Subset of HIV/HCV Co-infected at Risk for Hepatic Steatosis

By: MARY ANN MOON,
Internal Medicine News Digital Network
03/01/11

In patients co-infected with HIV and hepatitis C virus, alcohol use and a high body mass index are associated with progression of hepatic steatosis, whereas exposure to certain antiretrovirals and a high baseline CD4 count appear to be protective against steatosis, Dr. Tinsay A. Woreta and her colleagues reported in the March issue of Gastroenterology.

In their study of 222 patients who were co-infected with HIV and HCV, more than 90% showed no progression of steatosis during nearly 3 years of follow-up.

The findings indicate that efforts to diagnose and prevent hepatic steatosis "should be focused on persons with a high body mass index and excessive alcohol intake," said Dr. Woreta of Johns Hopkins University, Baltimore, and her associates (Gastroenterology 2011 March [doi:10.1053/j.gastro.2010.11.052]).

Hepatitis C virus is not uncommon in patients with HIV infection, and hepatic steatosis affects 30%-70% of those with both infections. The steatosis is associated with hepatic fibrosis and is thought to contribute to the more rapid progression of liver disease in co-infected patients than in those who don’t have concomitant HIV.

"The natural history of hepatic steatosis is incompletely understood" because most studies have been cross-sectional rather than longitudinal," wrote Dr. Woreta and her colleagues. They performed their longitudinal study to prospectively examine the natural history of steatosis, using data from HIV/HCV–co-infected patients who underwent serial liver biopsies while attending an urban HIV clinic.

There were 345 pairs of serial biopsies available for analysis. The study subjects had a median age of 44 years; 66% were men and 87% were black. Nearly half were overweight or obese. Almost all (94%) had HCV genotype 1.

Most patients (194, or 87%) had no or only trivial hepatic steatosis at baseline, and it did not progress during follow-up in 165 (74%) of them. The other 29 patients who had no or only trivial hepatic steatosis at baseline progressed to significant steatosis during follow-up.

In all, 28 patients had significant hepatic steatosis at baseline, and the steatosis actually regressed in 21 (75%) of them. The other seven patients who had significant hepatic steatosis at baseline maintained that steatosis.

Persistence or progression of steatosis was strongly associated with a history of alcohol abuse. Although few patients reported current alcohol abuse, the medical records showed chronic alcoholism or abuse in approximately half. Many study subjects were probably underreporting their current exposure, particularly because they were aware that they were participating in a study of liver outcomes. "Clinicians evaluating fatty liver disease in HIV-infected patients should remain cognizant about the likelihood of underreporting of alcohol consumption," the investigators noted.

Obesity also was strongly associated with persistent or progressive steatosis, which was not unexpected. Although HIV infection was, until a short time ago, "a progressively fatal disease characterized by severe wasting, the advent of HAART [highly active antiretroviral therapy] has transformed HIV into a chronic disease with an increase in the prevalence of obesity."

"These data underscore the importance of measures to prevent and treat obesity in HIV/HCV–co-infected patients, [given] the development or worsening of hepatic steatosis in these patients," the researchers said.

Longer exposure to antiretroviral therapy appeared to be protective against persistent or progressive steatosis. One possible mechanism for this finding is that HIV infection may promote steatosis by facilitating HCV replication in hepatocytes, so reducing the HIV load would ease steatosis.

"Another possibility is that HIV acts synergistically with HCV to disrupt lipid metabolism. Thus, direct inhibition of HIV viral replication could decrease steatosis, particularly if the antiretroviral agent [has] minimal impact on mitochondrial replication and function," Dr. Woreta and her colleagues said.

They emphasized that stavudine, which has been designated as a "nonpreferred" antiretroviral agent because it was thought to contribute to steatosis, was used by only 6% of patients in this study, so the authors were unable to assess its effects.

A higher CD4 cell count at baseline also appeared to be protective against steatosis. The investigators did not offer any possible explanations for this effect. No association was found between steatosis progression and patient age, sex, race, diabetes status, HCV genotype, fibrosis status, or HCV therapy, they noted.

This study was supported by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the National Center for Complementary and Alternative Medicine, the Agency for Healthcare Policy and Research, and the clinical research unit at the Johns Hopkins Medical Institutions. The investigators reported that they had no financial conflicts of interest.