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Liu CH, Chang YP, Kao JH. Cutting-edge pharmacotherapy for hepatitis C virus infection: a comprehensive review. Expert Opin Pharmacother 2024; 25:1691-1706. [PMID: 39169665 DOI: 10.1080/14656566.2024.2396024] [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: 07/17/2024] [Revised: 08/17/2024] [Accepted: 08/20/2024] [Indexed: 08/23/2024]
Abstract
INTRODUCTION Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV. AREAS COVERED We review the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs. EXPERT OPINION Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Yu-Ping Chang
- Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Atsukawa M, Tsubota A, Kondo C, Toyoda H, Takaguchi K, Nakamuta M, Watanabe T, Morishita A, Tani J, Okubo H, Hiraoka A, Nozaki A, Chuma M, Kawata K, Uojima H, Ogawa C, Asano T, Mikami S, Kato K, Matsuura K, Ikegami T, Ishikawa T, Tsuji K, Tada T, Tsutsui A, Senoh T, Kitamura M, Okubo T, Arai T, Kohjima M, Morita K, Akahane T, Nishikawa H, Iwasa M, Tanaka Y, Iwakiri K. ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis. J Gastroenterol 2024; 59:709-718. [PMID: 38727822 DOI: 10.1007/s00535-024-02109-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 04/21/2024] [Indexed: 07/29/2024]
Abstract
BACKGROUND This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-Ku, Tokyo, Japan.
| | - Akihito Tsubota
- Project Research Units (PRU) Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-Ku, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Makoto Nakamuta
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Toru Asano
- Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
| | - Tadashi Ikegami
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hygo, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Michika Kitamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-Ku, Tokyo, Japan
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-Ku, Tokyo, Japan
| | - Motoyuki Kohjima
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Kiyoshi Morita
- Department of Gastroenterology, Toyota Kosei Hospital, Toyota, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan
| | - Hiroki Nishikawa
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-Ku, Tokyo, Japan
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Nakagawa C, Oikawa T, Yamada K, Tsubota A, Saeki C, Katagiri K, Tago N, Kamioka H, Ueda K, Haruki K, Furukawa K, Nakano M, Torisu Y, Ikegami T, Yoshida K, Saruta M. Protein kinase C delta enhances the diagnostic performance of hepatocellular carcinoma. Biomarkers 2024; 29:55-67. [PMID: 38361436 DOI: 10.1080/1354750x.2024.2312990] [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: 10/23/2023] [Accepted: 01/27/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need. OBJECTIVE This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs. METHODS PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC. RESULTS In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels. CONCLUSIONS PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.
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Affiliation(s)
- Chika Nakagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kohji Yamada
- Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kuniko Katagiri
- Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan
| | - Naoko Tago
- Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroshi Kamioka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Koichiro Haruki
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Kenei Furukawa
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Toru Ikegami
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Kiyotsugu Yoshida
- Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Garza KY, Pandey A, Marzinke MA. Development and validation of a liquid chromatographic-tandem mass spectrometric assay for the quantification of the direct acting antivirals glecaprevir and pibrentasvir in plasma. J Pharm Biomed Anal 2023; 235:115629. [PMID: 37619293 DOI: 10.1016/j.jpba.2023.115629] [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: 06/27/2023] [Revised: 07/31/2023] [Accepted: 08/04/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Direct acting antiviral (DAA) therapies are effective in the treatment and management of chronic HCV infections. Glecaprevir (GLE) and pibrentasvir (PIB) are pangenotypic DAAs that are delivered alone or as a fixed-dose oral formulation to treat chronic HCV infections with or without cirrhosis. Sensitive and dynamic bioanalytical assays are needed to understand the pharmacology of GLE and PIB. METHODS Drug free K2EDTA plasma was spiked with GLE, PIB, and their internal standards. Drugs were extracted from plasma via protein precipitation, and subsequently quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated according to regulatory recommendations, and evaluated in remnant plasma samples from individuals prescribed GLE and PIB. RESULTS The analytical measuring ranges for GLE and PIB were 0.25-2000 ng/mL and 0.25-1000 ng/mL, respectively. The method showed acceptable accuracy and precision for both DAAs. GLE and PIB in plasma were stable following six freeze thaw cycles and at room temperature for up to 67 h. All analytes were stable in whole blood incubated at room temperature for 24 h, and at 40 °C and 100% humidity for 2 h. Negligible percent matrix effects were observed for PIB and PIB-IS across the measuring range of the assay. Significant ion suppression was observed for GLE, with an average matrix effects of 27.9%. However, relative matrix effects were < 6.3% between drug and internal standard, and deemed acceptable. Assay validation assessments in alternative matrices also met acceptance criteria. Both DAAs were successfully measured in remnant plasma samples from individuals administered GLE and PIB. CONCLUSIONS An LC-MS/MS method for GLE and PIB quantification in plasma has been developed and validated. The assay met acceptable performance criteria and may be used in downstream applications to characterize DAA pharmacology for HCV treatment.
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Affiliation(s)
- Kyana Y Garza
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Aashish Pandey
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mark A Marzinke
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Toyoda H, Kikuchi K. Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy. Ther Apher Dial 2023; 27:831-838. [PMID: 37217295 DOI: 10.1111/1744-9987.14003] [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: 03/03/2023] [Revised: 04/24/2023] [Accepted: 05/06/2023] [Indexed: 05/24/2023]
Abstract
The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kan Kikuchi
- Division of Nephrology, Shimoochiai Clinic, Tokyo, Japan
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Chen R, Xiong Y, Zeng Y, Wang X, Xiao Y, Zheng Y. The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis. Front Public Health 2023; 11:1179531. [PMID: 37841743 PMCID: PMC10570741 DOI: 10.3389/fpubh.2023.1179531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 08/31/2023] [Indexed: 10/17/2023] Open
Abstract
Background Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making. Methods We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods. Results Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients. Conclusion The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles. Systematic review registration https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.
