Fatty liver present in 40% of HIV/HCV coinfected patients: drug choice and weight may contribute

Hepatic steatosis, or fatty liver, was present in 40% of a cohort of American patients coinfected with HIV and hepatitis C, researchers from Johns Hopkins School of Medicine report in the April 8th edition of the journal AIDS. The risk of hepatic steatosis was greatest in patients with more advanced liver disease, and in those receiving treatment with stavudine (Zerit) and those suffering from hyperglycemia and/or obesity. Almost half of the patients exposed to a drug combination that included both stavudine and a protease inhibitor had hepatic steatosis.

Hepatic steatosis – the accumulation of fatty acids in the liver - occurs frequently in people who are obese and in those with hyperglycemia, hyperlipidemia and/or high alcohol consumption. It also occurs in people with hepatitis C infection and may worsen liver inflammation and fibrosis (Martin-Carbonero 2005).

Dr Mark Sulkowski and colleagues randomly selected 112 patients with HIV/HCV coinfection exposed to at least two years of antiretroviral therapy from the Johns Hopkins University HIV Clinic population. Patients who had already received treatment for hepatitis C were excluded.

Liver inflammation, fibrosis and steatosis were assessed by liver biopsy. Fibrosis was assessed using the Modified Hepatic Activity Index scoring system, and hepatic steatosis was classified on a five point scale (0 – no steatosis; 1 – steatosis involving <5% of hepatocytes; 2 – 5-29%; 3 – 30-60%; 4 >60%).

The patient population selected was predominantly African American (94%), male (64%) and infected with HCV genotype 1 (99%). Twenty-six per cent weighed more than 86kg, 28% had hyperglycemia (glucose > 2.0g/l) and 22% had hypercholesterolemia (total cholesterol >200g/l). Forty-six per cent had been diagnosed with alcoholism previously, although few reported current alcohol use. Seventy-four per cent were taking antiretroviral therapy at the time of biopsy, of whom 86% had been exposed to stavudine. The median duration of NRTI exposure was 5.8 years.

Forty per cent of patients were found to have hepatic steatosis, of whom 22% had grade 1 steatosis, 13% had grade 2 steatosis and 5% had grade 3 steatosis. None had lactic acidosis. There was no difference in the prevalence of steatosis between those patients receiving antiretroviral treatment and those who had stopped treatment.

Fibrosis of MHAI grade 3 or above was present in 36% of patients with steatosis compared to 16% of those without steatosis (p=0.02). Necroinflammatory activity was also more frequent in those with steatosis (p=0.005).

Multivariate analysis showed that hepatic steatosis was independently associated with Caucasian race (OR 11.2), weight > 86kg (OR 3.2), hyperglycemia (OR 3.4) and prior exposure to stavudine (OR 5.1). Hepatic steatosis was not detected in any patient without prior exposure to stavudine plus a protease inhibitor, and was not associated with past alcohol use.

The authors say that their findings are consistent with other cohorts, and that the association with stavudine is presumably due to inhibition of mitochondrial DNA and possible depletion of hepatic mitochondrial DNA.

“These data…suggest that stavudine should be avoided in HIV-HCV coinfected patients with hepatic steatosis,” ther authors state. “If confirmed, our findings suggest that weight reduction and discontinuation of stavudine should be investigated as measures that could reduce hepatic steatosis in affected or at-risk individuals.”

In an accompanying editorial, Spanish coinfection experts Vincent Soriano and Luz Martin-Carbonero note that since only 4 of 112 patients had not received stavudine, and no difference was noted between patients currently receiving the drug and those who had discontinued it, caution should be used in interpretation of these findings.

Whilst experts increasingly support early HIV treatment for coinfected patients in order to limit the impact of immunodeficiency on liver disease, the editorial authors remark that, “depending on the antiretroviral drugs in use, the positive effects of HAART over HCV-related liver disease might be overshadowed by the development of drug-associated liver toxicities…a closer look is warranted.”