detect AFP-negative HCV-HCC, the ASAP score also demonstrated a higher AUROC than the GALAD score to detect any stage HCV-HCC in the AFP-negative subgroup (0.815 vs. 0.764, P=0.063). Conclusions The ASAP score had better diagnostic performance for early detection of HCV-HCC compared with the GALAD score. The ASAP score may be preferrable to the GALAD score for HCC screening and surveillance among HCV-infected patients.
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Affiliation(s)
- Si-Yu Liu
- Department of Laboratory Medicine, Lishui Municipal Central Hospital, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China,The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Li-Yang Sun
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China
| | - Ming-Cheng Guan
- Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Li-Hui Gu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Dong-Xu Yin
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China,Eastern Hepatobiliary Clinical Research Institute (EHCRI), Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Hong Zhu
- Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, United States
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China,Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China,Eastern Hepatobiliary Clinical Research Institute (EHCRI), Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Xiang-Min Tong
- Department of Laboratory Medicine, Lishui Municipal Central Hospital, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China,The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China,*Correspondence: Tian Yang, ; Xiang-Min Tong,
| | - Tian Yang
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China,Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China,School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China,Eastern Hepatobiliary Clinical Research Institute (EHCRI), Third Affiliated Hospital of Navy Medical University, Shanghai, China,*Correspondence: Tian Yang, ; Xiang-Min Tong,
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Dana J, Venkatasamy A, Saviano A, Lupberger J, Hoshida Y, Vilgrain V, Nahon P, Reinhold C, Gallix B, Baumert TF. Conventional and artificial intelligence-based imaging for biomarker discovery in chronic liver disease. Hepatol Int 2022; 16:509-522. [PMID: 35138551 PMCID: PMC9177703 DOI: 10.1007/s12072-022-10303-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 01/17/2022] [Indexed: 12/14/2022]
Abstract
Chronic liver diseases, resulting from chronic injuries of various causes, lead to cirrhosis with life-threatening complications including liver failure, portal hypertension, hepatocellular carcinoma. A key unmet medical need is robust non-invasive biomarkers to predict patient outcome, stratify patients for risk of disease progression and monitor response to emerging therapies. Quantitative imaging biomarkers have already been developed, for instance, liver elastography for staging fibrosis or proton density fat fraction on magnetic resonance imaging for liver steatosis. Yet, major improvements, in the field of image acquisition and analysis, are still required to be able to accurately characterize the liver parenchyma, monitor its changes and predict any pejorative evolution across disease progression. Artificial intelligence has the potential to augment the exploitation of massive multi-parametric data to extract valuable information and achieve precision medicine. Machine learning algorithms have been developed to assess non-invasively certain histological characteristics of chronic liver diseases, including fibrosis and steatosis. Although still at an early stage of development, artificial intelligence-based imaging biomarkers provide novel opportunities to predict the risk of progression from early-stage chronic liver diseases toward cirrhosis-related complications, with the ultimate perspective of precision medicine. This review provides an overview of emerging quantitative imaging techniques and the application of artificial intelligence for biomarker discovery in chronic liver disease.
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Affiliation(s)
- Jérémy Dana
- Institut de Recherche sur les Maladies Virales et Hépatiques, Institut National de la Santé et de la Recherche Médicale (Inserm), U1110, 3 Rue Koeberlé, 67000, Strasbourg, France.
- Institut Hospitalo-Universitaire (IHU), Strasbourg, France.
- Université de Strasbourg, Strasbourg, France.
- Department of Diagnostic Radiology, McGill University, Montreal, Canada.
| | - Aïna Venkatasamy
- Institut Hospitalo-Universitaire (IHU), Strasbourg, France
- Streinth Lab (Stress Response and Innovative Therapies), Inserm UMR_S 1113 IRFAC, Interface Recherche Fondamentale et Appliquée à la Cancérologie, 3 Avenue Moliere, Strasbourg, France
- Department of Radiology Medical Physics, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Killianstrasse 5a, 79106, Freiburg, Germany
| | - Antonio Saviano
- Institut de Recherche sur les Maladies Virales et Hépatiques, Institut National de la Santé et de la Recherche Médicale (Inserm), U1110, 3 Rue Koeberlé, 67000, Strasbourg, France
- Université de Strasbourg, Strasbourg, France
- Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Joachim Lupberger
- Institut de Recherche sur les Maladies Virales et Hépatiques, Institut National de la Santé et de la Recherche Médicale (Inserm), U1110, 3 Rue Koeberlé, 67000, Strasbourg, France
- Université de Strasbourg, Strasbourg, France
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Division of Digestive and Liver Diseases, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, USA
| | - Valérie Vilgrain
- Radiology Department, Hôpital Beaujon, Université de Paris, CRI, INSERM 1149, APHP. Nord, Paris, France
| | - Pierre Nahon
- Liver Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris Seine Saint-Denis, Bobigny, France
- Université Sorbonne Paris Nord, 93000, Bobigny, France
- Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Paris, France
| | - Caroline Reinhold
- Department of Diagnostic Radiology, McGill University, Montreal, Canada
- Augmented Intelligence and Precision Health Laboratory, Research Institute of McGill University Health Centre, Montreal, Canada
- Montreal Imaging Experts Inc., Montreal, Canada
| | - Benoit Gallix
- Institut Hospitalo-Universitaire (IHU), Strasbourg, France
- Université de Strasbourg, Strasbourg, France
- Department of Diagnostic Radiology, McGill University, Montreal, Canada
| | - Thomas F Baumert
- Institut de Recherche sur les Maladies Virales et Hépatiques, Institut National de la Santé et de la Recherche Médicale (Inserm), U1110, 3 Rue Koeberlé, 67000, Strasbourg, France.
- Université de Strasbourg, Strasbourg, France.
- Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
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Nagra N, Kozarek RA, Burman BE. Therapeutic Advances in Viral Hepatitis A-E. Adv Ther 2022; 39:1524-1552. [PMID: 35220557 DOI: 10.1007/s12325-022-02070-z] [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: 12/16/2021] [Accepted: 01/31/2022] [Indexed: 11/25/2022]
Abstract
Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.
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Affiliation(s)
- Navroop Nagra
- Department of Gastroenterology, University of Louisville, Louisville, KY, 40202, USA
| | - Richard A Kozarek
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA
| | - Blaire E Burman
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA.
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Maesaka K, Sakamori R, Yamada R, Tahata Y, Oshita M, Hagiwara H, Sakakibara M, Tamura S, Hiramatsu N, Inada M, Iio S, Ito T, Yakushijin T, Doi Y, Kodama T, Hikita H, Tatsumi T, Takehara T. Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment. Hepatol Res 2021; 51:517-527. [PMID: 33507588 DOI: 10.1111/hepr.13623] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/16/2020] [Accepted: 01/05/2021] [Indexed: 12/12/2022]
Abstract
AIM The aim of the present study was to investigate the clinical course in hepatitis C virus (HCV)-positive patients with decompensated liver cirrhosis after direct-acting antivirals (DAAs) have been used for HCV infection. METHODS This multicenter study prospectively analyzed a registered cohort composed of 73 HCV-positive patients with decompensated cirrhosis who attended our 11 institutions between January 2018 and July 2018. Prognoses, including changes in the liver reserve, hepatocellular carcinoma (HCC), decompensation events, and survival, were analyzed up to July 2020, as was the initiation of DAA treatment. RESULTS Sixty-four (87.7%) and nine (12.3%) patients had Child-Pugh class (C-P) B and C at baseline, respectively. Within 2 years after enrollment, 17 patients (23.3%) received treatment with DAAs, and 31 patients (42.5%) developed uncontrolled HCC, switched to palliative care, or died. Patients who received DAA treatment were significantly younger and had significantly higher alanine aminotransferase levels and lower platelet counts than the patients who did not receive DAA treatment. The rates of overall survival, cumulative HCC occurrence, and cumulative hospitalization for any hepatic decompensation event at 2 years were 64.8%, 13.1%, and 65.6%, respectively. Overall survival was significantly shorter and the HCC occurrence and hospitalization rates were significantly higher in C-P C patients than in C-P B patients. CONCLUSIONS Among HCV-positive patients with decompensated cirrhosis, approximately one-fourth received DAA treatment, but more than 40% of the patients lost the opportunity for treatment with DAAs.