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Affiliation(s)
- Ruochan Chen
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yinghui Xiong
- Department of Respiration, Hunan Children's Hospital, Changsha, China
| | - Yanyang Zeng
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaolei Wang
- Hunan Provincial Center for Disease Control and Prevention, Hunan Workstation for Emerging Infectious Disease Control and Prevention, Chinese Academy of Medical Sciences, Changsha, China
| | - Yinzong Xiao
- Burnet Institute, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia
| | - Yixiang Zheng
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Yoshida Y, Atsukawa M, Kondo C, Kitamura M, Shioda-Koyano K, Kawano T, Ono H, Hayama K, Okubo T, Arai T, Itokawa N, Iwakiri K. A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C. PLoS One 2023; 18:e0292019. [PMID: 37733802 PMCID: PMC10513247 DOI: 10.1371/journal.pone.0292019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 09/08/2023] [Indexed: 09/23/2023] Open
Abstract
Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.
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Affiliation(s)
- Yuji Yoshida
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Michika Kitamura
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Kaori Shioda-Koyano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hiroki Ono
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Korenobu Hayama
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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8
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Balk EM, Adam GP, Jadoul M, Martin P, Gordon CE. A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD. Kidney Int Rep 2023; 8:240-253. [PMID: 36815114 PMCID: PMC9939364 DOI: 10.1016/j.ekir.2022.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/11/2022] [Accepted: 11/15/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs). Methods We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12 ≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61). Conclusion Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.
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Affiliation(s)
- Ethan M. Balk
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Gaelen P. Adam
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Michel Jadoul
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Florida, USA
| | - Craig E. Gordon
- Division of Nephrology, Department of Medicine, Tufts University School of Medicine, Boston, Massachussetts, USA
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Jadoul M, Awan A, Berenguer M, Bruchfeld A, Fabrizi F, Goldberg D, Jia J, Kamar N, Mohamed R, Pessôa M, Pol S, Sise M, Martin P. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:S129-S205. [PMID: 36410841 DOI: 10.1016/j.kint.2022.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022]
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10
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Recent Information on Pan-Genotypic Direct-Acting Antiviral Agents for HCV in Chronic Kidney Disease. Viruses 2022; 14:v14112570. [PMID: 36423179 PMCID: PMC9696517 DOI: 10.3390/v14112570] [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: 10/08/2022] [Revised: 11/14/2022] [Accepted: 11/14/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is still common in patients with chronic kidney disease. It has been recently discovered that chronic HCV is a risk factor for increased incidence of CKD in the adult general population. According to a systematic review with a meta-analysis of clinical studies, pooling results of longitudinal studies (n = 2,299,134 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD; the summary estimate for adjusted HR across the surveys was 1.54 (95% CI, 1.26; 1.87), (p < 0.0001). The introduction of direct-acting antiviral drugs (DAAs) has caused a paradigm shift in the management of HCV infection; recent guidelines recommend pan-genotypic drugs (i.e., drugs effective on all HCV genotypes) as the first-choice therapy for HCV, and these promise to be effective and safe even in the context of chronic kidney disease. AIM The purpose of this narrative review is to show the most important data on pan-genotypic DAAs in advanced CKD (CKD stage 4/5). METHODS We recruited studies by electronic databases and grey literature. Numerous key-words ('Hepatitis C' AND 'Chronic kidney disease' AND 'Pan-genotypic agents', among others) were adopted. RESULTS The most important pan-genotypic combinations for HCV in advanced CKD are glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL). Two clinical trials (EXPEDITION-4 and EXPEDITION-5) and some 'real-world' studies (n = 6) reported that GLE/PIB combinations in CKD stage 4/5 gave SVR12 rates ranging between 86 and 99%. We retrieved clinical trials (n = 1) and 'real life' studies (n = 6) showing the performance of SOF/VEL; according to our pooled analysis, the summary estimate of SVR rate was 100% in studies adopting SOF/VEL antiviral combinations. The drop-out rate (due to AEs) in patients on SOF/VEL ranged between 0 and 4.8%. CONCLUSIONS Pan-genotypic combinations, such as GLE/PIB and SOF/VEL, appear effective and safe for HCV in advanced CKD, even if a limited number of studies with small sample sizes currently exist on this issue. Studies are under way to assess whether successful antiviral therapy with DAAs will translate into better survival in patients with advanced CKD.
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ERÜRKER ÖZTÜRK T, GÜREL S, ORUÇ A, ERSOY A. The efficacy of the direct-acting antiviral combination in hemodialysis patients with chronic hepatitis C virus Genotype 1 infection. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.994659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background Interferon and ribavirin treatments previously used in treating chronic hepatitis C virus (HCV) infection cannot be used effectively in hemodialysis patients due to dose adjustment and drug-related side effects. Direct-acting antivirals (DAAs) therapies have been reported to be effective in hemodialysis patients. This study aimed to evaluate the effectiveness of DAAs in hemodialysis patients with chronic hepatitis C.
Material and Methods Twenty hemodialysis patients with chronic hepatitis C followed in the gastroenterology outpatient clinic between 2016 and 2018 were evaluated retrospectively.
Results Twelve of the 20 patients were male, and eight were female. The mean age of the patients was 50.7±8.6 years. Six patients had no treatment experience. Fourteen patients had been previously treated with interferon and/or ribavirin but did not achieve sustained virological response (SVR). Genotype 1b was detected in 14 patients, genotype 1a in 4 patients, and genotype 1 in 2 patients. Patients were treated with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) and dasabuvir (DSV) or ribavirin (RBV) for 12 or 24 weeks. Two patients were cirrhotic and had a Child-Pugh score of A. Treatment was discontinued in 2 patients due to thrombus formation in the arteriovenous fistula in the first month of DAAs treatment. SVR12 was evaluated in 14 of 18 patients and found to be 100%. One of the ten patients accepted as SVR24 had a relapse. This rate of SVR24 was similar to that in the general population.
Conclusions Our results supported that the OBV/PTV/r and DSV or RBV regimen was a safe and effective therapy for hemodialysis patients with chronic hepatitis C virus genotype 1.
