|
1
|
Choi JW, Kwak JY, Lee SS, Kim HG, Son HJ, Jeon H, Kim HJ, Cha RR, Lee JM, Kim HJ. Clinical Features of Hepatitis C Virus-related Acute-on-chronic Liver Failure in a Korean Population. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2022; 80:169-176. [DOI: 10.4166/kjg.2022.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/30/2022] [Accepted: 06/01/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Jung Woo Choi
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ji Yoon Kwak
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Hyun-gyu Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ho Jin Son
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hankyu Jeon
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hee Jin Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
| | - Ra Ri Cha
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| |
Collapse
|
|
2
|
Spanoudaki A, Papadopoulos N, Trifylli EM, Koustas E, Vasileiadi S, Deutsch M. Hepatitis C Virus Infections in Patients with Hemophilia: Links, Risks and Management. J Multidiscip Healthc 2022; 15:2301-2309. [PMID: 36247180 PMCID: PMC9562981 DOI: 10.2147/jmdh.s363177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 10/05/2022] [Indexed: 11/05/2022] Open
Abstract
Haemophilia is a rare, hereditary bleeding disorder. Clotting factor concentrates were a revolutionary treatment which changed the life of people with haemophilia. However, early generation of clotting factor concentrates, without viral inactivation procedures in the manufacturing process, led to an increased risk of transmission of blood-borne viral infections, mainly due to hepatitis C virus and human immunodeficiency virus. As only 20% of HCV-infected patients clear the infection naturally, chronic HCV infection constitutes a serious health problem and a major cause of chronic liver disease in this group of patients. Fortunately, the use of viral inactivation procedures in the plasma-derived factor concentrates manufacturing process and the availability of alternative treatment options, led to a significant reduction of transfusion-associated viral infections. The advent of multiple, orally administrated, highly effective direct-acting antivirals (DAAs) is changing the natural history of HCV infection in patients with haemophilia as these drugs have an excellent safety profile and achieve very high sustained virological response rates, similar to the general population. Eradication of HCV-infection in patients with haemophilia is feasible via micro-elimination projects.
Collapse
Affiliation(s)
- Anastasia Spanoudaki
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Papadopoulos
- 1st Department of Internal Medicine, 417 Army Share Fund Hospital, Athens, Greece,Correspondence: Nikolaos Papadopoulos, 1st Department of Internal Medicine, 417 Army Share Fund Hospital, Ravine 14-16 str, Athens, 11521, Greece, Tel +302117100671, Email
| | - Eleni-Myrto Trifylli
- 1st Department of Internal Medicine, 417 Army Share Fund Hospital, Athens, Greece
| | - Evangelos Koustas
- 1st Department of Internal Medicine, 417 Army Share Fund Hospital, Athens, Greece
| | - Sofia Vasileiadi
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| | - Melanie Deutsch
- 2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Medical School of National & Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
3
|
Kumar M, George R, Vaithiyam V, Sakhuja P, Dahale AS, Dayal A, Dalal A, Sonika U, Sachdeva S, Kumar A. Enhanced Liver Fibrosis Score: Is It Useful for Evaluation of Fibrosis Severity in Chronic Hepatitis C Infection? Cureus 2022; 14:e21168. [PMID: 35165618 PMCID: PMC8831389 DOI: 10.7759/cureus.21168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2022] [Indexed: 11/05/2022] Open
Abstract
Introduction: The assessment of liver fibrosis is important in patients with chronic hepatitis C (CHC). In recent years, non-invasive tests like enhanced liver fibrosis (ELF) have been developed as an alternative to liver biopsy for estimating the severity of liver fibrosis. Therefore, we aimed to assess whether the ELF score can be used for fibrosis severity estimation using liver biopsy as the gold standard. Materials and methods: Forty-nine patients with CHC were enrolled in this study. Liver biopsy, ELF assessment, and transient elastography (TE) were performed in all patients, and severity of fibrosis on histopathology was assessed by meta-analysis of histological data in viral hepatitis (METAVIR) score. In addition, the diagnostic performance of ELF was evaluated by receiver operator characteristic curve (ROC) analyses, and liver biopsy histopathology was taken as the gold standard for the severity of liver fibrosis. Results: The area under receiver operator characteristic curve (AUROC) for significant fibrosis of ELF score was 0.64 (95% confidence interval {CI}, 0.48-0.79) and of TE was 0.85 (95% CI, 0.73-0.96). The AUROC for advance fibrosis of ELF was 0.77 (95% CI, 0.57-0.97) and TE was 0.98 (95% CI, 0.94-1.0). The calculated cut-offs of ELF overestimated fibrosis in 53.06% (26/49) of patients and underestimated fibrosis in 6.12% (3/49) patients. AUROC of TE was significantly better than ELF for diagnosis of significant fibrosis (p=0.004) and advanced fibrosis (p=0.034). Conclusion: The ELF score can be used for estimating the severity of fibrosis but it is inferior to TE in estimating liver fibrosis severity.
Collapse
|
|
4
|
Delgado ME, Cárdenas BI, Farran N, Fernandez M. Metabolic Reprogramming of Liver Fibrosis. Cells 2021; 10:3604. [PMID: 34944111 PMCID: PMC8700241 DOI: 10.3390/cells10123604] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/13/2021] [Accepted: 12/17/2021] [Indexed: 12/12/2022] Open
Abstract
Liver fibrosis is an excessive and imbalanced deposition of fibrous extracellular matrix (ECM) that is associated with the hepatic wound-healing response. It is also the common mechanism that contributes to the impairment of the liver function that is observed in many chronic liver diseases (CLD). Despite the efforts, no effective therapy against fibrosis exists yet. Worryingly, due to the growing obesity pandemic, fibrosis incidence is on the rise. Here, we aim to summarize the main components and mechanisms involved in the progression of liver fibrosis, with special focus on the metabolic regulation of key effectors of fibrogenesis, hepatic stellate cells (HSCs), and their role in the disease progression. Hepatic cells that undergo metabolic reprogramming require a tightly controlled, fine-tuned cellular response, allowing them to meet their energetic demands without affecting cellular integrity. Here, we aim to discuss the role of ribonucleic acid (RNA)-binding proteins (RBPs), whose dynamic nature being context- and stimuli-dependent make them very suitable for the fibrotic situation. Thus, we will not only summarize the up-to-date literature on the metabolic regulation of HSCs in liver fibrosis, but also on the RBP-dependent post-transcriptional regulation of this metabolic switch that results in such important consequences for the progression of fibrosis and CLD.
Collapse
Affiliation(s)
- M. Eugenia Delgado
- IDIBAPS Biomedical Research Institute, University of Barcelona, 08036 Barcelona, Spain; (B.I.C.); (N.F.)
| | | | | | - Mercedes Fernandez
- IDIBAPS Biomedical Research Institute, University of Barcelona, 08036 Barcelona, Spain; (B.I.C.); (N.F.)
| |
Collapse
|
|
5
|
Königshofer P, Brusilovskaya K, Petrenko O, Hofer BS, Schwabl P, Trauner M, Reiberger T. Nuclear Receptors in Liver Fibrosis. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166235. [PMID: 34339839 DOI: 10.1016/j.bbadis.2021.166235] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/18/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022]
Abstract
Nuclear receptors are ligand-activated transcription factors that regulate gene expression of a variety of key molecular signals involved in liver fibrosis. The primary cellular driver of liver fibrogenesis are activated hepatic stellate cells. Different NRs regulate the hepatic expression of pro-inflammatory and pro-fibrogenic cytokines that promote the transformation of hepatic stellate cells into fibrogenic myofibroblasts. Importantly, nuclear receptors regulate gene expression circuits that promote hepatic fibrogenesis and/or allow liver fibrosis regression. In this review, we highlight the direct and indirect influence of nuclear receptors on liver fibrosis, with a focus on hepatic stellate cells, and discuss potential therapeutic effects of nuclear receptor modulation in regard to anti-fibrotic and anti-inflammatory effects. Further research on nuclear receptors-related signaling may lead to the clinical development of effective anti-fibrotic therapies for patients with liver disease.
