Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance

Abstract

Liver damage may result from multiple factors in HIV-infected patients. The availability of reliable noninvasive tools to measure liver fibrosis has permitted the screening of large patient populations. Cross-sectional study of all consecutive HIV outpatients who underwent examination by transient elastometry (FibroScan) at one HIV reference clinic during 2007. Advanced liver fibrosis (ALF) was defined as hepatic stiffness >9.5 kilopascals, which corresponds to Metavir stages F3-F4 in the liver biopsy. A total of 681 consecutive HIV-infected patients (64% injecting drug users; mean age 43; 78% male; 98% on antiretroviral therapy) had at least one valid FibroScan evaluation. ALF was diagnosed in 215 (32%) of them. In the univariate analysis, ALF was significantly associated with older age, low CD4 counts, chronic hepatitis C, past alcohol abuse, elevated ALT, high triglycerides, low cholesterol, high homeostasis model assessment (HOMA) index and exposure to didanosine and/or stavudine. In a multivariate model (OR, 95% CI), chronic hepatitis C (2.83, 1.57-5.08), past alcohol abuse (2.26, 1.37-3.74), exposure to didanosine and/or stavudine (1.85, 1.14-3.01), high HOMA index (1.25, 1.04-1.51), older age (1.09, 1.05-1.14) and elevated ALT (1.04, 1.03-1.06) remained as independently associated with ALF. Therefore, in addition to chronic hepatitis C and alcohol abuse, insulin resistance and/or exposure to dideoxy-nucleosides may contribute to ALF in HIV-infected patients.

Modeling the Probability of Sustained Virological Response to Therapy with Pegylated Interferon plus Ribavirin in Patients Coinfected with Hepatitis C Virus and HIV

“…Thus, the performance of our model in different ethnicities or in obese (or slim) persons might be lower. Given that our model was developed in HIV-HCV-coinfected populations, in whom other conditions interfering with treatment outcomes (eg, insulin resistance, drug interactions, and immunodeficiency) are generally more frequent than in HCV-monoinfected persons [3,7,31,32], it is reasonable to assume that our predictive model might perform even better in HCV-monoinfected patients. Studies are ongoing to test this hypothesis.…”

Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: Results from ANRS CO13 HEPAVIH

“…This progression is not linear over time and may occur after only a few years [1,2]. Significant fibrosis in this setting has been linked to a low CD4 cell count, a longer estimated duration of HCV infection, daily alcohol intake, a higher necroinflammation score, steatosis, uncontrolled HIV replication, late initiation of antiretroviral therapy, mitochondrial toxicity due to antiretroviral drugs such as didanosine and insulin resistance (IR) [3][4][5][6][7]. The risk of hepatocellular carcinoma (HCC) is two to six times higher in HIV/HCV-co-infected patients than in HCVmono-infected patients [8].…”

Liver Test Abnormalities in Patients with HIV Mono-Infection: Assessment with Simple Non-Invasive Fibrosis Markers

“…In our study, the duration of ART was the only factor independently associated with the presence of fibrosis based on FIB-4. The impact of ART on liver fibrosis is controversial, as highlighted by conflicting reports on worsening with long-term use of ART, especially didanosine or stavudine [9,31], absence of significant effect [22], or even improvement following commencement of PIs [32,33]. Furthermore, Mendeni et al followed a cohort of 1112 HIV-mono-infected patients for approximately 6 years and found that progression of fibrosis, assessed by APRI and FIB4, was prevented by viral control with early ART, provided that didanosine use was avoided [33].…”

“…Moreover, specific HIV-related factors, such as lipodystrophy or the HIV virus per se, may predispose to NAFLD [7,8]. NAFLD has a prevalence of 20% in the general population of industrialized countries, which rises to more than 50% among those with HIV infection [9,10].…”