Background:  In hepatitis C virus (HCV)-infected persons, liver biopsy remains the only proven means of staging liver disease and assessing the treatment need. However, the test is invasive and not uniformly available. The objective of this study was to examine the hypothesis that serologic tests (markers) could identify the stage of liver disease.

Methods:  In another study, 137 HIV/HCV-co-infected persons were randomly selected from patients enrolled in the Johns Hopkins HIV Clinic cohort. Of the 137, 113 underwent liver biopsy and 96 had complete testing for fibrosis markers in sera collected at the time of biopsy. Biopsies were scored by a single pathologist according to Ishak modified histological activity index from F0 (no fibrosis) to F6 (cirrhosis). Liver fibrosis scores were evaluated against the following candidate serum markers (thresholds) alanine aminotranferase (ALT<93 IU/L), aspartate aminotransferase (AST <61 IU/L), albumin (>3.6 g/dL), total bilirubin (TB <1.2 mg/dL), and hyaluronic acid (HA <42 [median], 42 to 85 [quartile 3], and >85 ng/mL [quartile 4]).

Results:  The median age of the biopsied subjects was 38 years (interquartile range [IQR], 33 to 41); 65% were male; 95% were black; 49% acknowledged current alcohol use; 51% were taking ART; the median CD4 count was 340 cells/mm³ (IQR 171 to 526); median HIV RNA level was 340 copies/mL (IQR 31 to 26924). Of the 96 subjects with a liver biopsy and complete fibrosis marker testing, 60 (62%) had no or just portal fibrosis (F0-2) and were compared with the remaining subjects with more severe fibrosis/cirrhosis (F3-6). Results of ALT and AST testing were highly correlated and considered separately. After adjusting for age and gender, fibrosis scores of more than 2 were found 12 times more often in persons with HA levels > 85 ng/mL (95% CI:  3.46, 43.35) and 2.8 times more often in persons with HA levels 42-85 (95% CI:  0.87, 9.20). Less significant associations were detected with levels of albumin (OR 3.54 95% CI:  0.94, 13.31) and AST (OR 2.22 95% CI:  0.74, 6.68). All 35 subjects who had favorable results of HA, albumin, and AST had fibrosis scores of 2 or less.

Conclusions:  In this HIV/HCV-co-infected clinic-based cohort, persons who did not have advance stages of hepatic fibrosis could be identified by serum testing for HA, albumin, and AST. If these results are confirmed, the data suggest that serum fibrosis markers might be used to identify persons with a low stage of liver disease.

Keywords: HCV; liver; fibrosis marker