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Rapid pace of liver damage in recent HCV co-infection
18 January 2013
In high-income countries such as Canada, Australia and the U.S. and regions such as Western Europe, screening of the blood supply
has virtually eliminated transmission of hepatitis C virus (HCV) via blood transfusions. In these countries and regions HCV is
now mostly transmitted in the following ways:
- sharing contaminated equipment for substance use (including needles, straws, crack pipes, rolled-up currency bills)
- exposure to unsterilized equipment for tattooing and piercing
- among HIV-positive people, particularly men who have sex with men (MSM): having unprotected anal sex, sharing sex toys and not
changing condoms and gloves between partners
HCV infects the liver, causing inflammation and dysfunction within this vital organ. Over the long term, HCV infection causes healthy
tissue to be replaced with useless scar tissue. As more of the liver becomes injured, serious complications ensue and liver failure,
liver cancer and death can occur.
Among HIV-positive people, subsequent HCV infection is associated with an accelerated pace of liver damage compared to people infected
with HCV alone, though the pace of such damage varies from one person to another.
Scientists are not certain about the cause(s) of this accelerated liver damage. However, a team of researchers in New York City thinks
that they may have uncovered an important clue. The team has been monitoring 15 HIV-positive men who subsequently became infected with
HCV. Four of these 15 men either refused treatment for HCV or did not recover from this infection when given a combination of
interferon and ribavirin and have subsequently undergone long-term monitoring.
The livers of these four men sustained relatively rapid damage, occurring between one and a half and six years after HCV co-infection.
Three of the men died within eight years after becoming infected with HCV. Liver biopsy confirmed that fatal damage to that organ arose
from HCV and not from other causes. The U.S. team cautions that HIV-positive people who later become co-infected with HCV are at risk
for an accelerated pace of liver damage perhaps caused by underlying immunological dysfunction.
Details
Doctors in high-income countries have been reporting an outbreak of HCV infection among some HIV-positive men. In these cases, HCV
appears to be sexually transmitted. As part of a study of this outbreak, a team of researchers in the U.S. has been monitoring
HIV-HCV co-infected men. Here are some details about four cases of an astonishingly rapid pace of liver damage.
Case 1
In February 2008 a 39-year-old HIV-positive man underwent routine laboratory testing of his blood. Technicians noticed that levels of
his liver enzymes in the blood were very high, as follows:
- ALT (alanine aminotransferase) - 529 U/L
- AST (aspartate aminotransferase) - 306 U/L
The man tested negative for HBV (hepatitis B virus). In the past 12 months he had been tested for HCV but was negative at those times
so in February doctors did not retest him.
In late 2007 he had initiated anti-HIV therapy (commonly called ART or HAART) with the following combination of drugs:
- Atripla - tenofovir + FTC + efavirenz
At the time that his liver enzymes were first elevated, the man's CD4+ count was 53 cells and his viral load was less than 400 copies/ml.
When interviewed by the study researchers, he disclosed that in the past year he had unprotected receptive anal intercourse with multiple men.
He denied use of street drugs and alcohol.
In May 2008 his skin became yellow and his stool was tan coloured. Doctors stopped his anti-HIV therapy and ordered further blood tests.
He continued to test negative for antibodies to HCV.
In July 2008 he was still undetectable for HCV antibodies. However, further testing detected HCV's genetic material in his blood. Doctors
found that he was infected with a subtype, or strain, of HCV called genotype 1a. Furthermore, his HCV viral load was high, just over
6 million IU/ml. The next month doctors performed a liver biopsy and, shockingly, found that he had severe liver damage (fibrosis).
The man restarted ART. To treat the HCV, doctors gave him a long-lasting form of interferon, injected once weekly, and twice-daily doses
of the broad-spectrum antiviral drug ribavirin. However, HCV therapy did not significantly decrease the amount of this virus in his blood,
so they stopped it after five months.
Seventeen months after elevated liver enzymes were first detected, the man began to develop complications of severe liver disease-swollen
feet, swollen veins in the esophagus (the tube that connects the mouth and stomach). Fluid began to accumulate in his abdomen as his liver
continued to degrade. He later received a liver transplant. When surgeons were removing his liver they found that it was shrunken and
severely scarred.