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12
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Liu CH, Kao JH. Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5. Hepatol Int 2022; 16:1001-1019. [PMID: 35876967 PMCID: PMC9309604 DOI: 10.1007/s12072-022-10390-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/03/2022] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection is a major health problem with significant clinical and economic burdens in patients with chronic kidney disease (CKD) stage 4 or 5. Current guidelines recommend pan-genotypic direct-acting antivirals (DAAs) to be the first-line treatment of choice for HCV. This review summarizes the updated knowledge regarding the epidemiology, natural history, public health perspectives of HCV in patients with CKD stage 4 or 5, including those on maintenance dialysis, and the performance of pan-genotypic DAAs in these patients. The prevalence and incidence of HCV are much higher in patients with CKD stage 4 or 5 than in the general population. The prognosis is compromised if HCV patients are left untreated regardless of kidney transplantation (KT). Following treatment-induced HCV eradication, patient can improve the health-related outcomes by maintaining a long-term aviremic state. The sustained virologic response (SVR12) rates and safety profiles of pan-genotypic DAAs against HCV are excellent irrespective of KT. No dose adjustment of pan-genotypic DAAs is required across CKD stages. Assessing drug-drug interactions (DDIs) before HCV treatment is vital to secure on-treatment safety. The use of prophylactic or preemptive pan-genotypic DAAs in HCV-negative recipients who receive HCV-positive kidneys has shown promise in shortening KT waiting time, achieving excellent on-treatment efficacy and safety, and maintaining post-KT patient and graft survival. HCV elimination is highly feasible through multifaceted interventions, including mass screening, treatment scale-up, universal precautions, and post-SVR12 reinfection surveillance.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, 7 Chung-Shan South Road, Taipei, 10002 Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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13
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Mochida S, Matsuzaki T, Kawana K, Ohchi K, Sakuma R, Kurosaki M. Safety and effectiveness of glecaprevir/pibrentasvir in patients with chronic hepatitis C or compensated cirrhosis in daily clinical practice: a drug-use results survey. KANZO 2022; 63:120-150. [DOI: 10.2957/kanzo.63.120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University
| | | | | | | | | | - Masayuki Kurosaki
- Department of Gastroenterology, Japanese Red Cross Musashino Hospital
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Atsukawa M, Tsubota A, Kondo C, Toyoda H, Nakamuta M, Takaguchi K, Watanabe T, Hiraoka A, Uojima H, Ishikawa T, Iwasa M, Tada T, Nozaki A, Chuma M, Fukunishi S, Asano T, Ogawa C, Abe H, Kato K, Hotta N, Shima T, Matsuura K, Mikami S, Tachi Y, Fujioka S, Okubo H, Shimada N, Tani J, Morishita A, Hidaka I, Moriya A, Tsuji K, Akahane T, Okubo T, Arai T, Kitamura M, Morita K, Kawata K, Tanaka Y, Kumada T, Iwakiri K. Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis. Hepatol Res 2022; 52:235-246. [PMID: 34861090 DOI: 10.1111/hepr.13739] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/15/2021] [Accepted: 11/30/2021] [Indexed: 12/24/2022]
Abstract
AIM Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.
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Affiliation(s)
- Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Himeji Red Cross Hospital, Hyogo, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Toru Asano
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Naoki Hotta
- Department of Internal Medicine, Division of Hepatology, Masuko Memorial Hospital, Nagoya, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Kentaro Matsuura
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Yoshihiko Tachi
- Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Noritomo Shimada
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
| | - Kunihiko Tsuji
- Gastroenterology Center, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Tomomi Okubo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Michika Kitamura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | | | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuhito Tanaka
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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15
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Yamana Y, Kanda T, Matsumoto N, Honda M, Kumagawa M, Sasaki R, Kanezawa S, Mizutani T, Yamagami H, Masuzaki R, Ishii T, Nirei K, Moriyama M. Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan. J Clin Med 2021; 10:5529. [PMID: 34884231 PMCID: PMC8658140 DOI: 10.3390/jcm10235529] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 11/24/2021] [Accepted: 11/25/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatis virus C (HCV) infection causes liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The objective of our study was to examine the effects of the HCV nonstructural protein (NS) 3/4A inhibitor glecaprevir/NS5A inhibitor pibrentasvir on real-world HCV patients in the northern part of Tokyo, Japan. Although 106 patients were consecutively included, a total of 102 HCV-infected patients with chronic hepatitis or compensated cirrhosis, who received 8- or 12-week combination treatment with glecaprevir/pibrentasvir and were followed up to week 12 after the end of treatment were analyzed retrospectively. Only three patients discontinued treatment due to adverse events; however, they achieved a sustained virologic response at 12 weeks (SVR12). Finally, SVR rates were 99.0% (101/102). Only one patient without liver cirrhosis was a treatment relapser who received hepatic resection for HCC approximately two years after commencement of the 8-week combination treatment with glecaprevir/pibrentasvir. After the exclusion of patients with HCV genotype 1b and P32 deletion in the HCV NS5A region, a 12-week combination of glecaprevir/pibrentasvir led to SVR12 in all nine direct-acting antiviral-experienced patients. Glecaprevir/pibrentasvir had a high efficacy and an acceptable safety profile for real-world HCV patients in a single hospital in Japan.
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Affiliation(s)
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (Y.Y.); (N.M.); (M.H.); (M.K.); (R.S.); (S.K.); (T.M.); (H.Y.); (R.M.); (T.I.); (K.N.); (M.M.)
