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Fedorchenko SV, Klimenko Z, Martynovich T, Solianyk I, Suprunenko T. Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks. J Virol 2025; 99:e0184324. [PMID: 39840947 PMCID: PMC11852967 DOI: 10.1128/jvi.01843-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025] Open
Abstract
The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The efficacy of SOF+GLE/PIB+RIB 16-24 weeks of treatment has been shown. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response. When velpatasvir treatment fails, pibrentasvir should be used as the first choice for retreatment.
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Affiliation(s)
- Sergii V. Fedorchenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Zhanna Klimenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Martynovich
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Iryna Solianyk
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Suprunenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
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Kwon LH, Griffiths J, DiFranza L. Acute kidney injury and ANCA positivity in a patient treated with glecaprevir/pibrentasvir: a case report. Front Med (Lausanne) 2025; 11:1434497. [PMID: 39882516 PMCID: PMC11774644 DOI: 10.3389/fmed.2024.1434497] [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: 05/17/2024] [Accepted: 11/20/2024] [Indexed: 01/31/2025] Open
Abstract
Background Glecaprevir/pibrentasvir is an effective antiviral therapy for hepatitis C virus infection and is generally regarded safe in patients with renal impairment. However, renal complications are a notable, albeit rare, concern. Case presentation We report a case of acute kidney injury in a man in his 50s with chronic hepatitis C virus, chronic obstructive pulmonary disease, morbid obesity, a history of heroin dependence, and untreated type 2 diabetes mellitus. About four weeks into an eight-week glecaprevir/pibrentasvir regimen he developed progressive lower extremity edema, bullae, and skin ulcers with worsening renal function. His serum creatinine rose to 4.46 mg/dL and blood urea nitrogen to 44 mg/dL. ANCA serology revealed dual perinuclear and cytoplasmic positivity, though anti-proteinase 3 and anti-myeloperoxidase antibody tests were negative. Kidney biopsy revealed diffuse tubulointerstitial injury with erythrocyte casts indicative of glomerular bleeding into the distal nephrons, though without glomerular crescent formation. Conclusion This case illustrates the potential for glecaprevir/pibrentasvir to induce acute kidney injury, acute interstitial nephritis and possibly ANCA-associated vasculitis. Recognizing these adverse renal effects is critical for making timely diagnosis and management in hepatitis C virus patients undergoing antiviral therapy.
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Affiliation(s)
- Lawrence Hyun Kwon
- Department of Nephrology, Westchester Medical Center Advanced Physician Services, Mid-Hudson Regional Hospital, Poughkeepsie, NY, United States
| | - Jennifer Griffiths
- Department of Nephrology, Westchester Medical Center Advanced Physician Services, Mid-Hudson Regional Hospital, Poughkeepsie, NY, United States
| | - Lanny DiFranza
- Department of Pathology, Montefiore Medical Center, Bronx, NY, United States
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Choi SA, Umashankar K, Maheswaran A, Martin MT, Lee J, Odishoo M, Lin JY, Touchette DR. Cost-effectiveness analysis of emergency department-based hepatitis C screening and linkage-to-care program. BMC Health Serv Res 2024; 24:1308. [PMID: 39472900 PMCID: PMC11523774 DOI: 10.1186/s12913-024-11793-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 10/18/2024] [Indexed: 11/02/2024] Open
Abstract
BACKGROUND In the United States (US), hepatitis C virus (HCV) screening is not covered by payers in settings outside of primary care. A non-traditional, emergency department (ED)-based HCV screening program can be cost-effective and identify infection in vulnerable populations with a high HCV risk. This study examined the long-term cost-effectiveness of routine HCV screening and linkage-to-care for high-risk patients in the ED from the payer's perspective. METHODS The University of Illinois Hospital and Health Sciences System (UIH) implemented Project HEAL (HIV & HCV Screening, Education, Awareness, Linkage-to-Care). Under this initiative, patients who presented to the ED received opt-out HCV screening if they were at high risk for HCV infection (birth cohort between 1945 and 1964, persons who inject drugs, and HIV infection) with subsequent linkage-to-care if infected. Using the summary data from Project HEAL, a hybrid decision-analytic Markov model was developed based on the HCV screening procedure in the ED and the natural history of HCV. A 30-year time horizon and 1-year cycle length were used. All patients who received the ED-based HCV screening were referred for treatment with direct-acting antiviral (DAA) regardless of their fibrosis stage. RESULTS When unscreened/untreated patients received DAA treatment at F1, F2, F3, and compensated cirrhosis stages, the incremental cost-effectiveness ratio (ICER) ranged from $6,084 to $77,063 per quality-adjusted life year (QALY) gained. When unscreened/untreated patients received DAA treatment at the decompensated cirrhosis stage, no HCV screening was dominated. CONCLUSION ED-based HCV screening and linkage-to-care was cost-effective at the willingness-to-pay (WTP) threshold of $100,000/QALY in all scenarios. A reduction in infected persons in the community may provide additional benefits not evaluated in this study.
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Affiliation(s)
- Sun A Choi
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Kandavadivu Umashankar
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Anjana Maheswaran
- Department of Emergency Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Michelle T Martin
- Liver Clinic, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA
- Department of Pharmacy Practice College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Jean Lee
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Matt Odishoo
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Janet Y Lin
- Department of Emergency Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Daniel R Touchette
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
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Yu ML, Tai CM, Mo LR, Kuo HT, Huang CF, Tseng KC, Lo CC, Bair MJ, Wang SJ, Huang JF, Yeh ML, Chen CT, Tsai MC, Huang CW, Lee PL, Yang TH, Huang YH, Chong LW, Chen CL, Yang CC, Hung CH, Yang SS, Cheng PN, Hsieh TY, Hu JT, Wu WC, Cheng CY, Chen GY, Zhou GX, Tsai WL, Kao CN, Lin CL, Wang CC, Lin TY, Lin CL, Su WW, Lee TH, Chang TS, Liu CJ, Dai CY, Chen CY, Kao JH, Lin HC, Chuang WL, Peng CY. An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan. Hepatol Int 2024; 18:461-475. [PMID: 38246899 PMCID: PMC11014878 DOI: 10.1007/s12072-023-10609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/10/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.
