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CATIE - www.catie.ca

CATIE News - Study finds recovery from hepatitis C does not confer protection from future infection

04/05/2010 - Hepatitis C virus (HCV) can infect the liver and damage this organ. If HCV infection becomes chronic, then over the long term the liver is gradually destroyed and there is an increased risk for liver cancer.

HCV is most commonly spread through the sharing of equipment used for injecting or inhaling illicit substances. However, in the past decade, research teams in several high-income countries have increasingly documented the sexual transmission of HCV among HIV-positive men who have engaged in one or more of these high-risk activities:

  • unprotected anal sex
  • unprotected group sex
  • unprotected fisting
  • sharing of sex toys

In the setting of HIV infection, HCV-related liver damage is accelerated. Furthermore, HCV infection appears to weaken the immune system. Although there is treatment for HCV infection, recovery rates are not as good in people co-infected with HIV compared to people infected with HCV alone. At best, treatment for HCV infection is highly unpleasant and expensive.

Hospital-based researchers in London, England, conducted a study to understand why some HIV-positive men who had apparently recovered from HCV infection had HCV yet again. Investigation was needed because researchers were unsure whether the men were re-infected or had a relapse of their initial HCV infection. The study's findings have implications for HCV prevention efforts among gay and bisexual men.

Study details

Researchers reviewed their database containing health-related information on HIV-positive people who had also been diagnosed with acute HCV infection between 1999 and 2008. The study team focused on people who developed a second bout of HCV after apparently recovering from their first episode of this infection. Researchers collected blood samples and reviewed medical histories of 22 participants, all of whom were gay and bisexual men who did not inject illicit substances. Virologists conducted extensive analysis of the HCV found in the men during the first and second episodes of this infection.

On average, these 22 men were 40 years old and had 463 CD4+ cells at the time they were initially infected with HCV.

Results

During their first episode of HCV infection, 20 of the 22 men each received six months of anti-HCV treatment-the usual length of therapy for acute HCV infection in research centres. The remaining two men spontaneously recovered from HCV infection.

The second episode of HCV occurred an average of 22 months after the first. During this interval, medical records revealed 27 sexually transmitted infections (STIs) among 18 of the men. The most commonly diagnosed STIs were syphilis and gonorrhea. The research team noted that these infections were evidence of unprotected sex.

All cases of a second episode of HCV were symptom free and HCV infection was only detected with routine laboratory testing of blood. The average CD4+ cell count during the second episode of HCV was 512 cells.

Comparing viruses

Researchers were able to isolate HCV from the first and second episodes of HCV infection in nine of the 22 men. A sophisticated virologic analysis (called a phylogenetic analysis) was done to assess how closely HCV from the first and second episodes were related.

In six out of eight men, phylogenetic analysis revealed that HCV from the first and second episodes were only distantly related. According to the researchers, this finding provided "powerful evidence that these individuals were re-infected with a different strain of HCV."

Researchers discovered that the ninth man was initially infected with HCV genotype 4 and during his second episode the type of HCV was found be to genotype 1a. This finding was also suggestive of re-infection.

In several other cases in which virus samples were not available for phylogenetic analysis, the HCV genotype was recorded in the men's medical charts. In at least three cases the genotypes were different between the first and second episodes of HCV infection, evidence of re-infection.

An important finding from this study is that previous exposure to HCV does not provide protection from future exposure(s). Experiments with chimpanzees who are exposed to HCV and then recover from this initial infection have found that they are "highly susceptible" to subsequent infection, according to the London team.

The researchers stated that re-infection "remains strongly related to levels of ongoing risk behaviour."

Given the relatively high rate of HCV re-infection rather than relapse, the research team encourages doctors who detect an apparent re-emergence of HCV to ask their patients about these issues:

  • recent sexual activity
  • substance use
  • The researchers also recommend that doctors have HCV genotyped, as this may help determine whether relapse or re-infection has occurred. Finally, where research centres are willing and able to assess the relatedness of HCV, the UK study team suggests that phylogenetic analysis may also help clarify whether relapse or re-infection has occurred.

    Although highly active antiretroviral therapy (HAART) can suppress levels of HIV and raise CD4+ cell counts, it does not fully restore the immune system. Much of the immune system is found in lymph nodes and tissues scattered around the intestinal tract. The rectum and anus represent the end points of the intestinal tract. The immune system resident at that end of the intestinal tract may still be relatively weak and unable to contain and vanquish some infections. This may, in part, explain why some HIV-positive men who engage in unprotected anal sex and other behaviours remain susceptible to complications arising from sexually transmitted infections such as HCV, HPV, Lymphogranuloma venereum (LGV) and syphilis.

    The findings from the London study suggest that intensified efforts are needed to educate gay and bisexual men about the dangers of HCV infection and other STIs.

    -Sean R. Hosein


    REFERENCES:

    1. 1. Jones R, Nelson M, Low E, et al. Re-emergent hepatitis C viremia after apparent clearance in HIV-positive men who have sex with men: re-infection or late recurrence? Journal of Acquired Immune Deficiency Syndromes. 2010 Apr 1;53(4):547-50.

    2. 2. Kamarashev J, Riess CE, Mosimann J, et al. Lymphogranuloma venereum in Zurich, Switzerland: Chlamydia trachomatis serovar L2 proctitis among men who have sex with men. Swiss Medical Weekly. 2010 Apr 3;140(13-14):209-12.

    3. 3. Rutland E, Harindra VK. Syphilis: an important cause of infectious hepatitis. International Journal of STDs and AIDS. 2010 Mar;21(3):215-6.

     

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    CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

    From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

    Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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