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16
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Fabrizi F, Cerutti R, Messa P. An Updated View on the Antiviral Therapy of Hepatitis C in Chronic Kidney Disease. Pathogens 2021; 10:1381. [PMID: 34832537 PMCID: PMC8619857 DOI: 10.3390/pathogens10111381] [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: 09/03/2021] [Revised: 10/18/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Hepatitis C virus infection remains common in patients with chronic kidney disease, including those on maintenance dialysis. The relationship between hepatitis C virus infection and chronic kidney disease is bi-directional; in fact, HCV is both a cause and consequence of chronic kidney disease. According to a systematic review with meta-analysis of observational studies (n = 23 studies) (n = 574,081 patients on long-term dialysis), anti-HCV positive serologic status was an independent and significant risk factor for death in patients with advanced chronic kidney disease on long-term dialysis. The overall estimate for adjusted mortality (all-cause death risk) with HCV was 1.26 (95% CI, 1.18; 1.34) (p < 0.0001). Interferon-based therapies are biased by low efficacy/safety in chronic kidney disease, but the advent of direct-acting antiviral drugs has made a paradigm shift in the treatment of HCV-infection. These medications give interruption of viral replication because they target specific non-structural viral proteins; four classes of DAAs exist-NS3/4A protease inhibitors, NS5A inhibitors, NS5B nucleoside and non-nucleoside polymerase inhibitors. All-oral, interferon-free, ribavirin-free combinations of DAAs are now available. AIM The goal of this narrative review is to report the available treatment options for HCV in advanced chronic kidney disease. METHODS We have made an extensive review of the medical literature and various research engines have been adopted. RESULTS Some combinations of DAAs are currently recommended for HCV in advanced CKD (including patients on maintenance dialysis): elbasvir/grazoprevir; glecaprevir/pibrentasvir; and sofosbuvir-based regimens. Solid evidence, based on registration and "real life" studies supports their efficacy (SVR rates > 90%) and safety even in patients with advanced CKD. No dosage adjustment is necessary and treatment duration is 8-12 weeks. However, recent data highlight that many patients with advanced CKD remain untreated, and numerous barriers to antiviral treatment of HCV still exist. Whether successful antiviral therapy with DAAs will translate into improved survival in the advanced CKD population is another point of future research.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
| | - Roberta Cerutti
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
| | - Piergiorgio Messa
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
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17
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Atsukawa M, Tsubota A, Kondo C, Uchida-Kobayashi S, Takaguchi K, Tsutsui A, Nozaki A, Chuma M, Hidaka I, Ishikawa T, Iwasa M, Tamai Y, Tobari M, Matsuura K, Nagura Y, Abe H, Kato K, Suzuki K, Okubo T, Arai T, Itokawa N, Toyoda H, Enomoto M, Tamori A, Tanaka Y, Kawada N, Takei Y, Iwakiri K. A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C. PLoS One 2021; 16:e0257166. [PMID: 34506563 PMCID: PMC8432856 DOI: 10.1371/journal.pone.0257166] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 08/24/2021] [Indexed: 12/26/2022] Open
Abstract
Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | | | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Maki Tobari
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan
| | - Kentaro Matsuura
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Yoshihito Nagura
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kenta Suzuki
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Chiba, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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18
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Torre P, Aglitti A, Masarone M, Persico M. Viral hepatitis: Milestones, unresolved issues, and future goals. World J Gastroenterol 2021; 27:4603-4638. [PMID: 34366625 PMCID: PMC8326259 DOI: 10.3748/wjg.v27.i28.4603] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
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Affiliation(s)
- Pietro Torre
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
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19
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Higuera-de la Tijera F, Servín-Caamaño A, Servín-Abad L. Progress and challenges in the comprehensive management of chronic viral hepatitis: Key ways to achieve the elimination. World J Gastroenterol 2021; 27:4004-4017. [PMID: 34326610 PMCID: PMC8311524 DOI: 10.3748/wjg.v27.i26.4004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/04/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis is a significant health problem throughout the world, which already represents high annual mortality. By 2040, chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria, vitellogenesis-inhibiting hormone, and tuberculosis altogether. In this review, we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups, the goals set by the World Health Organization for the year 2030, and the key points to achieve them, such as timely access to antiviral treatment of direct-acting antiviral, which represents the key to achieving hepatitis C virus elimination. Likewise, we review the strategies to prevent transmission and achieve control of hepatitis B virus. Finally, we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.
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MESH Headings
- Antiviral Agents/therapeutic use
- COVID-19
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/epidemiology
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/epidemiology
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
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Affiliation(s)
| | | | - Luis Servín-Abad
- Department of Gastroenterology, Saint Cloud Hospital, Saint Cloud, MN 56303, United States
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20
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Chang KC, Tung SY, Wei KL, Shen CH, Hsieh YY, Chen WM, Chen YH, Chen CH, Yen CW, Xu HW, Tung WL, Hung CH, Lu SN, Chang TS. Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan. Sci Rep 2021; 11:13543. [PMID: 34188161 PMCID: PMC8241842 DOI: 10.1038/s41598-021-93095-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/08/2021] [Indexed: 12/16/2022] Open
Abstract
Clinical trials showed pangenotypic direct-acting antivirals' (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.
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Affiliation(s)
- Kao-Chi Chang
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Shui-Yi Tung
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC.,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Kuo-Liang Wei
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC.,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Chen-Heng Shen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Yung-Yu Hsieh
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC.,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Wei-Ming Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Yi-Hsing Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Chun-Hsien Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Chi-Wei Yen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Huang-Wei Xu
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Wei-Lin Tung
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC
| | - Chao-Hung Hung
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC.,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Sheng-Nan Lu
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC.,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC
| | - Te-Sheng Chang
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, No. 6, Section West, Chiapu Road, Puzi, Chiayi, 613, Taiwan, ROC. .,Chang Gung University College of Medicine, Taoyuan, Taiwan, ROC.
