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Sharip A, Kunz J. Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy. Cells 2025; 14:266. [PMID: 39996739 PMCID: PMC11854242 DOI: 10.3390/cells14040266] [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] [Received: 12/09/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
Liver fibrosis, a consequence of chronic liver injury, represents a major global health burden and is the leading cause of liver failure, morbidity, and mortality. The pathological hallmark of this condition is excessive extracellular matrix deposition, driven primarily by integrin-mediated mechanotransduction. Integrins, transmembrane heterodimeric proteins that serve as primary ECM receptors, orchestrate complex mechanosignaling networks that regulate the activation, differentiation, and proliferation of hepatic stellate cells and other ECM-secreting myofibroblasts. These mechanical signals create self-reinforcing feedback loops that perpetuate the fibrotic response. Recent advances have provided insight into the roles of specific integrin subtypes in liver fibrosis and revealed their regulation of key downstream effectors-including transforming growth factor beta, focal adhesion kinase, RhoA/Rho-associated, coiled-coil containing protein kinase, and the mechanosensitive Hippo pathway. Understanding these mechanotransduction networks has opened new therapeutic possibilities through pharmacological manipulation of integrin-dependent signaling.
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Affiliation(s)
- Aigul Sharip
- Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana 020000, Kazakhstan;
- Laboratory of Bioinformatics and Systems Biology, National Laboratory Astana, Astana 020000, Kazakhstan
| | - Jeannette Kunz
- Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana 020000, Kazakhstan;
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Wu M, Ma J, Li S, Qin S, Tan C, Xie O, Li A, Lim AG, Wan X. Effects and Costs of Hepatitis C Virus Elimination for the Whole Population in China: A Modelling Study. PHARMACOECONOMICS 2024; 42:1345-1357. [PMID: 39222272 DOI: 10.1007/s40273-024-01424-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND OBJECTIVE China has the highest number of hepatitis C virus (HCV) infections in the world. However, it is unclear what levels of screening and treatment are needed to achieve the WHO 2030 hepatitis C elimination targets. We aimed to evaluate the impact of scaling up interventions on the hepatitis C epidemic and determine how and at what cost these elimination targets could be achieved for the whole population in China. METHODS We developed a compartmental model incorporating HCV transmission, disease progression, and care cascade for the whole population in China, calibrated with data on demographics, injecting drug use, HCV prevalence, and treatments. Five different scenarios were evaluated for effects and costs for 2022-2030. All costs were converted to 2021 US dollar (USD) and discounted at an annual rate of 5%. One-way sensitivity analyses were conducted to assess the robustness of the model. RESULTS Under the status quo scenario, the incidence of hepatitis C is projected to increase from 60.39 (57.60-63.45) per 100,000 person-years in 2022 to 68.72 (65.3-73.97) per 100,000 person-years in 2030, and 2.52 million (1.94-3.07 million) infected patients are projected to die between 2022 and 2030, of which 0.76 (0.61-1.08) million will die due to hepatitis C. By increasing primary screening to 10%, conducting regular rescreening (annually for PWID and every 5 years for the general population) and treating 90% of patients diagnosed, the incidence would be reduced by 88.15% (86.61-89.45%) and hepatitis C-related mortality by 60.5% (52.62-65.54%) by 2030, compared with 2015 levels. This strategy would cost USD 52.78 (USD 43.93-58.53) billion. CONCLUSIONS Without changes in HCV prevention and control policy, the disease burden of HCV in China will increase dramatically. To achieve the hepatitis C elimination targets, China needs to sufficiently scale up screening and treatment.
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Affiliation(s)
- Meiyu Wu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139 Renmin Rd, Changsha, 410011, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China
| | - Jing Ma
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Sini Li
- The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Shuxia Qin
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Chongqing Tan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139 Renmin Rd, Changsha, 410011, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China
| | - Ouyang Xie
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139 Renmin Rd, Changsha, 410011, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China
| | - Andong Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139 Renmin Rd, Changsha, 410011, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China
| | - Aaron G Lim
- Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
- Bristol Medical School, Population Health Sciences, University of Bristol, Oakfifield House, Oakfifield Grove, Clifton, BS8 2BN, UK.
| | - Xiaomin Wan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139 Renmin Rd, Changsha, 410011, Hunan, China.
- Institute of Clinical Pharmacy, Central South University, Changsha, 410011, Hunan, China.
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Abe H, Okamura Y, Yoshida N, Mitsuka Y, Aramaki O, Moriguchi M, Nakamura M, Kogure H, Okada M, Ohni S, Masuda S. Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy. Ann Surg Oncol 2024:10.1245/s10434-024-16453-9. [PMID: 39521742 DOI: 10.1245/s10434-024-16453-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. PATIENTS AND METHODS This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. RESULTS Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). CONCLUSIONS Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.
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Affiliation(s)
- Hayato Abe
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Yukiyasu Okamura
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
| | - Nao Yoshida
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Yusuke Mitsuka
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Aramaki
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masamichi Moriguchi
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masanori Nakamura
- Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Hirofumi Kogure
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiro Okada
- Division of Radiology, Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Sumie Ohni
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
| | - Shinobu Masuda
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
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Salama M, Darwesh N, Elsabaawy MM, Abdelsameea E, Gomaa A, Sabry A. Long-Term Outcomes of Patients with Liver Cirrhosis After Eradication of Chronic Hepatitis C with Direct-Acting Antiviral Drugs (DAAs). J Hepatocell Carcinoma 2024; 11:2115-2132. [PMID: 39493267 PMCID: PMC11531736 DOI: 10.2147/jhc.s475810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 10/15/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose This research was designed to determine the long-term outcomes in patients with liver cirrhosis who achieved sustained virological response (SVR) after direct-acting anti-viral drugs (DAAs) based regimens. Patients and Methods This study involved 193 patients with HCV-related cirrhosis who had previously completed DAAs regimens and accomplished SVR. Clinical, laboratory, and radiological features at the first and 3rd-year follow-up after the end of treatment were analyzed. Overall survival (OS) and incidence of liver decompensation or hepatocellular carcinoma (HCC) were determined at the 5-year follow-up. Results About 68.4% of our patients with HCV-related cirrhosis were males and their mean age was 54.8 ± 7.7 years. Follow-up at the first and the 3rd-year showed significant improvements in albumin (P = 0.001), liver enzymes (P = 0.001), alpha-fetoprotein (AFP) (P < 0.001), platelet count (P = 0.001), the model for end-stage liver disease (MELD) score (P = 0.001 and 0.01), FIB4 and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores (p < 0.001). The liver stiffness (LS) also significantly improved (p = 0.001). At the 5th year, the mean OS was 58.3 months, with 14.5% and 17.6% of patients developing de-novo HCC and decompensation, respectively. The mean OS at the 5th-year follow-up was shorter in patients who developed HCC and those with liver decompensation (p = 0.001). Alfa-fetoprotein and LS are predictive factors for HCC development. Conclusion Despite achieving SVR, continuous surveillance for HCC and new-onset decompensation is mandatory in patients with liver cirrhosis.
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Affiliation(s)
- Mohsen Salama
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Nehad Darwesh
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Maha Mohammad Elsabaawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Aliaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
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Bui TI, Brown AP, Brown M, Lawless S, Roemmich B, Anderson NW, Farnsworth CW. Comparison of a dual antibody and antigen HCV immunoassay to standard of care algorithmic testing. J Clin Microbiol 2024; 62:e0083224. [PMID: 39283072 PMCID: PMC11481485 DOI: 10.1128/jcm.00832-24] [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] [Received: 06/04/2024] [Accepted: 08/15/2024] [Indexed: 10/17/2024] Open
Abstract
The Centers for Disease Control and Prevention (CDC) guidelines for hepatitis C virus (HCV) testing, although effective, may miss crucial diagnostic opportunities. The goal of this study was to assess the utility of an antibody (Ab) and antigen (Ag) combination immunoassay as an alternative to traditional HCV screening. Remnant specimens from 1,341 patients with concurrent third-generation serologic (Roche anti-HCV-II) and nucleic acid amplification testing (NAAT) were assessed using the HCV Duo Ab/Ag immunoassay (Roche). Patient demographics, risk factors, and standard of care (SOC) laboratory results from the medical records were recorded. Overall, 99.0% (197/199) of the HCV Duo Ab+/Ag+specimens accurately identified active infections as confirmed by NAAT, and 99.9% (670/671) Ab-/Ag- samples corresponded to those without HCV infections. Individually, the HCV Duo Ab component demonstrated a 95.6% positive percent agreement (PPA) (95% CI = 93.8-96.9) and 99.1% negative percent agreement (NPA) (98.8-99.6) compared with SOC anti-HCV II Ab assay. The HCV Duo Ag had a 73.5% PPA (67.9-78.4) and 99.8% NPA (99.3-100) with NAAT. Among RNA+ specimens, 73.4% (197/267) were HCV Duo Ag+, and 265/267 (99.3%) were successfully detected on the HCV Duo Ab component. Notably, 5/7 (71.4%) Ab-/RNA +specimens were detected by HCV Duo, which would have been missed by traditional algorithmic testing. Fourth generation HCV Duo Ab/Ag assay demonstrated comparable performance to SOC testing and shortens the diagnostic window but does not eliminate the need for NAAT in all patients. Ab/Ag testing identified several Ab-/RNA+ cases, a subgroup often undiagnosed by current algorithmic testing, demonstrating promise for improved diagnostic efficiency and accuracy in HCV detection.IMPORTANCEThis study highlights the potential of a combined hepatitis C virus (HCV) Duo antibody (Ab) and antigen (Ag) immunoassay to improve early detection of HCV infections. Traditional Ab-only screening methods recommended by the Centers for Disease Control and Prevention may miss early-stage infections. The HCV Duo assay showed high accuracy, detecting nearly all active infections confirmed by nucleic acid amplification testing. Dual detection of HCV Ab and Ag shortens the diagnostic window, enabling intervention and treatment in a single visit, which is crucial for improving patient outcomes and reducing HCV transmission, especially in areas with limited access to confirmatory molecular testing.
