Therapy against HCV infection was prescribed according to the caring physician criteria, based on consensus recommendations in effect along the study period, usually guided by HCV genotype and liver fibrosis stage. End-of-treatment response (ETR) was defined as undetectable serum HCV RNA at the planned date of treatment cessation. Sustained virological ACP-196 mouse response (SVR) was defined as undetectable serum HCV RNA 24 weeks after the end of treatment. Liver steatosis and liver fibrosis were scored blindly by a central pathologist (M.A.J.). HS classification was based on the proportion of hepatocytes containing fat droplets using Brunt’s criteria18 and was classified as

follows: 0, absent steatosis; 1, less than 33% (i.e., mild HS); 2, 33%-66% (i.e., moderate HS); and 3, more than 66% (i.e., severe HS). Lobular inflammation was scored as follows: 0 = no foci; 1 = <2 foci (excludes 2 foci ×200 field); learn more 2 = 2-4 (includes 2 and 4 foci ×200 field) 3 = >4 foci (excludes 4

foci ×200 field). Cytologic ballooning was classified as follows: 0, none; 1, few balloon cells; and 2, many cells/prominent ballooning. The NAFLD activity score (NAS) was calculated as the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores.19 Scheuer’s score20 was applied to stage fibrosis as follows: 0, absent fibrosis; 1, portal fibrotic expansion; 2, extension of fibrosis to the lobule, but with few septa; 3, bridging fibrosis with numerous septa, with architectural distortion without cirrhosis; and 4, cirrhosis. The length of biopsies was recorded to assess their adequacy. The median (interquartile range; IQR) length of the initial biopsy was 17 (15-25) mm, whereas the respective figure of the second biopsy was 18 (16-25) mm. The primary outcome variable of the study was the progression in one or more grades in Brunt’s score. The associations of the following baseline factors with HS progression were analyzed: gender, age, body mass index (BMI), self-reported

selleck daily alcohol intake, diagnosis of diabetes mellitus (DM) following the American Diabetes Association criteria, fasting plasma glucose (FPG), cholesterol and triglycerides (TGs), HCV genotype, and Centers for Disease Control and Prevention (CDC) stage C. In addition, the following variables between biopsies and their relationship with HS progression were assessed: BMI, self-reported daily alcohol intake, FPG, cholesterol and TGs, response to treatment against HCV, CD4 cell counts at liver biopsies, plasma HIV RNA viral load at liver biopsies, exposure to ART, and changes in fibrosis stage. Cumulative exposure to individual antiretroviral drugs was calculated as the period in years receiving each antiretroviral drug between biopsies. Blood tests were drawn within 1 month before the liver biopsies. The secondary outcome variable was persistence of steatohepatitis between biopsies or progression to steatohepatitis in the final biopsy.