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Background:  In patients with HCV alone, hepatic steatosis is associated with genotype 3 infection and increased fibrosis progression rates. Little is known about the prevalence of steatosis in HIV/HCV-co-infected patients or the role which antiretroviral medications may play as potential risk factors in the development of fatty liver. 

Methods:  Retrospective chart reviews of 179 subjects with liver biopsies were conducted in 4 teaching hospitals in New England serving community and incarcerated patients. Data on demographics, medications, and laboratories were abstracted from medical records; all biopsies were read by 1 pathologist who was blinded to the clinical information. Steatosis was graded as absent, minimal, mild, moderate, or severe. Data were analyzed using SPSS version 11.5.

Results:  Characteristics of the 179 patients were:  mean age, 43 ± 7 years; male 79%; mean CD4 446 ± 248 cells/mm³, and median and interquartile range HIV RNA 68 (< 50 to 2683 copies/mL). Racial diversity was:  Hispanic 27%; African American 24%; other 49%; 58% were taking HAART; 69% were taking nucleoside analogs. The distribution of HCV genotypes were 1 (68%), 2 (9%), 3 (19%), and 4 (5%). Steatosis was absent (31%), minimal (23%), mild (28%), and moderate to severe (19%). Patterns of steatosis were macrovesicular (4%), microvesicular (17%), and mixed (52%). On univariate analysis, factors associated with the presence of steatosis included use of dideoxynucleosides (p = 0.029) and the number of nucleoside analogs used (p = 0.042). Borderline associations with higher triglycerides (OR 1.0, 95% CI 1.00 to 1.01, p = 0.08), male gender (OR 2.0, 95% CI 0.97 to 4.3, p = 0.06), and HCV genotype 3 (OR 2.5, 95% CI 0.9 to 6.9, p = 0.09) were also found. Age, race, duration of HIV, alcohol, CD4, HIV RNA, HCV RNA, cholesterol, and use of protease inhibitors were not associated with steatosis. On multivariate analysis, associated with the presence of steatosis were the use of dideoxynucleosides (OR 6.0, 95% CI 1.9 to 18.9; p = 0.002) and other nucleoside analogs (OR 3.0, 95% CI 1.05  to 8.4; p = 0.04) and HCV genotype 3 (OR 3.7, 95% CI 0.92 to 14.5; p = 0.065).

Conclusions:  Hepatic steatosis was prevalent in this racially diverse population of HIV/HCV co-infected patients and was associated with the use of nucleoside analogs, particularly dideoxynucleosides, and with HCV genotype 3. Through their deleterious effects on mitochondria and oxidative phosphorylation, the use of nucleoside analogs may increase hepatic steatosis thereby contributing to liver fibrosis progression.

Keywords: hepatitis C; mitochondrial toxicity; steatosis