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Affiliation(s)
- Tina I. Bui
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
| | - Abigail P. Brown
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
| | - Meghan Brown
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
| | - Sydney Lawless
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
| | - Brittany Roemmich
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
| | - Neil W. Anderson
- Department of Pathology, University Hospitals Health System, Cleveland, Ohio, USA
| | - Christopher W. Farnsworth
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, Missouri, USA
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Thi Thu PN, Hoang Van D, Ngo Thi Quynh M, Tran Thi N, Pham Minh K, Pham Van L. Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study. PLoS One 2023; 18:e0290235. [PMID: 37656689 PMCID: PMC10473482 DOI: 10.1371/journal.pone.0290235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/05/2023] [Indexed: 09/03/2023] Open
Abstract
The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.
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Affiliation(s)
- Phuong Nguyen Thi Thu
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | | | | | - Ngan Tran Thi
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Khue Pham Minh
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Linh Pham Van
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
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Marginean CM, Pirscoveanu D, Popescu M, Vasile CM, Docea AO, Mitruț R, Mărginean IC, Iacob GA, Firu DM, Mitruț P. Challenges in Diagnosis and Therapeutic Approach of Acute on Chronic Liver Failure-A Review of Current Evidence. Biomedicines 2023; 11:1840. [PMID: 37509478 PMCID: PMC10376368 DOI: 10.3390/biomedicines11071840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/23/2023] [Accepted: 06/25/2023] [Indexed: 07/30/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40-50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Corina Maria Vasile
- Department of Pediatric Cardiology, "Marie Curie" Emergency Children's Hospital, 041451 Bucharest, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitruț
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Mihai Firu
- Ph.D. School Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitruț
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Hoff E, Warden A, Taylor R, Nijhawan AE. Hepatitis C Epidemiology in a Large Urban Jail: A Changing Demographic. Public Health Rep 2023; 138:248-258. [PMID: 35238249 PMCID: PMC10031839 DOI: 10.1177/00333549221076546] [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: 12/09/2022] Open
Abstract
OBJECTIVES Nearly 1 in 3 people with hepatitis C virus (HCV) infection pass through the criminal justice system annually; the system is a crucial location for HCV screening, education, and linkage to care. We aimed to (1) determine the prevalence and incidence of HCV antibody positivity and (2) evaluate the demographic characteristics of people with HCV in a large urban jail. METHODS We offered universal opt-out HCV testing to any person undergoing a routine blood test at the Dallas County Jail from June 2015 through December 2019 (N = 14 490). We extracted data on demographic characteristics from the electronic medical record and collected data on risk factors from people with HCV antibody positivity. We performed univariate and multivariate analyses. RESULTS The prevalence of HCV antibody positivity was 16.7%; the incidence was 13.5 cases per 1000 person-years. HCV antibody positivity was significantly associated with older age (P < .001), female sex (P = .004), non-Hispanic White race versus non-Hispanic Black race (P < .001), and being released to prison versus not (P < .001). Among people born after 1965, those who were HCV antibody-positive were more frequently non-Hispanic White and Hispanic women, whereas among those born in 1965 or before, those who were HCV antibody-positive were more frequently non-Hispanic Black men. CONCLUSIONS The high prevalence and incidence of HCV antibody positivity in a large county jail argue for routine, universal HCV testing and prevention counseling in criminal justice settings. Changing demographic characteristics mirror those of the national injection drug use epidemic and shed insight into designing interventions for risk reduction, education, linkage to care, and treatment.
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Affiliation(s)
- Emily Hoff
- Division of Infectious Diseases,
Department of Internal Medicine, University of Texas Southwestern Medical Center,
Dallas, TX, USA
| | - Andrea Warden
- Parkland Health and Hospital Systems,
Dallas, TX, USA
| | - Ruby Taylor
- Parkland Health and Hospital Systems,
Dallas, TX, USA
| | - Ank E. Nijhawan
- Division of Infectious Diseases,
Department of Internal Medicine, University of Texas Southwestern Medical Center,
Dallas, TX, USA
- Parkland Health and Hospital Systems,
Dallas, TX, USA
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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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El-Sayed M, Elserafy M, El Raziky M, Elakel W, Saad Y, Fayad T, Korany M, Mehrez M, Salama R, Mahrous M, Zaki A, Hassany M, Ammar I, Elsaeed K, Elshazly Y, Doss W. Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease. Arab J Gastroenterol 2023; 24:29-33. [PMID: 36813580 DOI: 10.1016/j.ajg.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/05/2021] [Accepted: 10/12/2022] [Indexed: 02/22/2023]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.
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Affiliation(s)
- Mohammad El-Sayed
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Magdy Elserafy
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Maissa El Raziky
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Wafaa Elakel
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Yasmin Saad
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Tarek Fayad
- Department of Internal Medicine and Nephrology, Cairo University, Cairo, Egypt
| | | | - Mai Mehrez
- National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Rabab Salama
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | | | - Ayman Zaki
- Gastroenterology and Hepatology Unit, Al-Ahrar Educational Hospital, Sharkia, Egypt
| | - Mohamed Hassany
- National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Islam Ammar
- Department of Hepatology, Gastroenterology and Infectious Diseases, Al Azhar University, Cairo, Egypt.
| | - Kadry Elsaeed
- Department of Internal Medicine, Ain Shams University, Cairo, Egypt
| | - Yehia Elshazly
- Department of Internal Medicine, Ain Shams University, Cairo, Egypt
| | - Wahid Doss
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
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11
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Tanaka S, Noda T, Komeda K, Kosaka H, Iida H, Ueno M, Hokuto D, Ikoma H, Nakai T, Kabata D, Shinkawa H, Kobayashi S, Hirokawa F, Mori H, Hayami S, Morimura R, Matsumoto M, Ishizawa T, Kubo S, Kaibori M. Surgical Outcomes for Hepatocellular Carcinoma in Patients with Child-Pugh Class B: a Retrospective Multicenter Study. J Gastrointest Surg 2023; 27:283-295. [PMID: 36471191 DOI: 10.1007/s11605-022-05549-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/25/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUNDS Liver resection for hepatocellular carcinoma (HCC) in patients with Child-Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection. METHODS Clinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien-Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed. RESULTS Postoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL). CONCLUSION For patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection.
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Affiliation(s)
- Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan.
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Hisashi Kosaka
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Hiroya Iida
- Division of Gastrointestinal, Breast, and General Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Hisashi Ikoma
- Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Haruki Mori
- Division of Gastrointestinal, Breast, and General Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Ryo Morimura
- Department of Surgery, Nara Medical University, Kashihara, Nara, Japan
| | - Masataka Matsumoto
- Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeaki Ishizawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
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12
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Nguyen VH, Kam L, Yeo YH, Huang DQ, Henry L, Cheung R, Nguyen MH. Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States. JAMA Netw Open 2022; 5:e2245424. [PMID: 36477481 PMCID: PMC9856330 DOI: 10.1001/jamanetworkopen.2022.45424] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse. OBJECTIVE To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US. MAIN OUTCOMES AND MEASURES The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression. RESULTS A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90). CONCLUSIONS AND RELEVANCE In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.
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Affiliation(s)
- Vy H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Leslie Kam
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Daniel Q. Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, California
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13
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Liu CH, Kao JH. Noninvasive Diagnosis of Hepatic Fibrosis in Hemodialysis Patients with Hepatitis C Virus Infection. Diagnostics (Basel) 2022; 12:2282. [PMID: 36291971 PMCID: PMC9600350 DOI: 10.3390/diagnostics12102282] [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: 08/17/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 08/29/2023] Open
Abstract
Hepatitis C virus (HCV) is a major health problem in hemodialysis patients, which leads to significant morbidity and mortality through progressive hepatic fibrosis or cirrhosis. Percutaneous liver biopsy is the gold standard to stage hepatic fibrosis. However, it is an invasive procedure with postbiopsy complications. Because uremia may significantly increase the risk of fatal and nonfatal bleeding events, the use of noninvasive means to assess the severity of hepatic fibrosis is particularly appealing to hemodialysis patients. To date, researchers have evaluated the performance of various biochemical, serological, and radiological indices for hepatic fibrosis in hemodialysis patients with HCV infection. In this review, we will summarize the progress of noninvasive indices for assessing hepatic fibrosis and propose a pragmatic recommendation to diagnose the stage of hepatic fibrosis with a noninvasive index, in hemodialysis patients with HCV infection.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou 640203, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei 100225, Taiwan
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14
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Dai YK, Zhao ZM, Liu C. Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis. Front Pharmacol 2022; 13:942841. [PMID: 35903335 PMCID: PMC9315937 DOI: 10.3389/fphar.2022.942841] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 06/13/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives: To analyze the research hotspots, evolution, and trends of the treatment of liver fibrosis in the recent 20 years, bibliometric and knowledge-map analysis were used. Methods: Publications associated with the treatment of liver fibrosis were retrieved from the Web of Science Core Collection on 16 April 2022. CiteSpace 5.8.R3 and VOSviewer 1.6.18 were calculated to perform bibliometric and knowledge-map analysis. Results: A total of 72,686 authors from 200 institutions in 134 countries/regions published 15,237 studies in different academic journals. United States was the most productive country, and Shanghai Jiao Tong University was the most published institution. Trauner Michael had the most published articles, whereas Scott L. Friedman was the most frequently co-cited author. Moreover, there was frequent inter-institution cooperation between countries in the years 2015 and after, but the before years showed rare inter-institution cooperation. The journal HEPATOLOGY was both the most published publication and the most frequently co-cited one in this field. Screened keywords, such as virus infection, inflammation, oxidative stress, activation of hepatic stellate cell (HSC), and hepatocellular apoptosis, could be both therapeutic targets and pathological mechanisms in terms of liver fibrosis. Furthermore, long-term suppression of hepatitis B virus replication and the activation of HSC were the latest hotspots and topics related to the treatment of liver fibrosis. Besides, the treatments of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis were also involved in the treatment of liver fibrosis, which were both emerging topics and rapidly developing hot fields. Conclusion: This bibliometric analysis conducted a full overview of the treatment of liver fibrosis, which provided important clues and ideas for scholars focusing on this field. Not only that, the field is still in a stage of rapid development and will continue to be a research hotspot in the future.