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Affiliation(s)
- Ming-Lung Yu
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, Taiwan, 833
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, No. 1, Section 1, Xuecheng Rd, Dashu District, Kaohsiung City, Taiwan, 840
- School of Medicine for International Students, College of Medicine, I-Shou University, No. 1, Section 1, Xuecheng Rd, Dashu District, Kaohsiung City, Taiwan, 840
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), No. 670, Chongde Rd, East District, Tainan City, Taiwan, 701
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd, Yongkang District, Tainan City, Taiwan, 710
- School of Medicine, College of Medicine, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
| | - Chung-Feng Huang
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University and Academia Sinica, No. 128, Section 2, Academia Rd, Nangang District, Taipei City, Taiwan, 115
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd, Dalin Township, Chiayi County, Taiwan, 622
- School of Medicine, Tzuchi University, No. 701, Section 3, Zhongyang Rd, Hualien City, Hualien County, Taiwan, 970
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, No. 60, Minquan Rd, East District, Chiayi City, Taiwan, 600
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, No. 1, Lane 303, Zhangsha St, Taitung City, Taitung County, Taiwan, 950
- Mackay Medical College, No. 46, Section 3, Zhongzheng Rd, Sanzhi District, New Taipei City, Taiwan, 252
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, No. 162, Chenggong 1st Rd, Lingya District, Kaohsiung City, Taiwan, 802
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Rd, Neihu District, Taipei City, Taiwan, 114
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, No. 90, Qianliao, Magong City, Penghu County, Taiwan, 880
| | - Ming-Chang Tsai
- School of Medicine, Chung Shan Medical University, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Section 1, Jianguo N Rd, South District, Taichung City, Taiwan, 402
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Rd, Lingya District, Kaohsiung City, Taiwan, 802
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd, Yongkang District, Tainan City, Taiwan, 710
| | - Tzeng-Hue Yang
- Lotung Poh-Ai Hospital, No. 83, Nanchang St, Luodong Township, Yilan County, Taiwan, 265
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 112
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Shilin District, Taipei City, Taiwan, 111
- School of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Rd, Xinzhuang District, New Taipei City, Taiwan, 242
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, No. 701, Section 3, Zhongyang Rd, Hualien City, Hualien County, Taiwan, 970
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, No. 542, Section 1, Zhongshan Rd, Changhua City, Changhua County, Taiwan, 500
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, Taiwan, 833
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung City, Taiwan, 407
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1, Dasyue Rd, East District, Tainan City, Taiwan, 701
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Rd, Neihu District, Taipei City, Taiwan, 114
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, No. 280, Section 4, Ren'ai Rd, Da'an District, Taipei City, Taiwan, 106
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan, 830
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd, Taoyuan District, Taoyuan City, Taiwan, 330
- Institute of Public Health, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, No. 10, Zhongzheng Rd, Magong City, Penghu County, Taiwan, 880
| | | | - Wei-Lun Tsai
- Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung City, Taiwan, 813
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, No. 25, Lane 442, Section 1, Jingguo Rd, North District, Hsinchu City, Taiwan, 300
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, No. 222, Maijin Rd, Anle District, Keelung City, Taiwan, 204
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, No. 289, Jianguo Rd, Xindian District, New Taipei City, Taiwan, 231
| | - Ta-Ya Lin
- Cishan Hospital, Ministry of Health and Welfare, No. 60, Zhongxue Rd, Qishan District, Kaohsiung City, Taiwan, 842
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, No. 10, Section 4, Ren'ai Rd, Da'an District, Taipei City, Taiwan, 106
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, No. 176, Zhonghua Rd, Changhua City, Changhua County, Taiwan, 500
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya S Rd, Banqiao District, New Taipei City, Taiwan, 220
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan and College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan District, Taoyuan City, Taiwan, 333
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, No. 1, Section 4, Roosevelt Rd, Da'an District, Taipei City, Taiwan, 106
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, No. 539, Zhongxiao Rd, East District, Chiayi City, Taiwan, 600
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, No. 1, Section 4, Roosevelt Rd, Da'an District, Taipei City, Taiwan, 106
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 112
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807.
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807.
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Rd, North District, Taichung City, Taiwan, 404.
- School of Medicine, China Medical University, No. 91, Xueshi Rd, North District, Taichung City, Taiwan, 404.
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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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6
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Wong YJ, Tran S, Huang CF, Hsu YC, Preda C, Toyoda H, Liu J, Jun DW, Landis C, Huang DQ, Gila A, Negoita L, Yasuda S, Tseng CH, Tsai PC, Uojima H, Nozaki A, Chuma M, Atsukawa M, Ishigami M, Itokawa N, Iio E, Lam CPM, Watanabe T, Asai A, Yokohama K, Abe H, Enomoto M, Kawada N, Tamori A, Lee DH, Jun MJ, Do S, Vo DKH, Liu L, Li J, Ji F, Wang W, Li Y, Wang X, Guo F, Xu Q, Jing L, Ye Q, Pan H, Zhang J, Wen X, Wang Q, Ren H, Cai D, Shang J, Liu J, Lu C, Zang W, Li J, Niu J, Zhang M, Wu C, Huang R, Maeda M, Nakanishi A, Yeh ML, Chuang WL, Huang JF, Dai C, Ishikawa T, Takaguchi K, Senoh T, Trinh HN, Takahashi H, Eguchi Y, Quek SXZ, Haga H, Ogawa E, Wong G, Buti M, Fukunishi S, Ueno Y, Yuen MF, Tanaka Y, Lim SG, Cheung R, Yu ML, Nguyen MH. Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study. Hepatol Int 2023; 17:1150-1161. [PMID: 37273170 DOI: 10.1007/s12072-023-10547-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 05/04/2023] [Indexed: 06/06/2023]
Abstract
INTRODUCTION Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population. METHODS We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment. RESULTS From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77). CONCLUSION Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.