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Affiliation(s)
- Kazuki Maesaka
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masahide Oshita
- Department of Gastroenterology and Hepatology, Osaka Police Hospital, Osaka, Japan
| | - Hideki Hagiwara
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan
| | - Mitsuru Sakakibara
- Department of Gastroenterology and Hepatology, Yao Municipal Hospital, Yao, Osaka, Japan
| | - Shinji Tamura
- Department of Gastroenterology and Hepatology, Minoh City Hospital, Minoh, Osaka, Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Masami Inada
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Sadaharu Iio
- Department of Gastroenterology and Hepatology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
| | - Toshifumi Ito
- Department of Gastroenterology and Hepatology, Japan Community Healthcare Organization, Osaka Hospital, Osaka, Japan
| | - Takayuki Yakushijin
- Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan
| | - Yoshinori Doi
- Department of Gastroenterology and Hepatology, Otemae Hospital, Osaka, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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Ahn YH, Park H, Lee MJ, Kim DH, Cho SB, Cho E, Jun CH, Choi SK. Comparison of the Clinical Characteristics and Outcomes between Leprosy-Affected Persons in Sorokdo and the General Population Affected by Chronic Hepatitis C in Korea. Gut Liver 2020; 13:549-556. [PMID: 30970433 PMCID: PMC6743803 DOI: 10.5009/gnl18432] [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: 09/27/2018] [Revised: 12/04/2018] [Accepted: 12/13/2018] [Indexed: 11/05/2022] Open
Abstract
Background/Aims Patients with Hansen’s disease are the most vulnerable to hepatitis C. However, no data on the treatment efficacy of direct-acting antiviral agents (DAAs) are available in this group. Therefore, we elucidated the prevalence and clinical outcomes of hepatitis C in persons affected by leprosy in Sorokdo, Jeollanam-do, Korea. Methods We retrospectively included 50 leprosy patients with positive hepatitis C virus (HCV) RNA test results (group A) hospitalized at the Sorokdo National Hospital from May 2016 to March 2018 and 73 patients with chronic hepatitis C who were treated with DAAs at the Chonnam National University Hospital (group B) from May 2016 to December 2017. Results Overall, at the Sorokdo National Hospital, positive HCV antibody and HCV RNA rates were 18.4% and 11.0%, respectively. The mean participant age was 76.5±7 years, and 58% of participants were men. The genotypes were type 1b in 44% (22 out of 50) and type 2 in 56% (28 out of 50). Sustained virologic response was achieved at a rate of 95.5% (21/22) in genotype 1b and 92.9% (26/28) in genotype 2 patients. Ribavirin-induced hemolytic anemia occurred in 57.1% (16/28) of patients with genotype 2. Among these, 28.5% (8/28) received blood transfusions. Conclusions Treatment efficacy was not different between the leprosy-affected population and the general population. However, severe ribavirin-induced hemolytic anemia requiring transfusion was present in 28.5% of genotype 2 patients. Therefore, we suggest ribavirin-free DAAs for the treatment of genotype 2 hepatitis C in leprosy-affected persons in the future.
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Affiliation(s)
- Young-Hwan Ahn
- Departments of Internal Medicine, Sorokdo National Hospital, Goheung, Korea
| | - Hyungcheol Park
- Departments of Preventive Medicine, Sorokdo National Hospital, Goheung, Korea
| | - Myeon Jae Lee
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
| | - Dong Hyun Kim
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
| | - Sung Bum Cho
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
| | - Eunae Cho
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
| | - Chung Hwan Jun
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
| | - Sung Kyu Choi
- Department of Gastroenterology, Chonnam National University Hospital, Gwangju, Korea
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Bardach A, Hernández-Vásquez A, Palacios A, Calderón M, Soto N, Balan D, Augustovski F. Epidemiología, consumo de recursos y costos del manejo médico de la Hepatitis C en Argentina, Colombia, Uruguay y Venezuela. Value Health Reg Issues 2019; 20:180-190. [PMID: 31654963 DOI: 10.1016/j.vhri.2019.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 05/15/2019] [Accepted: 06/11/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To describe the epidemiology, the consumption of resources and the relevant costs in the management of hepatitis C in four Latin American countries: Argentina, Colombia, Uruguay and Venezuela. STUDY DESIGN Bibliographic review, study of costs and elicitation by experts METHODS: A literature search was carried out to collect epidemiological and cost data for the management of the disease. Information was additionally elicited with hepatologists from each country using the modified Delphi Panel technique. For the estimation of costs, the perspective of the health system was adopted. The direct medical costs of the different stages associated with the natural history of the disease were considered through micro-costing. RESULTS Extensive epidemiological and economic information is provided for the four countries under study. The age range between 40 and 60 years was the most affected. The frequency of genotypes showed a predominance of genotype 1 (68 to 88%), genotype 1b having been reported as the most prevalent in Argentina and Colombia and 1a in Uruguay and Venezuela. The costs of drug regimens, associated health events and adverse events present important differences in the four selected countries of Latin America. CONCLUSION Hepatitis C presents a high burden of disease in the countries under study, and its management imposes significant costs on health systems.
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Affiliation(s)
- Ariel Bardach
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina; CIESP Centro de Investigaciones en Epidemiología y Salud Pública, Instituto para la Efectividad Clínica y Sanitaria, Buenos Aires, Argentina.
| | | | - Alfredo Palacios
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - María Calderón
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Natalie Soto
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Dario Balan
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Federico Augustovski
- IECS Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina; CIESP Centro de Investigaciones en Epidemiología y Salud Pública, Instituto para la Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
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10
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Izumi T, Sho T, Morikawa K, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Kawagishi N, Umemura M, Shimazaki T, Kimura M, Nakai M, Suda G, Natsuizaka M, Ogawa K, Kudo Y, Nishida M, Ono K, Baba M, Furuya K, Sakamoto N. Assessing the risk of hepatocellular carcinoma by combining liver stiffness and the controlled attenuation parameter. Hepatol Res 2019; 49:1207-1217. [PMID: 31219667 DOI: 10.1111/hepr.13391] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 06/08/2019] [Accepted: 06/12/2019] [Indexed: 12/11/2022]
Abstract
AIM Ultrasound technology can now be used for liver stiffness measurement (LSM) and for evaluating the amount of hepatic fat quantitatively known as the controlled attenuation parameter (CAP). This study aimed to determine the applicable cut-off values of LSM and the CAP for primary hepatocellular carcinoma (HCC), and to investigate their clinical usefulness for assessing HCC risk in patients with chronic liver disease. METHODS A total of 1054 patients (88 with primary HCC and 966 without HCC) whose LSM and the CAP were measured by transient elastography with clinically evident hepatitis C virus (419 patients), hepatitis B virus (377 patients), and non-alcoholic fatty liver disease (258 patients) were enrolled in this study. Subsequently, a total of 966 patients who did not have HCC initially were followed, and the usefulness of the cut-off values of LSM and CAP for HCC development were evaluated. RESULTS In hepatitis C virus patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥8.0 kPa and CAP ≤221 dB/m than among those with other values (log-rank test 0.0239, hazard ratio 2.66, 95%CI 1.07-6.47, P = 0.0362). In non-alcoholic fatty liver disease patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥5.4 kPa and CAP ≤265 dB/m than among others (log-rank test 0.0040, hazard ratio 8.91, 95% CI 1.47-67.97, P = 0.0192). CONCLUSION In the hepatitis C virus and non-alcoholic fatty liver disease groups, a combination of LSM and the CAP cut-off values would be useful for screening to identify the high-risk group for primary HCC development.