Collapse
Affiliation(s)
- Philipp Königshofer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Ksenia Brusilovskaya
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Oleksandr Petrenko
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Benedikt Silvester Hofer
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
| |
Collapse
|
|
6
|
Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment. Int J Mol Sci 2021; 22:ijms22157961. [PMID: 34360721 PMCID: PMC8348577 DOI: 10.3390/ijms22157961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 11/29/2022] Open
Abstract
Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.
Collapse
|
|
7
|
Rockey DC, Friedman SL. Fibrosis Regression After Eradication of Hepatitis C Virus: From Bench to Bedside. Gastroenterology 2021; 160:1502-1520.e1. [PMID: 33529675 PMCID: PMC8601597 DOI: 10.1053/j.gastro.2020.09.065] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/01/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection and its complications have been the major cause of cirrhosis and its complications for several decades in the Western world. Until recently, treatment for HCV with interferon-based regimens was associated with moderate success but was difficult to tolerate. More recently, however, an arsenal of novel and highly effective direct-acting antiviral (DAA) drugs has transformed the landscape by curing HCV in a broad range of patients, including those with established advanced fibrosis, cirrhosis, comorbidities, and even those with complications of cirrhosis. Fibrosis is a dynamic process comprising both extracellular matrix deposition, as well as its degradation. With almost universal sustained virologic response (SVR) (ie, elimination of HCV), it is timely to explore whether HCV eradication can reverse fibrosis and cirrhosis. Indeed, fibrosis in several types of liver disease is reversible, including HCV. However, we do not know with certainty in whom fibrosis regression can be expected after HCV elimination, how quickly it occurs, and whether antifibrotic therapies will be indicated in those with persistent cirrhosis. This review summarizes the evidence for reversibility of fibrosis and cirrhosis after HCV eradication, its impact on clinical outcomes, and therapeutic prospects for directly promoting fibrosis regression in patients whose fibrosis persists after SVR.
Collapse
Affiliation(s)
- Don C Rockey
- The Medical University of South Carolina, Charleston, South Carolina.
| | - Scott L Friedman
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York
| |
Collapse
|
|
8
|
Chung JW, Choi HY, Ki M, Jang ES, Jeong SH. Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide, Population-Based Study. Gut Liver 2021; 15:295-306. [PMID: 32616682 PMCID: PMC7960981 DOI: 10.5009/gnl19387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 03/16/2020] [Accepted: 04/13/2020] [Indexed: 12/16/2022] Open
Abstract
Background/Aims Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients. Methods All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected. Results Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of "contraindicated medication" or "required dose-reduction/additional monitoring" was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen. Conclusions The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.
Collapse
Affiliation(s)
- Jung Wha Chung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hwa Young Choi
- National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
| | - Moran Ki
- National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea
| | - Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| |
Collapse
|
|
9
|
BAKIR A, GÜNEY M, ERDAL H, YAVUZ Ö, GÜNAL A, GÜLŞEN M, YAVUZ MT. Assessment of The Performances of Hepatitis C Virus Viral Markers, Age-Platelet Index and Aspartate aminotransferase to Alanine Aminotransferase Ratio Scores, in Predicting Liver Histopathology. TURKISH JOURNAL OF INTERNAL MEDICINE 2020. [DOI: 10.46310/tjim.825814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
|
|
10
|
Mohamed AA, Hemeda AA, Aziz RK, Abdel-Hakeem MS, Ali-Tammam M. Body mass index (BMI) and alpha-fetoprotein (AFP) level correlate with the severity of HCV-induced fibrosis in a cohort of Egyptian patients with chronic HCV. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2020. [DOI: 10.1186/s43094-020-00085-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Abstract
Background
Viral hepatitis is the seventh leading cause of mortality globally, and half of this mortality is attributed to hepatitis C virus (HCV). Egypt has the highest HCV prevalence worldwide, with an estimated 14.7% of the population being HCV-positive. HCV infection is the primary cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Liver fibrosis varies in severity during chronic HCV infection, and 10–20% of chronic hepatitis C (CHC) patients with severe fibrosis develop cirrhosis. The goal of this work was to assess the clinico-demographic predictors of severity of HCV-induced fibrosis in a cohort of Egyptian patients.
Results
A cohort of Egyptian patients with chronic HCV genotype 4a infection showed significant association between severe fibrosis stages and obesity, represented by a higher body mass index (BMI), low albumin level, high alpha-fetoprotein (AFP) level, low thyroid-stimulating hormone (TSH) level, and high alkaline phosphatase (ALP) level. Multivariate analysis delineated BMI, TSH, and ALP as independent significant variables that could predict the risk of fibrosis severity in HCV infections.
Conclusion
This study argues in favor of using the biomarker profile of CHC patients infected with HCV genotype 4a to identify patients at higher risk of developing severe fibrosis, which is a necessary first step towards precision medicine via patient stratification.
Collapse
|
|
11
|
Rezaee N, Babaeekhou L, Ghane M. Hepatitis C virus in Iran; transmission routes, growth in 3a genotype distribution, and lack of liver marker relation with genotypes. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2020; 25:96. [PMID: 33273941 PMCID: PMC7698380 DOI: 10.4103/jrms.jrms_482_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 02/24/2020] [Accepted: 05/27/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND The hepatitis C virus (HCV) outbreak in Iran is increasing. This study investigated the dissemination and transmission routes of HCV genotypes in different regions of Iran. The relationship between serum biochemical markers and viral genotypes was also assessed to find whether liver enzymes level can be considered as the markers for HCV genotypes. MATERIALS AND METHODS HCV-infected patients from different provinces of Iran (from August 2017 to March 2019) were enrolled. Nested reverse transcriptase polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time PCR were used to discover the genotypes. The infection transmission routes in the study population were investigated and recorded. Serum samples with equal viral loud from the patients without other liver disorders were recruited to explore the association between the genotypes and the liver biochemical markers. RESULTS One thousand serum samples positive for the HCV genome were recruited. Genotype 3a was the most prevalent in the north, while genotype 1a was dominant at the center. In total, genotype 3a was the dominant genotype closely followed by 1a. Needle sharing by addicts was the most common transmission way of infection in Iran. This way was also the most for genotype 3a dissemination, and genotype 1a was transmitted mostly between family members. No significant association (P > 0.05) was observed between biochemical marker titers and HCV genotypes. CONCLUSION A shift in the distribution profile of HCV genotypes, related to the transmission routes, has happened over time. Public awareness of the main routes of HCV transmission can break the cycle of transmission. Liver enzyme values in HCV-infected patients showed no relation with genotypes and only represented hepatocellular dysfunction.
Collapse
Affiliation(s)
- Nastaran Rezaee
- Department of Biology, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran
| | - Laleh Babaeekhou
- Department of Biology, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran
| | - Maryam Ghane
- Department of Biology, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran
| |
Collapse
|
|
12
|
Diniz KGD, Vieira DA, Colosimo EA, Coelho MPP, Bering T, Teixeira R, Correia MITD, Rocha GA, Silva LD. Derivation and validation of a simple anthropometric equation to predict fat-free mass in patients with chronic hepatitis C. Clin Nutr 2020; 40:1281-1288. [PMID: 32861484 DOI: 10.1016/j.clnu.2020.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/11/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Loss of skeletal muscle mass is very common in chronic liver diseases and affects 30.0-70.0% of the patients with cirrhosis. Given the relevance of muscle wasting in hepatic diseases, a practical screening tool for earlier detection of skeletal muscle mass loss is of utmost significance. AIMS To develop and validate a simple anthropometric prediction equation for fat-free mass estimation by using Bioelectrical Impedance Analysis (BIA) as a reference method in patients with chronic hepatitis C (CHC). METHODS We prospectively, included 209 CHC patients, randomly allocated into two groups, 158 patients in a development model (derivation sample) and 51 patients in a validation group (validation sample). Predictive equations were developed using backward stepwise multiple regression and the most adequate and simplest derived predictive equation was further explored for agreement and bias in the validation sample. The accuracy of the predictive equation was evaluated using the coefficient of determination (R2). RESULTS The predictive equation with an optimal R2 was Fat-Free Mass (Kg) = Sex × 0.17 + Height (m) × 16.83 + Weight (Kg) × 0.62 + Waist Circumference (cm) × (-0.15) + Weight (Kg) × Sex × (-0.30) + Sex × Waist Circumference (cm) × 0.14-6.23; where sex = 1 for female and 0 for male. R2 = 0.93, standard error of the estimate = 2.6 Kg and coefficient of variation = 20.0%, p < 0.001. CONCLUSIONS Our developed and cross-validated anthropometric prediction equation for fat-free mass estimation by using BIA attained a high coefficient of determination, a low standard error of the estimate, and lowermost coefficient of variation. This study indicates that predictive equations may be reliable and useful alternative methods for clinical evaluation of fat-free mass in patients with CHC.
