HS severity progresses with time frequently in HIV/HCV-coinfected patients, both in those who receive ART and in those who do not. HS regression is rarely observed in this setting. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are associated with HS progression. In addition, steatohepatitis is frequently observed in HIV/HCV-coinfected patients, and NAS score increases over time in these individuals. Steatohepatitis tends to be associated with more-prolonged exposures to ART and dideoxynucleoside

analogs. Importantly, persistence of or progression to steatohepatitis is linked to fibrosis progression in HIV/HCV coinfection. The results of the herein reported study are in contrast with the study by Woreta et al. that assessed HS progression in paired liver biopsies from HIV/HCV-coinfected patients.15 In that study, fewer patients presented HS at baseline and HS did not progress Selleckchem Enzalutamide in approximately 90% of patients in the follow-up biopsies.15 On the contrary,

in our study, 60% of patients showed some degree of HS in the initial biopsy, increases of 1 stage in HS was observed in 40% of patients, and progression to moderate or severe HS was observed in 23% of individuals. The reasons for Autophagy Compound Library ic50 such conflicting data are unclear. The participants in the study by Woreta et al. were overwhelmingly HCV genotype 1–infected African Americans,15 whereas patients in the present study were Caucasians with infection by more-diverse HCV genotypes. This may partly explain the lower prevalence and progression of HS in the study by Woreta et al., given that individuals with African ancestry might have a lower

propensity to develop NAFLD.21 However, a recent meta-analysis did not selleck find a significantly different prevalence of HS among HIV/HCV-coinfected African Americans.12 The high prevalence of HCV genotype 3 may partially account for the higher rates of HS in our study, given the association between this genotype and HS.2-4, 11 Nevertheless, HCV genotype 3 was not associated with HS progression in our study. The role of ART in the development of HS is controversial. We found that HS progression between liver biopsies was associated with cumulative exposure to dideoxynucleoside analogs. This finding is in agreement with previous cross-sectional studies.4, 6, 14 Dideoxynucleoside analogs, susc as didanosine, stavudine, and zalcitabine, are potent inhibitors of mitochondrial DNA (mtDNA) polymerase-gamma, the enzyme responsible for mtDNA replication. mtDNA depletion impairs respiratory chain activity and thus inhibits mitochondrial β-oxidation, finally causing abnormal deposition of fatty acids in hepatocytes.22 However, most reported cross-sectional studies failed to find an association with ART or individual antiretroviral drugs.1-3, 5, 7 One possible explanation might be different exposures to dideoxynucleoside analogs across studies.