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21
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Tada T, Kurosaki M, Nakamura S, Hasebe C, Kojima Y, Furuta K, Kobashi H, Kimura H, Ogawa C, Yagisawa H, Uchida Y, Joko K, Akahane T, Arai H, Marusawa H, Narita R, Ide Y, Sato T, Kusakabe A, Tsuji K, Mori N, Kondo M, Mitsuda A, Izumi N. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol 2021; 93:6247-6256. [PMID: 34170517 DOI: 10.1002/jmv.27157] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 06/22/2021] [Indexed: 11/12/2022]
Abstract
The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child-Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV-related decompensated cirrhosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Mie, Japan
| | - Koichiro Furuta
- Department of Gastroenterology, Japanese Red Cross Masuda Hospital, Shimane, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital,, Gunma, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Japanese Red Cross Oita Hospital, Oita, Japan
| | - Yasushi Ide
- Department of Gastroenterology, Japanese Red Cross Karatsu Hospital, Saga, Japan
| | - Takashi Sato
- Department of Gastroenterology, Japanese Red Cross Nasu Hospital, Tochigi, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
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22
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Takahashi H, Kanda T, Matsumoto N, Mizutani T, Kaneko T, Honda M, Yamana Y, Ishii T, Kumagawa M, Sasaki R, Masuzaki R, Nirei K, Yamagami H, Ogawa M, Matsuoka S, Moriyama M. HCV GT1b-patient with alanine aminotransferase elevation and sustained virologic response achieved by grazoprevir/elbasvir discontinuation. Future Virol 2021. [DOI: 10.2217/fvl-2020-0181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In the present Japanese female patient with alanine aminotransferase (ALT) elevation greater than 500 IU/l during combination therapy with grazoprevir/elbasvir against HCV infection, this therapy was stopped at week 8. However, sustained virologic response was achieved. In the present report, we also focused on ALT elevation and sustained virologic response during and after antiviral therapies. The current case report demonstrates that careful monitoring of liver function tests may be required during direct-acting antiviral therapy against HCV infection because it is now possible to treat patients with polypharmacy, patients with chronic kidney disease, patients with cirrhosis or aged patients. Careful attention should be paid to liver damage as one of the adverse events in the use of HCV nonstructural protein 3/4A protease inhibitors. Of interest, many publications have addressed both ALT elevations during direct-acting antiviral therapy and viral clearance in relatively short treatment durations.
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Affiliation(s)
- Hiroshi Takahashi
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Tatsuo Kanda
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Naoki Matsumoto
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Taku Mizutani
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Tomohiro Kaneko
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Masayuki Honda
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Yoichiro Yamana
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Tomotaka Ishii
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Mariko Kumagawa
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Reina Sasaki
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Ryota Masuzaki
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Kazushige Nirei
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Hiroaki Yamagami
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Masahiro Ogawa
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Shunichi Matsuoka
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
| | - Mitsuhiko Moriyama
- Department of Medicine, Division of Gastroenterology & Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173 8610, Japan
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23
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Liu X, Hu P. Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients with Chronic HCV Infection. J Clin Transl Hepatol 2021; 9:125-132. [PMID: 33604263 PMCID: PMC7868694 DOI: 10.14218/jcth.2020.00078] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 12/03/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease, including decompensated cirrhosis and hepatocellular carcinoma. Over 95% of patients with HCV infection have achieved sustained virologic response at 12 weeks under the treatment of several pan-genotypic regimens approved for patients with HCV infection. The glecaprevir/pibrentasvir (G/P) regimen has some features that distinguish it from others and is the only 8-week regimen approved for treatment-naive patients and patients experienced in regimens containing (peg)interferon, ribavirin, and/or sofosbuvir, without an HCV NS3/4A protease inhibitor or NS5A inhibitor (except those with genotype 3). This review aims to summarize the efficacy and safety of G/P in HCV-infected patients from clinic trials and real-world studies, including those who have historically been considered difficult to cure.
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Affiliation(s)
| | - Peng Hu
- Correspondence to: Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing 400010, China. Tel: +86-23-62887083, Fax: +86-23-63703790, E-mail: ,
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24
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 734] [Impact Index Per Article: 146.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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25
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Watanabe S, Morimoto N, Miura K, Murohisa T, Tahara T, Sato T, Tano S, Fukaya Y, Kurata H, Okamura Y, Numao N, Uehara K, Murayama K, Nakazawa K, Sugaya H, Yoshizumi H, Iijima M, Tsukui M, Hirosawa T, Takaoka Y, Nomoto H, Maeda H, Goka R, Isoda N, Yamamoto H. Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection. J Rural Med 2020; 15:139-145. [PMID: 33033533 PMCID: PMC7530586 DOI: 10.2185/jrm.2020-004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 04/23/2020] [Indexed: 12/11/2022] Open
Abstract
Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has
been shown to provide a sustained virologic response (SVR) rate of >97% in patients
with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese
data. However, a recently published study showed that the treatment was often discontinued
in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis.
Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of
age, the population density of which is high in “rural” regions. Patients and Methods: We conducted a multicenter study to assess the
efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in
Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment
according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was
97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants,
56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to
have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the
SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses,
respectively. Of 308 patients enrolled, adverse events were observed in 74 patients
(24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in
any grade and grade ≥3 adverse events between the old-aged group and the rest of the study
participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.