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Affiliation(s)
- Yun-Kai Dai
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhi-Min Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- *Correspondence: Chenghai Liu, ; Zhi-Min Zhao,
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai, China
- *Correspondence: Chenghai Liu, ; Zhi-Min Zhao,
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15
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Badami E, Busà R, Douradinha B, Russelli G, Miceli V, Gallo A, Zito G, Conaldi PG, Iannolo G. Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches. World J Gastroenterol 2022; 28:2417-2428. [PMID: 35979260 PMCID: PMC9258280 DOI: 10.3748/wjg.v28.i22.2417] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/22/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%–20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.
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Affiliation(s)
- Ester Badami
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Rosalia Busà
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Bruno Douradinha
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Giovanna Russelli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Vitale Miceli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Alessia Gallo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Giovanni Zito
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Pier Giulio Conaldi
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Gioacchin Iannolo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
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16
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Shahriar S, Araf Y, Ahmad R, Kattel P, Sah GS, Rahaman TI, Sadiea RZ, Sultana S, Islam MS, Zheng C, Hossain MG. Insights Into the Coinfections of Human Immunodeficiency Virus-Hepatitis B Virus, Human Immunodeficiency Virus-Hepatitis C Virus, and Hepatitis B Virus-Hepatitis C Virus: Prevalence, Risk Factors, Pathogenesis, Diagnosis, and Treatment. Front Microbiol 2022; 12:780887. [PMID: 35222296 PMCID: PMC8865087 DOI: 10.3389/fmicb.2021.780887] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/21/2021] [Indexed: 12/15/2022] Open
Abstract
Human immunodeficiency virus, hepatitis B virus, and hepatitis C virus are three blood-borne viruses that can cause major global health issues by increasing severe morbidity. There is a high risk of coinfection with these viruses in individuals because of their same transmission routes through blood using shared needles, syringes, other injection equipment, sexual transmission, or even vertical transmission. Coinfection can cause various liver-related illnesses, non-hepatic organ dysfunction, followed by death compared to any of these single infections. The treatment of coinfected patients is complicated due to the side effects of antiviral medication, resulting in drug resistance, hepatotoxicity, and a lack of required responses. On the other hand, coinfected individuals must be treated with multiple drugs simultaneously, such as for HIV either along with HBV or HCV and HBV and HCV. Therefore, diagnosing, treating, and controlling dual infections with HIV, HBV, or HCV is complicated and needs further investigation. This review focuses on the current prevalence, risk factors, and pathogenesis of dual infections with HIV, HBV, and HCV. We also briefly overviewed the diagnosis and treatment of coinfections of these three blood-borne viruses.
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Affiliation(s)
- Sagarika Shahriar
- Biotechnology Program, Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh
| | - Yusha Araf
- Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, Bangladesh
| | - Rasel Ahmad
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Pravakar Kattel
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Ganga Sagar Sah
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Tanjim Ishraq Rahaman
- Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
| | - Rahila Zannat Sadiea
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Shahnaj Sultana
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Md. Sayeedul Islam
- Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, Japan
| | - Chunfu Zheng
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
| | - Md. Golzar Hossain
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
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17
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Abstract
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
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Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, 9177Hannover Medical School Hannover, Hannover, Germany.,Centre for Individualised Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany
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18
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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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Lasmanovich R, Shaked O, Sivan A, Barak I, Nahari M, Mor O, Katchman H. Hepatitis C Virus Prevalence, Medical Status Awareness and Treatment Engagement among Homeless People Who use Drugs: Results of a Street Outreach Study. Subst Abuse 2022; 16:11782218221095871. [PMID: 35651594 PMCID: PMC9149611 DOI: 10.1177/11782218221095871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Hepatitis C virus (HCV) infection is a primary health concern among people
who use drugs (PWUDs). Homeless PWUDs that constitute a key population for
HCV transmission remain underrepresented in many surveys. Objectives: We performed a proactive street outreach to evaluate HCV infection prevalence
among homeless PWUDs in Tel Aviv, identify risk factors associated with HCV
infection, awareness of disease status and linkage to care rate. Results: Thirty-eight percent of approached PWUD were willing to participate in the
study. Out of 53 subjects who got tested for anti HCV by rapid test, 29
(54.72%) had a positive result, 20 of 29 anti-HCV positive (69%) patients
had positive HCV PCR. Risk factors were investigated using structured
questionnaires. Heroin use was reported significantly more frequently in the
HCV-positive group (P = .05, CI 95%),
whereas other established risk factors did not reach significance in our
cohort. While 21 of 29 (72%) HCV-positive participants were aware of their
condition, only 4 of 21 (19%) received treatment in the past, and 2 of 4
(50%) failed to achieve treatment goals, as assessed by HCV PCR. Conclusions: Our data indicate a high prevalence of HCV infection among homeless PWUDs.
Importantly, despite relatively high awareness of HCV status in this
population, we found strikingly low access to care. These findings motivate
novel interventional approaches targeted at improving patient access, and
compliance among homeless PWUDs, in an effort to reduce HCV
transmission.
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Affiliation(s)
| | - Or Shaked
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ayelet Sivan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Mor Nahari
- Faculty of Humanities and Social Sciences, Ben Gurion University, Beer Sheva, Israel
| | - Orna Mor
- Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat-Gan, Israel
| | - Helena Katchman
- Department of Gastroenterology Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
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20
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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21
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The Antimalaria Drug Artesunate Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication via Activating AMPK and Nrf2/HO-1 Signaling Pathways. J Virol 2021; 96:e0148721. [PMID: 34787456 DOI: 10.1128/jvi.01487-21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide. Currently, vaccine strategies provide limited protection against PRRSV transmission, and no effective drug is commercially available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV pandemics. This study showed that artesunate (AS), one of the antimalarial drugs, potently suppressed PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs) at micromolar concentrations. Furthermore, we demonstrated that this suppression was closely associated with AS-activated AMPK (energy homeostasis) and Nrf2/HO-1 (inflammation) signaling pathways. AS treatment promoted p-AMPK, Nrf2 and HO-1 expression, and thus inhibited PRRSV replication in Marc-145 and PAM cells in a time- and dose-dependent manner. These effects of AS were reversed when AMPK or HO-1 gene was silenced by siRNA. In addition, we demonstrated that AMPK works upstream of Nrf2/HO-1 as its activation by AS is AMPK-dependent. Adenosine phosphate analysis showed that AS activates AMPK via improving AMP/ADP:ATP ratio rather than direct interaction with AMPK. Altogether, our findings indicate that AS could be a promising novel therapeutics for controlling PRRSV and that its anti-PRRSV mechanism, which involves the functional link between energy homeostasis and inflammation suppression pathways, may provide opportunities for developing novel antiviral agents. Importance Porcine reproductive and respiratory syndrome virus (PRRSV) infections have been continuously threatened the pork industry worldwide. Vaccination strategies provide very limited protection against PRRSV infection, and no effective drug is commercially available. We show that artesunate (AS), one of the antimalarial drugs, is a potent inhibitor against PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs). Furthermore, we demonstrate that AS inhibits PRRSV replication via activation of AMPK-dependent Nrf2/HO-1 signaling pathways, revealing a novel link between energy homeostasis (AMPK) and inflammation suppression (Nrf2/HO-1) during viral infection. Therefore, we believe that AS may be a promising novel therapeutics for controlling PRRSV, and its anti-PRRSV mechanism may provide a potential strategy to develop novel antiviral agents.
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22
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Tanaka S, Shinkawa H, Tamori A, Takemura S, Uchida-Kobayashi S, Amano R, Kimura K, Ohira G, Nishio K, Tauchi J, Kinoshita M, Kawada N, Kubo S. Postoperative direct-acting antiviral treatment after liver resection in patients with hepatitis C virus-related hepatocellular carcinoma. Hepatol Res 2021; 51:1102-1114. [PMID: 34476874 DOI: 10.1111/hepr.13709] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/18/2021] [Accepted: 08/31/2021] [Indexed: 12/12/2022]
Abstract
AIM We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. RESULTS Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 years, 60%) and the other two groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither. CONCLUSIONS Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival.