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Affiliation(s)
- Yu Jun Wong
- Gastroenterology and Hepatology, Changi General Hospital, SingHealth, Singapore, Singapore
- SingHealth Duke-NUS Medicine Academic Clinical Program, Singapore, Singapore
| | - Sally Tran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Carmen Preda
- Clinical Institute of Fundeni, Gastroenterology and Hepatology, Bucharest, Romania
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Joanne Liu
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Andrei Gila
- Clinical Institute of Fundeni, Gastroenterology and Hepatology, Bucharest, Romania
| | - Livia Negoita
- Clinical Institute of Fundeni, Gastroenterology and Hepatology, Bucharest, Romania
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Etsuko Iio
- Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Carla Pui-Mei Lam
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Akira Asai
- 2nd Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Keisuke Yokohama
- 2nd Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Dong Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea
| | - Mi Jung Jun
- Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea
| | - Son Do
- Digestive Health Associates of Texas, Plano, TX, USA
| | - Dang K H Vo
- Digestive Health Associates of Texas, Plano, TX, USA
| | - Li Liu
- Department of Hepatology, The Third People's Hospital of Kunming City, Kunming, China
| | - Junyi Li
- Department of Hepatology, The Third People's Hospital of Kunming City, Kunming, China
| | - Fanpu Ji
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yu Li
- Department of Infectious Diseases, Shaanxi Provincial People's Hospital, Xi'an, China
| | - Xiaozhong Wang
- Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi, China
| | - Fen Guo
- Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi, China
| | - Qiang Xu
- Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi, China
| | - Liang Jing
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Hongying Pan
- Department of Hepatology, Zhejiang Provincial People's Hospital Affiliated to Zhejiang University, Hangzhou, China
| | - JiaJie Zhang
- Department of Hepatology, Zhejiang Provincial People's Hospital Affiliated to Zhejiang University, Hangzhou, China
| | - Xie Wen
- Center of Liver Diseases, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Qi Wang
- Center of Liver Diseases, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Junping Liu
- Department of Infectious Diseases, Henan Provincial People's Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Chengzheng Lu
- Department of Gastroenterology and Hepatology, The Second People's Hospital of Tianjin, Tianjin, China
| | - Wenqian Zang
- Department of Gastroenterology and Hepatology, The Second People's Hospital of Tianjin, Tianjin, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, The Second People's Hospital of Tianjin, Tianjin, China
| | - Junqi Niu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Mingyuan Zhang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
| | - Akiko Nakanishi
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, China
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - ChiaYen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Huy N Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, Saga, Japan
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga, Japan
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Sabrina Xin Zi Quek
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Hiroaki Haga
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, China
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universiti Valle d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Shinya Fukunishi
- 2nd Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Yasuhito Tanaka
- Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Seng Gee Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, and Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.
- Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
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7
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Kalluri HV, Oberoi RK, Chen Q, Jiang Q, Asatryan A, Alami NN, Yu C, Liu W. Pharmacokinetics, Tolerability, and Safety of Glecaprevir/Pibrentasvir Co-formulated Bilayer Tablet Following Repeated Administration in Healthy Chinese Adults. Clin Pharmacol Drug Dev 2023; 12:945-955. [PMID: 37661787 DOI: 10.1002/cpdd.1325] [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: 10/11/2021] [Accepted: 08/15/2023] [Indexed: 09/05/2023]
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is an all-oral, interferon- and ribavirin-free, pan-genotypic fixed-dose combination regimen approved for the treatment of all major genotypes of hepatitis C virus (HCV) infection in many countries worldwide. To support clinical development in China, an open-label, single-center phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of GLE/PIB in healthy Chinese adults in Mainland China. Eighteen participants received 3 tablets of coformulated GLE/PIB 100/40 mg once daily (QD) for 7 days. Following GLE/PIB 300 mg/120 mg administration, GLE and PIB reached maximum concentration in 4-5 hours with a terminal elimination half-life of 5.9 and 25 hours, respectively. Both GLE and PIB reached steady state by day 5, with no-to-minimal accumulation (≤17% higher). GLE/PIB exposures in healthy Chinese participants were similar to historical observations across phase 1 studies in healthy Western participants. GLE/PIB was safe and well-tolerated, with most adverse events being mild. These pharmacokinetics and safety data, together with existing global efficacy and safety data in healthy and HCV-infected Western participants, support the use of GLE/PIB 300 mg/120 mg QD in adult Chinese patients with chronic HCV infection.