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Affiliation(s)
- Shunji Watanabe
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Naoki Morimoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | | | - Toshiyuki Tahara
- Department of Gastroenterology, Saiseikai Utsunomiya Hospital, Japan
| | - Takashi Sato
- Department of Gastroenterology, Nasu Red Cross Hospital, Japan
| | - Shigeo Tano
- Department of Gastroenterology, Shin-Oyama City Hospital, Japan
| | - Yukimura Fukaya
- Department of Internal Medicine, Nasu Minami Hospital, Japan
| | - Hidekazu Kurata
- Department of Gastroenterology, Tochigi Medical Center Shimotsuga, Japan
| | | | - Norikatsu Numao
- Department of Gastroenterology, Haga Red Cross Hospital, Japan
| | - Keita Uehara
- Department of Gastroenterology, Tochigi Medical Center, Japan
| | - Kozue Murayama
- Department of Gastroenterology, Koga Red Cross Hospital, Japan
| | | | - Hitoshi Sugaya
- Department of Internal Medicine, Utsunomiya Higashi Hospital, Japan.,Department of Gastroenterology, Ashikaga Red Cross Hospital, Japan
| | | | - Makoto Iijima
- Department of Gastroenterology, Dokkyo Medical University, Japan.,Department of Gastroenterology, Yuai Memorial Hospital, Japan
| | - Mamiko Tsukui
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Takuya Hirosawa
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Yoshinari Takaoka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hiroaki Nomoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hiroshi Maeda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Rie Goka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Norio Isoda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
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Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study. Infect Dis Ther 2020; 9:851-866. [PMID: 32897520 PMCID: PMC7680481 DOI: 10.1007/s40121-020-00329-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Indexed: 02/07/2023] Open
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Liu CH, Yang SS, Peng CY, Lin WT, Liu CJ, Su TH, Tseng TC, Chen PJ, Chen DS, Kao JH. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection and severe renal impairment. J Viral Hepat 2020; 27:568-575. [PMID: 31981264 DOI: 10.1111/jvh.13265] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 01/02/2020] [Accepted: 01/03/2020] [Indexed: 12/16/2022]
Abstract
Data are limited regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI). We aimed to evaluate the performance of GLE/PIB in patients with chronic kidney disease (CKD) stage 4 or 5 in Taiwan. 108 chronic HCV patients with CKD stage 4 (n = 32) or 5 (n = 76) receiving GLE/PIB for 8-12 weeks were retrospectively recruited at 4 academic centres in Taiwan. The effectiveness was determined by sustained virologic response at off-therapy week 12 (SVR12 ) for evaluable (EP) and per-protocol populations (PP). The safety profiles were also assessed. By EP and PP analyses, the SVR12 rate was 99.1% (107 of 108 patients; 95% confidence interval (CI): 94.9%-99.8%) and 100% (107 of 107 patients; 95% CI: 96.5%-100%). The SVR12 rates were 100% (95% CI: 89.3%-100%) and 98.7% (95% CI: 92.9%-99.8%) in patients with CKD stage 4 and 5, respectively. One patient, who declined off-therapy follow-up after permanently discontinuing GLE/PIB at on-treatment week 9 due to scheduled cardiac surgery, had nonvirologic failure. Sixteen (14.8%) patients had serious adverse events (AEs), which were judged not related to GLE/PIB. The three most common AEs were pruritus (19.4%), fatigue (15.7%) and nausea (13.9%). None had ≥3-fold upper limit of normal for total bilirubin and alanine aminotransferase levels. None of the 9 patients with hepatitis B virus (HBV) coinfection developed HBV-associated hepatitis. In conclusion, GLE/PIB for 8-12 weeks is effective and well-tolerated in HCV patients with severe RI.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taipei, Taiwan.,Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Woan-Tyy Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Morishita A, Ogawa C, Moriya A, Tani J, Yoneyama H, Fujita K, Oryu M, Senoo T, Takaguchi K, Masaki T. Clinical outcomes of hepatitis C virus elimination using glecaprevir and pibrentasvir in hemodialysis patients: A multicenter study. Hepatol Res 2020; 50:557-564. [PMID: 31883211 DOI: 10.1111/hepr.13482] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/24/2019] [Accepted: 12/26/2019] [Indexed: 12/22/2022]
Abstract
AIM The incidence of hepatitis C virus (HCV) infection is much higher in hemodialysis patients than that in healthy individuals. The prognosis of hemodialysis patients with HCV infection is poorer than that without HCV infection. Therefore, antiviral intervention is pivotal for HCV infection in hemodialysis patients. Recent evaluations of the pangenotypic regimen of glecaprevir/pibrentasvir show that it is highly effective and safe for HCV-infected hemodialysis patients. However, a few reports showed that the effect of HCV elimination by glecaprevir/pibrentasvir improved liver dysfunction or anemia. The aim of the present study was to determine clinical outcomes after HCV elimination using the glecaprevir/pibrentasvir regimen in HCV-infected hemodialysis patients. METHODS This study was a retrospective, six-center study conducted in Japan, in which 24 hemodialysis patients with HCV genotype 1-2 treated with glecaprevir/pibrentasvir were recruited. Blood examinations were performed at end of treatment (EOT), and at 3, 6, and 12 months post-treatment during the 12-month follow-up period. RESULTS The overall sustained virologic response rate was 100% (24/24). During the DAA treatment period, adverse events were observed in 20.8% of patients (5/24), and pruritus was the most frequently observed in 12.5% (3/24). Interestingly, we observed an improved control of anemia after EOT with a significant increase in hemoglobin levels. In addition, total bilirubin was diminished, and platelet counts and albumin, total cholesterol, and alpha-fetoprotein levels remained unchanged after EOT in hemodialysis patients. Furthermore, erythropoietin concentration was not increased after EOT. CONCLUSIONS HCV elimination using glecaprevir/pibrentasvir treatment might be a major breakthrough for the control of anemia in hemodialysis patients.
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Affiliation(s)
- Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kanoji, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
| | - Makoto Oryu
- Department of Internal Medicine, Kagawa Saiseikai Hospital, Takamatsu, Japan
| | - Tomonori Senoo
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan
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Diagnostic performance of real-time tissue elastography in chronic hepatitis C patients with sustained virological response. Eur J Gastroenterol Hepatol 2020; 32:609-615. [PMID: 31688308 DOI: 10.1097/meg.0000000000001539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Real-time tissue elastography is a non-invasive method for measuring liver elasticity. However, there are no reports evaluating the value of real-time tissue elastography for liver fibrosis in hepatitis C virus-infected patients with sustained virological response. The aim of this study is to clarify the diagnostic performance of real-time tissue elastography in patients with sustained virological response. METHODS In this prospective study, we enrolled 425 chronic hepatitis C patients who underwent liver biopsy: 118 patients with sustained virological response (45.8% women) and 307 patients with hepatitis C virus (51.1% women). The post-sustained virological response biopsy was performed 5.9 ± 1.8 years after the therapy. Liver fibrosis index measurements as assessed using real-time tissue elastography were performed on the same day of biopsy. RESULTS The respective mean liver fibrosis index values for fibrosis stages F0, F1, F2, F3, and F4 were 2.82 ± 0.33, 2.90 ± 0.51, 3.06 ± 0.58, 3.65 ± 0.24, and 3.83 ± 0.65, respectively, in patients with sustained virological response. The diagnostic accuracies expressed as areas under the receiver operating characteristic curves in patients with sustained virological response were 0.776 for the diagnosis of significant fibrosis (≥F2), 0.885 for severe fibrosis (≥F3), and 0.860 for cirrhosis (F4), respectively. The optimum cut-off values liver fibrosis index were 3.14 for ≥F2, 3.24 for ≥F3, and 3.30 for F4 in patients with sustained virological response. CONCLUSION Real-time tissue elastography is an acceptable method for predicting the severity of fibrosis in hepatitis C virus patients with sustained virological response.