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Affiliation(s)
- Takaaki Izumi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Machiko Umemura
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Tomoe Shimazaki
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
| | - Yusuke Kudo
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital
| | - Mutsumi Nishida
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital
| | - Kota Ono
- Clinical Research and Medical Innovation Center, Hokkaido University Hospital
| | - Masaru Baba
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Japan
| | - Ken Furuya
- Department of Gastroenterology, JCHO Hokkaido Hospital, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine
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11
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Uyei J, Taddei TH, Kaplan DE, Chapko M, Stevens ER, Braithwaite RS. Setting ambitious targets for surveillance and treatment rates among patients with hepatitis C related cirrhosis impacts the cost-effectiveness of hepatocellular cancer surveillance and substantially increases life expectancy: A modeling study. PLoS One 2019; 14:e0221614. [PMID: 31449554 PMCID: PMC6709904 DOI: 10.1371/journal.pone.0221614] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 08/03/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocelluar cancer (HCC) is the leading cause of death among people with hepatitis C virus (HCV)-related cirrhosis. Our aim was to determine the optimal surveillance frequency for patients with HCV-related compensated cirrhosis. METHODS We developed a decision analytic Markov model and validated it against data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) study group and published epidemiologic studies. Four strategies of different surveillance intervals were compared: no surveillance and ultrasound surveillance every 12, 6, and 3 months. We estimated lifetime survival, life expectancy, quality adjusted life years (QALY), total costs associated with each strategy, and incremental cost effectiveness ratios. We applied a willingness to pay threshold of $100,000. Analysis was conducted for two scenarios: a scenario reflecting current HCV and HCC surveillance compliance rates and treatment use and an aspirational scenario. RESULTS In the current scenario the preferred strategy was 3-month surveillance with an incremental cost-effectiveness ratio (ICER) of $7,159/QALY. In the aspirational scenario, 6-month surveillance was preferred with an ICER of $82,807/QALY because treating more people with HCV led to a lower incidence of HCC. Sensitivity analyses suggested that surveillance every 12 months would suffice in the particular circumstance when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available. Compared with the current scenario, the aspirational scenario resulted in a 1.87 year gain in life expectancy for the cohort because of large reductions in decompensated cirrhosis and HCC incidence. CONCLUSIONS HCC surveillance has good value for money for patients with HCV-related compensated cirrhosis. Investments to improve adherence to surveillance should be made when rates are suboptimal. Surveillance every 12 months will suffice when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available.
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Affiliation(s)
- Jennifer Uyei
- Division of Comparative Effectiveness and Decision Science, Department of Population Health, New York University School of Medicine, New York, NY, United States of America
- * E-mail:
| | - Tamar H. Taddei
- VA Connecticut-Healthcare System, West Haven, CT, United States of America
| | - David E. Kaplan
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States of America
| | - Michael Chapko
- Center of Innovation for Veteran-Centered and Value-Driven Care, Health Services Research & Development, VA Puget Sound, Seattle, WA, United States of America
| | - Elizabeth R. Stevens
- Division of Comparative Effectiveness and Decision Science, Department of Population Health, New York University School of Medicine, New York, NY, United States of America
| | - R. Scott Braithwaite
- Division of Comparative Effectiveness and Decision Science, Department of Population Health, New York University School of Medicine, New York, NY, United States of America
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12
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D’Amico G, Perricone G. Prediction of Decompensation in Patients with Compensated Cirrhosis: Does Etiology Matter? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00473-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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13
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Nakagomi R, Tateishi R, Masuzaki R, Soroida Y, Iwai T, Kondo M, Fujiwara N, Sato M, Minami T, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Kondo Y, Tanaka Y, Otsuka M, Kato N, Moriya K, Ikeda H, Koike K. Liver stiffness measurements in chronic hepatitis C: Treatment evaluation and risk assessment. J Gastroenterol Hepatol 2019; 34:921-928. [PMID: 30393960 DOI: 10.1111/jgh.14530] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 10/21/2018] [Accepted: 10/23/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Liver stiffness (LS), measured by transient elastography, has been validated as a non-invasive surrogate for liver fibrosis. METHODS We investigated the long-term predictive ability of LS for hepatocellular carcinoma (HCC) development and overall survival in 1146 patients with chronic hepatitis C by using LS value at enrollment. We also investigated chronological changes in LS based on antiviral therapy and its outcome in 752 patients. RESULTS During the mean follow-up period of 6.6 years, 190 patients developed HCC. Cumulative HCC incidence rates at 5 years were clearly stratified as 1.7% in the ≤ 5 kPa, 3.3% in 5.1-10 kPa, 16.7% in 10.1-15 kPa, 24.4% in 15.1-20 kPa, 36.3% in 20.1-25 kPa, and 43.7% in > 25 kPa subgroups (P < 0.001). Overall survival was also stratified: 10-year survival rates were 99.3% in the ≤ 5 kPa, 95.4% in 5.1-10 kPa, 81.4% in 10.1-15 kPa, 79.5% in 15.1-20 kPa, 66.1% in 20.1-25 kPa, and 49.1% in > 25 kPa subgroups (P < 0.001). LS decreased at a rate of 8.1% per year in those who achieved sustained virological responses, but increased at 0.1% per year in those who could not achieve sustained virological response instead of antiviral therapy, and increased at 3.7% per year in those who did not undergo antiviral therapy. CONCLUSIONS Liver stiffness measurements can be useful in the prediction of HCC development and overall survival and in the evaluation of chronological changes in liver fibrosis grade during and after antiviral therapy.
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Affiliation(s)
- Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryota Masuzaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoko Soroida
- Department of Clinical Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Tomomi Iwai
- Department of Clinical Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Mayuko Kondo
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naoto Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Clinical Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuji Kondo
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasuo Tanaka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naoya Kato
- Unit of Disease Control Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Hitoshi Ikeda
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Clinical Laboratory Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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14
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The Changing Face of Hepatocellular Carcinoma: Forecasting Prevalence of Nonalcoholic Steatohepatitis and Hepatitis C Cirrhosis. J Clin Exp Hepatol 2019; 9:50-55. [PMID: 30765939 PMCID: PMC6363953 DOI: 10.1016/j.jceh.2018.02.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 02/08/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/OBJECTIVES The purpose of this research is to analyze the past and forecast the future prevalence of Hepatitis C Virus (HCV) and Nonalcoholic Steatohepatitis (NASH) and their respective contribution to Hepatocellular Carcinoma (HCC) incidence in the setting of novel anti-viral agents and rising obesity rates in the United States. METHODS Existing data of HCV and NASH prevalence in the United States utilizing the National Health and Nutrition Examination Survey (NHANES) and Organ Procurement and Transplantation Network (OPTN) was collected and analyzed to project future prevalence trends. RESULTS Prevalence of NASH and HCV are expected to increase and decline respectively over the next two decades with alcoholic cirrhosis expected to stay relatively unchanged. The estimated prevalence of NASH equaled and overtook the projected prevalence of HCV in 2007 at approximately 3 million persons. Estimates of NASH's contribution to HCC overtook HCV-HCC in 2015 at an approximately 25 million persons. Projection models suggest HCV prevalence declining to 1 million active cases by 2025, while NASH potentially increases to 17-42 million depending on a linear or exponential trendline. Projections of NASH-HCC similarly outpace HCV-HCC by 2025 with 45 million or 106 million (linear, exponential) versus 18 million persons respectively. CONCLUSIONS The future prevalence of HCV and NASH are expected to become further divergent with NASH emerging as the major contributor of cirrhosis and HCC in the United States.
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15
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Treatment of hepatitis C with direct-acting antivirals significantly reduces liver-related hospitalizations in patients with cirrhosis. Eur J Gastroenterol Hepatol 2018; 30:1378-1383. [PMID: 29975243 DOI: 10.1097/meg.0000000000001195] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The availability of direct-acting antivirals (DAA) for the treatment of hepatitis C (HCV) has resulted in the ability to safely and effectively treat patients with cirrhosis and end-stage liver disease. However, information is limited with regard to the impact of DAA treatment on inpatient health-related resource utilization in patients with advanced HCV-related cirrhosis. We aimed to ascertain the impact of DAA treatment on the frequency of liver-related hospitalizations and associated costs in patients with cirrhosis. PATIENTS AND METHODS Retrospective cohort analysis carried out at a single US reference center that compared patients with HCV cirrhosis according to treatment status: the untreated group (January 2011 to December 2013) and the DAA-treated group (January 2014 to March 2017). The primary outcome was the difference in the incidence rate of liver-related hospitalizations. Secondary outcomes included differences in the incidence of hepatocellular carcinoma, liver transplant, and all-cause mortality. We calculated the projected savings per-patient treated per-year on the basis of calculated hospitalization rate stratified by Child-Turquotte-Pugh (CTP) score. RESULTS Baseline characteristics were similar between the untreated (n=182) and DAA-treated (n=196) cohorts. Mean follow-up time in the untreated and treated cohort was 20.4 and 17.7 months, respectively. The incidence rates of liver-related hospitalizations were 29.1/100 and 10.4/100 person-years of follow-up (P≤0.0001) in the untreated and treated cohorts, respectively. This was accounted for by a decreased incidence of hospitalizations in patients with CTP-A (75.8%) and CTP-B (64.5%), but not CTP-C. CONCLUSION Successful DAA treatment reduces hospitalization rate and resource utilization costs in patients with CTP-A and CTP-B, but not in those with CTP-C.