Collapse
Affiliation(s)
- Kiara Gonçalves Dias Diniz
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Diego Alves Vieira
- Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Enrico Antonio Colosimo
- Department of Statistics, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Marta Paula Pereira Coelho
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Tatiana Bering
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Food and Nutrition, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Mato Grosso, Brazil
| | - Rosangela Teixeira
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | | | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Luciana Diniz Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
| |
Collapse
|
|
13
|
Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis. HPB (Oxford) 2020; 22:900-910. [PMID: 31734238 DOI: 10.1016/j.hpb.2019.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/15/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND To address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT). METHODS All patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). RESULTS The LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062). CONCLUSION This was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.
Collapse
|
|
14
|
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.
Collapse
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
| |
Collapse
|
|
15
|
Has Increased Rollout of Direct Acting Antiviral Therapy Decreased the Burden of Late Presentation and Advanced Liver Disease in Patients Starting Hepatitis C Virus Therapy in Germany? J Clin Gastroenterol 2020; 54:192-199. [PMID: 30789853 DOI: 10.1097/mcg.0000000000001189] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
GOALS AND BACKGROUND International guidelines recommend prioritized treatment initiation in hepatitis C virus (HCV)-infected patients with advanced liver disease. We aimed to evaluate whether the widespread usage of direct acting antivirals (DAAs) has led to a decrease in late presentation for care. STUDY Data derived from the multicenter German Hepatitis C Cohort (GECCO) was analyzed. Treatment naive HCV-infected patients initiating DAA-based treatment between January 2014 and September 2017 were included. Advanced liver disease was defined by aspartate aminotransferase to platelet ratio index score ≥1.5, METAVIR≥F3, or FibroScan ≥9.5 kPa. Period prevalence and risk factors for late presentation were evaluated. RESULTS Six hundred fifty-three HCV-monoinfected and 210 HIV/HCV-coinfected patients (mean age, 48.6±12.7 y; 65.5% male) were included. Overall 32.5% of patients had advanced liver disease. In 2014 39.4% of patients presented with advanced liver disease, decreasing to 30.1%, 34.4%, and 26.4% in the years 2015, 2016, and 2017 (P=0.057), respectively. Patients with and without advanced liver disease differed in age (P<0.0001), CD4 ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P<0.001), and time since diagnosis (P=0.007). In the multivariable binary logistic regression analysis GT3, age above 45 years and being diagnosed >2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease. CONCLUSIONS Overall 32.5% of patients presented with advanced liver disease. We observed a trend toward a lower proportion of patients starting treatment late.GT3, age, years since HCV diagnosis and HCV transmission route were identified as risk factors for presentation with advanced liver disease.
Collapse
|
|
16
|
Gupta T, Aggarwal HK, Goyal S, Singh V. Prediction of Cirrhosis in Patients with Chronic Hepatitis C by Genotype 3. Euroasian J Hepatogastroenterol 2020; 10:7-10. [PMID: 32742965 PMCID: PMC7376599 DOI: 10.5005/jp-journals-10018-1311] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Genotype 3 increases fibrosis in chronic hepatitis C (CHC). Aim To evaluate the effect of the hepatitis C virus (HCV) genotype on prevalence and severity of liver disease in CHC. Materials and methods Nine hundred and forty-nine individuals with positive anti-HCV from June 2016 to May 2017 were enrolled in the study. We compared biochemical and hematological parameters, HCV RNA load, transient elastography, and ultrasound, in genotype 3 and nongenotype 3 patients. Cirrhosis was diagnosed in patients with liver stiffness measurement (LSM) ≥13 kPa. Results Out of 835 CHC patients, overall, genotype 3 had higher LSM (11.3 vs 7.62, p = 0.01), higher aspartate aminotransferase (AST) (88.4 vs 68.6, p = 0.02), and low platelets (228.4 vs 261, p = 0.03) with higher prevalence of cirrhosis (115/415 vs 25/245, p = 0.01) than nongenotype 3. However, decompensation rates were not significantly different between two groups (32/115 vs 7/25, p = 0.98). The subgroup analysis revealed that cirrhotic genotype 3 had advanced age (50 vs 35, p < 0.01), male predominance, and higher AST (74.4 vs 57, p = 0.01) as compared to noncirrhotic genotype 3 patients. On multivariate analysis, age and AST values were higher in cirrhotic than noncirrhotic genotype 3 patients. Conclusion Genotype 3 patients have higher prevalence of cirrhosis and fibrosis compared to nongenotype 3 patients; however, decompensation was not different between two groups. How to cite this article Gupta T, Aggarwal HK, Goyal S, et al. Prediction of Cirrhosis in Patients with Chronic Hepatitis C by Genotype 3. Euroasian J Hepato-Gastroenterol 2020;10(1):7–10.
Collapse
Affiliation(s)
- Tarana Gupta
- Department of Medicine, Post Graduate Institute of Medical Sciences, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India
| | - Hari K Aggarwal
- Department of Medicine, Post Graduate Institute of Medical Sciences, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India
| | | | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
17
|
Loo N, Lawitz E, Alkhouri N, Wells J, Landaverde C, Coste A, Salcido R, Scott M, Poordad F. Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in real world hepatitis C patients. World J Gastroenterol 2019; 25:2229-2239. [PMID: 31143073 PMCID: PMC6526152 DOI: 10.3748/wjg.v25.i18.2229] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 03/21/2019] [Accepted: 04/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The hepatitis C virus (HCV) NS5A inhibitor ABT-267 (ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450 (paritaprevir, PTV), the CYP3A inhibitor ritonavir (r) and the non-nucleoside NS5B polymerase inhibitor ABT-333 (dasabuvir, DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1 (GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures. AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials. METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1 (GT1a, GT1b or GT1a/1b). Patients were treatment-naïve or previously failed a regimen including pegylated interferon/RBV +/- telaprevir, boceprevir, or simeprevir. One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/- RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment. RESULTS Many of the patients studied had comorbidities (44.2% hypertensive, 33.7% obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority (88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue (12%), headache (10%), insomnia (9%) and diarrhea (8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all (98%) patients were treatment compliant. CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV is highly effective and tolerable and results in better mental and physical health following treatment.
Collapse
Affiliation(s)
- Nicole Loo
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Eric Lawitz
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Naim Alkhouri
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Jennifer Wells
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Carmen Landaverde
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Angie Coste
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Rossalynn Salcido
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Michael Scott
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| | - Fred Poordad
- Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
| |
Collapse
|
|
18
|
Hepatitis C Infection in Hemodialysis Patients. CURRENT HEALTH SCIENCES JOURNAL 2019; 44:107-112. [PMID: 30746156 PMCID: PMC6320456 DOI: 10.12865/chsj.44.02.02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/27/2018] [Indexed: 01/01/2023]
Abstract
Three centuries after the identification of hepatitis C virus (HCV), specialized literature has outlined the epidemiology, viral kinetics and clinical manifestations of this infection. A major cause of morbidity-mortality in patients with renal transplantation and in hemodialysis patients is HCV infection. In high seroprevalence countries, internal accounts are not uniform. The European trend is to decrease the incidence and prevalence of HCV in hemodialysis patients. In Europe, the prevalence of HCV infection among hemodialysis patients tends to be higher than that of the general population, but it is variable by region. Some studies indicate a decrease in incidence in parallel with prevalence in dialysis centers over the last 10 years, while others maintain a high incidence. In some countries, as is the case with Romania, both prevalence and incidence remain high, with the major route of transmission being nosocomial, probably due to limited resources for a rapidly growing dialyzed population. Some authors recommend more isolation measures to be taken in centers with high prevalence of infection.