Doctors reported that his recovery after transplantation was slow but he has remained well nearly three years after this surgery.
The three other cases
The three other men had CD4+ counts between 200 and 442 cells and low viral loads (less than 300 copies) due to ART.
Additionally, here are key features of the three other cases:
- Elevated levels of liver enzymes were detected through routine laboratory testing. Prior to their elevation, liver enzyme levels
were within the normal range.
- The men disclosed having had unprotected receptive intercourse with multiple men in the past year.
- The research team emphasized the ages of the four men-between 39 to 55 years-at the time of HCV diagnosis. This is important because in studies of people who inject street drugs, HCV infection usually occurs between the ages of 20 and 30 years. They raise this point to underscore the fact that all four men were unlikely to have engaged in regular injection of street drugs.
- Liver biopsy revealed severe liver damage a few years after HCV infection. The pathologist examining the biopsy samples was able to rule out pre-existing fibrosis from alcoholism or exposure to certain anti-HIV drugs commonly called "d-drugs"-d4T (stavudine, Zerit) and ddI (didanosine, Videx).
- It is possible that the four men could have been infected with HCV for several years before this infection was diagnosed. However, the doctors noted that such stealthy infections are rare in patients with normal levels of liver enzymes, even when CD4+ cell counts are low.
What caused the rapid pace of liver damage?
The doctors are not certain as to the precise cause(s) of the rapid rate of liver damage in these cases of co-infection. However,
they strongly suspect that immune deficiency likely played a role. They base this idea on reports by other doctors treating patients
with immune deficiencies, some of which were unrelated to HIV, where HCV co-infection was also associated with a rapid course of
liver damage.
The research team cannot rule out the presence of a possible, as yet unrecognized co-factor (perhaps another germ) that the men may
have had that could have accelerated the rate of liver damage. Three of the men were from New York and the fourth was from San Diego,
and so the doctors noted that accelerated liver damage is not restricted to one region.
Now and in the future
The present report, while small, should serve to alert HIV-positive people, healthcare providers, clinics and counsellors who specialize
in dealing with HCV and sexually transmitted infections (STIs) about the risks of unprotected anal intercourse. Eight years ago, doctors
in the Netherlands reported the outbreak of another STI, lymphogranuloma venereum (LGV), chiefly among HIV-positive men. This infection
was also spread by unprotected anal intercourse. That outbreak of LGV quickly spread through sexual networks to other MSM in Western
Europe, the U.S. and Canada.
The U.S team states that more research is needed to better understand the reasons underpinning "this devastating rate of liver
damage" in HIV-HCV co-infection. However, social scientists also need to become involved in trying to find ways to help
HIV-positive men lead healthier lives. This is likely to become an international issue, as a recent report suggests
that the behaviours that led to co-infection in the U.S. study are also an issue in other countries.
Resources
-Sean R. Hosein
REFERENCES:
- Fierer DS, Dieterich DT, Fiel MI, et al. Rapid progression to decompensated cirrhosis, liver transplantation, and death in HIV-infected men after primary HCV infection. Clinical Infectious Diseases . 2013; in press .
- Schmidt AJ, Rockstroh JK, Vogel M, et al. Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany-a case-control study. PLoS One . 2011 Mar 8;6(3):e17781.
- van de Laar T, Pybus O, Bruisten S, et al. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology . 2009 May;136(5):1609-17.
- van der Helm JJ, Prins M, Del Amo J, et al. The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007. AIDS. 2011 May 15;25(8):1083-1091.
- Gambotti L, Batisse D, Colin-de-Verdiere N, et al. Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004. Euro Surveillance . 2005 May;10(5):115-7.
- Nieuwenhuis RF, Ossewaarde JM, Götz HM, et al. Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have sex with men. Clinical Infectious Diseases . 2004 Oct 1;39(7):996-1003.
- Centers for Disease Control and Prevention (CDC). Lymphogranuloma venereum among men who have sex with men--Netherlands, 2003-2004. Morbidity and Mortality Weekly Report . 2004 Oct 29;53(42):985-8.
- Kirby T, Thornber-Dunwell M. High-risk drug practices tighten grip on London gay scene. Lancet . 2013; Jan 12: 101-102.
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