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Affiliation(s)
- Hari V Kalluri
- Clinical Pharmacology, AbbVie Inc, North Chicago, IL, USA
| | | | - Qian Chen
- Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
| | - Qi Jiang
- Data and Statistical Sciences, AbbVie Inc, North Chicago, IL, USA
| | | | - Negar N Alami
- Infectious Diseases, AbbVie Inc, North Chicago, IL, USA
| | - Chen Yu
- Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
| | - Wei Liu
- Clinical Pharmacology, AbbVie Inc, North Chicago, IL, USA
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8
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Pratim Das P, Medhi S. Role of inflammasomes and cytokines in immune dysfunction of liver cirrhosis. Cytokine 2023; 170:156347. [PMID: 37639845 DOI: 10.1016/j.cyto.2023.156347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/28/2023] [Accepted: 08/21/2023] [Indexed: 08/31/2023]
Abstract
Liver cirrhosis develops as a result of persistent inflammation and liver injury. The prolonged inflammation triggers the buildup of fibrous tissue and regenerative nodules within the liver, leading to the distortion of the hepatic vascular structure and impaired liver function. Cirrhosis disrupts the ability of liver function to maintain homeostasis and hepatic immunosurveillance which causes immunological dysfunction in the body. In pathological conditions, the production of cytokines in the liver is carefully regulated by various cells in response to tissue stimulation. Cytokines and inflammasomes are the key regulators and systematically contribute to the development of cirrhosis which involves an inflammatory response. However, the crosstalk role of different cytokines in the cirrhosis progression is poorly understood. Tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), among others, are proinflammatory cytokines that contribute to liver cell necrosis, which in turn causes the development of fibrosis. While IL-10 exhibits a potent anti-inflammatory effect on the liver by inhibiting immune cell activation and neutralizing pro-inflammatory cytokine activity. Inflammasomes have also been implicated in the profibrotic processes of liver cirrhosis, as well as the production of chemokines such as CCL2/MCP-1. It is evident that inflammasomes have a role in the proinflammatory response seen in chronic liver illnesses. In conclusion, cirrhosis significantly impacts the immune system, leading to immunological dysfunction and alterations in both innate and acquired immunity. Proinflammatory cytokines like TNF-α, IL-1β, IL-6, and IFNγ are upregulated in cirrhosis, contributing to liver cell necrosis and fibrosis development. Managing cytokine-mediated inflammation and fibrosis is a key therapeutic approach to alleviate portal hypertension and its associated liver complications. This review attempted to focus largely on the role of immune dysfunction mediated by different cytokines and inflammasomes involved in the progression, regulation and development of liver cirrhosis.
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Affiliation(s)
- Partha Pratim Das
- Dept. of Bioengineering & Technology, Gauhati University, Assam 781014, India
| | - Subhash Medhi
- Dept. of Bioengineering & Technology, Gauhati University, Assam 781014, India.
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9
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Shiner B, Park JA, Rozema L, Hoyt JE, Watts BV, Gradus JL. Safety of Glecaprevir/Pibrentasvir for hepatitis C in patients with posttraumatic stress disorder: A post-marketing surveillance study. Gen Hosp Psychiatry 2023; 84:268-270. [PMID: 37380536 DOI: 10.1016/j.genhosppsych.2023.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/14/2023] [Accepted: 06/21/2023] [Indexed: 06/30/2023]
Affiliation(s)
- Brian Shiner
- Veterans Affairs Medical Center, White River Junction, Vermont, United States of America; National Center for Posttraumatic Stress Disorder, White River Junction, Vermont, United States of America; Geisel School of Medicine at Dartmouth, Hanover, NH, United States of America.
| | - Jenna A Park
- Veterans Affairs Medical Center, White River Junction, Vermont, United States of America; Geisel School of Medicine at Dartmouth, Hanover, NH, United States of America
| | - Luke Rozema
- Veterans Affairs Medical Center, White River Junction, Vermont, United States of America
| | - Jessica E Hoyt
- Veterans Affairs Medical Center, White River Junction, Vermont, United States of America
| | - Bradley V Watts
- Veterans Affairs Medical Center, White River Junction, Vermont, United States of America; Geisel School of Medicine at Dartmouth, Hanover, NH, United States of America
| | - Jaimie L Gradus
- Boston University School of Public Health, Boston, MA, United States of America; Boston University School of Medicine, Boston, MA, United States of America
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10
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Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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Kosloski MP, Li H, Wang S, Mensa F, Kort J, Liu W. Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine. Clin Transl Sci 2023; 16:593-605. [PMID: 36597378 PMCID: PMC10087067 DOI: 10.1111/cts.13471] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/12/2022] [Accepted: 12/16/2022] [Indexed: 01/05/2023] Open
Abstract
The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified.
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Affiliation(s)
| | - Hong Li
- Data and Statistical Sciences, AbbVie Inc., North Chicago, Illinois, USA
| | - Stanley Wang
- Infectious Disease, AbbVie Inc., North Chicago, Illinois, USA
| | - Federico Mensa
- Infectious Disease, AbbVie Inc., North Chicago, Illinois, USA
| | - Jens Kort
- Medical Affairs, AbbVie Inc., North Chicago, Illinois, USA
| | - Wei Liu
- Clinical Pharmacology, AbbVie Inc., North Chicago, Illinois, USA
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12
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Hung HY, Hung WL, Shih CL, Chen CY. Drug-induced liver injury by glecaprevir/pibrentasvir treatment for chronic hepatitis C infection: a systematic review and meta-analysis. Ann Med 2022; 54:108-120. [PMID: 34969349 PMCID: PMC8725884 DOI: 10.1080/07853890.2021.2012589] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. Objective: This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus.Materials and methods: We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). Results: The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis-without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182-6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration.Conclusions: DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.
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Affiliation(s)
- Hsuan-Yu Hung
- Department of Pharmacy, Ditmanson medical foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan
| | - Wei-Liang Hung
- Division of Nephrology, Department of Medicine, Zouying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Chia-Lung Shih
- Clinical Medicine Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Chung-Yu Chen
- Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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13
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Recombinant protein polymers as carriers of chemotherapeutic agents. Adv Drug Deliv Rev 2022; 190:114544. [PMID: 36176240 DOI: 10.1016/j.addr.2022.114544] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 09/02/2022] [Accepted: 09/13/2022] [Indexed: 01/24/2023]
Abstract
Chemotherapy is the standard of care for the treatment of cancer and infectious diseases. However, its use is associated with severe toxicity and resistance arising mainly due to non-specificity, resulting in disease progression. The advancement in recombinant technology has led to the synthesis of genetically engineered protein polymers like Elastin-like polypeptide (ELP), Silk-like polypeptide (SLP), hybrid protein polymers with specific sequences to impart precisely controlled properties and to target proteins that have provided satisfactory preclinical outcomes. Such protein polymers have been exploited for the formulation and delivery of chemotherapeutics for biomedical applications. The use of such polymers has not only solved the limitation of conventional chemotherapy but has also improved the therapeutic index of typical drug delivery systems. This review, therefore, summarizes the development of such advanced recombinant protein polymers designed to deliver chemotherapeutics and also discusses the key challenges associated with their current usage and their application in the future.
