You have reached the HIVandHepatitis.com legacy site. Please visit our new site at hivandhepatitis.com
and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic Infections (CROI 2010)
February 16 - 19, San Franciso, California
IL28B Gene Variation Linked to Spontaneous Clearance and Treatment Response in HIV/HCV Coinfected People
Andri Rauch from University Hospital Bern (abstract 162) began with an overview of the recent discovery of the IL28 phenomenon. The fact that people respond so differently despite receiving the same hepatitis C treatment, he noted, "strongly point to host genetic determinants for the control of HCV infection."
Researchers identified IL28B by scanning the human genome to look for differences between people who responded well and those who did not respond to interferon-based therapy. They initially examined genes already known to play role in immune control of HCV; when these were not confirmed, they performed genome-wide association studies (looking at the full set of genes from multiple individuals) to broaden their search.
Rauch and colleagues analyzed participants in the Swiss Hepatitis C Cohort, while other teams looked at genotype 1 hepatitis C patients in the U.S. (white and African-American participants in the IDEAL trial), Australia, and Japan.
All the research groups saw an association between favorable treatment response and single nucleotide polymorphisms (SNPs) in the IL28 gene near the "B" subunit that encodes interferon lambda-3. This finding was "very consistent" among 4 studies published during the past 6 months, all looking at HIV negative individuals, Rauch said.
Each research group identified several relevant SNPs, but one -- rs8099917, dubbed the "risk allele" -- was common to all of them, while 2 other (rs12980275 and 12979860) were also implicated.
Alleles are natural variations of a gene. In simple terms, for example, the eye color gene has blue and brown alleles (in actuality, eye color is controlled by multiple genes); the IL28B gene has risk and non-risk alleles. Because people inherit 1 copy of every gene from each parent, they may end up with either 2 copies of the risk alleles, 2 copies of the non-risk version, or 1 of each. The combination is known as the genotype: risk, non-risk, or mixed.
Across the studies, people who achieved sustained virological response (SVR) to interferon-based therapy were about half as likely to have the risk genotype as non-responders. This genotype was even less common among people who spontaneously cleared HCV without treatment.
Furthermore, the risk genotype occurred with higher frequency among people of African descent, intermediate frequency among Europeans, and lower frequency among Asians, which Rauch said "explains at least in part ethnic differences seen in HCV recovery rate both natural and with therapy."
IL28B and HIV/HCV Coinfection
same session, 3 research groups reported results from studies looking
at IL28B in HIV/HCV coinfected people.
Pegyalated Interferon lambda as a hepatitis C treatment is undergoing clinical trials. In a Phase 1b study reported at the American Association for the Study of Liver Diseases (AASLD) meeting this past fall, researchers found that interferon lambda had efficacy similar to that of the current standard HCV therapy, pegylated interferon alpha (Pegasys or PegIntron), but with fewer adverse side effects.
believe, however, that rs8099917 and the other risk SNPs are not themselves
the actual cause of poor response, but rather are linked to and serve
as markers for the causal gene(s).
3 groups included 15 people each, but the last configuration was uncommon
and the researcher could only find 2 such patients. All were HIV/HCV
coinfected except for 6 people in the third group who had HCV alone.
During the session, researchers discussed the clinical relevance of these findings for people with hepatitis C. Some suggested that IL28 genotypic testing might help guide treatment decisions, since it could show who is most likely to respond and therefore spare others futile therapy.
However, an audience member expressed concern that such a test might be used as a rationale for providers to deny treatment or for insurers to refuse payment. At an accompanying press conference, Rauch said, "It's part of a puzzle...It will certainly not be the only thing on which we base the decision to treat or not."
The discovery also introduces a potential confusion with regard to terminology. These human IL28B genotypes should be confused with HCV genotypes (1, 2, 3, 4, etc), which also predict treatment response. Speaking about a "favorable genotype" or "high-risk genotype" now has 2 distinct meanings.
Abstract 162: University Hospital Bern, Switzerland.
Abstract 163: University Hospital Lausanne and University of Lausanne, Switzerland; University Hosp Bern and University of Bern, Switzerland; University Hospital Geneva, Switzerland.
164: University of Bonn, Germany; Private Practice, Berlin, Germany;
Praxiszentrum Kaiserdamm, Berlin, Germany; ICH, Hamburg, Germany; St
Vincent's Clin Sch, Australia; Hosp Univ Germans Trias i Pujol, Autonomos
Univ of Barcelona, Spain; University of Pavia IRCCS, San Matteo Hosp,
A Rauch. The interleukin 28B gene and HCV recovery. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 162.
J di Iulio, P-Y Bochud, M Rotger, and others. Association of IL28B haplotypes with chronic HCV infection in HIV/HCV co-infected individuals. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 163.
M Vogel, A Baumgarten, and others. Genetic variation in IL28B and treatment-induced
clearance of HCV in HCV/HIV co-infected patients. 17th Conference on
Retroviruses & Opportunistic Infections (CROI 2010). San Francisco.
February 16-19, 2010. Abstract 164.