CATIE News

16 September 2014 

Uncovering cases of early HCV infection in HIV-positive men

Hepatitis C virus (HCV) infects the liver, causing inflammation. Over time as HCV-related inflammation continues, parts of this vital organ degrade as healthy tissue is replaced with useless scar tissue. This can lead to an increasingly dysfunctional liver. In turn, complications can develop, including serious infections, internal bleeding, kidney dysfunction and a greatly increased risk for liver cancer.

Increasingly effective and tolerable therapies for HCV are being licensed in Canada and other high-income countries. The earlier HCV is detected, the easier it is to treat. This is one reason that regular testing for HCV is important. Another important reason is that once HCV infection is diagnosed, HCV-positive people can take steps not to spread this infection.

Among HIV-positive MSM

For more than a decade, an outbreak of hepatitis C virus has been occurring among men who have sex with men (MSM) in Western Europe, North America and Australia. Most of these men are HIV positive and HCV appears to have been spread through sex. For details about how HCV is spread, see this CATIE News story.

Scientists in Amsterdam have been monitoring a group of HIV-positive men who have been sexually exposed to HCV. The scientists regularly took blood samples from the men for analysis and interviewed them about their behaviours. The men were in the study for about four years. The scientists found a substantial delay between the time that exposure to HCV occurred and the development of antibodies to HCV in the men’s blood. Due to this delay, they recommend that when doctors and nurses screen HIV-positive MSM for HCV, they consider tests that detect HCV’s genetic material (RNA) rather than use tests that solely rely on antibodies.

Study details and results

In 2009, researchers recruited 63 men between the ages of 35 and 47 years, all of whom were HIV positive but HCV negative. Most of the men were taking potent combination anti-HIV therapy (commonly called ART or HAART). Over a period of four years, the following events occurred:

  • Doctors diagnosed early (acute) HCV infection in all 63 men.
  • Common strains (or genotypes) of HCV detected were 1a, and 4d. Other genotypes detected included 1b, 2b and 3a.
  • Screening for HCV—checking blood samples for the presence of antibodies or HCV’s genetic material (RNA)—occurred about every six months.
  • HCV antibodies were not detected in 41% of the men during the first three months of this infection. During that time HCV RNA was detectable, which is how the scientists knew that the men were infected.

Therapy, cure and reinfection

A total of 43 men decided to take HCV treatment—a long-lasting form of interferon called pegylated interferon (peginterferon) with or without the broad spectrum antiviral drug ribavirin. Of these men, 31 were cured. Among these 31 men there were cases of HCV reinfection, as follows:

  • 16 men were reinfected once
  • one man was reinfected twice
  • one man was reinfected three times

Thus, a total of 21 reinfections occurred in 18 men.

HCV reinfection spontaneously resolved in only two of these 18 men.

Focus on antibodies

All 63 men in the study eventually developed antibodies to HCV. The development of these antibodies took between 47 and 125 days to occur after the men were infected with HCV. The time taken for these antibodies to develop was not influenced by any of the following factors:

  • age
  • current CD4+ cell count
  • lowest-ever CD4+ cell count
  • genotype of HCV

Among the men whose treatment resulted in a cure of HCV, their antibodies to this virus subsequently disappeared.

Among the men whose immune systems managed to spontaneously resolve HCV infection, levels of antibodies to HCV fell to a low level but never disappeared.

Liver enzymes vs. RNA

In the everyday world of patient care, doctors sometimes assess the level of the liver enzyme ALT (alanine aminotransferase) in the blood. This can be useful because during periods of liver injury caused by HCV, ALT levels can rise. These elevated ALT levels can indicate the need for further medical investigation.

The Dutch scientists investigated the men’s initial HCV infection. During these initial infections HCV RNA was detected in blood samples from all the men. Analysis of the blood samples also found that ALT levels were high (twice the upper limit of normal) in 72% of the men.

However, during subsequent cases of HCV infection, surges in ALT decreased and only 44% of the men had elevated ALT detected.

Implications

The scientists made the following points:

  • As some (41%) participants did not produce antibodies to HCV until as long as three months after becoming infected, they suggested that the preferred method for screening HCV infection should be with an HCV RNA test.
  • Although occasional testing of blood samples for elevated ALT levels may help uncover some cases of HCV infection, the scientists noted that ALT levels can be within the normal range during acute infection. Also, they stated that ALT levels are not always elevated during cases of HCV reinfection. Furthermore, they noted that higher-than-normal ALT levels “do not always indicate recent HCV infection.”

A review

Associate professor of hepatology Thomas Reiberger, MD, from the University of Vienna, reviewed the findings of the Dutch scientists in the journal Clinical Infectious Diseases. He noted that while screening the blood samples of patients for HCV antibodies can be useful, the findings from the Dutch work suggest that in some cases such antibodies may not appear for several months after HCV infection has occurred. In such cases, acute HCV infection might be missed if antibody tests alone are used for screening. He agrees with the Dutch scientists that RNA testing should be used to screen HCV infection.

An advantage with relatively frequent screening (using RNA tests) of HIV-positive men at high risk for HCV is that visits for screening can help reveal very early cases of HCV infection. During such visits, doctors and nurses can counsel and educate patients about the following:

  • protecting themselves from reinfection with HCV
  • protecting others from getting this infection
  • the benefits of early HCV treatment

Resources

Living with HIV and Hepatitis C Co-infection – information for those living with both viruses on staying healthy, treatment and protecting yourself and others

CATIE’s Hepatitis C information

Rapid pace of liver damage in recent HCV co-infectionCATIE News

German researchers dig deep to understand how hepatitis C virus is transmitted sexuallyCATIE News

—Sean. R Hosein

REFERENCES:

  1. van de Laar TJ, van der Bij AK, Prins M, et al. Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. Journal of Infectious Diseases. 2007 Jul 15;196(2):230-8.
  2. Vogel M, van de Laar T, Kupfer B, et al. Phylogenetic analysis of acute hepatitis C virus genotype 4 infections among human immunodeficiency virus-positive men who have sex with men in Germany. Liver International. 2010 Sep;30(8):1169-72.
  3. 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.
  4. Urbanus AT, Van De Laar TJ, et al. Trends in hepatitis C virus infections among MSM attending a sexually transmitted infection clinic; 1995-2010. AIDS. 2014 Mar 13;28(5):781-90.
  5. van de Laar TJ, Matthews GV, Prins M, et al. Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection. AIDS. 2010 Jul 31;24(12):1799-812.
  6. Vanhommerig JW, Thomas XV, van der Meer JT, et al. Hepatitis C virus (HCV) antibody dynamics following acute HCV infection and reinfection among HIV-infected men who have sex with men. Clinical Infectious Diseases. 2014; in press.
  7. Reiberger T. Acute hepatitis C virus infection in HIV+ MSM: Should we change our screening practice? Clinical Infectious Diseases. 2014; in press.