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14
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MASTROIANNI ANTONIO, VANGELI VALERIA, GRECO SONIA, CHIDICHIMO LUCIANA, URSO FILIPPO, MAURO MARIAVITTORIA, BONORA STEFANO, DE NICOLÒ AMEDEO, D’AVOLIO ANTONIO. Indirect hyperbilirubinemia and jaundice during chronic hepatitis C in an HIV-infected patient treated with glecaprevir/pibrentasvir (GLE/PIB) and antiretroviral therapy (ART). The first reported case in Italy. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2022; 63:E420-E423. [PMID: 36415300 PMCID: PMC9648555 DOI: 10.15167/2421-4248/jpmh2022.63.3.2137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 10/04/2022] [Indexed: 01/25/2023]
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Primary treatment and re-treatment with GLE/PIB are effective and safe for patients without decompensated liver cirrhosis and chronic hepatitis C in a real-world clinical setting. However, in the context of compensated cirrhosis and concomitant administration of inhibitors of cytochromes, a careful monitoring of liver biomarkers, as well as therapeutic drug monitoring (TDM), may be advisable during GLE/PIB therapy. The GLE / PIB combination is very effective and safe in achieving a sustained virological response, but it can be associated with the development of severe hepatic adverse events, which require virological and serum concentration monitoring of the two drugs to prevent a serious liver damage. The possible onset of hyperbilirubinemia must not necessarily lead to the suspension of therapy, because the phenomenon may be transient. We report what is likely the first known case of severe jaundice after treatment with GLE/PIB in Italy in a patient with compensated chronic hepatitis in the context of HIV disease.
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Affiliation(s)
- ANTONIO MASTROIANNI
- UOC Malattie Infettive & Tropicali &, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
- Correspondence: Antonio Mastroianni, UOC Malattie Infettive & Tropicali, Presidio Ospedaliero “Annunziata”, Azienda Ospedaliera di Cosenza, Viale della Repubblica s.n.c. 87100, Cosenza, Italy. - Tel.: +39 0984 68.18.33 - Mobile: +39 349 54.44.330 - Fax: +39 0984 68.15.58 - E-mail:
| | - VALERIA VANGELI
- UOC Malattie Infettive & Tropicali &, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
| | - SONIA GRECO
- UOC Malattie Infettive & Tropicali &, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
| | - LUCIANA CHIDICHIMO
- UOC Malattie Infettive & Tropicali &, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
| | - FILIPPO URSO
- UOC di Farmacia Ospedaliera & Unità di Farmacovigilanza, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
| | - MARIA VITTORIA MAURO
- UOC di Microbiologia & Virologia, Presidio Ospedaliero “Annunziata”, Cosenza, Italy
| | - STEFANO BONORA
- Clinica delle Malattie Infettive, “Amedeo di Savoia” Hospital, Turin University, Turin, Italy
| | - AMEDEO DE NICOLÒ
- Laboratorio di Farmacologia e Farmacogenetica, TDM and PK/PG Unit, Ospedale “Amedeo di Savoia”, Università degli Studi di Torino, Torino, Italy
| | - ANTONIO D’AVOLIO
- Laboratorio di Farmacologia e Farmacogenetica, TDM and PK/PG Unit, Ospedale “Amedeo di Savoia”, Università degli Studi di Torino, Torino, Italy
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15
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Cornberg M, Stoehr A, Naumann U, Teuber G, Klinker H, Lutz T, Möller H, Hidde D, Lohmann K, Simon KG. Real-World Safety, Effectiveness, and Patient-Reported Outcomes in Patients with Chronic Hepatitis C Virus Infection Treated with Glecaprevir/Pibrentasvir: Updated Data from the German Hepatitis C-Registry (DHC-R). Viruses 2022; 14:1541. [PMID: 35891520 PMCID: PMC9318383 DOI: 10.3390/v14071541] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/29/2022] [Accepted: 07/09/2022] [Indexed: 11/29/2022] Open
Abstract
Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.
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Affiliation(s)
- Markus Cornberg
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hannover Medizinische Hochschule, 30625 Hannover, Germany
| | | | | | - Gerlinde Teuber
- Practice PD Dr. med. G. Teuber, 60594 Frankfurt am Main, Germany;
| | - Hartwig Klinker
- Department of Internal Medicine, University Hospital Würzburg, 97080 Würzburg, Germany;
| | | | | | - Dennis Hidde
- AbbVie Germany GmbH & Co., KG, 65189 Wiesbaden, Germany; (D.H.); (K.L.)
| | - Kristina Lohmann
- AbbVie Germany GmbH & Co., KG, 65189 Wiesbaden, Germany; (D.H.); (K.L.)
| | - Karl-Georg Simon
- MVZ Dres Eisenbach/Simon/ Schwarz/GbR, 51375 Leverkusen, Germany; k.-
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16
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Wong YJ, Nguyen MH. Is it safe to treat chronic hepatitis C patients with decompensated cirrhosis with PI-based DAAs? J Hepatol 2022; 77:257-258. [PMID: 35074472 DOI: 10.1016/j.jhep.2021.12.037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 12/23/2021] [Indexed: 02/05/2023]
Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; Duke-NUS Medical School, Singapore.
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, USA.