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Affiliation(s)
- Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Ryosuke Amano
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenjiro Kimura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Go Ohira
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kohei Nishio
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Jun Tauchi
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masahiko Kinoshita
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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23
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Hasan M, Parvez MSA, Azim KF, Imran MAS, Raihan T, Gulshan A, Muhit S, Akhand RN, Ahmed SSU, Uddin MB. Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach. Biomed Pharmacother 2021; 140:111742. [PMID: 34052565 PMCID: PMC8130501 DOI: 10.1016/j.biopha.2021.111742] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/07/2021] [Accepted: 05/13/2021] [Indexed: 12/14/2022] Open
Abstract
Here, drug repurposing and molecular docking were employed to screen approved MPP inhibitors and their derivatives to suggest a specific therapeutic agent for the treatment of COVID-19. The approved MPP inhibitors against HIV and HCV were prioritized, while RNA dependent RNA Polymerase (RdRp) inhibitor remdesivir including Favipiravir, alpha-ketoamide were studied as control groups. The target drug surface hotspot was also investigated through the molecular docking technique. Molecular dynamics was performed to determine the binding stability of docked complexes. Absorption, distribution, metabolism, and excretion analysis was conducted to understand the pharmacokinetics and drug-likeness of the screened MPP inhibitors. The results of the study revealed that Paritaprevir (-10.9 kcal/mol) and its analog (CID 131982844) (-16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitors compared in this study, including remdesivir, Favipiravir, and alpha-ketoamide. A comparative study among the screened putative MPP inhibitors revealed that the amino acids T25, T26, H41, M49, L141, N142, G143, C145, H164, M165, E166, D187, R188, and Q189 are at potentially critical positions for being surface hotspots in the MPP of SARS-CoV-2. The top 5 predicted drugs (Paritaprevir, Glecaprevir, Nelfinavir, and Lopinavir) and the topmost analog showed conformational stability in the active site of the SARS-CoV-2 MP protein. The study also suggested that Paritaprevir and its analog (CID 131982844) might be effective against SARS-CoV-2. The current findings are limited to in silico analysis and lack in vivo efficacy testing; thus, we strongly recommend a quick assessment of Paritaprevir and its analog (CID 131982844) in a clinical trial.
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Affiliation(s)
- Mahmudul Hasan
- Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Md Sorwer Alam Parvez
- Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Kazi Faizul Azim
- Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Md Abdus Shukur Imran
- Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Topu Raihan
- Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Airin Gulshan
- Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Samuel Muhit
- Department of Epidemiology and Public Health, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Rubaiat Nazneen Akhand
- Department of Biochemistry and Chemistry, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Syed Sayeem Uddin Ahmed
- Department of Epidemiology and Public Health, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
| | - Md Bashir Uddin
- Department of Medicine, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
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24
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McGuire FH, André K, Bradsher ML, Harrison D, Sterling RK, Reddy KR, Serper M, Golin CE, Reau N, Lim JK, Nelson DR, Sarkar S, Evon DM. Willingness to participate in research among black patients with liver disease: A national cross-sectional study. J Viral Hepat 2021; 28:982-993. [PMID: 33665897 DOI: 10.1111/jvh.13493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/16/2021] [Accepted: 02/23/2021] [Indexed: 12/09/2022]
Abstract
In the United States, Black people are disproportionately diagnosed with hepatitis C virus (HCV) compared with White people but are under-represented in HCV studies. In this US-based cross-sectional telephone survey study, we assessed willingness to participate (WTP) in health/medical research and attitudes and beliefs that may influence WTP among Black patients with HCV. Two hundred participants who had current or prior HCV diagnosis and self-identified as Black or African American were recruited from a national HCV cohort study and an outpatient hepatology clinic. WTP responses ranged from 1 (not at all willing) to 5 (very willing). Multivariable models were used to identify factors associated with the overall mean WTP score. In addition, an open-ended question solicited strategies to help increase research participation from the Black community. Overall, participants reported moderate WTP in research (Mean [95% Confidence Interval (CI)] = 3.78 [3.68, 3.88]). Of 13 types of research presented, participants reported lowest WTP for randomized controlled trials of medications (Mean [95% CI] = 2.31 [2.11, 2.50]). The initial multivariable model identified higher subjective knowledge of research as positively associated with WTP (Parameter estimate [95% CI] = 0.15 [0.02, 0.27]). Sensitivity analyses also identified higher perceived benefits of research as an additional factor associated with WTP. Qualitative findings indicate that greater community-based outreach efforts would increase accessibility of research opportunities. When given the opportunity to participate, Black participants with HCV reported moderate WTP in health/medical research. Research sponsors and investigators should employ community-based outreach to expand access and awareness of research opportunities.
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Affiliation(s)
- F Hunter McGuire
- Department of Health Behavior, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA.,Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, NC, USA
| | - Kat André
- Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, NC, USA.,College of Psychology, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Minyone L Bradsher
- Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, NC, USA
| | - Dawn Harrison
- Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA
| | - Richard K Sterling
- Division of Gastroenterology, Hepatology & Nutrition, Virginia Commonwealth University, Richmond, VA, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Carol E Golin
- Department of Health Behavior, UNC Gillings School of Global Public Health, Chapel Hill, NC, USA.,Division of General Medicine and Epidemiology, UNC School of Medicine, Chapel Hill, NC, USA
| | - Nancy Reau
- Department of Internal Medicine, Section of Hepatology, Rush University Medical Center, Chicago, IL, USA
| | - Joseph K Lim
- Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - David R Nelson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Jacksonville, FL, USA
| | - Souvik Sarkar
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, CA, USA
| | - Donna M Evon
- Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, NC, USA.,Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA
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25
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Effect of Direct-Acting Antiviral Therapy on Thrombocytopenic Patients with Hepatitis C Virus-Related Chronic Liver Disease. Gastroenterol Res Pract 2021; 2021:8811203. [PMID: 34122539 PMCID: PMC8169259 DOI: 10.1155/2021/8811203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 03/25/2021] [Accepted: 04/16/2021] [Indexed: 12/11/2022] Open
Abstract
Background and Aims Thrombocytopenia is a common complication in patients with chronic hepatitis C virus (HCV) that increases the risk of bleeding. We aimed to analyze the hematologic effects of the new direct-acting antiviral (DAA) therapy, particularly on the platelet count in chronic HCV-infected patients with thrombocytopenia. Patients and Methods. One hundred thrombocytopenic patients chronically infected with HCV were included in a prospective study. All patients were eligible for receiving anti-HCV treatment with sofosbuvir-based regimens for 12 weeks, according to the protocol of the National Program for treatment of HCV in Egypt sponsored by the Ministry of Health. Results At the end of treatment (EOT), there was a highly significant increase in platelet count (p < 0.001), a significant increase in white blood cells (WBCs) count (p ≤ 0.032), and a highly significant decrease in hemoglobin level (p < 0.001) as compared to pretreatment levels. Patients with mild to moderate hepatic fibrosis had significantly higher median and interquartile range (IQR) platelet count at baseline and EOT than those with advanced fibrosis and cirrhosis (p ≤ 0.023 and p < 0.001, respectively). There was more elevation in platelet count at EOT in patients with mild to moderate fibrosis than those with advanced fibrosis and cirrhosis. Out of the hundred patients, 73% showed improvement of platelet count, while 27% showed no improvement or even decrease in the platelet count. Conclusion Sofosbuvir-based DAA therapy is a highly effective and safe treatment regimen that results in the improvement of platelet count in thrombocytopenic patients, particularly in mild to moderate stages of hepatic fibrosis.
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26
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Su PS, Su CW, Wu SH, Wei TH, Chu CJ, Lin CC, Lee SD, Wang YJ, Lee FY, Huang YH, Hou MC. Well tolerability and highly effective treatment response for hepatitis C virus-human immunodeficiency virus-coinfected patients treated by all-oral direct-acting antivirals. J Chin Med Assoc 2021; 84:465-471. [PMID: 33871393 DOI: 10.1097/jcma.0000000000000528] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is common because the two pathogens share their transmission route. Studies have suggested that coinfection is associated with accelerated hepatic fibrosis, increased hepatic decompensation, and hepatocellular carcinoma development. Historically, the sustained virological response (SVR) rates for patients undergoing pegylated interferon (PEG-IFN)-based therapy are poor owing to advanced liver disease, immune dysfunction, and poor medical adherence. This study aimed to investigate the efficacy and safety of oral direct-acting antivirals (DAAs) in HCV-HIV-coinfected patients. METHODS Between January 2017 and February 2020, 52 consecutive HCV-HIV-coinfected patients treated with oral DAAs (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 7; daclatasvir and asunaprevir: 1; glecaprevir and pibrentasvir: 15; and sofosbuvir-based drugs: 29) were enrolled. The DAA regimen was selected based on the genotype/subtypes, patient characteristics, potential drug-drug interaction profiles, and health insurance reimbursement criteria. SVR12 was defined as undetectable HCV RNA (<15 IU/mL) at the end of therapy and 12 weeks after therapy completion. RESULTS The mean age of the enrolled patients was 42 ± 10.2 years; 92.3% of the patients were male and 32.7% had advanced fibrosis or cirrhosis. Nine (17.3%) patients had failed previous IFN therapy. The genotype distribution was as follows: 1a: 8; 1b: 23; 2: 14; 3: 1; and 6: 6. The baseline HCV RNA level before DAA administration was 6.56 ± 0.9 log10 IU/mL, and 67.3% of patients had baseline HCV RNA >2 000 000 IU/mL. After posttreatment follow-up, all 52 patients (100%) achieved SVR12. Subjective and laboratory adverse events during therapy were generally mild, and none of the patients terminated therapy early. CONCLUSION A highly effective treatment response and good tolerability were achieved using the oral DAAs for the HCV-HIV-coinfected patient population, which has been considered difficult to treat using IFN-based therapy in the past with urgent unmet medical needs.
