Background:  Inflammation, steatosis, and fibrosis are common histologic findings in liver biopsies of HIV/hepatitis C virus (HCV) co-infected patients receiving ART. These ones can be caused by HCV, alcohol intake, obesity, ART, and other factors.

Methods:  For 164 HIV/HCV co-infected patients who underwent liver biopsies, necroinflamatory activity and fibrosis were scored by the Scheuer system. Steatosis was scored by a single pathologist according to the percentage of hepatocytes affected Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Logistic regression analysis were used to assess determinants of advanced fibrosis (F3 to 4), and necroinflammatory activity.

Results:  At the time of biopsy, patients were mean age was 38±4, male 76%, Caucasian 100%. Estimated median duration of HCV infection was 20 (15 to 22) years; 54% were HCV genotype 1, 28% type 3; 57% AIDS diagnosis; 15% prior alcohol abuse; median CD4 cell count 486 (357 to 653); 44% had HIV RNA <50 copies/mL; 88% had received ART and 78% were receiving HAART; 26% had advanced fibrosis (36 F3, 6 F4); 65% showed steatosis (17% in >30% of hepatocytes); 28% had necroinflammatory activity ≥3. On univariate analysis, factors associated (p <0.05) with advanced fibrosis were prior alcohol abuse, CD4 nadir ≤100, highest HIV viral load ≥10,000, steatosis, severity (>30%) of steatosis, necroinflammatory activity, indinavir (IDV) exposure and saquinavir (SQV) exposure (this last 1 as decreased risk; OR 0.42, 0.18 to 0.98, p = 0.047). We did not find any statistically significant association between advanced fibrosis and cumulative exposure in moths with any antiretroviral drug except for SQV (p = 0.055). On the multivariate analysis factors associated with advanced fibrosis were CD4 nadir <100 (OR 4.46, 1.38 to 14.3, p = 0.012), IDV exposure (OR 4.2, 1.25 to 14.09, p = 0.012), necroinflammatory activity (OR 58.5, 15.8 to 216.2; p = 0.000), and steatosis >30% (OR 3.6, 1.02 to 12.4, p = 0.046). On univariate analysis, factors associated (p <0.05) with necroinflammatory activity ≥3 were current alcohol abuse, advanced fibrosis, steatosis (but not steatosis>30%), and current therapy with lamivudine (3TC) as protector. No association between necroinflammatory activity and cumulative exposure in moths with any ART, including 3TC (p = 0.179). On multivariate analysis factors associated with necroinflammatory activity ≥3 were advanced fibrosis (OR 34.8, 12.6 to 96.5, p = 0.000) and current therapy not including 3TC (OR 3.75, 1.39 to 10.12, p = 0.009).

Conclusions:  Severity of steatosis, inflammation, low CD4 cell count, and IDV exposure were associated with advanced fibrosis. Use of 3TC was associated with a decreased level of necroinflammatory activity in the liver.