Background:  Assessment of hepatic fibrosis using a non-invasive tool, such as elastometry (FibroScan), allows to hepatic fibrosis staging in large number of patients. Identification of risk factors for advanced liver fibrosis (ALF) is crucial in HIV patients, as liver complications are frequent, mainly due to viral hepatitis and/or the toxicity of antiretroviral medications.
Methods:  Longitudinal study of all HIV outpatients attended at our clinic who underwent liver fibrosis assessment by FibroScan since 2005. ALF was defined as liver stiffness >9.5 kPa (Metavir F3-F4). Main demographics including alcohol abuse, antiretroviral exposure, biochemistry, immune, and viral parameters, homeostasis model assessment (HOMA), and hepatitis B  virus (HBV) and hepatitis C virus (HCV) status were recorded.
Results:  Liver fibrosis was measured by FibroScan in 681 randomly selected HIV patients, 72% of whom had plasma HIV RNA <50 copies/mL. ALF was diagnosed in 215 (32%). In the univariate analysis, significant differences were found between patients with and without ALF for: mean age (44 vs 42 years), alcohol abuse (51 vs 27%), CD4 count (469 vs 550 cells/mm³), HCV RNA⁺ (77 vs 52%), glucose (127 vs 116 mg/dL), triglycerides (223 vs 171 mg/dL), total cholesterol (177 vs 188 mg/dL), elevated ALT (29 vs 9%), HOMA (4.5 vs 3.2), past exposure to didanosine+stavudine (ddI+d4T) (51 vs 40%), and median months on nevirapine (NVP) (11 vs 15), lopinavir (LPV) (12 vs 8), other ritonavir-boosted protease inhibitor (PI) (23 vs 16), any PI (39 vs 31), as well as any antiretroviral (85 vs 78). Time under antiretroviral therapy was directly associated with the rate of ALF:  2% if <1 year, 11% if 1 to 3 years, 21% if 4 to 6 years, and 66% if >6 years (p = 0.14). In the multivariate analysis (OR, 95%CI), variables significantly associated with ALF were: elevated ALT (33, 11 to 100), older age (1.1, 1 to 1.12), hyperglycemia (1.01, 1 to 1.02), and low CD4 count (0.99, 0.99 to 1).
Conclusions:  A longer exposure to antiretroviral drugs might be associated with ALF, particularly if dideoxy-nucleosides or PI have been used. Mitochondrial toxicity and metabolic abnormalities might respectively be the underlying mechanism to explain this observation. On the contrary, immune recovery could protect against ALF.