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Affiliation(s)
- Pin-Shuo Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Tien-Hsin Wei
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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27
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Krassenburg LAP, Maan R, Ramji A, Manns MP, Cornberg M, Wedemeyer H, de Knegt RJ, Hansen BE, Janssen HLA, de Man RA, Feld JJ, van der Meer AJ. Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity. J Hepatol 2021; 74:1053-1063. [PMID: 33242501 DOI: 10.1016/j.jhep.2020.11.021] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 10/28/2020] [Accepted: 11/11/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. METHODS Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. RESULTS In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99). CONCLUSIONS Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. LAY SUMMARY Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.
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Affiliation(s)
- Lisette A P Krassenburg
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Alnoor Ramji
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
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Lee DH, Ryu SH, Myung HJ, Shin YJ, Lee SH, Park TY, Moon JS. Retreatment of Chronic Hepatitis C Failed to Daclatasvir Plus Asunaprevir by Other Direct-acting Antivirals. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 77:88-91. [PMID: 33633000 DOI: 10.4166/kjg.2020.145] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 12/22/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022]
Abstract
The pegylated interferon plus ribavirin combination therapy has been used as the primary treatment for chronic hepatitis C (CHC) but fails to produce a sustained viral response (SVR) in many patients. In recent years, the treatment of CHC has been rapidly changing because of the introduction of direct-acting antivirals (DAAs), which have a high cure rate. However, retreatment of patients after failure of the first DAA therapy is difficult. We report two rare cases of CHC that showed acquired SVR with other DAA combinations after failure to daclatasvir and asunaprevir.
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Affiliation(s)
- Dong Hoon Lee
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Soo Hyung Ryu
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Hee Jun Myung
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Yun Jae Shin
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Si Hyeong Lee
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Tae Young Park
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Jeong Seop Moon
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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29
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Treem WR, Palmer M, Lonjon-Domanec I, Seekins D, Dimick-Santos L, Avigan MI, Marcinak JF, Dash A, Regev A, Maller E, Patwardhan M, Lewis JH, Rockey DC, Di Bisceglie AM, Freston JW, Andrade RJ, Chalasani N. Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis. Drug Saf 2021; 44:133-165. [PMID: 33141341 PMCID: PMC7847464 DOI: 10.1007/s40264-020-01014-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/07/2020] [Indexed: 02/07/2023]
Abstract
With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD. This position paper focuses on defining best practices for the detection, monitoring, diagnosis, and management of suspected acute DILI during clinical trials in patients with CLD, including hepatitis C virus (HCV) and hepatitis B virus (HBV), both with and without cirrhosis and NASH with cirrhosis. This is one of several position papers developed by the IQ DILI Initiative, comprising members from 16 pharmaceutical companies in collaboration with DILI experts from academia and regulatory agencies. It is based on an extensive literature review and discussions between industry members and experts from outside industry to achieve consensus regarding the recommendations. Key conclusions and recommendations include (1) the importance of establishing laboratory criteria that signal potential DILI events and that fit the disease indication being studied in the clinical trial based on knowledge of the natural history of test fluctuations in that disease; (2) establishing a pretreatment value that is based on more than one screening determination, and revising that baseline during the trial if a new nadir is achieved during treatment; (3) basing rules for increased monitoring and for stopping drug for potential DILI on multiples of baseline liver test values and/or a threshold value rather than multiples of the upper limit of normal (ULN) for that test; (4) making use of more sensitive tests of liver function, including direct bilirubin (DB) or combined parameters such as aspartate transaminase:alanine transaminase (AST:ALT) ratio or model for end-stage liver disease (MELD) to signal potential DILI, especially in studies of patients with cirrhosis; and (5) being aware of potential confounders related to complications of the disease being studied that may masquerade as DILI events.
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Affiliation(s)
| | - Melissa Palmer
- Takeda, Cambridge, MA, USA
- Liver Consulting LLC, New York, NY, USA
| | | | | | | | - Mark I Avigan
- US Food and Drug Administration, Silver Spring, MD, USA
| | | | - Ajit Dash
- , Genentech, South San Francisco, CA, USA
| | - Arie Regev
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Eric Maller
- Pfizer, Collegeville, PA, USA
- MEMS Biopharma Consulting, LLC, Wynnewood, PA, USA
| | | | | | - Don C Rockey
- Medical University of South Carolina, Charleston, SC, USA
| | | | - James W Freston
- University of Connecticut Health Center, Farmington, CT, USA
| | - Raul J Andrade
- Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd, Universidad de Málaga, Málaga, Spain
| | - Naga Chalasani
- Indiana University School of Medicine, Indianapolis, IN, USA.
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30
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Extended panel of biomarkers for long term monitoring of effectiveness of 3 direct antiviral regimen in HCV genotype 1b infection: results from a Romanian infectious disease hospital. REV ROMANA MED LAB 2021. [DOI: 10.2478/rrlm-2020-0040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Background: Hepatitis C virus can be eradicated with antiviral therapy, thus reducing the risk of disease progression and death associated with the final stage of liver disease.
Methods: 241 patients received PrOD+RBV for 12 weeks. Clinical and laboratory data were assessed at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained virological response, SVR). Subsequently, biological and virological measurements were performed at least 48 weeks after obtaining SVR12 in responder patients.
Results: Per protocol SVR12 rate was 97,6%. Severe adverse events were reported in 3 patients (1.24%) and led to treatment discontinuation (liver decompensation). One 58-year-old patient who completed the treatment died before SVR evaluation due to acute mesenteric ischemia (not related to antiviral therapy). Baseline total bilirubin above 2 mg/dl can be considered a predictive factor for non-response to PrOD+RBV treatment (p = 0.004). Of the 30 patients evaluated at least 48 weeks after SVR no one presented relapses, with no statistically significant differences in biological parameters changes and no adverse events were noted during the 48-week follow up period.
Conclusion: Our study revealed the high effectiveness and good safety profile of PrOD +RBV in patients with genotype-1b HCV compensated cirrhosis (Child Pugh A) which were maintained during a 48-week period after treatment finalization.
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31
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Martinez MA, Franco S. Discovery and Development of Antiviral Therapies for Chronic Hepatitis C Virus Infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1322:139-157. [PMID: 34258740 DOI: 10.1007/978-981-16-0267-2_6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
At the beginning of this decade, an estimated 71 million people were living with chronic hepatitis C virus (HCV) infection worldwide. After the acute stage of HCV infection, 18-34% of individuals exhibit spontaneous clearance. However, the remaining 66-82% of infected individuals progress to chronic HCV infection and are at subsequent risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Chronic hepatitis C progression is generally slow during the first two decades of infection, but can be accelerated during this time in association with advancing age and cofactors, such as heavy alcohol intake and human immunodeficiency virus (HIV) co-infection. Since acute HCV infection is generally asymptomatic, HCV goes undiagnosed in a significant percentage of infected individuals. In 2014, direct-acting antiviral (DAA) therapy for chronic HCV was developed, which has increased the cure rates to nearly 100%. DAA therapy is among the best examples of success in the fight against viral infections. DAAs have transformed HCV management and have opened the door for the global eradication of HCV.
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Affiliation(s)
- Miguel Angel Martinez
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
| | - Sandra Franco
- IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
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32
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Roche B, Coilly A, Samuel D. Management of Transplant Patients Infected with HCV. HEPATITIS C: CARE AND TREATMENT 2021:153-173. [DOI: 10.1007/978-3-030-67762-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Martinez MA, Franco S. Therapy Implications of Hepatitis C Virus Genetic Diversity. Viruses 2020; 13:E41. [PMID: 33383891 PMCID: PMC7824680 DOI: 10.3390/v13010041] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/11/2020] [Accepted: 12/22/2020] [Indexed: 12/15/2022] Open
Abstract
Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC) infection, which carries the risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Similar to other RNA viruses, HCV has a high rate of genetic variability generated by its high mutation rate and the actions of evolutionary forces over time. There are two levels of HCV genetic variability: intra-host variability, characterized by the distribution of HCV mutant genomes present in an infected individual, and inter-host variability, represented by the globally circulating viruses that give rise to different HCV genotypes and subtypes. HCV genetic diversity has important implications for virus persistence, pathogenesis, immune responses, transmission, and the development of successful vaccines and antiviral strategies. Here we will discuss how HCV genetic heterogeneity impacts viral spread and therapeutic control.