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16
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Proeschold-Bell RJ, Evon DM, Makarushka C, Wong JB, Datta SK, Yao J, Patkar AA, Mannelli P, Hodge T, Naggie S, Wilder JM, Fried MW, Niedzwiecki D, Muir AJ. The Hepatitis C-Alcohol Reduction Treatment (Hep ART) intervention: Study protocol of a multi-center randomized controlled trial. Contemp Clin Trials 2018; 72:73-85. [PMID: 30006024 PMCID: PMC6711183 DOI: 10.1016/j.cct.2018.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 05/25/2018] [Accepted: 07/09/2018] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Among patients with hepatitis C virus (HCV) infection, alcohol synergistically increases the risk of cirrhosis, hepatocellular carcinoma, and death. Randomized controlled trials of integrated models of HCV-alcohol treatment have been recommended but only performed in patients with severe alcohol use disorders. OBJECTIVES This pragmatic randomized controlled trial seeks to compare clinical effectiveness and cost-effectiveness of integrated alcohol treatment compared to enhanced treatment as usual (TAU) on alcohol consumption and economic outcomes among patients ever infected with HCV. METHODS Patients recruited from three liver centers who had current or prior chronic HCV and qualifying alcohol screener scores were randomly assigned to enhanced TAU or the Hepatitis C-Alcohol Reduction Treatment (Hep ART) intervention. All patients received enhanced TAU, consisting of a patient-administered alcohol screener and care from medical providers who were trained in Screening, Brief Intervention and Referral to Treatment (SBIRT), including brief motivational interviewing counseling. The Hep ART intervention combined enhanced TAU with up to six months of integrated co-located individual and/or group therapy that provided motivational, cognitive, and behavioral strategies to reduce alcohol consumption. The Timeline Followback (TLFB) Method was used to evaluate alcohol use at baseline, 3, 6, and 12 months. Primary outcomes are alcohol abstinence and fewer heavy drinking days, and for the cost-effectiveness analysis, measures included grams of alcohol consumed. DISCUSSION This study will determine whether Hep ART, a six-month integrated alcohol treatment, compared to enhanced TAU, is both clinically effective and cost-effective in patients with a history of comorbid HCV and alcohol use.
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Affiliation(s)
- Rae Jean Proeschold-Bell
- Duke Global Health Institute, Duke University, Box 90392, Durham, NC 27708-0392, USA; Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - Donna M Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, CB# 7584, Chapel Hill, NC 27599-7584, United States.
| | - Christina Makarushka
- Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, 800 Washington St #302, Boston, MA 02111, USA.
| | - Santanu K Datta
- Department of Medicine, Duke University, 411 West Chapel Hill St, Suite 500, Durham, NC 27701, USA.
| | - Jia Yao
- Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - Ashwin A Patkar
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States; Department of Community and Family Medicine, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States.
| | - Paolo Mannelli
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States.
| | - Terra Hodge
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA.
| | - Susanna Naggie
- Duke University School of Medicine, Infectious Diseases, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA; Durham VA Medical Center, Durham, NC 27705, USA.
| | - Julius M Wilder
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA.
| | - Michael W Fried
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, CB# 7584, Chapel Hill, NC 27599-7584, United States.
| | - Donna Niedzwiecki
- Department of Biostatistics and Bioinformatics, Duke University, Box 2721, Durham, NC 27710, United States.
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA.
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D'Amico G, Morabito A, D'Amico M, Pasta L, Malizia G, Rebora P, Valsecchi MG. Clinical states of cirrhosis and competing risks. J Hepatol 2018; 68:563-576. [PMID: 29111320 DOI: 10.1016/j.jhep.2017.10.020] [Citation(s) in RCA: 349] [Impact Index Per Article: 49.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Revised: 09/26/2017] [Accepted: 10/24/2017] [Indexed: 12/12/2022]
Abstract
The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of these disease states prompted the concept of clinical states of cirrhosis. A multistate approach has been considered to describe the clinical course of the disease. Such an approach requires the assessment of the probabilities of different outcomes in each state, which compete with each other to occur first and mark the transition towards a different state. This requires the use of competing risks analysis, since the traditional Kaplan-Meier analysis should only be used in two-state settings. Accounting for competing risks also has implications for prognosis and treatment efficacy research. The aim of this review is to summarise relevant clinical states and to show examples of competing risks analysis in multistate models of cirrhosis.
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Affiliation(s)
- Gennaro D'Amico
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy.
| | | | - Mario D'Amico
- Radiology Department, Università di Palermo, Palermo, Italy
| | - Linda Pasta
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy
| | - Giuseppe Malizia
- Gastroenterology Unit, Ospedale V. Cervello, Via Trabucco 180, Palermo, Italy
| | - Paola Rebora
- Dipartimento di Medicina e Chirurgia Università di Milano-Bicocca, Milano, Italy
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Performing Gadoxetic Acid–Enhanced MRI After CT for Guiding Curative Treatment of Early-Stage Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. AJR Am J Roentgenol 2018; 210:W63-W69. [DOI: 10.2214/ajr.17.18300] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Risk Assessment of Hepatocellular Carcinoma in Patients with Hepatitis C in China and the USA. Dig Dis Sci 2017; 62:3243-3253. [PMID: 28948495 DOI: 10.1007/s10620-017-4776-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/19/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatitis C (HCV) infection is an increasingly common cause of hepatocellular carcinoma (HCC) in China. AIMS We aimed to determine differences in demographic and behavioral profiles associated with HCC in HCV+ patients in China and the USA. METHODS Consecutive HCV+ patients were recruited from centers in China and the USA. Clinical data and lifestyle profiles were obtained through standardized questionnaires. Multivariable analysis was conducted to determine factors associated with HCC diagnosis within groups. RESULTS We included 41 HCC patients from China and 71 from the USA, and 931 non-HCC patients in China and 859 in China. Chinese patients with HCC were significantly younger, less likely to be male and to be obese than US patients with HCC (all p < 0.001). Chinese patients with HCC had a significantly lower rate of cirrhosis diagnosis (36.6 vs. 78.9%, p < 0.001); however, they also had a higher rate of hepatitis B core antibody positivity (63.4 vs. 36.8%, p = 0.007). In a multivariable analysis of the entire Chinese cohort, age > 55, male sex, the presence of diabetes, and time from maximum weight were associated with HCC, while tea consumption was associated with a decreased HCC risk (OR 0.37, 95% CI 0.16-0.88). In the US cohort, age > 55, male sex, and cirrhosis were associated with HCC on multivariable analysis. CONCLUSIONS With the aging Chinese population and increasing rates of diabetes, there will likely be continued increase in the incidence of HCV-related HCC in China. The protective effect of tea consumption on HCC development deserves further validation.
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Meijerink H, White RA, Løvlie A, de Blasio BF, Dalgard O, Amundsen EJ, Melum E, Kløvstad H. Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973-2030. BMC Infect Dis 2017; 17:541. [PMID: 28774261 PMCID: PMC5543437 DOI: 10.1186/s12879-017-2631-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 07/25/2017] [Indexed: 02/08/2023] Open
Abstract
Background Lack of Hepatitis C virus (HCV) incidence data in (Norwegian) high-risk groups impedes the ability to make informed decisions on prevention measures. Thus we rely on modelling to estimate the incidence and burden of HCV infections. Methods We constructed a compartmental model for HCV infections in Norway among active and former people who inject drugs (PWIDs). We based yearly transition rates on literature. The model was fitted to absolute numbers of hepatitis C associated cirrhosis, hepatocellular carcinoma (HCC) and death from national data sources (2000–2013). We estimated the number (95%CI) of HCV infections, cirrhosis, HCC and death and disability adjusted life years (DALYs) due to HCV infections in Norway, 1973–2030. We assumed treatment rates in the projected period were similar to those in 2013. Results The estimated proportion of chronic HCV (including those with cirrhosis and HCC) among PWIDs was stable from 2000 (49%; 4441/9108) to 2013 (43%; 3667/8587). We estimated that the incidence of HCV among PWIDs was 381 new infections in 2015. The estimated number of people with cirrhosis, HCC, and liver transplant was predicted to increase until 2022 (1537 people). DALYs among active PWIDs estimated to peak in 2006 (3480 DALYs) and decrease to 1870 DALYs in 2030. Chronic HCV infection contributes most to the total burden of HCV infection, and peaks at 1917 DALYs (52%) in 2007. The burden of HCV related to PWID increased until 2006 with 81/100,000 DALYs inhabitants and decreased to 68/100,000 DALYs in 2015. Conclusion The burden of HCV associated with injecting drug use is considerable, with chronic HCV infection contributing most to the total burden. This model can be used to estimate the impact of different interventions on the HCV burden in Norway and to perform cost-benefit analyses of various public health measures. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2631-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hinta Meijerink
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway.,European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, (ECDC), Stockholm, Sweden
| | - Richard A White
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway
| | - Astrid Løvlie
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway
| | - Birgitte Freiesleben de Blasio
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway.,Department of Biostatistics, Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Olav Dalgard
- Akershus University Hospital, Lørenskog, Norway.,Medical Faculty, Oslo University, Oslo, Norway
| | - Ellen J Amundsen
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway
| | - Espen Melum
- Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Section of Gastroenterology, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Hilde Kløvstad
- Norwegian Institute of Public Health, Postboks 4404 Nydalen, 0403, Oslo, Norway.
