CROI 2007: Does Pre-existing HIV Infection Lead to Accelerated Liver Fibrosis in People with Acute Hepatitis C?

Multiple outbreaks of acute hepatitis C virus (HCV) infection have recently been reported in cities in the UK and Europe among HIV positive men who have sex with men (MSM). These outbreaks are notable because these patients were already infected with HIV when they acquired HCV. More typically, individuals with both HIV and HCV infection acquired HCV first, since it is easier to transmit (e.g., through shared use of injection drug equipment).

Although much is known about the course of liver disease in HCV-infected patients who later acquire HIV, little is known about the course of liver damage in HIV-infected patients who later acquire HCV.

Researchers at Mount Sinai School of Medicine in New York City conducted a prospective study of HIV-infected MSM with acute HCV infection, including examination of liver histology. At the 14th Conference on Retroviruses and Opportunistic Infections last month in Los Angeles, they reported data from the first 5 consecutively-enrolled patients.

The patients underwent serological testing for hepatitis A virus (HAV) antibodies; hepatitis B virus (HBV) antigens, antibodies, and HBV DNA; and HCV antibodies, HCV RNA, and HCV genotype. They also received liver biopsies within 4 months of the first-noted ALT elevation.

Acute hepatitis C was defined as the first 6 months of HCV infection. Because no single test result provides a definitive diagnosis of acute HCV infection, the researchers considered 3 factors in combination:

• Recent seroconversion to HCV antibody positive status;
• Marked elevations in serum ALT level;
• Wide fluctuations in HCV viral load.

The latter 2 factors are considered hallmarks of acute HCV infection and are uncommon during chronic infection.

All patients were MSM in their 40s who had:

• Recent seroconversion to anti-HCV antibody positive status; in 3 cases, this occurred within a year after a previous negative test, defining a narrow time window in which the new HCV infection could have occurred;
• Rapid changes in ALT levels, with elevations greater than 10 times the upper limit of normal (ULN), consistent with acute hepatitis;
• Wide HCV viral load fluctuations, in 4 cases exceeding 1.5 log₁₀ IU/mL.

Results

• Liver biopsies showed moderate portal fibrosis (stage 2 of 4; Scheuer system) in 3 of 4 patients, as well as acute HCV.
• 1 patient had central hyalin sclerosis.
• All patients denied heavy alcohol use and 1 had never received HAART.
• No cause of chronic liver disease common to all patients could be identified to explain the degree of fibrosis.
• All had negative evaluations for active HAV or HBV infection.
• No evidence for other etiologies of new hepatitis was found.
• All patients had recent histories of unprotected receptive anal intercourse, some with many partners.
• 3 acknowledged a single recent episode of injection drug use, but without clear recollection of sharing injection equipment.
• 1 shared paraphernalia for snorting drugs.
• All denied any other known risk factors for HCV infection.

The researchers concluded that 4 of 5 HIV-infected MSM had moderately advanced portal fibrosis during the acute phase of HCV infection. No other etiologies were found to explain the presence of moderate liver fibrosis in this population, suggesting that pre-existing HIV infection results in accelerated fibrosis progression in patients with acute hepatitis C.

The investigators noted that, “These cases suggest that HIV-infected patients presenting with acute HCV infection may already have significant liver disease, and that liver biopsy should be considered in theses patients.”

They added that further research is needed to define the prevalence and understand the pathogenesis of rapid liver fibrosis in this population.

3/16/07

Reference

D Fierer, A Uriel, D Carriero, and others. Portal Fibrosis During Acute HCV Infection of HIV-infected Men. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, February 25-28, 2007. Abstract 889 (poster).

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