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Affiliation(s)
- Miguel Angel Martinez
- Miguel Angel Martínez, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain;
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34
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Fuchs M, Monto A, Bräu N, Charafeddine M, Schmidt W, Kozal M, Naggie S, Cheung R, Schnell G, Yu Y, Richards K, Mullally V, Cohen DE, Toro D. Ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin for chronic HCV infection in US veterans with psychiatric disorders. J Med Virol 2020; 92:3459-3464. [PMID: 31829433 PMCID: PMC7687116 DOI: 10.1002/jmv.25655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 12/09/2019] [Indexed: 11/05/2022]
Abstract
Hepatitis C virus (HCV) infections are more common among US veterans receiving care through Veterans Affairs (VA) Medical Centers than among the general population. Historically, HCV therapies had lower efficacy rates in VA patients, possibly due to common comorbidities such as psychiatric disorders and substance abuse. The direct-acting antivirals ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV)±ribavirin (RBV) are approved in the US for HCV genotype 1 (GT1)-infected adults with or without cirrhosis. This study prospectively evaluated the safety and efficacy of OBV/PTV/r+DSV±RBV in VA patients with HCV GT1 infection. TOPAZ-VA was a phase 3b, open-label trial. Adult US veterans with HCV GT1 infection, without cirrhosis or with compensated cirrhosis, were eligible for enrollment. Patients with GT1a infection received OBV/PTV/r +DSV+RBV for 12 weeks or 24 weeks (for those with cirrhosis); GT1b-infected patients without cirrhosis received OBV/PTV/r +DSV for 12 weeks; those with cirrhosis received OBV/PTV/r +DSV with RBV. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12); safety was also assessed. Ninety-nine patients were enrolled at 10 sites from May through November 2015. The majority were male (96%), white (60%), and with GT1a infection (68%); 49% reported ongoing psychiatric disorders. Overall, 94% (93/99) achieved SVR12; three patients had a virologic failure. The most common AEs were fatigue (28%), headache (20%), and nausea (15%); six patients discontinued treatment due to AEs. In US veterans with HCV GT1 infection, OBV/PTV/r +DSV±RBV yielded a 94% overall SVR12 rate and was well tolerated. The presence of psychiatric disorders and/or injection drug use did not impact efficacy.
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Affiliation(s)
- Michael Fuchs
- Hepatology Section, Hunter Holmes McGuire VA Medical CenterVirginia Commonwealth UniversityRichmondVirginia
| | - Alexander Monto
- Department of GastroenterologySan Francisco VA Medical CenterSan FranciscoCalifornia
| | - Norbert Bräu
- Viral Hepatitis ProgramJames J Peters VA Medical CenterNew York CityNew York
| | | | - Warren Schmidt
- Department of Internal MedicineIowa City VA Healthcare SystemIowa CityIowa
| | - Michael Kozal
- Department of Internal Medicine, VA Connecticut Healthcare System, Yale School of MedicineYale UniversityNew HavenConnecticut
| | - Susanna Naggie
- Department of MedicineDurham VA Medical CenterDurhamNorth Carolina
| | - Ramsey Cheung
- Department of Gastroenterology and HepatologyVA Palo Alto Healthcare SystemPalo AltoCalifornia
| | | | - Yao Yu
- AbbVie IncNorth ChicagoIllinois
| | | | | | | | - Doris Toro
- Gastroenterology SectionVA Caribbean Healthcare SystemSan JuanPuerto Rico
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Alonso López S, Manzano ML, Gea F, Gutiérrez ML, Ahumada AM, Devesa MJ, Olveira A, Polo BA, Márquez L, Fernández I, Cobo JCR, Rayón L, Riado D, Izquierdo S, Usón C, Real Y, Rincón D, Fernández-Rodríguez CM, Bañares R. A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis. Hepatology 2020; 72:1924-1934. [PMID: 33022803 DOI: 10.1002/hep.31588] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antiviral Agents/therapeutic use
- Biomarkers, Tumor/blood
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Disease Progression
- Elasticity Imaging Techniques
- Female
- Follow-Up Studies
- Hepacivirus/isolation & purification
- Hepatitis C, Chronic/blood
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Liver/diagnostic imaging
- Liver/pathology
- Liver Cirrhosis/blood
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Liver Neoplasms/blood
- Liver Neoplasms/epidemiology
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Male
- Middle Aged
- Retrospective Studies
- Risk Assessment/methods
- Risk Factors
- Sustained Virologic Response
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Affiliation(s)
- Sonia Alonso López
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | | | - Francisco Gea
- Liver Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | - María José Devesa
- Gastroenterology Unit, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Antonio Olveira
- Hepatology Unit, Hospital Universitario La Paz, Madrid, Spain
| | - Benjamin Arturo Polo
- Gastroenterology Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Laura Márquez
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | - Laura Rayón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Daniel Riado
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - Sonia Izquierdo
- Gastroenterology Unit, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Clara Usón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Yolanda Real
- Gastroenterology Unit, Hospital Universitario La Princesa Madrid, Madrid, Spain
| | - Diego Rincón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Conrado M Fernández-Rodríguez
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain
- Universidad Rey Juan Carlos Madrid, Madrid, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Wang YK, Lee WP, Wang YW, Huang YH, Hou MC, Chang YL, Lan KH. Precipitating factors causing hyperbilirubinemia during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir. J Chin Med Assoc 2020; 83:1071-1078. [PMID: 33273269 DOI: 10.1097/jcma.0000000000000429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Hepatic decompensation is a fatal on-treatment side effect during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Prompt bilirubin testing can reveal hepatic failure in susceptible patients, and clinical parameters precipitating early elevation of bilirubin can warn clinicians to avoid PrOD prescription. METHODS This retrospective study included 169 Hepatitis C virus (HCV)-genotype 1b patients who underwent a 12-week course of PrOD with or without ribavirin. Laboratory data underwent χ analysis with Fisher's exact test to determine the precipitating factors causing hyperbilirubinemia in patients who had received 1 week of treatment. RESULTS Sustained viral response was achieved in 164 patients (97.0%). Total bilirubin was ≥2 mg/dL (21.3%) in 36 patients after 1 week of treatment. Pretreatment white blood cell (WBC) <4500/µL and platelet <100,000/µL correlated with total bilirubin ≥2 mg/dL (relative risk [RR]: 21.64, 95% CI: 5.23-89.64, p < 0.001) after 1 week of treatment. Pretreatment platelet ≥100 000/µL and WBC <4500/µL correlated with direct bilirubin ≥0.45 mg/dL (RR: 6.56, 95% CI: 1.42-30.38, p = 0.016) and indirect bilirubin ≥0.6 mg/dL (RR: 4.77, 95% CI: 1.03-22.15, p = 0.046). Pretreatment platelet <100,000/µL with F3/F4 fibrosis correlated with first week total bilirubin ≥2 mg/dL (RR: 3.57, 95% CI: 1.35-9.09, p = 0.010). CONCLUSION PrOD is an effective antiviral regimen for HCV genotype 1b patients. Total bilirubin ≥2 mg/dL after 1 week of treatment serves as an early warning of irreversible progression toward hepatic decompensation, and the current study provides a guide by which to monitor chronic hepatitis C patients undergoing PrOD treatment.
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Affiliation(s)
- Yi-Kai Wang
- Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Pharmacy, National Yang-Ming University Hospital, Yilan, Taiwan, ROC
| | - Wei-Ping Lee
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ying-Wen Wang
- Healthcare Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yuh-Lih Chang
- Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Keng-Hsin Lan
- Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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Leuştean A, Popescu C, Nichita L, Tilişcan C, Aramă V. Dynamics of APRI and FIB-4 in HCV cirrhotic patients who achieved SVR after DAA therapy. Exp Ther Med 2020; 21:99. [PMID: 33363610 PMCID: PMC7725022 DOI: 10.3892/etm.2020.9531] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 09/25/2020] [Indexed: 02/07/2023] Open
Abstract
There are limited data available on the regression of fibrosis in hepatitis C virus (HCV) patients who have achieved sustained virologic response (SVR) after interferon-free treatments. Moreover, a perfect method for assessing liver fibrosis and its dynamics has not been established yet. The main objective of this study was to evaluate the dynamics of aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores in patients with HCV who registered SVR. We performed ROC curve analysis to evaluate the diagnostic performance of APRI and FIB-4 scores in determining the presence of cirrhosis in comparison to FibroTest. In total 251 patients were enrolled: 164 cirrhotic and 83 non-cirrhotic patients, and they were evaluated at baseline, at 6 and at 12 months post-end of treatment (EOT). In the cirrhotic group, at baseline, there was a weak but statistically significant correlation between APRI and FibroTest (τ=0.173, P=0.001), as well as between FIB-4 and FibroTest (τ=0.265, P<0.001). At the 6-month follow-up, APRI no longer correlated with FibroTest (τ=0.144, P=0.057), while FIB-4 was correlated (τ=0.256, P=0.001). The same pattern was shown at 12 months post-EOT. Between baseline and the 6-month evaluation, there was a significant decrease in APRI (P<0.001) and FIB-4 (P<0.001) scores, but for the next follow-up period, there was no reduction. In the non-cirrhotic group, APRI and FIB-4 did not correlate with the FibroTest value at any of the evaluation times. There was a significant difference between baseline and the 6-month visit for APRI (P=0.01) and for FIB-4 (P=0.014). The areas under the receiver operating characteristics curve (AUROCs) for the presence of cirrhosis compared with FibroTest for APRI and FIB-4 were 0.682 [95% confidence interval (CI), 0.613-0.752] and 0.693 (95% CI 0.625-0.76). Both APRI and FIB-4 prove to be easy, quick and inexpensive tools for screening HCV cirrhosis, with moderate diagnostic accuracy and FIB-4 can be useful for monitoring patients post-EOT.