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22
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Abstract
It is critical to recognize that hepatitis C virus (HCV) infection is, in fact, a multifaceted systemic disease with both hepatic and extrahepatic complications. It is also important to recognize that the comprehensive burden of HCV should include not only its clinical burden but also its burden on the economic and patient-reported outcomes. It is only through this comprehensive approach to HCV infection that we can fully appreciate its true burden and understand the full benefit of curing HCV for the patient and the society.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
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23
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Risk for hepatitis B and C virus reactivation in patients with psoriasis on biologic therapies: A retrospective cohort study and systematic review of the literature. J Am Acad Dermatol 2017; 77:88-97.e5. [DOI: 10.1016/j.jaad.2017.01.037] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/23/2017] [Accepted: 01/24/2017] [Indexed: 12/25/2022]
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24
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McDonald SA, Innes HA, Aspinall E, Hayes PC, Alavi M, Valerio H, Goldberg DJ, Hutchinson SJ. Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era. J Viral Hepat 2017; 24:295-303. [PMID: 27885753 DOI: 10.1111/jvh.12646] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Accepted: 10/05/2016] [Indexed: 12/19/2022]
Abstract
At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.
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Affiliation(s)
- S A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - H A Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - E Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - P C Hayes
- Royal Infirmary of Edinburgh, Edinburgh, UK
| | - M Alavi
- Health Protection Scotland, Glasgow, UK
| | - H Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - D J Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - S J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
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25
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Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection. Mediterr J Hematol Infect Dis 2017; 9:e2017019. [PMID: 28293407 PMCID: PMC5333732 DOI: 10.4084/mjhid.2017.019] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 02/07/2017] [Indexed: 12/11/2022] Open
Abstract
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.
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26
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Younossi ZM, Birerdinc A, Henry L. Hepatitis C infection: A multi-faceted systemic disease with clinical, patient reported and economic consequences. J Hepatol 2016; 65:S109-S119. [PMID: 27641981 DOI: 10.1016/j.jhep.2016.07.005] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 07/02/2016] [Accepted: 07/04/2016] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus infection (HCV) affects approximately 170-200 million individuals globally. HCV is one of the primary causes of hepatocellular carcinoma (HCC) and cirrhosis and has been identified as the leading indication for liver transplantation in most Western countries. Because HCV is a systemic disease with hepatic, extrahepatic, economic and patient reported consequences, it is important for healthcare practitioners to understand the comprehensive and multi-faceted picture of this disease. In this context, it is important to fully appreciate the impact of HCV on the individual patient and the society. With the recent advent of the new generation of direct antiviral agents, the long standing goal of eradicating HCV in most infected patients has been accomplished. Therefore, now more than ever, it is critical to assess the total benefits of sustained virological response in a comprehensive manner. This should not be limited to the clinical benefits of HCV cure, but also to account for the improvement of patient reported health and economic outcomes of HCV cure. It is only through this comprehensive approach to HCV and its treatment that we will understand the full impact of this disease and the tremendous gains that have been achieved with the new antiviral regimens.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA.
| | - Aybike Birerdinc
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA
| | - Linda Henry
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA
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27
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Sundaram V, Kowdley KV. Dual daclatasvir and sofosbuvir for treatment of genotype 3 chronic hepatitis C virus infection. Expert Rev Gastroenterol Hepatol 2016; 10:13-20. [PMID: 26560449 DOI: 10.1586/17474124.2016.1116937] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40-50%), while genotype 3 had an intermediate response rate (60-70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3.
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Affiliation(s)
- Vinay Sundaram
- a Department of Medicine and Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , CA , USA
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28
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Velosa J. Why is viral eradication so important in patients with HCV-related cirrhosis? Antivir Ther 2016; 22:1-12. [PMID: 27553973 DOI: 10.3851/imp3077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2016] [Indexed: 02/07/2023]
Abstract
Approximately one-third of patients infected with chronic HCV have cirrhosis, and this is likely to increase in the near future. The risk of complications, mainly the development of hepatocellular carcinoma, depends on the presence of cirrhosis, and a significant increase in the incidence of cirrhosis-related events, including mortality, is likely in the following years. All-oral therapy with direct-acting antivirals (DAAs) offers a safe and short treatment, with cure rates over 90% in compensated cirrhosis. Cirrhotic patients should be given high priority for treatment because viral clearance has a significant impact on the natural history of HCV infection, halting the progression of the disease and inducing the regression of fibrosis, as well as reducing the need for liver transplantation and improving survival. The benefit of DAAs is great in patients with decompensated cirrhosis, up until recently a population for whom no alternative therapy was available. The efficacy of all-oral therapy has been reported to improve liver function in about 50% of Child-Pugh class C patients. The regression of cirrhosis observed in more than half of patients achieving viral eradication on prior interferon-based regimens still has to be demonstrated in patients treated with DAAs, although there is reason to believe that this will happen. Advanced cirrhosis will eventually become the last boundary of antiviral therapy that will soon be conquered with new drugs currently pending approval.
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Affiliation(s)
- José Velosa
- Hospital de Santa Maria - Gastroenterology and Hepatology, Lisbon, Portugal
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29
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Chin M, Hogan C, Nguyen D. The Natural History of Hepatit is C Viral Infection: Clinical Evaluation and Monitoring. ACTA ACUST UNITED AC 2016. [DOI: 10.2174/1874220301603010052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease in the world and represents a substantial burden on global health systems and individual patient wellbeing. Routine screening for HCV in certain high-risk populations is appropriate. HCV can cause both an acute and chronic hepatitis, and manifests as a variety of hepatic and extrahepatic symptoms, largely influenced by a combination of host and viral factors. It can be difficult to predict clinical outcomes in individual cases. In those who suffer a chronic infection, progression to cirrhosis carries the risk of decompensation and hepatocellular carcinoma. The natural history of HCV infection and our understanding of risk factors that are predictive of disease progression are discussed.
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30
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Attallah AM, El-Far M, Abdel Malak CA, Farid K, Omran MM, Yahya RS, Saad EA, Albannan MS, Attallah AA, El Basuni MA, Ali IS, Abed SB, El Naggar MA. A simple diagnostic index comprising epithelial membrane antigen and fibronectin for hepatocellular carcinoma. Ann Hepatol 2016; 14:869-80. [PMID: 26436359 DOI: 10.5604/16652681.1171774] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC). RESULTS A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC. CONCLUSIONS A four-marker index may improve the early detection of HCC with a high degree of accuracy.
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Affiliation(s)
- Abdelfattah M Attallah
- Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt
| | - Mohamed El-Far
- Faculty of Science, Mansoura University, Mansoura, Egypt
| | | | - Khaled Farid
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | | | - Raida S Yahya
- Faculty of Medicine, Children's Hospital, Mansoura University, Mansoura, Egypt
| | - Entsar A Saad
- Faculty of Science, Damietta University, New Damietta, Egypt
| | - Mohamed S Albannan
- Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt
| | - Ahmed A Attallah
- Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt
| | - Mohamed A El Basuni
- Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt
| | | | - Safaa B Abed
- Research & Development Department, Biotechnology Research Center, New Damietta City, Egypt
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31
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Abstract
Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Among the six HCV genotypes, genotype 1 was significantly more aggressive when utilizing the combination of pegylated interferon and ribavirin, as genotype 1-infected patients had the lowest likelihood of achieving cure (40%-50%) and required twice as long duration of treatment, as compared to genotypes 2 and 3. Recently, however, significant advances have been made with the advent of all-oral direct-acting antiviral agents, which have significantly improved the safety, efficacy, and tolerability of the treatment of HCV genotype 1. Among the available treatments for HCV genotype 1, the combination therapy of ledipasvir/sofosbuvir provides several advantages compared to other regimens, including use of a single-pill regimen, possibility to shorten the duration of treatment to 8 weeks, efficacy in patients exposed to protease inhibitors, safety in decompensated cirrhosis, and potential to avoid ribavirin. In this review, we discuss the pharmacotherapy of the combination of ledipasvir/sofosbuvir therapy and summarize the results of the Phase III clinical trials for this treatment in HCV genotype 1 patients. We will also discuss the data for special populations, including decompensated cirrhosis, human immunodeficiency virus (HIV) coinfected patients, African-Americans, the elderly, and those who failed sofosbuvir-containing regimens.