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Kinoshita A, Koike K, Mizuno Y, Ogata I, Kobayashi Y, Hasegawa K, Shiraishi K, Yoshida H, Nakata R, Yamada N, Yasuda K. Efficacy and safety of glecaprevir/pibrentasvir in patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; 20:578-583. [PMID: 32267087 DOI: 10.1111/ggi.13919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 03/05/2020] [Accepted: 03/10/2020] [Indexed: 01/24/2023]
Abstract
AIM Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; ••: ••-••.
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Affiliation(s)
- Akiyoshi Kinoshita
- Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Tokyo, Japan.,Department of Internal Medicine, Sakuragaoka Hospital, Shizuoka, Japan.,Department of Internal Medicine, Johsai Hospital, Tokyo, Japan
| | - Kazuhiko Koike
- Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Tokyo, Japan.,Department of Internal Medicine, Sakuragaoka Hospital, Shizuoka, Japan
| | - Yusuke Mizuno
- Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Itsuro Ogata
- Division of Gastroenterology and Hepatology, Kawakita General Hospital, Tokyo, Japan
| | | | | | - Koichi Shiraishi
- Division of Gastroenterology, Tokai University Tokyo Hospital, Tokyo, Japan
| | - Hideo Yoshida
- Division of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Ryo Nakata
- Division of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Norie Yamada
- Division of Gastroenterology, Kiyokawa Hospital, Tokyo, Japan
| | - Kiyomi Yasuda
- Division of Gastroenterology, Kiyokawa Hospital, Tokyo, Japan
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Liu CH, Liu CJ, Hung CC, Hsieh SM, Su TH, Sun HY, Tseng TC, Chen PJ, Chen DS, Kao JH. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real-world effectiveness and safety in Taiwan. Liver Int 2020; 40:758-768. [PMID: 31710759 DOI: 10.1111/liv.14295] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/09/2019] [Accepted: 10/28/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Large-scale data regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) for patients with chronic hepatitis C virus (HCV) infection were limited in East Asia. We aimed to evaluate the clinical performance of GLE/PIB in different HCV populations in Taiwan. METHODS A total of 658 chronic HCV patients with compensated liver diseases receiving GLE/PIB for 8 (n = 549), 12 (n = 103) or 16 (n = 6) weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response at off-therapy 12 weeks (SVR12 ). Patient characteristics potentially related to SVR12 and the safety profiles were also assessed. RESULTS By evaluable population (EP) and per-protocol (PP) analyses, the overall SVR12 rate was 98.2% (95% confidence interval (CI): 96.8%-99.0%) and 99.4% (95% CI: 98.4%-99.8%). The SVR12 rates were 98.9% (95% CI: 97.6%-99.5%), 94.2% (95% CI: 87.9%-97.3%) and 100% (95% CI: 60.1%-100%) in patients receiving 8, 12 and 16 weeks of treatment respectively. A total of 656 (99.7%) patients completed the scheduled treatment. The SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline. Twenty (3.0%) patients had serious adverse events (AEs), but none were not related to GLE/PIB. The two most common AEs were pruritus (7.8%) and fatigue (5.5%). Two (0.3%) and no patients had ≥3-fold upper limit of normal (ULN) for total bilirubin and alanine aminotransferase (ALT) levels. CONCLUSIONS GLE/PIB for 8-16 weeks is effective and well-tolerated for patients with chronic HCV infection in Taiwan.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Szu-Min Hsieh
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Nozaki A, Atsukawa M, Kondo C, Toyoda H, Chuma M, Nakamuta M, Uojima H, Takaguchi K, Ikeda H, Watanabe T, Ogawa S, Itokawa N, Arai T, Hiraoka A, Asano T, Fujioka S, Ikegami T, Shima T, Ogawa C, Akahane T, Shimada N, Fukunishi S, Abe H, Tsubota A, Genda T, Okubo H, Mikami S, Morishita A, Moriya A, Tani J, Tachi Y, Hotta N, Ishikawa T, Okanoue T, Tanaka Y, Kumada T, Iwakiri K, Maeda S. The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study. Hepatol Int 2020; 14:225-238. [PMID: 32128704 DOI: 10.1007/s12072-020-10019-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 01/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment. METHODS In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. RESULTS Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients. CONCLUSIONS G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.
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Affiliation(s)
- Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
| | - Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Makoto Nakamuta
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Hiroki Ikeda
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toru Asano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Tadashi Ikegami
- Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Kashiwa, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Takuya Genda
- Department of Gastroenterology, Juntendo Shizuoka University Hospital, Shizuoka, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Shigeru Mikami
- Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
| | - Joji Tani
- Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan
| | - Yoshihiko Tachi
- Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Naoki Hotta
- Division of Hepatology, Department of Internal Medicine, Masuko Memorial Hospital, Nagoya, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Shin Maeda
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.,Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Cheema SUR, Rehman MS, Hussain G, Cheema SS, Gilani N. Efficacy and tolerability of sofosbuvir and daclatasvir for treatment of hepatitis C genotype 1 & 3 in patients undergoing hemodialysis- a prospective interventional clinical trial. BMC Nephrol 2019; 20:438. [PMID: 31779583 PMCID: PMC6883698 DOI: 10.1186/s12882-019-1631-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 11/20/2019] [Indexed: 12/14/2022] Open
Abstract
Background There is paucity of data using direct anti-viral agents (DAA) in patients on maintenance hemodialysis (MHD) infected with HCV-genotype 1 & 3. Aim of the study was to evaluate DAA therapy in patients infected with HCV-genotype 1 & 3 on MHD. Methods A prospective open label, parallel, non-randomized interventional trial was conducted in patients with Hepatitis-C on maintenance hemodialysis. Total of Sixty two (62) patients with hepatitis-C on maintenance hemodialysis were screened and 36 patients were enrolled and then equally allocated in 1:1 ratio to group 1 who received 400 mg daily sofosbuvir/ 60 mg daily daclatasvir and group 2 who received thrice a week 400 mg Sofosbuvir and daily 60 mg daclatasvir for 12 weeks. Patients with compensated cirrhosis received therapy for 24 weeks. Relevant data was obtained before, during and after therapy. HCV viral load was assessed at week 4, 8, at end of therapy and 12 weeks after treatment. Results Eighteen (18) patients were allocated in each group. Three patients in group 1 withdrawn from the study after 2 weeks due to refusal to participate, while one withdrawn in group 2 due to development of adverse effect. Mean age of patients was 47.22 + 14.17 in group 1 and 53.89 + 14.11 in group 2. Genotype 3 was most common in group 1 patients, n = 12 (66.6%), and n = 11 (61.1%) in group 2. All patients in both groups achieved undetectable viral load at 12th week. As per intention to treat analysis overall 29/36 (80.55%) patients achieved SVR (group 1 = 15/18; group 2 = 14/18) and as per-protocol analysis overall 29/32 (90.62%) patients achieved SVR (group 1 = 15/15; group 2 = 14/17). Conclusion Direct acting antiviral therapy using sofosbuvir and declatsavir is highly effective and tolerable in patients with HCV genotype 1 & 3 undergoing maintenance hemodialysis, especially when given daily. Trial registration This trial is registered in WHO, International Clinical Trial Registry Platform, through Iranian Registry of Clinical Trials (IRCT) having IRCT ID: IRCT20170614034526N3, registered retrospectively on 2019-03-08.
