Recent outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) have been reported in England, France, Germany, Holland, and the United States. Many of these cases were sexually transmitted, which is unusual because HCV is typically transmitted via injection drug use. Furthermore, many of these men were HIV-positive before they acquired HCV.
Now, researchers in New York report a worrisome new finding: significant liver damage in HIV-positive MSM within months of HCV infection. Acute HCV may be a "whole different level of worry" for HIV-positive people, says Dr. Daniel Fierer of New York's Mount Sinai Medical Center. At this year's 14th Conference on Retroviruses and Opportunistic Infections, Fierer and colleagues presented disturbing data from liver biopsies of five HIV-positive men. Within months of acute HCV infection, four already had developed stage-two liver fibrosis (on a scale of four). Alcohol, recreational drugs, and antiretroviral therapy were eliminated as causing the damage; acute HCV was the sole culprit among all four men.
Significant liver damage has never been reported in otherwise healthy people with acute HCV. Fierer went to medical literature from the pre-HAART era, finding a few reports of rapid HCV progression in people who were already HIV-positive or may have been infected with both viruses at once. In one report, three patients had liver failure within three years; in another, the patient died from liver failure in less than three years. "These cases seem to have been considered 'zebras' [medical oddballs]. In retrospect, they may have been the first reports of the same rapid liver disease progression that we are seeing now in HIV-positive men with acute HCV. I'm concerned that this accelerated pace of liver damage may actually be the usual course, not the 'zebra'," says Fierer.
Acute HCV is difficult to diagnose-there are usually no symptoms. Most cases are detected by chance, during routine liver enzyme testing. "This is a new clinical syndrome. Providers need to be aware that HIV-positive men are getting acute HCV, and many of them do not have traditional risk factors [injection drug use]," says Fierer. He has been talking with HIV specialists around the city, asking them to join the New York Acute HCV Surveillance Network, which he set up to facilitate patient care and research. Surveillance Network providers perform routine liver testing every three months, as well as yearly HCV antibody testing, and repeat these tests when patients acquire sexually transmitted infections, which may pave the way for HCV infection. "We need to get all New York providers involved," Fierer says. "So far we've seen only the tip of the iceberg; for every case we have, there are probably 10 more that we haven't found."
Detecting acute HCV is important, because treating it may prevent progression to chronic infection. "It is one thing to miss acute HCV in an HIV-negative person, who has a good chance of curing it later on and a low risk of getting sick in the meantime. When you miss acute HCV in someone who is HIV-positive, the chance for curing it later is much worse," says Fierer. "Given our recent findings, there may already be significant liver damage, and it may continue to progress rapidly. But the good news is that acute HCV is much easier to treat than chronic HCV, even in HIV-positive patients."
Treatment issues are not necessarily straightforward. HCV therapy has serious side effects. Not everyone with acute HCV needs treatment, regardless of HIV status, since some people are cured by their own immune systems. "Diagnosing acute HCV is not clear-cut, and there are no guidelines or 'standard treatment approach' for acute HCV. When acute HCV is suspected, immediate referral to a specialist is recommended," Fierer cautions.
Fierer admits, "As worrisome as our findings are, these five biopsies many not be representative of all cases. I hope we are wrong in the end, but our findings are too serious to ignore." More research is clearly needed to understand how HCV is spreading in these men and how the accelerated liver damage is occurring. "We have important science left to do," says Fierer.
Tracy Swan is HCV/HIV Coinfection Project Director for the Treatment Action Group (TAG).
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