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Affiliation(s)
- Anca Leuştean
- Department of Infectious Diseases, Faculty of Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Third Clinical Department, 'Prof. Dr. Matei Bals' National Institute for Infectious Diseases, 021105 Bucharest, Romania
| | - Cristina Popescu
- Department of Infectious Diseases, Faculty of Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Third Clinical Department, 'Prof. Dr. Matei Bals' National Institute for Infectious Diseases, 021105 Bucharest, Romania
| | - Luciana Nichita
- Department of Pathology, Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Pathology, Colentina University Hospital, 020125 Bucharest, Romania
| | - Cătălin Tilişcan
- Third Clinical Department, 'Prof. Dr. Matei Bals' National Institute for Infectious Diseases, 021105 Bucharest, Romania.,Department of Pathophysiology and Immunology, Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Victoria Aramă
- Department of Infectious Diseases, Faculty of Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Third Clinical Department, 'Prof. Dr. Matei Bals' National Institute for Infectious Diseases, 021105 Bucharest, Romania
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Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment. Surg Oncol 2020; 36:42-50. [PMID: 33307490 DOI: 10.1016/j.suronc.2020.11.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 11/15/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.
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Semmo N, Müllhaupt B, Ruckstuhl L, Magenta L, Clerc O, Torgler R, Semela D. A prospective, multicenter, post-marketing observational study to measure the quality of life of HCV genotype 1 infected, treatment naïve patients suffering from fatigue and receiving 3D regimen: The HEMATITE study. PLoS One 2020; 15:e0241267. [PMID: 33147283 PMCID: PMC7641439 DOI: 10.1371/journal.pone.0241267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 10/08/2020] [Indexed: 01/27/2023] Open
Abstract
Aim Fatigue is the most commonly reported symptom of Hepatitis C Virus (HCV) infected patients and severely impacts their quality of life. The aim of this study was to measure the impact of 3D regimen treatment on the fatigue, daytime physical activity and sleep efficiency of HCV infected patients with fatigue. Methods HEMATITE was an observational, prospective, open-label, single-arm, Swiss multi-centric study in mono-infected HCV genotype 1 patients. The 28 week observation period comprised of 4 weeks preparation, 12 weeks treatment and 12 weeks follow-up. Fatigue was assessed using the fatigue severity scale (FSS) questionnaire. Patients with FSS ≥ 4 (clinically significant fatigue) were included. The activity tracker, ActiGraph GT9X Link®, was used to measure daytime physical activity and sleep efficiency. Outcome analysis was performed on a scaled down intention to treat (sdITT) population, which excluded patients with insufficient tracker data at all study visits and a modified ITT (mITT) population, which consisted of patients with complete tracker data at all study visits. Results Forty of 41 patients in the ITT population had a sustained virologic response 12 weeks post-treatment (SVR12). Mean baseline FSS score was 6.0 for the sdITT population and 5.9 for the mITT population and decreased from baseline to 12 weeks post-treatment by 2.6 (95% confidence interval [CI]: 2.1, 3.1) for the sdITT (n = 37) population and 2.8 (95% CI: 2.2, 3.4) for the mITT (n = 24) population. Mean daytime physical activity or sleep efficiency did not change considerably over the course of the study. Conclusion Measurement by the activity tracker of mean day time physical activity did not show a considerable change from baseline to SVR12 upon treatment with 3D regimen. Nevertheless, a reduction of fatigue as assessed with the validated fatigue severity scale (FSS) was observed, suggesting a causative role of HCV in this extrahepatic manifestation. Trial registration ClinicalTrials.gov identifier:NCT03002818.
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Affiliation(s)
- Nasser Semmo
- Hepatology, Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Beat Müllhaupt
- Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | | | | | - Olivier Clerc
- Infectious Diseases Department, Hospital Pourtalès, Neuchâtel, Switzerland
| | | | - David Semela
- Division of Gastroenterology, Kantonsspital St. Gallen, St. Gallen, Switzerland
- * E-mail:
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Dultz G, Shimakami T, Schneider M, Murai K, Yamane D, Marion A, Zeitler TM, Stross C, Grimm C, Richter RM, Bäumer K, Yi M, Biondi RM, Zeuzem S, Tampé R, Antes I, Lange CM, Welsch C. Extended interaction networks with HCV protease NS3-4A substrates explain the lack of adaptive capability against protease inhibitors. J Biol Chem 2020; 295:13862-13874. [PMID: 32747444 PMCID: PMC7535904 DOI: 10.1074/jbc.ra120.013898] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/26/2020] [Indexed: 12/20/2022] Open
Abstract
Inhibitors against the NS3-4A protease of hepatitis C virus (HCV) have proven to be useful drugs in the treatment of HCV infection. Although variants have been identified with mutations that confer resistance to these inhibitors, the mutations do not restore replicative fitness and no secondary mutations that rescue fitness have been found. To gain insight into the molecular mechanisms underlying the lack of fitness compensation, we screened known resistance mutations in infectious HCV cell culture with different genomic backgrounds. We observed that the Q41R mutation of NS3-4A efficiently rescues the replicative fitness in cell culture for virus variants containing mutations at NS3-Asp168 To understand how the Q41R mutation rescues activity, we performed protease activity assays complemented by molecular dynamics simulations, which showed that protease-peptide interactions far outside the targeted peptide cleavage sites mediate substrate recognition by NS3-4A and support protease cleavage kinetics. These interactions shed new light on the mechanisms by which NS3-4A cleaves its substrates, viral polyproteins and a prime cellular antiviral adaptor protein, the mitochondrial antiviral signaling protein MAVS. Peptide binding is mediated by an extended hydrogen-bond network in NS3-4A that was effectively optimized for protease-MAVS binding in Asp168 variants with rescued replicative fitness from NS3-Q41R. In the protease harboring NS3-Q41R, the N-terminal cleavage products of MAVS retained high affinity to the active site, rendering the protease susceptible for potential product inhibition. Our findings reveal delicately balanced protease-peptide interactions in viral replication and immune escape that likely restrict the protease adaptive capability and narrow the virus evolutionary space.
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Affiliation(s)
- Georg Dultz
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Tetsuro Shimakami
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Markus Schneider
- Center for Integrated Protein Science Munich (CIPSM) at the Department of Life Sciences, Technical University Munich, Freising-Weihenstephan, Germany
| | - Kazuhisa Murai
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Daisuke Yamane
- Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
| | - Antoine Marion
- Center for Integrated Protein Science Munich (CIPSM) at the Department of Life Sciences, Technical University Munich, Freising-Weihenstephan, Germany
| | - Tobias M Zeitler
- Center for Integrated Protein Science Munich (CIPSM) at the Department of Life Sciences, Technical University Munich, Freising-Weihenstephan, Germany
| | - Claudia Stross
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Christian Grimm
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Rebecca M Richter
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Katrin Bäumer
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - MinKyung Yi
- Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
| | - Ricardo M Biondi
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany; Biomedicine Research Institute of Buenos Aires - CONICET - Partner Institute of the Max Planck Society, Buenos Aires, Argentina
| | - Stefan Zeuzem
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany; University Center for Infectious Diseases, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Robert Tampé
- Institute of Biochemistry, Biocenter and Cluster of Excellence-Macromolecular Complexes, Goethe University Frankfurt, Frankfurt, Germany
| | - Iris Antes
- Center for Integrated Protein Science Munich (CIPSM) at the Department of Life Sciences, Technical University Munich, Freising-Weihenstephan, Germany
| | - Christian M Lange
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany
| | - Christoph Welsch
- Department of Internal Medicine 1, Goethe University Hospital Frankfurt, Frankfurt, Germany; University Center for Infectious Diseases, Goethe University Hospital Frankfurt, Frankfurt, Germany.
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Jie Y, Lin C, Yuan J, Zhao Z, Guan Y, Zhou Y, Zhou X, Zhong B, Ye Y, Zhang L, Tao L, Li J, Zhang X, Chong Y. Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China: A multicenter prospective observational study. LIVER RESEARCH 2020. [DOI: 10.1016/j.livres.2020.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
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Tanaka S, Shinkawa H, Tamori A, Takemura S, Takahashi S, Amano R, Kimura K, Ohira G, Kawada N, Kubo S. Surgical outcomes for hepatocellular carcinoma detected after hepatitis C virus eradiation by direct-acting antivirals. J Surg Oncol 2020; 122:1543-1552. [PMID: 32856301 DOI: 10.1002/jso.26184] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/13/2020] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.
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Affiliation(s)
- Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shinji Takahashi
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ryosuke Amano
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenjiro Kimura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Go Ohira
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Mathur P, Comstock E, Makuza JD, Emmanuel B, Sebeza J, Kiromera A, Wilson E, Kattakuzhy S, Nelson A, Kottilil S, Riedel DJ. Implementation of a unique hepatitis C care continuum model in Rwanda. J Public Health (Oxf) 2020; 41:e203-e208. [PMID: 29982813 DOI: 10.1093/pubmed/fdy115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/22/2018] [Accepted: 06/13/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND There has been an evolution in the treatment of chronic hepatitis C (HCV) due to highly effective direct-acting antivirals, however, restriction of treatment to medical specialists hinders escalation of HCV treatment. This is particularly true in resource-limited settings (RLS), which disproportionately represent the burden of HCV worldwide. The ASCEND study in Washington, DC, demonstrated that complete task-shifting can safely and effectively overcome a low provider-to-patient ratio and expand HCV treatment. However, this model has not been applied internationally to RLS. METHOD The validated ASCEND model was translated to an international clinical program in Kigali, Rwanda, aimed at training general medicine providers on HCV management and obtaining HCV prevalence data. RESULTS The didactic training program administered to 11 new HCV providers in Rwanda increased provider's knowledge about HCV management. Through the training program, 26% of patients seen during the follow-up period were screened for HCV and a prevalence estimate of 2% was ascertained. Of these patients, 30% were co-infected with hepatitis B. CONCLUSION The ASCEND paradigm can be successfully implemented in RLS to escalate HCV care, in a self-sustaining fashion that educates more providers about HCV management, while increasing the public's awareness of HCV and access to treatment.
