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Background:  The relationship of liver histology and hyperglycemia is unknown. The purpose of this investigation was to examine the relationship between liver histology, ART, and hyperglycemia among HIV/HCV-co-infected individuals attending an urban HIV clinic.

Methods:  We conducted a cross-sectional analysis that was further confirmed by a prospective study among 203 HIV/HCV-co-infected members of the Johns Hopkins HIV clinic who had a liver biopsy and glucose levels before and after biopsy. Biopsies were evaluated by a single pathologist and scored according to the Ishak modified histological activity index scoring system from F0 (no fibrosis) to F6 (cirrhosis). Steatosis was characterized from no fat, to < 5% fat, 5 to 30% fat, and > 30% fat. Hyperglycemia was defined as plasma glucose > 200 mg/dL. Exposure to ART was prospectively ascertained.    

Results:  Prevalence of Hyperglycemia:  Median age was 55 years, 67% were male, 85% African American, and 18% had prevalent hyperglycemia. Prevalence of hyperglycemia was significantly higher among those with ≥ F3 fibrosis (28%) compared with < F3 fibrosis (15%, p = 0.03). Moreover, the prevalence of hyperglycemia increased with higher degree of steatosis, (no fat, 15%; < 5% fat, 23%; 5 to 30% fat, 28%; > 30% fat, 43%; p = 0.02). In multivariate logistic regression analysis, body weight > 190 pounds (OR, 2.3; 95% CI 1.1 to 5.2), ≥ 5 years of ART (OR, 2.9; 95% CI 1.3 to 6.3) and ≥ F3 fibrosis (OR, 2.2; 95% CI 1.1 to 4.8) were independently associated with hyperglycemia. Prevalence of hyperglycemia was highest in those with ≥ F3 fibrosis and ≥ 5 years of ART (44%; OR compared with < F3 fibrosis and < 5 years of ART, 6.7; 95% CI 2.3 to 19.2). Incidence of Hyperglycemia:  These histologic findings were subsequently confirmed in a prospective analysis. Of 166 individuals without hyperglycemia at biopsy, 11% developed hyperglycemia during follow-up, for a cumulative incidence of 27%. Cumulative incidence of hyperglycemia was higher in persons with ≥ F3 fibrosis (40%) compared with < F3 fibrosis (23%, p = 0.02) and in persons with steatosis (38%) compared with without steatosis (21%, p < 0.01).  

Conclusions:  In this HIV/HCV-co-infected population, there is a strong relationship between hepatic steatosis, fibrosis, and hyperglycemia. If confirmed, these data support efforts to treat HCV and to use ART regimens that have the least associated risk of hyperglycemia in HIV/HCV-co-infected persons.

Keywords: Hepatitis C virus/HIV coinfection; Hyperglycemia; Liver histology