A genetic mutation that typically improves the chances of being cured of hep C using a treatment regimen than contains interferon may actually increase the risk of serious liver scarring (cirrhosis) in people coinfected with HIV, according to a report published in the June 1 issue of The Journal of Infectious Diseases (JID). This finding appears to be unique among HIV/HCV-coinfected patients; similar findings have not been documented in people living with HCV but not HIV.
Interleukin 28B (IL-28B) is a human gene that plays a role in the immune system’s defense against certain viruses. Recently discovered changes, or polymorphisms, in the gene have been linked to higher (or lower) rates of spontaneous clearance of HCV during the first six months of infection, as well as cure rates in people with HCV genotype 1—one of the hardest-to-treat forms of the virus—using one of the most important drugs used to treat hepatitis C: pegylated interferon alpha. People with the “CC” IL-28B polymorphism, which is more common in whites, are two- to three-times more likely to be cured of their HCV with a treatment regimen consisting of pegylated interferon and ribavirin, compared with those who have either the “CT” or “TT” IL-28B type.
It has also been suggested that the CC IL-28B polymorphism is less likely to be associated with the development of advanced liver scarring, according to at least one study looking at the prevalence of the CC, CT or TT polymorphisms in people living with HCV (but not HIV) who developed cirrhosis.
The opposite appears to be true in people coinfected with HIV and HCV, according to the JID paper authored by Pablo Barreiro, MD, PhD, of the Hospital Carlos III in Madrid and his colleagues.
The study enrolled 304 HIV/HCV coinfected patients, all of whom underwent Fibroscan testing—a noninvasive technique of measuring liver stiffness—and IL-28B testing. While most patients were receiving antiretroviral therapy for their HIV, none had been treated for hepatitis C. Sixty-eight percent of the patients had HCV genotypes 1 or 4, another form of the virus that remains difficult to treat.
Forty-six percent of the patients had the CC IL-28B polymorphism, whereas 43 and 11 percent had the CT and TT IL-28B polymorphisms, respectively.
Cirrhosis was documented in 24 percent of the CC carriers, compared with 13 percent of the CT and TT carriers combined. In fact, compared with other risk factors—such as older age and alcohol use—IL-28B genotype was, statistically speaking, the single most important risk factor for cirrhosis in the coinfected patients.
Barreiro and his colleagues also documented that volunteers with the CC IL-28B polymorphism appeared to progress faster to liver cirrhosis than their peers with either the CT or TT IL-28B genotype.
“The IL-28B…CC genotype is associated with a higher prevalence of cirrhosis in HIV-HCV–coinfected patients than CT/TT genotypes,” the authors conclude, “suggesting that IL-28B CC carriers may experience a more rapid progression of HCV-related liver fibrosis, perhaps as [a] result of increased liver inflammation. Thus, access to HCV treatment is of utmost importance in IL-28B CC carriers, in whom treatment response is better and in whom progression to cirrhosis might occur more rapidly.”