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17
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Wang Y, Mitchell JW, Zhang C, Liu Y. Evidence and implication of interventions across various socioecological levels to address pre-exposure prophylaxis uptake and adherence among men who have sex with men in the United States: a systematic review. AIDS Res Ther 2022; 19:28. [PMID: 35754038 PMCID: PMC9233830 DOI: 10.1186/s12981-022-00456-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/16/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Pre-exposure prophylaxis (PrEP) represents a proven biomedical strategy to prevent HIV transmissions among men who have sex with men (MSM) in the United States (US). Despite the design and implementation of various PrEP-focus interventions in the US, aggregated evidence for enhancing PrEP uptake and adherence is lacking. The objective of this systematic review is to synthesize and evaluate interventions aimed to improve PrEP uptake and adherence among MSM in the US, and identify gaps with opportunities to inform the design and implementation of future PrEP interventions for these priority populations. METHODS We followed the PRISMA guidelines and conducted a systematic review of articles (published by November 28, 2021) with a focus on PrEP-related interventions by searching multiple databases (PubMed, MEDLINE, Web of Science and PsycINFO). Details of PrEP interventions were characterized based on their socioecological level(s), implementation modalities, and stage(s) of PrEP cascade continuum. RESULTS Among the 1363 articles retrieved from multiple databases, 42 interventions identified from 47 publications met the inclusion criteria for this review. Most individual-level interventions were delivered via text messages and/or apps and incorporated personalized elements to tailor the intervention content on participants' demographic characteristics or HIV risk behaviors. Interpersonal-level interventions often employed peer mentors or social network strategies to enhance PrEP adoption among MSM of minority race. However, few interventions were implemented at the community-, healthcare/institution- or multiple levels. CONCLUSIONS Interventions that incorporate multiple socioecological levels hold promise to facilitate PrEP adoption and adherence among MSM in the US given their acceptability, feasibility, efficacy and effectiveness. Future PrEP interventions that simultaneously address PrEP-related barriers/facilitators across multiple socioecological levels should be enhanced with a focus to tackle contextual and structural barriers (e.g., social determinants of health, stigma or medical mistrust) at the community- and healthcare/institution-level to effectively promote PrEP use for MSM of color.
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Affiliation(s)
- Ying Wang
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA
| | - Jason W Mitchell
- Department of Health Promotion and Disease Prevention, Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA
| | - Chen Zhang
- School of Nursing, University of Rochester Medical Center, Rochester, NY, USA
| | - Yu Liu
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.
- Division of Epidemiology, Department of Public Health Sciences, University of Rochester Medical Center, 256 Crittenden Blvd, Ste. 3305, Rochester, NY, 14642, USA.
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18
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Yen HH, Chen YY, Lai JH, Chen HM, Yao CT, Huang SP, Liu IL, Zeng YH, Yang FC, Siao FY, Chen MW, Su PY. Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis. J Clin Med 2022; 11:1853. [PMID: 35407462 PMCID: PMC8999637 DOI: 10.3390/jcm11071853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/17/2022] [Accepted: 03/24/2022] [Indexed: 11/17/2022] Open
Abstract
Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.
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Affiliation(s)
- Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- General Education Center, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Electrical Engineering, Chung Yuan University, Taoyuan 320, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
- Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua 500, Taiwan
- Department of Hospitality, MingDao University, Changhua 500, Taiwan
| | - Jun-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua 500, Taiwan;
| | - Hung-Ming Chen
- Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan;
| | - Chih-Ta Yao
- Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua 500, Taiwan;
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
| | - Fang-Chi Yang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
| | - Fu-Yuan Siao
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Kinesiology, Health and Leisure, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Mechanical Engineering, Chung Yuan Christian University, Taoyuan 320, Taiwan
| | - Mei-Wen Chen
- Department of Information Management, Chien-Kuo Technology University, Chunghua 500, Taiwan;
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (H.-H.Y.); (Y.-Y.C.); (S.-P.H.); (I.-L.L.); (Y.-H.Z.); (F.-C.Y.)
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19
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Pabjan P, Brzdęk M, Chrapek M, Dziedzic K, Dobrowolska K, Paluch K, Garbat A, Błoniarczyk P, Reczko K, Stępień P, Zarębska-Michaluk D. Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals? Viruses 2022; 14:96. [PMID: 35062302 PMCID: PMC8779728 DOI: 10.3390/v14010096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open
Abstract
Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.
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Affiliation(s)
- Paweł Pabjan
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Magdalena Chrapek
- Faculty of Natural Sciences, Jan Kochanowski University, 25-369 Kielce, Poland;
| | - Kacper Dziedzic
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Krystyna Dobrowolska
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Katarzyna Paluch
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Anna Garbat
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Błoniarczyk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Katarzyna Reczko
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Stępień
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
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20
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Huang CF, Kuo HT, Chang TS, Lo CC, Hung CH, Huang CW, Chong LW, Cheng PN, Yeh ML, Peng CY, Cheng CY, Huang JF, Bair MJ, Lin CL, Yang CC, Wang SJ, Hsieh TY, Lee TH, Lee PL, Wu WC, Lin CL, Su WW, Yang SS, Wang CC, Hu JT, Mo LR, Chen CT, Huang YH, Chang CC, Huang CS, Chen GY, Kao CN, Tai CM, Liu CJ, Lee MH, Tsai PC, Dai CY, Kao JH, Lin HC, Chuang WL, Chen CY, Tseng KC, Yu ML. Nationwide registry of glecaprevir plus pibrentasvir in the treatment of HCV in Taiwan. Sci Rep 2021; 11:23473. [PMID: 34873250 PMCID: PMC8648748 DOI: 10.1038/s41598-021-03006-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/03/2021] [Indexed: 12/25/2022] Open
Abstract
The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 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
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Deppartment of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | | | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
- School of Medicine, Tzuchi University, Hualien, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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21
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Torgersen J, Newcomb CW, Carbonari DM, Rentsch CT, Park LS, Mezochow A, Mehta RL, Buchwalder L, Tate JP, Bräu N, Bhattacharya D, Lim JK, Taddei TH, Justice AC, Re VL. Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation. J Hepatol 2021; 75:1312-1322. [PMID: 34333102 PMCID: PMC8604762 DOI: 10.1016/j.jhep.2021.07.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 07/14/2021] [Accepted: 07/18/2021] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs. METHODS We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25). RESULTS Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. LAY SUMMARY Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.