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Affiliation(s)
- Vinay Sundaram
- Department of Medicine and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Kris V Kowdley
- Liver Care Network, Swedish Medical Center, Seattle, WA, USA
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32
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Management of post liver transplantation recurrent hepatitis C infection with directly acting antiviral drugs: a review. Hepatol Int 2016; 10:749-61. [PMID: 27337961 DOI: 10.1007/s12072-016-9744-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 05/17/2016] [Indexed: 12/20/2022]
Abstract
Recurrent HCV infection (rHCV) of the liver allograft following transplantation is universal and is associated with poor graft and patient survival in comparison with other indications. Treatment of rHCV infection in the previous era with pegylated interferon and ribavirin was associated with low sustained virological response (SVR) due to poor tolerability, adverse events and graft rejection. Recently, directly acting antiviral drugs (DAA) have been approved for the treatment of hepatitis C infection and a number of clinical trials have been conducted across various centers in the management of rHCV infection of the graft. In this review we discuss about recent studies that have emerged on the use of NS5b polymerase inhibitor, sofosbuvir in combination with second generation protease inhibitor, simeprevir, fixed dose ledipasvir or daclatasvir with or without ribavirin in the treatment of post transplant rHCV infection.
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33
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Kanda T. Interferon-free treatment for HCV-infected patients with decompensated cirrhosis. Hepatol Int 2016; 11:38-44. [PMID: 27282879 DOI: 10.1007/s12072-016-9749-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 05/27/2016] [Indexed: 02/06/2023]
Abstract
Progress in interferon-free treatment against hepatitis C virus (HCV) has remained a challenge in patients with decompensated cirrhosis due to a paucity of information on efficacy and safety profiles. This review illustrates that interferon-free treatment could result in greater than 85 % sustained virological response (SVR) rates in patients with HCV genotype 1 and decompensated cirrhosis. The combination of pangenotypic HCV NS5A inhibitor velpatasvir and HCV NS5B inhibitor sofosbuvir has demonstrated high SVR rates in patients with HCV genotypes 1, 2, 3, 4 or 6 and decompensated cirrhosis. Certain patients discontinued treatment due to adverse events, death or having liver transplantation. Taken together, interferon-free treatment could produce higher SVR rates in decompensated hepatic cirrhosis. However, as adverse events were occasionally observed, liver transplantation should always be considered as well. Further improvements in treatment are called for in patients with decompensated cirrhosis.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 220-8677, Japan.
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34
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Wang LS, D'Souza LS, Jacobson IM. Hepatitis C-A clinical review. J Med Virol 2016; 88:1844-55. [PMID: 27097298 DOI: 10.1002/jmv.24554] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/10/2016] [Indexed: 12/18/2022]
Abstract
With an estimated prevalence of about 170 million people worldwide, chronic hepatitis C is an important cause of chronic liver disease associated with a substantial risk of cirrhosis and hepatocellular carcinoma. The recent past has borne witness to remarkable advancements in the treatment of chronic hepatitis C with the development of novel, effective, and well tolerated medications that have resulted in paradigm shifts in treatment approaches and may potentially affect the natural history of the disease. We provide a clinical review of current concepts and future developments in the management of chronic hepatitis C to aid in the understanding and individualization of chronic hepatitis C treatment. J. Med. Virol. 88:1844-1855, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Lan S Wang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Texas Health Science Center at Houston, Houston, Texas
| | - Lionel S D'Souza
- Division of Digestive Diseases, Department of Medicine, Mount Sinai Beth Israel Medical Center, New York, New York
| | - Ira M Jacobson
- Division of Digestive Diseases, Department of Medicine, Mount Sinai Beth Israel Medical Center, New York, New York
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35
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Matsuoka S, Fujikawa H, Hasegawa H, Ochiai T, Watanabe Y, Moriyama M. Onset of Tuberculosis from a Pulmonary Latent Tuberculosis Infection during Antiviral Triple Therapy for Chronic Hepatitis C. Intern Med 2016; 55:2011-7. [PMID: 27477407 DOI: 10.2169/internalmedicine.55.6448] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 62-year-old man was diagnosed with the onset of tuberculosis (Tb) from a pulmonary latent tuberculosis infection (LTBI) during triple therapy with pegylated interferon α2a, ribavirin, and telaprevir for a chronic hepatitis C infection in 2013 before interferon (IFN)-free anti-viral therapy was introduced in Japan. A liver biopsy before IFN treatment revealed the presence of epithelioid cell granulomas (ECGs). IFN may also be employed for chronic hepatitis B infection and malignant tumors, thus, special attention must be paid to the development of Tb from a LTBI when ECGs are observed before treatment. It is also necessary to review the significance of the liver biopsy.
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Affiliation(s)
- Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan
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36
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Shakado S, Sakisaka S, Chayama K, Okanoue T, Toyoda J, Izumi N, Matsumoto A, Takehara T, Ido A, Hiasa Y, Yoshioka K, Nomura H, Ueno Y, Seike M, Kumada H. Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development. World J Hepatol 2015; 7:2757-2764. [PMID: 26644819 PMCID: PMC4663395 DOI: 10.4254/wjh.v7.i27.2757] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 07/18/2015] [Accepted: 11/17/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate risk factors for development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-related liver cirrhosis (LC-C).
METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon (IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.
RESULTS: HCC was diagnosis in 50 (21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older (P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein (AFP) (P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio (OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/mL (P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin (DCP) levels of ≥ 40 mAU/mL at 24 wk after the completion of IFN and ribavirin therapy (P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).
CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.
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Mohamed AA, Elbedewy TA, El-Serafy M, El-Toukhy N, Ahmed W, Ali El Din Z. Hepatitis C virus: A global view. World J Hepatol 2015; 7:2676-2680. [PMID: 26609344 PMCID: PMC4651911 DOI: 10.4254/wjh.v7.i26.2676] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 07/29/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a global challenge; 130-175 million are chronically infected. Over 350000 die each year from HCV. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. Management of chronic HCV is aimed at preventing cirrhosis, reducing the risk of HCC, and treating extra hepatic complications. New treatments for chronic HCV has been devoted based on direct-acting antivirals, as pegylated interferon (peginterferon) is responsible for many side effects and limits treatment access. Sofosbuvir is the first compound to enter the market with Peginterferon-free combination regimens.
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Lee SS, Jeong SH, Jang ES, Kim YS, Lee YJ, Jung EU, Kim IH, Bae SH, Lee HC, Kee MK, Kang C. Prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis in South Korea. J Gastroenterol Hepatol 2015; 30:1281-7. [PMID: 25778783 DOI: 10.1111/jgh.12950] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS The outcomes of hepatitis C virus (HCV)-related liver cirrhosis was limitedly studied in a hepatitis B virus-endemic area. This multicenter, prospective cohort study was conducted to elucidate the incidence of hepatocellular carcinoma (HCC) and mortality in the Korean patients with HCV-related cirrhosis. METHODS From January 2007 through June 2012, 196 patients with HCV-related cirrhosis were prospectively enrolled and regularly followed at six university hospitals to determine HCC occurrence and mortality. A multivariable analysis using Cox proportional hazards regression was performed to clarify the related factors to the outcomes. RESULTS During a mean follow-up period of 39.2 months, 31 (15.8%) patients developed HCC, and 33 (16.8%) patients died or underwent liver transplantation. The estimated HCC incidence was 5.8 per 100 person-years, and the independent factors for HCC were absence of anti-HBV surface antibody (HBs hazard ratio [HR], 5.018; 95% confidence interval [CI], 1.710-14.726; P = 0.003) and serum albumin < 3.8 g/dL (HR, 3.051; 95% CI, 1.318-7.067; P = 0.009). The overall mortality rate was 5.1 per 100 person-years, and the related independent factors were the presence of ascites (HR, 2.448; 95% CI, 1.142-5.210; P = 0.022), serum albumin < 3.8 g/dL (HR, 3.067; 95% CI, 1.254-8.139, P = 0.014), and nonachievement of sustained virologic response (SVR) (HR, 0.066; 95% CI, 0.001-0.484, P = 0.002). CONCLUSION The incidence of HCC in HCV-related cirrhosis seems to be high in Korea, and advanced liver disease and no achievement of SVR were associated with mortality. The absence of anti-HBs in hepatocarcinogenesis related to HCV warrants further study.