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Affiliation(s)
| | - Muhammad Salman Rehman
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
| | - Ghulam Hussain
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
| | | | - Nooman Gilani
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
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Ohya K, Imamura M, Osawa M, Teraoka Y, Morio K, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Hiramatsu A, Tsuge M, Aikata H, Hayes CN, Chayama K. Successful retreatment with 12 weeks of glecaprevir and pibrentasvir for a genotype 2a HCV-infected hemodialysis patient who failed to respond to 8 weeks of prior glecaprevir and pibrentasvir therapy. Clin J Gastroenterol 2019; 13:267-270. [PMID: 31463795 DOI: 10.1007/s12328-019-01039-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 08/20/2019] [Indexed: 12/31/2022]
Abstract
Although NS3/4 protease inhibitor glecaprevir (GLE) plus NS5A inhibitor pibrentasvir (PIB) therapy has a high efficacy for chronic hepatitis C virus (HCV)-infected patients with hemodialysis, some patients fail to respond to the therapy. Here, we report a hemodialysis genotype 2 HCV-infected patient who achieved sustained virological response (SVR) by 12 weeks of GLE/PIB therapy after failing to respond to 8 weeks of GLE/PIB therapy. A 44-year-old man with chronic genotype 2a HCV-infection without any evidence of cirrhosis and who was undergoing hemodialysis received GLE/PIB therapy. He completed 8 weeks of therapy, but his serum HCV relapsed after the end of therapy. No resistance-associated substitutions were detected in the NS3 region, but NS5A-C92C/S was detected by direct sequence analysis prior to the start of therapy and subsequently shifted to NS5A-C92S at the time of HCV relapse. Four months after initial GLE/PIB therapy, he started a 12-week course of GLE/PIB retreatment. Serum HCV RNA level became and remained undetectable during the therapy and never relapsed after the end of the treatment. Finally, he succeeded in achieving sustained virological response following 12 weeks of GLE/PIB retreatment.
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Affiliation(s)
- Kazuki Ohya
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
| | - Mitsutaka Osawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Masami Yamauchi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan
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Kawagishi N, Nakamura A, Takayama T, Haga I. Safety of Direct-Acting Antiviral Therapy for Renal Function in Post-Kidney Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response: A Single-Center Study. Ther Apher Dial 2019; 24:184-188. [PMID: 31290282 DOI: 10.1111/1744-9987.13350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/02/2019] [Accepted: 07/03/2019] [Indexed: 12/13/2022]
Abstract
Treatment of chronic hepatitis C infection after renal transplantation has been controversial due to the high rate of graft rejections with interferon (IFN)-based therapies. The aim of this study is to review our experience of direct acting antiviral therapy for the recipients of renal transplantation. Eleven recipients who were hepatitis C virus-polymerase chain reaction (PCR) positive were eligible for the treatment with direct acting antivirals. Six recipients were treated with sofosbuvir and ledipasvir, three were treated with elbasvir and grazoprevir, and one was treated with sofosbuvir and ribavirin for 12 weeks. One recipient was treated with glecaprevir and pibrentasvir for 8 weeks. All of the 11 recipients exhibited sustained virologic response at week 12 after the end of treatment. Adverse events were scarce including the two recipients who switched to tacrolimus from cyclosporine at the beginning of the treatment. The direct acting antiviral therapy including new agents appears to be safe and highly efficacious for the recipients after renal transplantation.
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Affiliation(s)
- Naoki Kawagishi
- Division of Transplant Surgery, JCHO Sendai Hospital, Sendai, Japan
| | - Atsushi Nakamura
- Division of Transplant Surgery, JCHO Sendai Hospital, Sendai, Japan
| | - Tetsuro Takayama
- Division of Transplant Surgery, JCHO Sendai Hospital, Sendai, Japan
| | - Izumi Haga
- Division of Transplant Surgery, JCHO Sendai Hospital, Sendai, Japan
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Hsu SJ, Chiu MC, Fang YJ, Yang TH, Yu JJ, Chen CC, Kuo CC, Lee JY, Chen CH, Chen DS, Kao JH. Real-world effectiveness and safety of glecaprevir/pibrentasvir in Asian patients with chronic hepatitis C. J Formos Med Assoc 2019; 118:1187-1192. [PMID: 31279502 DOI: 10.1016/j.jfma.2019.06.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 06/15/2019] [Accepted: 06/20/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited. We thus investigated the effectiveness and safety profile of GLE/PIB in Taiwanese patients with chronic hepatitis C (CHC). METHODS CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled. The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy. The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed. RESULTS A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Forty-five (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics. The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred. Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death. CONCLUSION Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis.
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Affiliation(s)
- Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Min-Chin Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Tsung-Hua Yang
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Jian-Jyun Yu
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Chi Kuo
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Ji-Yuh Lee
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Douliou, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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