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Affiliation(s)
- Jessie Torgersen
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Craig W. Newcomb
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Dena M. Carbonari
- Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Christopher T. Rentsch
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK,VA Connecticut Healthcare System, West Haven, CT, USA
| | - Lesley S. Park
- Stanford Center for Population Health Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Alyssa Mezochow
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rajni L. Mehta
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Lynn Buchwalder
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Janet P. Tate
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Norbert Bräu
- James J. Peters VA Medical Center, Bronx, NY and Icahn School of Medicine at Mount Sinai, New York, NY
| | - Debika Bhattacharya
- VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Joseph K. Lim
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Tamar H. Taddei
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Amy C. Justice
- VA Connecticut Healthcare System, West Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA,Division of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA,Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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22
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Su PY, Chen YY, Lai JH, Chen HM, Yao CT, Liu IL, Zeng YH, Huang SP, Hsu YC, Wu SS, Siao FY, Yen HH. Real-World Experience of Chronic Hepatitis C-Related Compensated Liver Cirrhosis Treated with Glecaprevir/Pibrentasvir: A Multicenter Retrospective Study. J Clin Med 2021; 10:jcm10225236. [PMID: 34830518 PMCID: PMC8619604 DOI: 10.3390/jcm10225236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen that has been approved for the treatment of chronic hepatitis C. The present study aimed to evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis in a real-world setting. Methods: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from five hospitals in the Changhua Christian Care System, who underwent treatment between August 2018 and October 2020. The primary endpoint was a sustained virological response observed 12 weeks after completion of the treatment. Results: Ninety patients, including 70 patients who received the 12-week therapy and 20 patients who received the 8-week therapy, were enrolled. The mean age of the patients was 65 years, and 57.8% of the patients were males. Sixteen (17.8%) patients had end-stage renal disease, and 15 (16.7%) had co-existing hepatoma. The hepatitis C virus genotypes 1 (40%) and 2 (35.6%) were most common. The common side effects included anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%), and malaise (7.8%). Laboratory adverse grade ≥3 events included anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%). The overall sustained virological response rates were 94.4% and 97.7% in the intention-to-treat and per-protocol analyses, respectively. Conclusions: the glecaprevir/pibrentasvir treatment regimen was highly effective and well tolerated among patients with compensated cirrhosis in the real-world setting.
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Affiliation(s)
- Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua 500, Taiwan
- Department of Hospitality, MingDao University, Changhua 500, Taiwan
| | - Jun-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua 500, Taiwan;
| | - Hung-Ming Chen
- Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan;
| | - Chih-Ta Yao
- Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua 500, Taiwan;
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Fu-Yuan Siao
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Kinesiology, Health and Leisure, Chienkuo Technology University, Changhua 500, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- General Education Center, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Electrical Engineering, Chung Yuan University, Taoyuan 320, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
- Correspondence: ; Tel.: +886-4-723-8595-5501
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23
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Hara T, Ohara T, Taniguchi M, Sakai H, Oka K, Iwai N, Tsuji T, Okuda T, Nagata A, Komaki T, Sakagami J, Kagawa K. Severe Liver Injury Associated with Glecaprevir Plus Pibrentasvir Therapy in a Patient with Treatment-naïve Hepatitis C Virus Infection. Intern Med 2021; 60:2437-2443. [PMID: 33612683 PMCID: PMC8381168 DOI: 10.2169/internalmedicine.6664-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A 49-year-old man underwent treatment with glecaprevir plus pibrentasvir (G/P) for chronic hepatitis C infection. Six weeks later, he was admitted to our hospital because of jaundice and fatigue with no accompanying skin rash. A laboratory examination and evaluation of the patient's history resulted in a diagnosis of acute liver injury. Discontinuation of G/P and a rigorous medical protocol, including plasma exchange and hemodiafiltration, successfully mitigated the liver damage. The patient was also found to be allergic to two drugs other than the G/P therapy. In such cases with a history of drug allergy, careful observation may be required to detect serious adverse events.
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Affiliation(s)
- Tasuku Hara
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Tomoya Ohara
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Masashi Taniguchi
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Hiroaki Sakai
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Kohei Oka
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Naoto Iwai
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Toshifumi Tsuji
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Takashi Okuda
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Akihiro Nagata
- Department of Pathology, Fukuchiyama City Hospital, Japan
| | - Toshiyuki Komaki
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Junichi Sakagami
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Keizo Kagawa
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
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24
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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: 4] [Impact Index Per Article: 1.0] [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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25
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Baesi K, Velayati AA, Ashtiani MF, Fakhredini K, Banifazl M, Larijani MS, Basimi P, Ramezani A. Prevalence of Naturally Occurring Resistance Associated Substitutions in NS3/4A Protease Inhibitors in Iranian HCV/HIV Infected Patients. Curr HIV Res 2021; 19:391-397. [PMID: 34238162 DOI: 10.2174/1566523221666210707142838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/03/2021] [Accepted: 04/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) acts in host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions(RASs) make some obstacles to this antiviral therapy success. OBJECTIVE In this study, we aimed at determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients. METHODS A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region wasanalyzed using geno2pheno HCV. RESULTS Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects wereobserved in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L,Q80L,S122G/L,R155T/G,A156S,D168Y/N and S174A/N/T mutations were detected in this study. CONCLUSION Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also investigation on a large population could be of high value.