Collapse
|
|
19
|
Bellin A, Franchin G, Bolcato J, Bettiol A, Pirolo R, Schiavon A, Giusti P, Tessarin M, Chinellato A. Twenty Years of Hepatitis C in the Treviso District (Local Health Unit 2): Treatments, Clinical Management and Cost Analysis. GLOBAL & REGIONAL HEALTH TECHNOLOGY ASSESSMENT 2019. [DOI: 10.1177/2284240319835865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Annachiara Bellin
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Giulia Franchin
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Jenny Bolcato
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alessandra Bettiol
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Roberta Pirolo
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alberto Schiavon
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Pietro Giusti
- Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy
| | - Michele Tessarin
- U.O.C Direzione Sanitaria, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| | - Alessandro Chinellato
- U.O.C. Politiche del Farmaco e Governo della Spesa Farmaceutica, Azienda ULSS2, Distretto di Treviso, Treviso, Italy
| |
Collapse
|
|
20
|
Chronic Viral Hepatitis and Metabolic Syndrome/Cardiovascular Risk. Can J Gastroenterol Hepatol 2018; 2018:7369314. [PMID: 30519548 PMCID: PMC6241355 DOI: 10.1155/2018/7369314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 10/11/2018] [Indexed: 11/17/2022] Open
|
|
21
|
Dultz G, Müller T, Petersen J, Mauss S, Zimmermann T, Muche M, Simon KG, Berg T, Zeuzem S, Hüppe D, Böker K, Wedemeyer H, Welzel TM. Effectiveness and Safety of Direct-Acting Antiviral Combination Therapies for Treatment of Hepatitis C Virus in Elderly Patients: Results from the German Hepatitis C Registry. Drugs Aging 2018; 35:843-857. [PMID: 30084012 DOI: 10.1007/s40266-018-0572-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND With the aging of the hepatitis C virus (HCV)-infected patient cohort and the availability of highly effective and tolerable treatment regimens, an increasing number of elderly patients are now eligible for HCV therapy. This study investigated clinical and epidemiologic characteristics of elderly HCV-infected patients as well as the effectiveness and safety of available therapies. METHODS Patients were enrolled into the German Hepatitis C Registry (DHC-R), a prospective, multicenter, real-world cohort study. Patients were treated at the discretion of the physician, and data were collected by a web-based system. RESULTS Of 7133 patients who initiated treatment, 686 (9.6%) were > 70 years of age. In patients > 70 years, intent-to-treat (ITT) SVR12 was 92.6% (514/555) compared to 90.7% (4521/4985) in patients ≤ 70 years of age. Overall, adverse events (AEs) were reported in 374 (54.5%) and 3435 patients (53.3%) > 70 or ≤ 70 years of age; 7.6% (52) and 3.6% (235) in the respective age groups had a serious AE. Twenty-two (3.2%) and 62 (1.0%) of the patients > 70 or ≤ 70 years discontinued treatment due to AEs. Death was reported in 34 patients, of whom eight were > 70 years of age. Frequent comorbidities in patients > 70 years of age were cardiac disease, renal disease and diabetes. Psychiatric disorders, substance abuse and viral co-infection were more frequent in younger patients. CONCLUSION Direct-acting antiviral therapies were well tolerated in patients older than 70 years. SVR12 rates in the elderly patient group were similar to those observed in younger patients. Differences in the prevalence of comorbidities between age groups warrant individualized attention with respect to drug-drug interactions and therapy adherence. The study was registered in the German Clinical Trials Register, DRKS-ID: DRKS00009717.
Collapse
Affiliation(s)
- Georg Dultz
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
| | - Tobias Müller
- Charité Campus Virchow-Klinikum (CVK), Berlin, Germany
| | - Jörg Petersen
- ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Tim Zimmermann
- University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Marion Muche
- Charité Campus Virchow-Klinikum (CVK), Berlin, Germany
| | | | - Thomas Berg
- University Hospital Leipzig, Leipzig, Germany
| | - Stefan Zeuzem
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany
| | | | | | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg Essen, Essen, Germany
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Leberstiftungs-GmbH Deutschland, Hannover, Germany
| | - Tania M Welzel
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany
| |
Collapse
|
|
22
|
Brook G, Brockmeyer N, van de Laar T, Schellberg S, Winter AJ. 2017 European guideline for the screening, prevention and initial management of hepatitis B and C infections in sexual health settings. Int J STD AIDS 2018; 29:949-967. [PMID: 29716442 DOI: 10.1177/0956462418767576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This guideline updates the 2010 European guideline for the management of hepatitis B and C virus infections. It is primarily intended to provide advice on testing, prevention and initial management of viral hepatitis B and C for clinicians working in sexual health clinical settings in European countries. The guideline is in a new question and answer format based on clinical situations, from which population/intervention/comparison/outcome questions were formulated. Updates cover areas such as epidemiology, point-of-care tests for hepatitis B, hepatitis C risk and 'chemsex', and HIV pre-exposure prophylaxis and hepatitis B. We have also included a short paragraph on hepatitis E noting there is no evidence for sexual transmission. The guideline has been prepared in accordance with the Europe protocol for production available at http://www.iusti.org/regions/europe/pdf/2017/ProtocolForProduction2017.pdf.
Collapse
Affiliation(s)
- Gary Brook
- 1 Genitourinary Medicine, London North West Healthcare NHS Trust, London, UK
| | - Norbert Brockmeyer
- 2 Klinik für Dermatologie, Venerologie und Allergologie, Ruhr-Universität Bochum, Bochum, Germany
| | - Thijs van de Laar
- 3 Department of Bloodborne Infections, Sanquin Blood Supply, Amsterdam, Netherlands
| | | | | |
Collapse
|
|
23
|
Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic hepatitis C-affected patients treated with new drugs. Cancer Chemother Pharmacol 2018; 81:615-620. [PMID: 29356898 DOI: 10.1007/s00280-018-3520-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 01/10/2018] [Indexed: 01/26/2023]
Abstract
PURPOSE Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated with new anti-HCV drugs. METHODS Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1, CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were analyzed. RESULTS HCC was present in six patients, all taking sofosbuvir, all males and five/six had cirrhosis. HCV-RNA log levels at baseline were statistically different between patients with and without HCC. VDR FokI T > C SNP resulted associated with HCC: all the CC patients were free from HCC. An association between HCC presence and undetectable HCV-RNA at 1 month of therapy was suggested; cirrhosis was related to HCC. HCC risk factors were age, ribavirin administration, IL28Brs12979860CC and previous treatments; VDR FokICC, sex and insulin resistance were protective factors. CONCLUSIONS These data highlighted vitamin D pathway gene SNPs and HCC relationship in the Italian population; further studies are required.
Collapse
|
|
24
|
St. John TM. Chronic Hepatitis. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
25
|
Koutb F, Abdel-Rahman S, Hassona E, Haggag A. Association of C-myc and p53 Gene Expression and Polymorphisms with Hepatitis C (HCV) Chronic Infection, Cirrhosis and Hepatocellular Carcinoma (HCC) Stages in
Egypt. Asian Pac J Cancer Prev 2017; 18:2049-2057. [PMID: 28843220 PMCID: PMC5697458 DOI: 10.22034/apjcp.2017.18.8.2049] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The aim of this study is to investigate c-myc and p53 gene expression and polymorphisms in different stages of HCV infection,. Expression levels of c-myc and p53 were evaluated by RT-PCR and polymorphisms were determined by PCR-RFLP in 60 HCV patients classified into chronic infection, cirrhosis and HCC groups along with 30 controls. c-myc gene expression significant increased through the stages as compared to the control level (1.17, 1.82, 3.33 and 0.32, respectively), whereas p53 significantly declined (4,375, 3,842, 525 and 5,498, respectively). The C-myc CC genotype was predominant in the HCC group (90%) to a greater extent than in the cirrhosis, chronic infection and control cases (80%, 20% and 10%, respectively), while the GG genotype was predominant in controls (83%, as compared to 65%, 10% and 10%). The CG genotype was most common in chronic infection (15%). The p53 PP genotype predominated in controls (87%, with 15%, 10% and 20%, respectively, for the three stages) while the AA genotype demonstrated only slight increase to HCC (13%, 25% and 30%, respectively) and PA genotype was predominant in cirrhosis cases (90%). These findings reveal that c-myc and p53 gene expression and polymorphisms may be considered as promising sensitive genetic biomarkers for progression of HCV infection.
