SUMMARY: A poster presented last week at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) in Vienna suggests that HIV/HCV coinfection may not significantly accelerate liver fibrosis progression compared with HCV alone. This biopsy study adds to a conflicting body of evidence about the impact of HIV on hepatitis C pathogenesis.

By Liz Highleyman

It is generally assumed that HIV/HCV coinfected is associated with more rapid liver disease progression compared with hepatitis C virus (HCV) infection alone, but studies to date have produced conflicting results, during both early and later stages of HCV infection.

Researchers at Mt. Sinai School of Medicine in New York City first reported in 2007 that liver biopsies from HIV positive men showed alarmingly high rates of fibrosis progression after only a short duration of HCV infection.

At the recent 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010), European investigators reported an extremely high rate of apparent fibrosis progression over a short interval in HIV positive people with recent HCV infection using the FibroScan method. The rate was so high, in fact, that the investigators concluded that dramatic short-term changes in FibroScan measurements during acute infection likely do not reflect actual rapid fibrosis, but may be influenced by inflammation.

FibroScan, or transient elastometry, uses ultrasound to measure liver "stiffness," which is used to estimate fibrosis stage. Though not as accurate as liver biopsy, it is non-invasive and less expensive, making it more acceptable for serial assessments over time.

Looking at longer-term chronic hepatitis C, Spanish investigators reported reported at CROI that despite effective antiretroviral therapy (ART), liver fibrosis progresses in a significant proportion of HIV/HCV coinfected patients over a relatively short period, again based on a FibroScan analysis.

Now, in the study presented this year at EASL, U.S. researchers have found -- using the liver biopsy "gold standard" -- that fibrosis progression appears similar in HIV positive and HIV negative individuals with chronic HCV infection.

Richard Sterling and colleagues from Virginia Commonwealth University conducted a prospective longitudinal cohort study to compare fibrosis progression using paired liver biopsies in HIV/HCV coinfected people and those with HCV alone, and to assess factors associated with worsening liver disease.

Out of a cohort of about 300 HIV/HCV coinfected patients, the researchers identified 56 people without cirrhosis at baseline who underwent paired liver biopsies. The average age was 44 years, about 80% were on ART, and the median CD4 count was high at 571 cells/mm3, but only 40% had HIV viral load < 400 copies/mL.

These coinfected participants were matched with HCV monoinfected patients based on demographic characteristics, initial fibrosis stage, and hepatitis C treatment status. The coinfected patients had a shorter average interval between biopsies than the HCV monoinfected individuals (4.7 vs 5.9 years).

Results

	Liver biopsies from HIV/HCV coinfected patients showed significantly higher piecemeal necrosis (dead liver cells) and lobular inflammation compared with HCV monoinfected participants.
	Between the first and second biopsies, coinfected participants and those with HCV alone experienced the following outcomes:
	Fibrosis remained unchanged: 55% of coinfected vs 45% of HCV monoinfected; Fibrosis progressed 1 stage: 18% vs 30%, respectively; Fibrosis progressed 2 stages: 18% vs 9%, respectively.
	The fibrosis progression rate was statistically similar between the HIV/HCV coinfected and HCV monoinfected groups (0.13 vs 0.064 units/year; P = 0.72).
	Among the coinfected participants, no associations were observed between fibrosis progression and any of the following factors:
	Demographics (age, sex, race/ethnicity); CD4 cell count; Antiretroviral therapy use; ALT and AST liver enzyme levels; Baseline liver disease (inflammation, fibrosis, or steatosis); Response to hepatitis C therapy.

Based on these findings, the researchers concluded, "When matched for baseline fibrosis, fibrosis progression is similar in HIV/HCV coinfection and HCV monoinfection."

The previous reports of rapid disease progression in coinfected patients, they suggested, "may have been biased by patient selection in the early HAART era."

However, since there were no clinical or laboratory parameters that predicted disease progression, the researchers recommended that "all coinfected patients should be considered for repeat assessment of disease severity by liver biopsy at periodic intervals in order to identify those who progress."

Gastroenterology, Hepatology, and Nutrition, Biostatistics, Virginia Commonwealth University, Richmond, VA.

4/20/10

Reference
R Sterling, JA Wegelin, PG Smith, and others. A prospective evaluation by paired biopsy of fibrosis progression in HIV-HCV coinfection compared to HCV monoinfection. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. Abstract 1082.