Liver Fibrosis, Host Genetic and Hepatitis C Virus Related Parameters as Predictive Factors of Response to Therapy against Hepatitis C Virus in HIV/HCV Coinfected Patients
Open Access
- 11 July 2014
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 9 (7), e101760
- https://doi.org/10.1371/journal.pone.0101760
Abstract
To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism). A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, −238 TNF-α and −592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count. Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of −238 TNF-α genotype GG was detected in patients with significant liver fibrosis. In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a −238 TNF-α polymorphism in these patients.Keywords
This publication has 46 references indexed in Scilit:
- Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected PatientsPLOS ONE, 2013
- TelaprevirDrugs, 2012
- A new standard of care for the treatment of chronic HCV infectionNature Reviews Gastroenterology & Hepatology, 2011
- Prediction of Response to Pegylated Interferon plus Ribavirin byIL28BGene Variation in Patients Coinfected with HIV and Hepatitis C VirusClinical Infectious Diseases, 2010
- Diagnosis, management, and treatment of hepatitis C: An updateHepatology, 2008
- Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis CHepatology, 2008
- Rapid and early virological response to chronic hepatitis C treatment with IFN 2b or PEG-IFN 2b plus ribavirin in HIV/HCV co-infected patientsGut, 2007
- Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus*Journal of Viral Hepatitis, 2006
- Treatment of Chronic Hepatitis C in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients in the Era of Pegylated Interferon and RibavirinSeminars in Liver Disease, 2005
- Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10Proceedings of the National Academy of Sciences of the United States of America, 2000