Collapse
Affiliation(s)
- Fayed Koutb
- Department of Nucleic Acid Research, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Egypt.
| | | | | | | |
Collapse
|
|
26
|
Drees JC, Wi S, Ready JB, Dlott RS, Fetterman BJ, Seo SI, Pat Pauly M, Petrie MS, Lorey TS. Serum Fibrosis Marker Panels FIB-4 Index and Aspartate Aminotransferase (AST)-to-Platelet Ratio Index (APRI) Are Equivalent to AST Alone at Predicting Liver Fibrosis in a Cohort of 1731 Patients Infected with Hepatitis C Virus. J Appl Lab Med 2017; 2:76-85. [PMID: 33636957 DOI: 10.1373/jalm.2016.022509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Accepted: 03/28/2017] [Indexed: 11/06/2022]
Abstract
BACKGROUND Efficient tools are needed to stage liver disease before treatment of patients infected with hepatitis C virus (HCV). Compared to biopsy, several studies demonstrated favorable performance of noninvasive multianalyte serum fibrosis marker panels [fibrosis-4 (FIB-4) index] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI), but suggested cutoffs vary widely. Our objective was to evaluate FIB-4 index and APRI and their component tests for staging fibrosis in our HCV-infected population and to determine practical cutoffs to help triage an influx of patients requiring treatment. METHODS Transient elastography (TE) results from 1731 HCV-infected patients were mapped to an F0-F4 equivalent scale. Each patient's APRI and FIB-4 index were calculated. Areas under the receiver operator curve (AUROCs) and false-positive and false-negative rates were calculated to retrospectively compare the performance of the indices and their component tests. RESULTS The highest AUROCs for distinguishing severe (F3-F4) from mild-to-moderate (F0-F2) fibrosis had overlapping 95% CIs: APRI (0.77; 0.74-0.79), FIB-4 index (0.76; 0.73-0.78), and AST (0.74; 0.72-0.77). Cutoffs had false-negative rates of 2.7%-2.8% and false-positive rates of 6.4%-7.4% for all 3 markers. CONCLUSIONS AST was as effective as FIB-4 index and APRI at predicting fibrosis. Published cutoffs for APRI and FIB-4 index would have been inappropriate in our population, with false-negative rates as high as 11%. For our purposes, no serum fibrosis marker was sufficiently sensitive to rule-out significant fibrosis, but cutoffs developed for AST, FIB-4 index, and APRI all had specificities of 79.2%-80.3% for ruling-in severe fibrosis and could be used to triage 1/3 of our population for treatment without waiting for TE or liver biopsy.
Collapse
Affiliation(s)
- Julia C Drees
- Kaiser Permanente, TPMG Regional Laboratory, Berkeley, CA
| | - Soora Wi
- Kaiser Permanente, TPMG Regional Laboratory, Berkeley, CA
| | - Joanna B Ready
- Kaiser Permanente, TPMG Gastroenterology and Hepatology, Santa Clara, CA
| | | | | | - Suk I Seo
- Kaiser Permanente, TPMG Gastroenterology and Hepatology, Walnut Creek, CA
| | - Mary Pat Pauly
- Kaiser Permanente, TPMG Gastroenterology and Hepatology, Sacramento, CA
| | | | - Thomas S Lorey
- Kaiser Permanente, TPMG Regional Laboratory, Berkeley, CA
| |
Collapse
|
|
27
|
Gonzalez SA, Fierer DS, Talal AH. Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for Hepatitis C Virus Infection. ADDICTIVE DISORDERS & THEIR TREATMENT 2017; 16:S1-S23. [PMID: 28701904 PMCID: PMC5491232 DOI: 10.1097/adt.0000000000000104] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Direct-acting antivirals for hepatitis C virus infection may revolutionize treatment among persons with substance use disorders. Despite persons with substance use disorders having the highest hepatitis C virus prevalence and incidence, the vast majority have not engaged into care for the infection. Previously, interferon-based treatments, with substantial side effects and the propensity to exacerbate mental health conditions, were major disincentives to pursuit of care for the infection. Direct-acting antivirals with viral eradication rates of >90%, significantly improved side effect profiles, and shorter treatment duration are dramatic improvements over prior treatment regimens that should promote widespread hepatitis C virus care among persons with substance use disorders. The major unmet need is strategies to promote persons with substance use disorders engagement into care for hepatitis C virus. Although physical integration of treatment for substance use and co-occurring conditions has been widely advocated, it has been difficult to achieve. Telemedicine offers an opportunity for virtual integration of behavioral and medical treatments that could be supplemented by conventional interventions such as hepatitis C virus education, case management, and peer navigation. Furthermore, harm reduction and strategies to reduce viral transmission are important to cease reinfection among persons with substance use disorders. Widespread prescription of therapy for hepatitis C virus infection to substance users will be required to achieve the ultimate goal of global virus elimination. Combinations of medical and behavioral interventions should be used to promote persons with substance use disorders engagement into and adherence with direct-acting antiviral-based treatment approaches. Ultimately, either physical or virtual colocation of hepatitis C virus and substance use treatment has the potential to improve adherence and consequently treatment efficacy.
Collapse
Affiliation(s)
- Stevan A. Gonzalez
- Division of Hepatology, Baylor Simmons Transplant Institute, Fort Worth, TX
| | | | - Andrew H. Talal
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Jacobs School of Medicine, State University of New York at Buffalo, Buffalo, NY
| |
Collapse
|
|
28
|
El Raziky M, Zayed NA, Abdel Baki A, Mansour SA, Shahin RMH. ITPA gene polymorphism (94C>A) effects on ribavirin-induced anemia during therapy in Egyptian patients with chronic hepatitis C. J Med Virol 2017; 89:1823-1829. [PMID: 28480960 DOI: 10.1002/jmv.24844] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 04/11/2017] [Indexed: 12/13/2022]
Abstract
Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)-infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV-containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.
Collapse
Affiliation(s)
- Maissa El Raziky
- Department of Endemic Medicine and Hepatology, Kasr Al Ainy Hospital, School of Medicine, Cairo University, Cairo, Egypt
| | - Naglaa A Zayed
- Department of Endemic Medicine and Hepatology, Kasr Al Ainy Hospital, School of Medicine, Cairo University, Cairo, Egypt
| | - Amin Abdel Baki
- Department of Tropical Medicine, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Shimaa A Mansour
- Department of Tropical Medicine, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Rasha M H Shahin
- Department of Clinical Pathology, Kasr Al Ainy, School of Medicine, Cairo University, Cairo, Egypt
| |
Collapse
|
|
29
|
Stravitz RT, Ilan Y. Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic? Liver Int 2017; 37:328-336. [PMID: 27718326 DOI: 10.1111/liv.13268] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 09/23/2016] [Indexed: 02/13/2023]
Abstract
The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis.
Collapse
Affiliation(s)
- R Todd Stravitz
- Section of Hepatology, Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA, USA
| | - Yaron Ilan
- Gastroenterology and liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| |
Collapse
|
|
30
|
Vukotic R, Conti F, Andreone P. Hepatitis C virus eradication in the elderly: The challenge worth a long-life elixir? J Hepatol 2017; 66:476-477. [PMID: 28012863 DOI: 10.1016/j.jhep.2016.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 12/12/2016] [Indexed: 01/16/2023]
Affiliation(s)
- Ranka Vukotic
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy
| | - Fabio Conti
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy.
| |
Collapse
|
|
31
|
Burza MA, Marschall HU, Napoleone L, Molinaro A. The 35-year odyssey of beta blockers in cirrhosis: any gender difference in sight? Pharmacol Res 2017; 119:20-26. [PMID: 28099882 DOI: 10.1016/j.phrs.2017.01.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Revised: 12/15/2016] [Accepted: 01/13/2017] [Indexed: 12/11/2022]
Abstract
Cirrhosis is the end-stage of chronic liver disease and leads to the development of portal hypertension and its complications such as esophagogastric varices. Non-selective beta blockers (NSBB) are the keystone for the treatment of portal hypertension since the 1980s and, over the decades, several studies have confirmed their beneficial effect on the prevention of variceal (re)bleeding. Pharmacological studies showed effects of gender, sex hormones, oral contraceptives, and pregnancy on cytochrome P450 (CYPs) enzymes that metabolise NSBB, suggesting that gender differences might exist in the effect of NSBB. In this review, we focused on the 35-year knowledge about the use of beta blockers in cirrhosis and potential gender differences. We specifically examined the role of NSBB in pre-primary, primary and secondary prophylaxis of variceal bleeding, compared two commonly used NSBB (i.e., Propranolol and Carvedilol), and present the current controversies about the window of treatment in advanced cirrhosis with a specific focus on gender differences in NSBB effects. NSBB are not currently recommended in pre-primary prophylaxis of varices mainly because of lack of proven efficacy. On the other hand, NSBB are strongly recommended in patient with cirrhosis as primary (as alternative to endoscopic band ligation, EBL) and secondary prophylaxis (in addition to EBL) of variceal bleeding. To date, no studies have focused specifically on the effect of gender on NSBB treatment. Data extrapolated from clinical studies show that gender was neither a risk factor for the development of varices nor associated with a different response to treatment in primary or secondary prophylaxis. According to the available guidelines, no different, gender-based treatment for portal hypertension is recommended.
