Background:  Recently, cases of severe liver disease of an unknown origin have been reported in HIV-infected patients without hepatitis B (HBV) or C (HCV) co-infection. An association with previous prolonged didanosine (ddI) exposure has been suggested. The objective of this study was to look for the presence of moderate-severe liver fibrosis (MSLF) of uncertain origin in a cohort of HIV-infected patients.

Methods:  This was a cross-sectional study. We evaluated the presence of MSLF using transient hepatic elastography (THE) in consecutive HIV-infected patients who attended our Infectious Diseases Unit and who did not have HBV or HCV co-infection or evidence of autoimmune or metabolic liver disease or acute hepatotoxicity. A liver stiffness >7.1 kilopascal (kPa) was chosen to define MSLF. In those patients showing MSLF, we exclude occult HBV or HCV infection by testing plasma for the presence of HBV DNA or HCV RNA using polymerase chain reactions assays. Liver biopsy was also performed in those patients with a liver stiffness >7.1 kPa.

Results:  We included 45 patients. The median value (Q1-Q3) of liver stiffness in the study population was 4.5 kPa (3.8 to 5.5). MSLF was present in 4 (8.8%) patients. Occult HBV or HCV infection was excluded in the 4 cases. One patient with a liver stiffness of 7.8 kPa, who had not previously received ddI treatment and did not report alcohol consumption, did not undergo a liver biopsy because he was lost to the follow-up. In a second individual, who showed a liver stiffness of 10.2 kPa, liver biopsy was completely normal. In the third patient, liver stiffness was 14.5 kPa; he was a severe alcohol drinker and had received ddI for 65 months. Liver biopsy revealed typical histological findings of chronic alcoholic liver disease. The last patient showed a liver stiffness of 26 kPa; he did not report alcohol consumption in the last 6 years, but previously had been a heavy drinker. Additionally, he had been exposed to ddI for 69 months. Liver biopsy revealed only moderate microvesicular steatosis.

Conclusions:  THE reveals values of MSLF in a significant proportion of HIV-infected patients without HBV or HCV co-infection. Alcoholic liver disease or false positives of THE may explain most of these cases. Thus, liver biopsy should be performed in patients suspected of presenting MSLF. According to these data, the prevalence of MSLF of uncertain origin seems to be very low.