Unhealthy Alcohol Use, HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C

HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C. PLoS ONE 7(10): e46810. doi:10.1371/journal.pone.0046810 Unhealthy Alcohol Use, HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C Roberto Muga 0 Arantza Sanvisens 0 Daniel Fuster 0 Jordi Tor 0 Elisenda Martnez 0 Santiago Pe rez- 0 Hoyos 0 Alvaro Mun oz 0 Michael Alan Polis, National Institute of Allergy and Infectious Diseases, United States of America 0 1 Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Auto` noma Barcelona , Barcelona , Spain , 2 Section of General Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, United States of America, 3 Department of Public Health, Institut de Recerca Hospital Vall d'Hebro n, Universitat Auto` noma Barcelona , Barcelona , Spain , 4 Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health , Baltimore, Maryland , United States of America Aim: To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods: Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Sociodemographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results: A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27-35 years), and the median duration of drug use was 10 years (IQR 5.5-15 years). Unhealthy drinking (.50 grams/ day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76-1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56-1.11) (p,0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p,0.001), higher GGT (p,0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p,0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p,0.001) and a longer drug addiction duration (p,0.001) were significantly associated with higher FIB-4 values. Conclusions: Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIVcoinfected patients are important risk factors associated with liver fibrosis in the respective populations PLOS ONE | www.plosone.org - Funding: This work was funded by grants from Ministry of Science and Innovation, Spain (grants RD06/001, RD06/006 and PI05/1550), the Age`ncia de Gestio dAjuts Universitaris i de Recerca (AGAUR) (grant 2008 BE-2 00269), Ministry of Health (grant EC11-042) and Ministry of Education (grant 2010-0945). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Liver fibrosis is the main predictor of whether chronic hepatitis C will progress to cirrhosis and end-stage liver disease [1]. Because the complications of liver disease mainly occur in patients with advanced-stage fibrosis, assessing chronic hepatitis C early is essential when evaluating at-risk patients [2]. In Western countries, more than 50% of new HCV infections are associated with drug abuse. However, this particular population also has lower rates of clinical assessment and chronic hepatitis C treatment. Given the likelihood of new and more effective treatments, drug abusers with chronic hepatitis C would benefit from simple, non-invasive measurements of liver fibrosis. The cofactors associated with chronic hepatitis C progression differ among studies; alcohol abuse, male gender, age at infection, body mass index, and coinfection with human immunodeficiency virus infection (HIV) and Hepatitis B virus infection (HBV) have been related to more rapid disease progression [15]. In HCV/ HIV-coinfected individuals, CD4 cell counts below 200 cells/mL have been associated with liver fibrosis progression [6]. In parallel, highly active antiretroviral therapy (HAART) has been shown to reduce liver-related deaths [7,8]. In HIV-negative patients, it is well established that alcohol abuse and HCV infection have a synergistic effect on liver fibrosis. However, there are conflicting results regarding the independent effect of alcohol on liver damage in HCV/HIV-coinfected patients [6,9,10]. Liver biopsy is the gold standard for assessing fibrosis [11]. However, assessing liver disease through an invasive procedure is unlikely in patients with substance abuse [12]. Furthermore, eligibility for chronic hepatitis C treatment in this population is low compared with eligibility in other populations [13,14]. To a certain extent, the evolution of liver disease in drug abusers parallels the natural history of chronic hepatitis C. Several non-invasive markers of liver fibrosis have been proposed as alternatives to liver biopsy. Some of these markers reflect the modified extracellular matrix turnover that occurs during fibrogenesis [15,16], whereas others reflect alterations in hepatic function [17,18]. FIB-4 was initially described in 2006 [18], and since then, it has been proposed as reliable marker of fibrosis in both HCV-monoinfected and HCV/HIV-coinfected individuals [18,19]. FIB-4 correlates well with liver biopsy in patients with and without advanced fibrosis [20,21]. Moreover, non-invasive markers of liver fibrosis have been proposed as predictors of all-cause and liver-related mortality [22,23]. Although abuse of alcohol and illegal drugs is frequent in patients with HIV infection and HCV infection, it is unclear how non-invasive liver fibrosis tests may reflect disease progression. In this study, we hypothesize that certain clinical and laboratory characteristics may influence a simple index of fibrosis and that the cofactors associated with elevated FIB-4 scores may differ between HCV-monoinfected patients and HCV/HIV-coinfected patients. Hence, the primary objective of the study was to characterize the putative differences in risk factors for elevated liver function biomarkers between HCV-monoinfected and HCV/HIV-coinfected patients. Patients and Methods Study Population This was a cross-sectional study of patients admitted for substance abuse treatment between 1994 and 2006. The demographic and drug use characteristics were recorded through a structured questionnaire a (...truncated)