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Affiliation(s)
- Sang Soo Lee
- Department of Internal Medicine, *Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Sook-Hyang Jeong
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Eun Sun Jang
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Young Seok Kim
- Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
| | - Youn Jae Lee
- Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - Eun Uk Jung
- Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - In Hee Kim
- Chonbuk National University Hopital, Chonbuk National University College of Medicine, Chonju, South Korea
| | - Si Hyun Bae
- The Catholic University of Korea Seoul Saint Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea
| | - Han Chu Lee
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Mee-Kyung Kee
- Division of AIDS, Korea National Institute of Health, Osong, South Korea
| | - Chun Kang
- Division of AIDS, Korea National Institute of Health, Osong, South Korea
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Karageorgopoulos DE, Allen J, Bhagani S. Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a "special population"? World J Hepatol 2015; 7:1936-52. [PMID: 26244068 PMCID: PMC4517153 DOI: 10.4254/wjh.v7.i15.1936] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 06/24/2015] [Accepted: 07/21/2015] [Indexed: 02/06/2023] Open
Abstract
A substantial proportion of individuals with chronic hepatitis C virus (HCV) are co-infected with human immunodeficiency virus (HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals (DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.
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Affiliation(s)
- Drosos E Karageorgopoulos
- Drosos E Karageorgopoulos, Joanna Allen, Sanjay Bhagani, Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
| | - Joanna Allen
- Drosos E Karageorgopoulos, Joanna Allen, Sanjay Bhagani, Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
| | - Sanjay Bhagani
- Drosos E Karageorgopoulos, Joanna Allen, Sanjay Bhagani, Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
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Harada N, Hiramatsu N, Oze T, Tatsumi T, Hayashi N, Takehara T. Efficacy of pegylated interferon and ribavirin combination therapy for patients with hepatitis C virus infection after curative resection or ablation for hepatocellular carcinoma-A retrospective multicenter study. J Med Virol 2015; 87:1199-206. [DOI: 10.1002/jmv.24173] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2015] [Indexed: 12/15/2022]
Affiliation(s)
- Naoki Harada
- Department of Gastroenterology and Hepatology; Osaka University Graduate School of Medicine; Suita Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology; Osaka University Graduate School of Medicine; Suita Japan
| | - Tsugiko Oze
- Department of Gastroenterology and Hepatology; Osaka University Graduate School of Medicine; Suita Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology; Osaka University Graduate School of Medicine; Suita Japan
| | - Norio Hayashi
- Department of Gastroenterology and Hepatology; Kansai Rosai Hospital; Amagasaki Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology; Osaka University Graduate School of Medicine; Suita Japan
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Abstract
The efficacy of antiviral treatment depends on which of the seven genotypes (G1-G7) of hepatitis C virus (HCV) has infected the patient. Conventionally, clinicians regarded G2 and G3 infections as 'easy-to-treat': dual therapy with pegylated interferon and ribavirin produces a sustained virologic response in approximately 40-50% of patients with G1 infection, compared with 80% when analyses report combined data for G2 and G3 patients, which is standard practice in many clinical studies. However, sustained virologic response rates appear to be lower in certain subgroups of people infected with G3 compared with those with G2 or the general HCV-infected population. This review examines the growing evidence that factors related to the virus (e.g., baseline viral load and a rapid virologic response) and host characteristics (e.g., steatosis and fibrosis, metabolic syndrome, host polymorphisms and ethnicity) contribute to variations in therapeutic success in G3 HCV.
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Affiliation(s)
- Maria Buti
- Liver Unit, Hospital Universitario Valle Hebron and Ciberehd del Instituto, Carlos III Paseo Valle Hebron 119, Barcelona 08035, Spain
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Abstract
Historically, pegylated interferon in combination with ribavirin was the standard of care in hepatitis C virus; however, this combination is often poorly tolerated, has a significant side-effect profile and is of limited efficacy in hepatitis C virus genotype-1. More recently, pegylated interferon/ribavirin has been combined with direct acting antiviral agents such as the first generation NS3/4A protease inhibitors. Faldaprevir, a first generation, second-wave protease inhibitor, when used with a pegylated interferon/ribavirin regimen, has also been shown to increase treatmentsuccess while shortening treatment duration; however, second generation direct acting antiviral agents offer even betterefficacy and tolerability. Various direct acting antiviral agent combinations in interferon-free regimens have been effective in over 95% of patients and are now in licensed use. While faldaprevir was a pioneering drug, by the time it reached late phase development it was superseded by newer agents.
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Affiliation(s)
- Kosh Agarwal
- Kings College Hospital, Institute for liver studies, London, UK
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van der Meer AJ, Hansen BE, Fattovich G, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Manns MP, Ieluzzi D, Zeuzem S, Hofmann WP, de Knegt RJ, Veldt BJ, Janssen HLA. Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters. Gut 2015; 64:322-31. [PMID: 24815676 DOI: 10.1136/gutjnl-2013-305357] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking. DESIGN Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis. RESULTS In the derivation cohort, 100/405 patients died during a median 8.1 (IQR 5.7-11.1) years of follow-up. Multivariate Cox analyses showed age (HR=1.06, 95% CI 1.04 to 1.09, p<0.001), male sex (HR=1.91, 95% CI 1.10 to 3.29, p=0.021), platelet count (HR=0.91, 95% CI 0.87 to 0.95, p<0.001) and log10 aspartate aminotransferase/alanine aminotransferase ratio (HR=1.30, 95% CI 1.12 to 1.51, p=0.001) were independently associated with mortality (C statistic=0.78, 95% CI 0.72 to 0.83). In the validation cohort, 58/296 patients with cirrhosis died during a median of 6.6 (IQR 4.4-9.0) years. Among patients with estimated 5-year mortality risks <5%, 5-10% and >10%, the observed 5-year mortality rates in the derivation cohort and validation cohort were 0.9% (95% CI 0.0 to 2.7) and 2.6% (95% CI 0.0 to 6.1), 8.1% (95% CI 1.8 to 14.4) and 8.0% (95% CI 1.3 to 14.7), 21.8% (95% CI 13.2 to 30.4) and 20.9% (95% CI 13.6 to 28.1), respectively (C statistic in validation cohort = 0.76, 95% CI 0.69 to 0.83). The risk score for cirrhosis-related complications also incorporated HCV genotype (C statistic = 0.80, 95% CI 0.76 to 0.83 in the derivation cohort; and 0.74, 95% CI 0.68 to 0.79 in the validation cohort). CONCLUSIONS Prognosis of patients with chronic HCV infection and compensated advanced liver disease can be accurately assessed with risk scores including readily available objective clinical parameters.
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Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | - Jordan J Feld
- Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Heiner Wedemeyer
- Departments of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Jean-François Dufour
- Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Andres Duarte-Rojo
- Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Michael P Manns
- Departments of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | | | - Stefan Zeuzem
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - W Peter Hofmann
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bart J Veldt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Harry L A Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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Lim KC, Wang VW, Siddiqui FJ, Shi L, Chan ESY, Oh HC, Tan SB, Chow PKH. Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria. Hepatology 2015; 61:227-37. [PMID: 24638991 DOI: 10.1002/hep.27135] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 03/13/2014] [Indexed: 12/13/2022]
Abstract
UNLABELLED Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.
