Bob Roehr

November 08, 2010

November 8, 2010 (Boston, Massachusetts) — HIV infection itself appears to negatively affect liver histology, according to research presented here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting.

Abnormal liver enzymes are common in patients infected with HIV, even in the absence of viral hepatitis or known precipitating factors, such as diabetes or alcohol, but there are few data on the histology that explain why this is so, said Richard K. Sterling, MD, from Virginia Commonwealth University in Richmond, although he added that there has been a suggestion that it might be steatohepatitis.

Dr. Sterling and colleagues undertook a prospective pilot study of liver histology in HIV-positive patients with abnormal liver function tests (>1.25 upper limit of normal in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase [ALP]), but without viral hepatitis, diabetes, or high levels of alcohol consumption (defined as >30 g/day for males and >20 g/day for females). Of the 25 referred patients, to date, 10 have met the entry criteria for this ongoing study.

Dr. Sterling told Medscape Medical News that he wanted to include ALP "because studies in fatty liver patients have shown that some present only with an isolated ALP. By excluding them, I might be excluding something that's out there."

All patients were receiving highly active antiretroviral therapy (HAART) and most had HIV RNA below the level of detection (<48 copies/mL). It is not known how long the patients have been infected or how long they have been on an antiretroviral regimen, factors that might influence disease state. The sample was too small to stratify by HAART regimens, Dr. Sterling noted.

Of the study population, 70% were male and 60% were white. Average age was 46 years, mean weight was 90 kg, mean body mass index (BMI) was 30 kg/m2, mean waist-to-hip ratio was 0.9 5, mean body fat was 33%, mean abdominal fat was 3652 g, and abdomen-to-gynoid-fat ratio was 1.36.

Patients underwent a 2-hour oral glucose tolerance test, had fasting lipids measured, and underwent dual-energy x-ray absorptiometry for fat distribution at the time of liver biopsy. Insulin resistance (IR) was assessed by homeostatic model assessment (HOMA). All histology was blinded and read by the same person.

"The bottom line is that about 60% had steatosis; 20% had grade 1, 30% had grade 2, and 10% had grade 3 steatosis. Cytologic ballooning was seen in 40%, the nonalcoholic steatohepatitis activity score was 2.7, and 40% had steatohepatitis," Dr. Sterling reported.

He added that the lack of difference in body fat, IR, HAART use, and BMI in the patient population did not surprised him. "If you look at the 4 patients who did not have steatosis but did have abnormal liver enzymes, even though their liver enzymes were lower, they still had hepatic inflammation and a fibrosis score of 1."

"There is something going on there. If it is not fat, what is it? I think it may be oxidative stress and other systemic issues related to HIV or HIV treatment. That is what we are trying to explore," he said.

"This has been a population that has been ignored because everyone is so happy that their HIV is under control," said Dr. Sterling. "Perhaps it will be important to identify patients with steatosis because they have an increased cardiovascular risk — which is the number 3 cause of death [in HIV-positive patients], behind HIV [infection itself] and liver [disease]. There may be a relationship between HIV, steatosis, and cardiovascular disease. It is not something that should be ignored."

Clinical implications might include changing HAART regimen to reduce exposure to drugs associated with IR or steatosis. "If they have steatosis, you might start to screen for cardiovascular disease when otherwise you wouldn't," advised Dr. Sterling. "But we don't know for sure, because no one has looked; you have to identify the problem first."

Raymond T. Chung, MD, director of hepatology at Massachusetts General Hospital, in Boston, cautioned against reading too much into a study of 10 patients receiving HAART. Nucleoside reverse-transcriptase inhibitors and protease inhibitors can either "cause intrinsic hepatotoxicity that may include steatosis, or promote peripheral lipolysis and hepatic steatosis, even without clear-cut increases in HOMA-IR. In this group of patients who were on both sets of agents, one must think of their contribution," he told Medscape Medical News.

However, work in his lab suggests that HIV "appears to exert oxidative stress in hepatocytes, likely through the engagement of chemokine coreceptors found in low levels on those cells. This oxidative stress can contribute to a milieu that may promote steatosis and even fibrosis." Perhaps this is sufficient to trigger hepatic injury, particularly when coupled with other insults such as a mild increase in IR or moderate alcohol use.

The National Institutes of Health sponsored the research under an R03 grant. Dr. Sterling and Dr. Chung have disclosed no relevant financial relationships relevant to this study.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 674. Presented October 30, 2010.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.