Rapid Liver Fibrosis Progression and Successful Treatment of Acute Infection Suggest Benefits of Routine HCV Screening for HIV Positive Men

		SUMMARY: Researchers from Mt. Sinai School of Medicine presented data last week at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston that further characterize a cohort of HIV positive men with apparently sexually transmitted acute hepatitis C virus (HCV) infection. This group continues to experience more rapid than expected liver fibrosis progression. Hepatitis C treatment has been highly successful if started during the acute phase, but less so thereafter. The researchers recommended routine ALT and HCV antibody testing to allow for prompt treatment and to prevent liver disease progression.

By Liz Highleyman

Starting around 2002, clinicians in large cities in the U.K. and Europe began reporting outbreaks of acute HCV infection among HIV positive gay and bisexual men, which were associated with sexual risk factors and reflected social and sexual networks. Such outbreaks have since been reported in Australia and the U.S.

Dr. Daniel Fierer and colleagues have been following a cohort of HIV/HCV coinfected men seen at Mt. Sinai in New York City. They first reported on rapid fibrosis progression in this group at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2007, following up with data from the growing cohort at CROI 2008 and CROI 2009, and in the September 1, 2008 Journal of Infectious Diseases.

This year at AASLD, Dr. Fierer presented data from 51 HIV positive men who have sex with men (MSM) who experienced 53 episodes of acute hepatitis C (some were infected twice). Acute HCV infection was defined as newly identified HCV antibody seroconversion, marked elevation in liver function tests (ALT > 5 times the upper limit of normal), or large fluctuations in HCV RNA level (>1 log in 4 weeks).

ACUTE HEPATITIS C

The median age of the coinfected cohort was 40 years. About half (27 men) were white, 17 were Hispanic, 6 were black, and 1 was Asian. Most (49 men) had HCV genotype 1. The median duration of HIV infection was 7 years (range 0 to 20 year) and the median CD4 cell count was 471 cells/mm3; 14 men -- 27% of the cohort -- had never received antiretroviral therapy for HIV.

Out of this group, 21 patients and 21 age-matched HIV positive but HCV uninfected men were included in a case-control analysis to identify sexual and drug use risk factors for acute HCV infection. In addition, 30 of the coinfected men underwent liver biopsy histology evaluation (median 4.4 months after their first ALT elevation) and 34 were treated with pegylated interferon plus ribavirin.

Results

	Spontaneous HCV clearance occurred in only 5 cases (9%), with 3 still under evaluation.
	In the case-control study of 21 matched pairs, the factors significantly associated with increaed risk of HCV infection were:
	Unprotected receptive anal intercourse with ejaculation (P = 0.04); Unprotected receptive anal intercourse without ejaculation (P = 0.03); Unprotected receptive oral sex with ejaculation (P = 0.03); Use of sex toys (P = 0.03); Sex while "high" (P = 0.01); Marijuana use (P = 0.04).
	Protected receptive anal intercourse, protected receptive oral sex, and fisting -- risk factors reported in some other HIV positive MSM coinfection cohorts -- were not significantly associated with acute HCV infection (all P > 0.05).
	The traditional risk factors of injection drug use and sharing injection equipment also were not significantly linked to HCV infection (again, all P > 0.05).
	Among the treated patients:
	1 was lost to follow-up; 15 were still receiving therapy; 16 were assessed for sustained virological response (SVR) 24 weeks after completing treatment; 1 achieved an end-of-treatment response and was pending further follow-up to assess SVR.
	Of the 16 patients who completed therapy and were evaluated for SVR:
	12 (75%) achieved a sustained response. 1 never suppressed HCV RNA; 2 responded but experienced viral breakthrough during treatment; 1 achieved virological response but relapsed after completing treatment.
	3 of the 4 patients who did not achieve SVR started treatment after the acute phase (i.e., more than 6 months after their first ALT elevation).
	Among the 30 participants who underwent liver biopsies:
	21 (70%) had stage 2 (moderate) fibrosis using the Scheuer scale (0 to 4); 2 (7%) had stage 3 (advanced) fibrosis; 5 (17%) had stage 1 (mild) fibrosis; 2 (7%) had stage 0 (absent) fibrosis.
	77% participants had fibrosis stage > 2 at this phase of infection, while just 24% had stage < 2.
	Fibrosis stage increased with time-to-biopsy; of the 7 biopsies performed more than 1 year after the first ALT elevation, all showed stage > 2 fibrosis.

These findings indicate poorer outcomes among individuals who are already HIV positive at the time of acute HCV infection. The spontaneous clearance rate of 9% is considerable lower than the approximately 25% reported in most studies of HIV negative people. Furthermore, the extent of liver damage during acute or early infection was dramatically greater than that observed in most studies of HIV negative patients. One such study, for example, found that all 87 patients assessed during acute infection had stage 0 fibrosis, with none having stage 1 or higher.

Participants in the Mt. Sinai study had none of the usual risk factors associated with pre-existing liver fibrosis, including a history of ALT elevation or heavy alcohol use. Hepatitis B triple infection was rare. Most had a healthy body weight and normal blood sugar levels. One-quarter had never taken antiretroviral drugs and some reported never using any recreational drugs.

Based on these findings, the researchers concluded that acute HCV infection of HIV positive MSM in New York City is sexually transmitted and results in "rapid and significant" liver fibrosis progression. They added that acute HCV infection was associated with unprotected receptive sex.

"This epidemic represents a new clinical syndrome for HCV infection that turns much of our knowledge on its ear," Dr. Fierer said in a press release issued by AASLD. This is "a new risk group becoming infected through a previously rare route of transmission resulting in unprecedented progression of liver fibrosis."

"Treatment is highly successful when initiated in the acute phase, but may be less successful if initiated soon after," the investigators noted. "Thus, it is crucial to detect HCV infection in the acute phase to allow successful treatment and prevent further progression of the already significant liver fibrosis."

"We therefore recommend ALT testing every 3 months and HCV antibody testing every 6-12 months for all HIV-infected MSM," they advised. "Promotion of safe sex is also warranted."

Department of Medicine and Department of Pathology, Mount Sinai School of Medicine, New York, NY.

11/10/09

Reference
DS Fierer, AJ Uriel, DC Carriero, and others. Characterization of an Epidemic of Sexually-transmitted Acute Hepatitis C Infection in HIV-infected Men in New York City. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 82.

Other source
AASLD. New Epidemic of Sexually Transmitted Hepatitis C Infection in HIV-infected Men in NYC. Press release. October 30, 2009.