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Affiliation(s)
- Kazem Baesi
- Hepatitis & AIDS Dept., Pasteur Institute of Iran, Tehran, Iran
| | - Ali Akbar Velayati
- Masih Daneshvari Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | | | - Kamal Fakhredini
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Banifazl
- Iranian Society for Support of Patients with Infectious Disease, Tehran, Iran
| | | | - Parya Basimi
- Hepatitis & AIDS Dept., Pasteur Institute of Iran, Tehran, Iran
| | - Amitis Ramezani
- Clinical Research Dept., Pasteur Institute of Iran, Tehran, Iran
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26
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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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27
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Hong J, Wright RC, Partovi N, Yoshida EM, Hussaini T. Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents. J Clin Transl Hepatol 2020; 8:322-335. [PMID: 33083256 PMCID: PMC7562806 DOI: 10.14218/jcth.2020.00034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/28/2020] [Accepted: 06/30/2020] [Indexed: 12/12/2022] Open
Abstract
In this review, we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C, specifically sofosbuvir/velpatasvir (Epclusa®), sofosbuvir/velpatasvir/voxilaprevir (Vosevi®), glecaprevir/pibrentasvir (Maviret®), and elbasvir/grazoprevir (Zepatier®). We searched MEDLINE (1948-January 2020), Embase (1964-January 2020), Google, and GoogleScholar using the terms pharmacokinetics, drug interaction, drug metabolism, sofosbuvir, velpatasvir, Epclusa, voxilaprevir, Vosevi, glecaprevir, pibrentasvir, Maviret, elbasvir, grazoprevir, and Zepatier, from inception to January 13, 2020. The search was limited to randomized controlled trials, in vitro studies, prospective and retrospective human studies, drug monographs, abstracts, and conference proceedings. All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted. Numerous clinically relevant drug-drug interactions (DDIs) were identified with the newer generation DAAs and commonly prescribed drugs. NS3/4A protease inhibitors are more likely to be involved in DDIs, followed by NS5A inhibitors and NS5B polymerase inhibitor. The majority of clinically relevant DDIs are predictable, according to known pharmacokinetic, pharmacodynamics, and physicochemical properties of DAAs; however, in select cases, unpredictable DDIs do occur. As expected, many drug interactions exist between newer generation DAAs and commonly prescribed medications. While the majority of clinically relevant interactions are predictable, many require therapeutic dose adjustment or careful selection of non-interacting drugs. In select cases, severe and unpredictable drug interactions can occur. Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.
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Affiliation(s)
- Jenny Hong
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, BC, Canada
| | - Robert C. Wright
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, BC, Canada
| | - Nilu Partovi
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, BC, Canada
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
| | - Eric M. Yoshida
- Liver Transplant Program, Vancouver General Hospital, Vancouver, BC, Canada
- Division of Gastroenterology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Trana Hussaini
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, BC, Canada
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
- Liver Transplant Program, Vancouver General Hospital, Vancouver, BC, Canada
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28
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Abstract
Hepatitis C virus (HCV) is the most common bloodborne pathogen in the United States, chronically affecting approximately 2.4 million Americans, most of whom are unaware of the infection. Highly effective, well-tolerated therapies are now available with markedly simplified treatment algorithms. Eradication of HCV is a national goal. Increased efforts to extend access to treatment to populations that traditionally are difficult to treat, such as persons who inject drugs, are critical to achieving eradication. Given the magnitude of the disease burden, an increased role of primary care providers in screening, patient stratification, and treatment will be needed.
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Affiliation(s)
- David E Kaplan
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (D.E.K.)
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29
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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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Fontana RJ, Lens S, McPherson S, Elkhashab M, Ankoma-Sey V, Bondin M, Dos Santos AGP, Xue Z, Trinh R, Porcalla A, Zeuzem S. Efficacy and Safety of 8 Weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve, HCV-Infected Patients with APRI ≤ 1 in a Single-Arm, Open-Label, Multicenter Study. Adv Ther 2019; 36:3458-3470. [PMID: 31646465 PMCID: PMC6860464 DOI: 10.1007/s12325-019-01123-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The presence or absence of cirrhosis in patients with chronic hepatitis C virus (HCV) infection influences the type and duration of antiviral therapy. Non-invasive markers, like serum aspartate aminotransferase (AST) to platelet ratio index (APRI), may help identify appropriate HCV treatment-naive patients for 8-week treatment with the pangenotypic regimen of glecaprevir/pibrentasvir. METHODS This single-arm, open-label, international, prospective study (NCT03212521) evaluated the efficacy and safety of 8-week glecaprevir/pibrentasvir regimen in HCV treatment-naïve adults with chronic HCV genotypes 1-6 infection, APRI ≤ 1, and no prior evidence of cirrhosis. The primary and secondary outcomes were sustained virologic response at 12 weeks post-treatment (SVR12) by modified intent-to-treat (mITT) and intent-to-treat (ITT) analyses, respectively. Additional endpoints included virologic failures, treatment adherence, and genotype-specific SVR12 rates. RESULTS Among the 230 patients enrolled, most were less than 65 years old (90%); 37% and 43% had a history of injection drug use or psychiatric disorders, respectively. SVR12 rates were 100% (222/222; 95% CI 98.3-100%) and 96.5% (222/230; 95% CI 94.2-98.9%) by mITT and ITT analyses, respectively. There were no virologic failures. ITT SVR12 rates were greater than 94% for all HCV genotypes. In patients with available data, treatment adherence was 99% (202/204). There were no grade 3 or higher laboratory abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, and low rates of serious adverse events (2%). CONCLUSIONS Glecaprevir/pibrentasvir was highly efficacious and well tolerated in HCV treatment-naïve patients with APRI ≤ 1 and no prior evidence of cirrhosis. TRIAL REGISTRATION ClinicalTrials.gov number, NCT03212521. FUNDING AbbVie. Plain language summary available for this article.
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Affiliation(s)
- Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
| | - Sabela Lens
- Liver Unit, Hospital Clinic, IDIBAPS and CIBERehd, University of Barcelona, Barcelona, Spain
| | - Stuart McPherson
- Liver Unit, The Newcastle upon Tyne Hospitals NHS Foundation and Trust and Newcastle University, Newcastle upon Tyne, UK
| | | | - Victor Ankoma-Sey
- Division of Gastroenterology, Sherri and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, TX, USA
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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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