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Affiliation(s)
- Poonam Mathur
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Emily Comstock
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | | | - Benjamin Emmanuel
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | | | | | - Eleanor Wilson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Sarah Kattakuzhy
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Amy Nelson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - Shyamasundaran Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
| | - David J Riedel
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA
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Laursen TL, Sandahl TD, Kazankov K, George J, Grønbæk H. Liver-related effects of chronic hepatitis C antiviral treatment. World J Gastroenterol 2020; 26:2931-2947. [PMID: 32587440 PMCID: PMC7304101 DOI: 10.3748/wjg.v26.i22.2931] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/26/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.
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Affiliation(s)
- Tea L Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Thomas D Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney NSW 2145, Australia
- University of Sydney, Sydney NSW 2145, Australia
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Elbasvir/grazoprevir for hepatitis C virus genotype 1b East-Asian patients receiving hemodialysis. Sci Rep 2020; 10:9180. [PMID: 32513953 PMCID: PMC7280513 DOI: 10.1038/s41598-020-66182-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 05/12/2020] [Indexed: 11/26/2022] Open
Abstract
Data regarding the efficacy and tolerability of elbasvir/grazoprevir (EBR/GZR) for East-Asian hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. We prospectively recruited 40 HCV GT1b hemodialysis patients who received EBR/GZR for 12 weeks at 6 academic centers in Taiwan. The efficacy endpoints were sustained virologic response 12 weeks off-therapy (SVR12) by intention-to-treat (ITT) modified ITT (mITT) analyses. Patients’ baseline characteristics, early viral kinetics and HCV resistance-associated substitutions (RASs) at HCV non-structural 3 and 5 A (NS3 and NS5A) regions potentially affecting SVR12 were analyzed. The tolerability for EBR/GZR was also assessed. The SVR12 rates by ITT and mITT analyses were 95% (38 of 40 patients; 95% confidence interval (CI): 83.5–98.6%) and 100% (38 of 38 patients; 95% CI: 90.8–100%), respectively. Patients’ baseline characteristics, on-treatment viral decline, and baseline HCV RASs did not affect SVR12. All patients tolerated treatment well. Among 5 patients who had serious adverse events (AEs) including one death due to on-treatment suicide and the other death due to off-therapy acute myocardial infarction, none of these events were judged related to EBR/GZR. The common AEs included upper respiratory tract infection (7.5%), fatigue (5.0%) and anorexia (5.0%). Nine (22.5%) and 8 (20.0%) patients had on-treatment hemoglobin levels of 9.0–10.0 g/dL and 7.0–9.0 g/dL. Three (7.5%) patients had on-treatment elevated alanine aminotransferase (ALT) quotient > 2.5, in whom one (2.5%) had EBR/GZR-induced late ALT elevation. No patients developed hyperbilirubinemia or hepatic decompensation. In conclusion, treatment with EBR/GZR is effective and well-tolerated for East-Asian HCV GT1b patients receiving hemodialysis.
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Squires JE, Balistreri WF. Treatment of Hepatitis C: A New Paradigm toward Viral Eradication. J Pediatr 2020; 221:12-22.e1. [PMID: 32446469 DOI: 10.1016/j.jpeds.2020.02.082] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 01/27/2020] [Accepted: 02/28/2020] [Indexed: 12/18/2022]
Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh PA.
| | - William F Balistreri
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital, Cincinnati, OH
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47
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: part (I) general population. J Formos Med Assoc 2020; 119:1019-1040. [PMID: 32359879 DOI: 10.1016/j.jfma.2020.04.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) infection remains a major public health issue with high prevalence in Taiwan. Recently, the advent of direct-acting antiviral (DAA) agents, with higher efficacy, excellent safety profile, and truncated treatment duration, has revolutionized the paradigm of hepatitis C treatment and made HCV elimination possible. To provide timely guidance for optimal hepatitis C management, the Taiwan Association for the Study of the Liver (TASL) established an expert panel to publish a 2-part consensus statement on the management of hepatitis C in the DAA era. After comprehensive literature review and a consensus meeting, patient-oriented, genotype-guided recommendations on hepatitis C treatment for the general and special populations have been provided based on the latest indications and scientific evidence. In the first part of this consensus, we present the epidemiology and treatment situation of hepatitis C in Taiwan, the development of DAA, pre-treatment evaluation, post sustained virologic response (SVR) monitoring, and most importantly the treatment recommendations for the general population with compensated liver disease. The second part will focus on the treatment recommendations for the special populations.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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Rinaldi L, Nevola R, Franci G, Perrella A, Corvino G, Marrone A, Berretta M, Morone MV, Galdiero M, Giordano M, Adinolfi LE, Sasso FC. Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics. Cancers (Basel) 2020; 12:1351. [PMID: 32466400 PMCID: PMC7352473 DOI: 10.3390/cancers12061351] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/18/2020] [Accepted: 05/20/2020] [Indexed: 02/05/2023] Open
Abstract
Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short-medium term but reduces the risk of HCC in the medium-long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects' post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
| | - Gianluigi Franci
- Department of Medicine, Surgery, Dentistry, University of Salerno “Scuola Medica Salernitana”, 84100 Salerno, Italy;
| | - Alessandro Perrella
- Immunological and Neurological Infectious Diseases, Cotugno Hospital, 80100 Naples, Italy;
| | - Giusy Corvino
- Department of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (G.C.); (M.V.M.); (M.G.)
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
| | - Massimiliano Berretta
- Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, 33081 Aviano, Italy;
| | - Maria Vittoria Morone
- Department of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (G.C.); (M.V.M.); (M.G.)
| | - Marilena Galdiero
- Department of Experimental Medicine, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (G.C.); (M.V.M.); (M.G.)
| | - Mauro Giordano
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “L. Vanvitelli”, 80100 Naples, Italy; (R.N.); (A.M.); (M.G.); (L.E.A.); (F.C.S.)
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Provider Perceptions of Hepatitis C Treatment Adherence and Initiation. Dig Dis Sci 2020; 65:1324-1333. [PMID: 31642008 PMCID: PMC8108400 DOI: 10.1007/s10620-019-05877-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 09/30/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Significant disparities in hepatitis C (HCV) treatment existed in the interferon treatment era, such that patients with mental health and substance use disorders were less likely to be treated. We aimed to evaluate whether these perceptions continue to influence HCV treatment decisions. METHODS We e-mailed HCV providers a survey to assess their perceptions of barriers to HCV treatment adherence and initiation. We assessed the frequency of perceived barriers and willingness to initiate HCV treatment in patients with these barriers. We identified a group of providers more willing to treat patients with perceived barriers to adherence and determined the associated provider characteristics using Spearman's rho and Wilcoxon rank-sum tests. RESULTS A total of 103 providers (29%) responded to the survey. The most commonly endorsed perceived barriers to adherence were homelessness (65%), ongoing drug (58%), and ongoing alcohol use (33%). However, 90%, 68%, and 90% of providers were still willing to treat patients with these comorbidities, respectively. Ongoing drug use was the most common reason providers were never or rarely willing to initiate HCV treatment. Providers who were less willing to initiate treatment more frequently endorsed patient-related determinants of adherence, while providers who were more willing to initiate treatment more frequently endorsed provider-based barriers to adherence (e.g., communication). CONCLUSIONS Most responding providers were willing to initiate HCV treatment in all patients, despite the presence of perceived barriers to adherence or previous contraindications to interferon-based treatments. Ongoing substance use remains the most prominent influencer in the decision not to treat.
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Poordad F, Castro RE, Asatryan A, Aguilar H, Cacoub P, Dieterich D, Marinho RT, Carvalho A, Siddique A, Hu YB, Charafeddine M, Bondin M, Khan N, Cohen DE, Felizarta F. Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials. J Viral Hepat 2020; 27:497-504. [PMID: 31954087 DOI: 10.1111/jvh.13261] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/27/2022]
Abstract
The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) were achieved regardless of presence or absence of cirrhosis.In this report, we assessed the long-term progression of liver disease and incidence of clinical outcomes up to 3 years of post-treatment follow-up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ-I and TOPAZ-II studies. Improvements were observed in liver disease markers including FIB-4, METAVIR and Child-Pugh scores as well as platelet counts. Clinical outcomes related to long-term progression of liver disease such as liver decompensation were infrequent (<1%). Hepatocellular carcinoma (HCC) occurred in 1.4% of cirrhotic patients.
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Affiliation(s)
- Fred Poordad
- The Texas Liver Institute, University of Texas Health, San Antonio, TX, USA
| | - RuiSarmento E Castro
- Hospital Centre of Porto (Portugal), Biomedical School of Medicine (University of Porto), Porto, Portugal
| | | | | | - Patrice Cacoub
- Department of Internal Medicine and Clinical Immunology, AP HP, Groupe hospitalier La Pitié-Salpêtrière, Paris, France.,Sorbonne Universités, UPMC Univ, Paris, France
| | - Douglas Dieterich
- Mount Sinai School of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Rui Tato Marinho
- Gastroenterology and Hepatology Department, Centro Hospitalar de Universitário Lisboa Norte and Medical School of Lisbon, University of Lisbon, Lisbon, Portugal
| | - Armando Carvalho
- Internal Medicine Department, Hospitais da Universidade de Coimbra (Centro Hospitalar e Universitário de Coimbra), Coimbra, Portugal
| | - Asma Siddique
- Virginia Mason Hospital and Seattle Medical Center, Seattle, WA, USA
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