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Affiliation(s)
- Kheng Choon Lim
- Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore; Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore
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Kato M, Nishida T, Hamasaki T, Kawai N, Yoshio T, Egawa S, Yamamoto K, Ogiyama H, Komori M, Nakahara M, Yabuta T, Nishihara A, Hayashi Y, Yamada T, Takehara T. Outcomes of ESD for patients with early gastric cancer and comorbid liver cirrhosis: a propensity score analysis. Surg Endosc 2014; 29:1560-6. [PMID: 25294528 DOI: 10.1007/s00464-014-3841-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Accepted: 08/20/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Gastric cancer and liver cirrhosis (LC) are often comorbid. However, little is known about the clinical outcomes of gastric endoscopic submucosal dissection (ESD) in patients with comorbid LC. METHODS This case-control study used a multicentre retrospective cohort. We identified 69 LC patients from the cohort of patients with early gastric cancer, who underwent gastric ESD at 12 hospitals from March 2003 to November 2010. Using the propensity score matching method, 69 patients without LC were used to compare the short- and long-term outcomes of ESD. RESULTS Among the 69 LC patients, 53 (77 %) were Child-Pugh grade A (CP-A) and 16 (28 %) had past or present histories of hepatocellular carcinoma (HCC). Short-term outcomes did not differ between the LC patients and controls or between the CP-A and CP-B/C patients. Although the LC patients had significantly worse long-term outcomes than the controls (the 5-year overall survival rates were 60 vs. 91 %, respectively), patients with CP-A liver function without HCC histories had an overall survival almost equivalent to that of patients without LC (controls). CONCLUSIONS LC patients appear to be good candidates for ESD if they have CP-A liver function and no history of HCC. Although their short-term outcomes were not inferior, the patients with Child-Pugh grades B/C or with histories of HCC benefited less from ESD.
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Affiliation(s)
- Motohiko Kato
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan,
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Shakado S, Sakisaka S, Okanoue T, Chayama K, Izumi N, Toyoda J, Tanaka E, Ido A, Takehara T, Yoshioka K, Hiasa Y, Nomura H, Seike M, Ueno Y, Kumada H. Interleukin 28B polymorphism predicts interferon plus ribavirin treatment outcome in patients with hepatitis C virus-related liver cirrhosis: A multicenter retrospective study in Japan. Hepatol Res 2014; 44:983-92. [PMID: 24400682 DOI: 10.1111/hepr.12280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 11/15/2013] [Accepted: 11/17/2013] [Indexed: 12/22/2022]
Abstract
AIM This study evaluated the efficacy of interferon plus ribavirin and examined whether interleukin 28B (IL28B) polymorphism influenced treatment outcome in Japanese patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). METHODS Fourteen collaborating centers provided details of 261 patients with HCV-related LC undergoing treatment with interferon plus ribavirin. Univariate and multivariate analyses were used to establish which factors predicted treatment outcome. RESULTS Eighty-four patients (32.2%) achieved a sustained virological response (SVR). SVR rates were 21.6% (41/190) in patients with HCV genotype 1 with high viral load (G1H) and 60.6% (43/71) in patients with non-G1H. In patients with non-G1H, treatment outcome was effective irrespective of IL28B polymorphism. In those with G1H, SVR was achieved in 27.1% of patients with the IL28B rs8099917 TT allele compared with 8.8% of those with the TG/GG alleles (P = 0.004). In patients with G1H having TT allele, treatments longer than 48 weeks achieved significantly higher SVR rates than treatments less than 48 weeks (34.6% vs 16.4%, P = 0.042). In patients with G1H having TG/GG alleles, treatments longer than 72 weeks achieved significantly higher SVR rates than treatments less than 72 weeks (37.5% vs 4.1%, P = 0.010). CONCLUSION Interferon plus ribavirin treatment in Japanese patients with non-G1H HCV-related LC was more effective than those with G1H and not influenced by IL28B polymorphism. In those with G1H, IL28B polymorphism may predict SVR and guide treatment duration: SVR rates were higher in those with the TT allele treated for more than 48 weeks and those with the TG/GG alleles treated for more than 72 weeks.
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Affiliation(s)
- Satoshi Shakado
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Division of Advanced Clinical Research for Viral Hepatitis and Liver Cancer, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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Fernández Rodriguez CM, Gutierrez Garcia ML. [Impact of antiviral therapy on the natural history of hepatitis C virus]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:583-92. [PMID: 25066318 DOI: 10.1016/j.gastrohep.2014.05.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 05/28/2014] [Indexed: 02/08/2023]
Abstract
Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitis C with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitis C virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitis C virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease.
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Toshikuni N, Arisawa T, Tsutsumi M. Nutrition and exercise in the management of liver cirrhosis. World J Gastroenterol 2014; 20:7286-7297. [PMID: 24966599 PMCID: PMC4064074 DOI: 10.3748/wjg.v20.i23.7286] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2014] [Revised: 03/22/2014] [Accepted: 05/05/2014] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.
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Ikeda K, Kawamura Y, Kobayashi M, Fukushima T, Sezaki H, Hosaka T, Akuta N, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H. Prevention of disease progression with anti-inflammatory therapy in patients with HCV-related cirrhosis: a Markov model. Oncology 2014; 86:295-302. [PMID: 24924385 DOI: 10.1159/000357713] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 11/26/2013] [Indexed: 01/13/2023]
Abstract
BACKGROUND The significance of anti-inflammatory therapy has not been fully evaluated in hepatitis C virus (HCV)-related cirrhosis. PATIENTS AND METHODS We analyzed stepwise progression rates from cirrhosis to hepatocellular carcinoma (HCC) and to death using a Markov model in 1,280 patients with HCV-related cirrhosis. During the observation period, 303 patients received interferon and 736 received glycyrrhizin injections as anti-inflammatory therapy. RESULTS In the entire group, annual progression rates from cirrhosis to HCC and from cirrhosis to death were 6.8 and 1.9%, and the rate from HCC to death was 19.0%. When sustained virological response (SVR) or biochemical response (BR) was attained with interferon, the annual rate to HCC decreased to 2.6%. On the contrary, the progression rates to HCC and to death in the patients without SVR and BR were 7.2 and 2.0%, respectively (p < 0.0001). Continuous interferon administration significantly decreased the carcinogenesis rate to 5.5% (p = 0.0087). In the analysis of the remaining patients with high alanine transaminase of 75 IU/l or more but without interferon response or without interferon administration, glycyrrhizin injection significantly decreased annual non-progression probability (no glycyrrhizin 88.0% vs. glycyrrhizin therapy 92.3%, p = 0.00055). CONCLUSION Glycyrrhizin injection therapy is useful in the prevention of disease progression in interferon-resistant or intolerant patients with HCV-related cirrhosis.
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Affiliation(s)
- Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Zeng QL, Feng GH, Zhang JY, Chen Y, Yang B, Huang HH, Zhang XX, Zhang Z, Wang FS. Risk factors for liver-related mortality in chronic hepatitis C patients: A deceased case-living control study. World J Gastroenterol 2014; 20:5519-5526. [PMID: 24833882 PMCID: PMC4017067 DOI: 10.3748/wjg.v20.i18.5519] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 01/09/2014] [Accepted: 02/27/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the risk factors for liver-related mortality in chronic hepatitis C (CHC) patients.
METHODS: All deceased CHC inpatient data were collected from the Beijing 302 Hospital clinical database, which includes more than 8250 CHC inpatients during the period from 2002 to 2012. The controls were matched to cases by age (± 2 years), sex and date of hospital admission (within the same year). Potential risk factors were included for the evaluation, and odds ratios (OR) and 95%CI were estimated using univariate (unadjusted) and multivariate (adjusted OR, AOR) conditional logistic regression. All statistical tests were two-sided. P values < 0.05 were considered statistically significant.
RESULTS: Based on examinations of 144 CHC-related deceased cases and 576 controls, we found that antiviral therapy with interferon-α was associated with a 47% decrease in the risk of hepatic mortality (AOR = 0.53, 95%CI: 0.28-0.99, P = 0.048). Additionally, the initial diagnostic stage of the disease (AOR = 2.89, 95%CI: 1.83-4.56 and P < 0.001 for liver cirrhosis/AOR = 8.82, 95%CI: 3.99-19.53 and P < 0.001 for HCC compared with CHC), diabetes (AOR = 2.35, 95%CI: 1.40-3.95, P = 0.001), hypertension (AOR = 1.76, 95%CI: 1.09-2.82, P = 0.020), alcohol consumption (AOR = 1.73, 95%CI: 1.03-2.81, P = 0.037) and HBsAg positivity (AOR = 22.28, 95%CI: 5.58-89.07, P < 0.001) were associated with a significant increase in the risk of liver-related mortality in CHC patients.
CONCLUSION: This study indicates that interferon-α treatment, the stage at the initial diagnosis of the disease and comorbidities are all independent risk factors for liver-related mortality in CHC patients.
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