The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection

Abstract

In the era of antiretroviral therapy (ART), liver disease has emerged as an important cause of death among persons with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. The objective of this study was to estimate the burden of liver disease and evaluate determinants of liver fibrosis and necroinflammatory activity among HIV/HCV coinfected patients receiving ART. We studied 112 randomly selected and 98 referred HCVinfected patients undergoing care in the Johns Hopkins University HIV clinic. Liver disease was characterized clinically and histologically. Of the 210 individuals studied-64% of whom had received ART within 2 years of liver disease assessment-33% had no fibrosis (F0), and 26% had bridging fibrosis or cirrhosis (>F3). The median necroinflammatory activity score was 3 (range, 0-9 of 18). ART was not associated with fibrosis; however, significantly less hepatic necroinflammatory activity was observed among persons who had received highly active antiretroviral therapy longer (P ‫؍‬ .02) and more effectively (defined by HIV RNA suppression; P < .01). Twelve percent of individuals had previous ARTassociated liver enzyme elevations (grades 3-4), but liver fibrosis was not more severe if the liver enzyme elevation resolved. On the other hand, liver fibrosis was more severe in persons with persistent liver enzyme elevations (grades 1-4). In conclusion, despite widespread exposure to ART and documented instances of ART-related hepatitis, we found no evidence that ART caused serious histological liver disease. Recognition of bridging fibrosis and cirrhosis in some but not most patients underscores the importance of identifying and treating liver disease in HIV/HCV coinfected persons. (HEPATOLOGY 2005;41:123-131.)

Clinical syndromes and consequences of antiretroviral-related hepatotoxicity

“…Three other retrospective cross-sectional studies do not support those results. [95][96][97] Therefore, based on the available data, we cannot affirm that nevirapine accelerates liver fibrosis progression in HIV/HCV-coinfected patients.…”

“…Thus, adequate control of HIV replication has been shown to be associated with lower necroinflammatory scores, slower liver disease progression, and decreased mortality, whereas alcohol intake contributes to more advanced fibrosis. [96][97][98][99] Therefore, in order to determine a possible negative impact of antiretroviral drug(s) on the liver disease of HIV/HCV-coinfected patients, longitudinal studies with pathology information and inclusion of multiple factors in the analysis would be most valuable. The role of transient elastography as a noninvasive tool for monitoring of liver disease progression remains to be elucidated.…”

Progression to end-stage liver disease in patients with inherited bleeding disorders and hepatitis C: an international, multicenter cohort study

“…[7][8][9][10][11] Whether highly active antiretroviral therapy (HAART) improves the natural course in patients coinfected with HCV/HIV remains controversial. [12][13][14][15] Growing evidence indicates that progression of fibrosis in patients with chronic hepatitis C may not be linear. 16,17 Patients infected for several decades may be at higher risk for developing ESLD.…”

Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus

“…5 Most data on liver fibrosis progression in HIV and HCV coinfection come from cross-sectional studies that relied on a single liver biopsy. [6][7][8][9][10][11] In those studies, the date of HCV infection is usually estimated as the date of the first use of injection drugs. At HCV infection, it is assumed that liver fibrosis is absent.…”

“…These assumptions are probably one reason for the conflicting results of those studies, especially regarding the effect of ART on fibrosis progression. [6][7][8][9][10][11] Serial liver biopsy studies may have some advantages over single liver biopsy studies. Changes in fibrosis stage are observed between two dates, and fibrosis at the initial date is known.…”