Collapse
Affiliation(s)
- Maria Antonella Burza
- Department of Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Hanns-Ulrich Marschall
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Laura Napoleone
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
| | - Antonio Molinaro
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
32
|
Gray E, Norris S, Schmitz S, O'Leary A. Do disparities between populations in randomized controlled trials and the real world lead to differences in outcomes? J Comp Eff Res 2016; 6:65-82. [PMID: 27854129 DOI: 10.2217/cer-2016-0042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To conduct a systematic review investigating reasons for the disparity between the efficacy and effectiveness rates reported in randomized controlled trials (RCTs) and observational studies of direct-acting antiviral treatment regimens licensed for use in genotype1 hepatitis C virus-infected individuals. METHODS This systematic review was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. RESULTS Statistically significant (p < 0.05) differences in the baseline demographics and sustained virological response rates were observed between RCT and observational studies. CONCLUSION In order for outcomes from RCTs to be generalizable to the real world, greater consideration needs to be taken to include patient populations that are more representative of those awaiting treatment in the clinical setting.
Collapse
Affiliation(s)
- Emma Gray
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Suzanne Norris
- School of Medicine, Trinity College Dublin, Dublin, Ireland.,Departmentof Hepatology, St James' Hospital, Dublin, Ireland
| | - Susanne Schmitz
- HealthEconomics & Evidence Synthesis Research Unit, Department of PopulationHealth, Luxembourg Health Institute, Luxembourg
| | - Aisling O'Leary
- Schoolof Pharmacy, Royal College of Surgeons of Ireland, Dublin, Ireland.,NationalCentre for Pharmacoeconomics, St James' Hospital, Dublin, Ireland
| |
Collapse
|
|
33
|
Lewis H, Kunkel J, Axten D, Dalton J, Gardner H, Tippett A, Wynne S, Wilkinson M, Foster GR. Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment. Eur J Gastroenterol Hepatol 2016; 28:1258-63. [PMID: 27487966 DOI: 10.1097/meg.0000000000000711] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Chronic hepatitis C is common in people who inject drugs (PWID) and this population serves as a reservoir for infection. Treatment levels are low among this group, ranging from 1 to 19%. We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies. METHODS This was a cluster randomized trial of nurse-initiated versus physician-initiated antiviral therapy with pegylated interferon and ribavirin for hepatitis C virus in community clinics (trial registration: ISRCTN07774040). RESULTS The proportion of participants initiating treatment during follow-up was 10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy. Adherence was similar in both groups, with only one patient in each arm not adhering to therapy. There were no serious adverse events, but interferon-related side effects were common. Drug and alcohol use did not change during therapy. CONCLUSION Despite easy access to antiviral therapy, uptake of treatment was poor, with no significant difference between the groups. Nurse-led initiation of interferon-based antiviral therapy in PWID did not lead to increased uptake of, response to or adherence with treatment. Further service improvement is unlikely to increase the proportion of PWID undergoing antiviral therapy for hepatitis C virus and early adoption of interferon-free regimens may increase the proportion initiating and completing treatment.
Collapse
Affiliation(s)
- Heather Lewis
- aDepartment of Gastroenterology, Frimley Health Foundation Trust, Surrey bHepatology Unit, Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London cBlood Borne Virus Team, Tower Hamlets Specialist Addiction Unit, East London NHS Foundation Trust, Beaumont House, Mile End Hospital, London, UK
| | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Fraser I, Burger J, Lubbe M, Dranitsaris G, Sonderup M, Stander T. Cost-Effectiveness Modelling of Sofosbuvir-Containing Regimens for Chronic Genotype 5 Hepatitis C Virus Infection in South Africa. PHARMACOECONOMICS 2016; 34:403-417. [PMID: 26666639 DOI: 10.1007/s40273-015-0356-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
BACKGROUND The recently launched nucleotide polymerase inhibitor sofosbuvir represents a significant turn in the treatment paradigm of chronic hepatitis C. While effective, sofosbuvir is also associated with a considerable cost. OBJECTIVE The objective of this study was to evaluate the cost effectiveness of sofosbuvir-containing regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 5 (HCV-G5) mono-infection in South Africa (SA). DESIGN We constructed a lifetime horizon decision-analytic Markov model of the natural history of HCV infection to evaluate the cost effectiveness of sofosbuvir-ledipasvir (SOF/LDV) monotherapy against sofosbuvir triple therapy (SOF-TT) (sofosbuvir + pegylated interferon and ribavirin [peg-INF/RBV]) and the current standard of care (SOC) (peg-INF/RBV) for patients with chronic HCV-G5 in the South African context. The model was populated with data from published literature, expert opinion and South African private sector cost data. The price modelled for sofosbuvir was the predicted South African private sector price of 82,129.32 South African rand (R) (US$7000) for 12 weeks. The analysis was conducted from a third-party payer perspective. OUTCOME MEASURES The outcome measures were discounted and undiscounted costs (in 2015 South African rand and US dollars) and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS Outcomes from the cost-effectiveness model show that SOF/LDV yields the most favourable future health economic outcomes compared with SOF-TT and the current SOC in SA. Findings relating to the lifetime incremental cost per QALY gained for patients infected with HCV-G5 indicate that SOF/LDV dominated both SOF-TT and SOC, i.e. SOF/LDV is less costly and more effective. CONCLUSION Outcomes from this analysis suggest that at a price of R123,190 ($US10,500) for 12 weeks of SOF/LDV might be cost effective for South African patients infected with HCV-G5.
Collapse
Affiliation(s)
- Ilanca Fraser
- Medicine Usage in South Africa (MUSA), Faculty of Health Sciences, North-West University (Potchefstroom Campus), Potchefstroom, South Africa
| | - Johanita Burger
- Medicine Usage in South Africa (MUSA), Faculty of Health Sciences, North-West University (Potchefstroom Campus), Potchefstroom, South Africa.
| | - Martie Lubbe
- Medicine Usage in South Africa (MUSA), Faculty of Health Sciences, North-West University (Potchefstroom Campus), Potchefstroom, South Africa
| | | | - Mark Sonderup
- Department of Medicine and Division of Hepatology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
| | | |
Collapse
|
|
35
|
Husic-Selimovic A, Sofic A, Huskic J, Bulja D. Effect of Antiviral Therapy on Serum Activity of Angiotensin Converting Enzyme in Patients with Chronic Hepatitis C. Med Arch 2016; 70:92-6. [PMID: 27147779 PMCID: PMC4851539 DOI: 10.5455/medarh.2016.70.92-96] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 03/15/2016] [Indexed: 12/15/2022] Open
Abstract
Introduction: Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis. Aim of the study: Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group. Materials and methods: We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit “Infinity TN ACE Liquid Stable Reagent”. HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients’ response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis. Results: Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934). Conclusion: Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage.
Collapse
Affiliation(s)
- Azra Husic-Selimovic
- Institute of Gastroenterohepatology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Amela Sofic
- Clinic of Radiology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Jasminko Huskic
- Institute for Physiology, Medical Faculty Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Deniz Bulja
- Clinic of Radiology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| |
Collapse
|
|
36
|
Marcos R, Lopes C, Malhão F, Correia-Gomes C, Fonseca S, Lima M, Gebhardt R, Rocha E. Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells. J Anat 2016; 228:996-1005. [PMID: 26892301 DOI: 10.1111/joa.12448] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2016] [Indexed: 12/11/2022] Open
Abstract
There is long-standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes (HEP), Kupffer cells (KC) and hepatic stellate cells (HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co-localisation of these cell types. Immunohistochemistry and design-based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ.
Collapse
Affiliation(s)
- Ricardo Marcos
- Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.,Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal
| | - Célia Lopes
- Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.,Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal
| | - Fernanda Malhão
- Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.,Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal
| | - Carla Correia-Gomes
- Scotland's Rural College, Epidemiology Research Unit - Future Farming Systems Group, Inverness, UK
| | - Sónia Fonseca
- Laboratory of Cytometry, Department of Hematology, UMIB - Unit for Multidisciplinary Research in Biomedicine, CHP - Centro Hospitalar do Porto, ICBAS - Institute of Biomedical Sciences Abel Salazar, HSA - Hospital de Santo António, U.Porto - University of Porto, Porto, Portugal
| | - Margarida Lima
- Laboratory of Cytometry, Department of Hematology, UMIB - Unit for Multidisciplinary Research in Biomedicine, CHP - Centro Hospitalar do Porto, ICBAS - Institute of Biomedical Sciences Abel Salazar, HSA - Hospital de Santo António, U.Porto - University of Porto, Porto, Portugal
| | - Rolf Gebhardt
- Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, Germany
| | - Eduardo Rocha
- Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Porto, Portugal.,Histomorphology, Physiopathology and Applied Toxicology Group, CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, U.Porto - University of Porto, Porto, Portugal
| |
Collapse
|
|
37
|
Brook G, Bhagani S, Kulasegaram R, Torkington A, Mutimer D, Hodges E, Hesketh L, Farnworth S, Sullivan V, Gore C, Devitt E, Sullivan AK. United Kingdom National Guideline on the Management of the viral hepatitides A, B and C 2015. Int J STD AIDS 2016; 27:501-25. [PMID: 26745988 DOI: 10.1177/0956462415624250] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 12/01/2015] [Indexed: 12/13/2022]
Affiliation(s)
- Gary Brook
- London North West Healthcare NHS Trust, London, UK
| | | | | | | | - David Mutimer
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Louise Hesketh
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Simon Farnworth
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | | | - Emma Devitt
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | - Ann K Sullivan
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | |
Collapse
|
|
38
|
Nemr N, Kishk R, Mandour M. Role of ITPA gene polymorphism in ribavirin-induced anemia and thrombocytopenia in Egyptian patients with chronic hepatitis C. Indian J Gastroenterol 2016; 35:7-13. [PMID: 26880169 DOI: 10.1007/s12664-016-0618-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 01/10/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Ribavirin (RBV)-induced anemia is one of the major causes of dose reduction and discontinuation of therapy for chronic hepatitis C (CHC) patients. We investigated the role of inosine triphosphate pyrophosphatase (ITPA) single nucleotide polymorphism (SNP) (rs1127354) in predicting RBV-induced anemia and thrombocytopenia among Egyptian patients with CHC genotype 4 infection. METHODS One hundred and twenty Egyptian patients with CHC genotype 4 who had received standard of care combination therapy were enrolled in this study. Single nucleotide polymorphism at ITPA (rs1127354) was genotyped by real-time detection polymerase chain reaction. RESULTS Hb levels between CC and non-CC groups were significantly different at weeks 4, 8, and 12. Hemoglobin decline was significantly higher among CC patient than non-CC patients at week 4 and week 8 of treatment. The RBV dose reduction was higher in CC than non-CC group. Platelet decline was significantly lower in CC patients than non-CC patients at baseline, 4, 12 weeks only. CONCLUSION Rs1127354 ITPA polymorphism was associated with RBV-induced anemia and thrombocytopenia in Egyptian patients with hepatitis C virus genotype 4 infection.
Collapse
Affiliation(s)
- Nader Nemr
- Department of Endemic and Infectious Diseases, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Rania Kishk
- Department of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
| | - Mohamed Mandour
- Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| |
Collapse
|
|
39
|
Maan R, Toes-Zoutendijk E, Veldt BJ, Hansen BE, van der Meer AJ, de Knegt RJ. Epidemiological trends among the population with chronic HCV infection in the Netherlands. Antivir Ther 2015; 21:207-15. [PMID: 26436201 DOI: 10.3851/imp2996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND As the field of antiviral therapy for chronic HCV infection is rapidly evolving, this study aimed to assess the epidemiological changes in patient and disease characteristics among individuals with chronic HCV infection. METHODS This study included all consecutive patients with chronic HCV monoinfection who were referred between 1990 and 2013 to the Erasmus MC University Medical Center Rotterdam, a large tertiary centre in the Netherlands. To identify trends over time, the study population was divided into six equal eras based on date of first visit to the outpatient clinic. RESULTS A total of 1,779 patients were diagnosed with chronic HCV infection. Mean age increased over time from 43.6 (sd 13.8) years to 51.7 (sd 11.2) years (P<0.001). The number of patients who were referred with cirrhosis increased over time, from 31 (25%) patients in Era 1 to 118 (42%) patients in Era 6 (P<0.001), respectively. More patients were referred with HCV genotype 1a and 3 in the last era, with 27 (48.2%) and 15 (14.0%) patients in Era 1 and 58 (54.2%) and 60 (21.8%) patients in Era 6 (P<0.001 both), respectively. The vast majority of patients (69.5%) were born between 1950 to 1975, with 62.5% of the patients being born between 1945 and 1965. CONCLUSIONS The HCV-infected population is ageing and is more often referred with severe liver disease. This study stresses the importance of urgently implementing national HCV screening programmes in order to be able to decrease the future burden of chronic HCV infection in the Netherlands.
Collapse
Affiliation(s)
- Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | | | | | | | | | | |
Collapse
|
|
40
|
|
|
41
|
Marinaki S, Boletis JN, Sakellariou S, Delladetsima IK. Hepatitis C in hemodialysis patients. World J Hepatol 2015; 7:548-558. [PMID: 25848478 PMCID: PMC4381177 DOI: 10.4254/wjh.v7.i3.548] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 12/10/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the “silent” clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the “beneficial” impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of “hepatoprotective” cytokines such as interferon (IFN)-α and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking.
Collapse
|
|
42
|
Jafari A, Khalili H, Izadpanah M, Dashti-Khavidaki S. Safely treating hepatitis C in patients with HIV or hepatitis B virus coinfection. Expert Opin Drug Saf 2015; 14:713-31. [PMID: 25813487 DOI: 10.1517/14740338.2015.1019461] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION There are several clinical trials and prospective studies which support the use of direct-acting antiviral agents (DAAs) in hepatitis C virus (HCV)-coinfected patients. In this review, the safety of DAAs in HCV patients coinfected with hepatitis B virus (HBV) or HIV has been evaluated. AREAS COVERED All available prospective studies, clinical trials and congress abstracts in the English language that assessed the safety and efficacy of DAAs in HCV coinfections have been considered. EXPERT OPINION The newer DAAs in the treatment of HCV/HIV-coinfected patients resolved major limitations of the first-generation protease inhibitors including complex dosing, poor tolerability and interactions with antiretroviral drugs. There are not yet enough data regarding the safety and efficacy of DAAs in some coinfected patients with comorbidities, nor for pregnant, lactating or pediatric patients. Evaluating the safety and efficacy of these agents in these subgroups with HCV coinfection is recommended for future studies. The role of new direct-acting antiviral-based therapy for the treatment of patients with HCV/HBV coinfection remains to be evaluated.
Collapse
Affiliation(s)
- Atefeh Jafari
- Tehran University of Medical Sciences, Department of Clinical Pharmacy, Faculty of Pharmacy , Tehran , Iran
| | | | | | | |
Collapse
|
|
43
|
Mandorfer M, Payer BA, Schwabl P, Steiner S, Ferlitsch A, Aichelburg MC, Stättermayer AF, Ferenci P, Obermayer-Pietsch B, Grabmeier-Pfistershammer K, Trauner M, Peck-Radosavljevic M, Reiberger T. Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3. Liver Int 2015; 35:876-85. [PMID: 24905495 DOI: 10.1111/liv.12615] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 05/22/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. RESULTS Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.
Collapse
Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Neutrophil-to-lymphocyte ratio as a predictor of response to peginterferon plus ribavirin therapy for chronic hepatitis C. DISEASE MARKERS 2014; 2014:462958. [PMID: 25505815 PMCID: PMC4255057 DOI: 10.1155/2014/462958] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 11/04/2014] [Indexed: 12/15/2022]
Abstract
We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM (P = 0.039) and higher hepatitis C viral load (P = 0.002) and white cell count (P < 0.001). NLR was significantly lower in patients with RVR and SVR compared to those without (P = 0.032 and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, P = 0.038) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.
Collapse
|
|
45
|
Negro F. Facts and fictions of HCV and comorbidities: steatosis, diabetes mellitus, and cardiovascular diseases. J Hepatol 2014; 61:S69-78. [PMID: 25443347 DOI: 10.1016/j.jhep.2014.08.003] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 07/16/2014] [Accepted: 08/01/2014] [Indexed: 12/16/2022]
Abstract
The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.
Collapse
Affiliation(s)
- Francesco Negro
- Divisions of Gastroenterology and Hepatology, University Hospitals, Geneva, Switzerland; Division of Clinical Pathology, University Hospitals, Geneva, Switzerland.
| |
Collapse
|
|
46
|
Catamo E, Zupin L, Crovella S, Celsi F, Segat L. Non-classical MHC-I human leukocyte antigen (HLA-G) in hepatotropic viral infections and in hepatocellular carcinoma. Hum Immunol 2014; 75:1225-31. [PMID: 25318079 DOI: 10.1016/j.humimm.2014.09.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Revised: 09/27/2014] [Accepted: 09/27/2014] [Indexed: 01/05/2023]
Abstract
The human leukocyte antigen (HLA)-G is a "nonclassical" major histocompatibility complex (MHC) class Ib gene, located at chromosome 6, in the 6p21.3 region. The HLA-G presents immunomodulatory functions essential in pregnancy for the tolerance of the semi-allogenic fetus, but an abnormal expression of HLA-G has been observed in numerous pathological conditions, such as tumors, autoimmune diseases and viral infections. In recent years, numerous studies have assessed the clinical relevance of HLA-G expression in different types of cancer: in general, a higher HLA-G expression correlates with a lower survival rate or a shorter disease-free survival. Altered expression of HLA-G has been found in both HCV and HBV infection, and some genetic polymorphisms have been associated with altered susceptibility/disease development for these infections, however, whether the biologic role of HLA-G in HCV and HBV infection is beneficial or hazardous, it is not completely clear. In the context of hepatocellular carcinoma, HLA-G has shown a potential diagnostic role, moreover a prognostic value in HCC patients has been also attributed to HLA-G molecules. We revise here the role of HLA-G in hepatotropic HBV/HCV infections and in hepatocellular carcinoma (HCC).
Collapse
Affiliation(s)
- Eulalia Catamo
- Medical Science Department, University of Trieste, Italy
| | - Luisa Zupin
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
| | - Sergio Crovella
- Medical Science Department, University of Trieste, Italy; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
| | - Fulvio Celsi
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
| | - Ludovica Segat
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
| |
Collapse
|
|
47
|
Sato M, Kato N, Tateishi R, Muroyama R, Kowatari N, Li W, Goto K, Otsuka M, Shiina S, Yoshida H, Omata M, Koike K. Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Hepatol Res 2014; 44:E137-44. [PMID: 24125181 DOI: 10.1111/hepr.12258] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 10/02/2013] [Accepted: 10/04/2013] [Indexed: 02/06/2023]
Abstract
AIM The PNPLA3 rs738409 C>G polymorphism (encoding for I148M) has recently been identified as a susceptibility factor for steatosis-mediated liver damage. We evaluated the influence of this polymorphism on hepatocarcinogenesis in patients with chronic hepatitis C (CHC) virus infection. METHODS We genotyped the rs738409 single nucleotide polymorphism in 358 hepatitis C-associated hepatocellular carcinoma (HCC) patients and correlated the age at onset of HCC and the interval between hepatitis C virus (HCV) infection and the development of HCC in patients with each genotype. RESULTS The frequencies of CC, CG and GG genotypes were 27.9% (100/358), 49.2% (176/358) and 22.9% (82/358), respectively, and were in Hardy-Weinberg equilibrium. The median age at onset of HCC for the GG genotype was significantly younger compared to for non-GG genotypes (67.81 vs 69.87 years, P < 0.001), and the median interval between HCV infection and the development of HCC was significantly shorter in patients with the GG genotype (39.96 vs 40.85 years, P = 0.008). PNPLA3 GG genotype was also associated with a higher aspartate aminotransferase level (69.5 vs 59.0 IU/L, P = 0.02), lower prothrombin time (73.0% vs 78.0%, P = 0.008) and a higher prevalence of histological steatosis (40.0% vs. 22.2%, P = 0.01) at the time of HCC onset. CONCLUSION The PNPLA3 genotype GG may be associated with accelerated hepatocarcinogenesis in CHC patients through increased steatosis in the liver.
Collapse
Affiliation(s)
- Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Roeder C, Jordan S, Schulze zur Wiesch J, Pfeiffer-Vornkahl H, Hueppe D, Mauss S, Zehnter E, Stoll S, Alshuth U, Lohse AW, Lueth S. Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection. World J Gastroenterol 2014; 20:10984-10993. [PMID: 25152602 PMCID: PMC4138479 DOI: 10.3748/wjg.v20.i31.10984] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Revised: 02/20/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection.
METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data.
RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was “virological non-response” (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR.
CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.
Collapse
|
|
49
|
Samonakis DN, Koulentaki M, Coucoutsi C, Augoustaki A, Baritaki C, Digenakis E, Papiamonis N, Fragaki M, Matrella E, Tzardi M, Kouroumalis EA. Clinical outcomes of compensated and decompensated cirrhosis: A long term study. World J Hepatol 2014; 6:504-512. [PMID: 25068002 PMCID: PMC4110542 DOI: 10.4254/wjh.v6.i7.504] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 03/21/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study these characteristics and prognostic patterns in a Greek patient population.
METHODS: We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period. We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma (HCC) occurrence and ultimately patient survival.
RESULTS: Five hundreds and twenty-two patients with median age 67 (range, 29-91) years and average follow up 9 years-10 mo (range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus (HCV, 41%) followed by alcohol (31%). The median survival time in compensated cirrhotics was 115 mo (95%CI: 95-133), whereas in decompensated patients was 55 mo (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV patients). Hepatitis B virus (HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression.
CONCLUSION: Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time.
Collapse
|
|
50
|
Elesawy BH, Abd El Hafez A, Dorgham LS, El-Askary A. Limited reliability of five non-invasive biomarkers in predicting hepatic fibrosis in chronic HCV mono-infected patients opposed to METAVIR scoring. Pathol Res Pract 2014; 210:922-8. [PMID: 25123964 DOI: 10.1016/j.prp.2014.07.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 06/16/2014] [Accepted: 07/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver biopsy is gold standard for fibrosis assessment in hepatitis C virus (HCV) infection but its limitations led to the identification of non-invasive biomarkers. This study assesses the reliability of five biomarkers in estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus METAVIR scoring. METHODS One hundred HCV monoinfected patients who underwent liver biopsy and blood sampling were included. Liver fibrosis was staged (F0-4) and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl score were calculated and their receiver operating curves (ROCs), sensitivities, specificities, predictive values and accuracies were evaluated. RESULTS There were 27, 44, and 29 patients at F0-F1, F2-F3, and F4 groups. Significant statistical differences were found regarding AST, vireamia, platelet count, prothrombin time and all biomarkers. From ROCs only Pohl score predicted significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI showed moderate performance at low cut-offs, but had limited predictive values or accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic reliability of these biomarkers was limited to patients with suspected insignificant fibrosis. CONCLUSIONS This study verified the limited reliability for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic fibrosis in HCV infected patients opposed to METAVIR scoring.
Collapse
Affiliation(s)
- Basem Hasan Elesawy
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Amal Abd El Hafez
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Laila Shehata Dorgham
- Department of Public Health, National Liver Institute, Menoufia University, Egypt; Faculty of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
| | - Ahmad El-Askary
- Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Egypt; Department of Medical Laboratory Sciences, Taif University, College of Applied Medical Sciences, Taif, Saudi Arabia.
| |
Collapse
|