Gene associated with increased risk of cirrhosis for HIV/HCV-co-infected patients

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A genetic mutation is associated with an increased risk of cirrhosis for patients co-infected with HIV and hepatitis C, according to Spanish research published in the June 1st edition of the Journal of Infectious Diseases.

Carriage of the IL28B gene was the single biggest risk factor for cirrhosis, possibly explained by its association with long-term disturbances in liver function.

Paradoxically, earlier research has shown that individuals who carry the gene are more likely to spontaneously clear hepatitis C infection and respond to interferon-based therapies.



A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.


Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

alanine aminotransferase (ALT)

An enzyme found primarily in the liver. Alanine aminotransferase may be measured as part of a liver function test. Abnormally high blood levels of ALT are a sign of liver inflammation or damage from infection or drugs.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 


Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

Indeed, it was this relationship between the gene and improved outcomes that prompted investigators in Madrid and Andalusia to carry out a retrospective study to assess the gene’s association with cirrhosis.

The study involved 304 co-infected patients.

FibroScan, a non-invasive test that assesses liver stiffness, was used to assess the patients’ fibrosis stage. In addition, blood tests were used to monitor patients for the presence of the IL28B gene, and to determine hepatitis C genotype, liver function, and HIV-related parameters.

Participants had a mean age of 43 years, 80% were male, 86% were former injecting drug users, and 19% had a history of alcohol abuse. None of the patients had received hepatitis C therapy.

Most patients (85%) were taking antiretroviral therapy, and 79% had an undetectable HIV viral load. The mean CD4 cell count was 552 cells/mm3.

Abnormal liver function was common, and 72% of patients had ALT levels above the upper limit of normal. Mean hepatitis C viral load was 6.12 log10 copies iu/ml, and 68% had a level above 600,000 copies iu/ml. The harder to treat hepatitis C genotypes (1 and 4) were present in 68% of patients.

Cirrhosis was diagnosed in 18% of individuals. However, none of the patients had decompensated liver disease.

The IL28B gene was present in 46% of patients. Patients carrying this gene had significantly lower mean CD4 cell counts (518 vs 581 cells/mm3; p = 0.04), and there was also a trend for them to have higher mean ALT levels (93 vs 82 iu/ml; p = 0.14). Moreover, in the five years before baseline analysis, mean ALT levels were significantly greater in the IL28B carriers than other patients (p = 0.01).

FibroScan tests showed that liver stiffness values were significantly greater in carriers of the gene (p < 0.05), and these patients were also significantly more likely to have cirrhosis than non-carriers of the gene (24 vs 13%, p = 0.01).

In addition, patients with cirrhosis were also significantly older (43 vs 41 years; p = 0.04), had longer duration of hepatitis C infection (25 vs 23 years; p = 0.03), and were marginally more likely to have a history of alcohol abuse (28 vs 17%; p = 0.06).

Regardless of the hepatitis C genotype with which a patient was infected, the IL28B gene was associated with a greater prevalence of cirrhosis  (genotype 1: 28 vs 15%, p = 0.04; genotype 3: 22 vs 6%, p = 0.04; genotype 4: 18 vs 15%).

Statistical analysis that controlled for potential confounders showed that carriage of the IL28B gene was the single most important risk factor for the development of cirrhosis (odds ratio [OR] = 2.32; 95% CI, 1.22 to 4.41; p = 0.01).

By contrast, the association with older age (p = 0.08) and prior alcohol abuse (p = 0.07) was only of borderline significance.

Further analysis showed that patients carrying the IL28B gene developed cirrhosis more frequently and within a shorter duration of time than other individuals (hazard ratio = 3.02; 95% CI, 1.24 to 7.39; p = 0.015).

“HIV-HCV-coinfected patients carrying the IL28B…genotype are at greater risk of developing liver cirrhosis,” conclude the investigators; “enhanced immune-mediated damage in the liver of chronically HCV-infected persons who harbour the genotype could hypothetically explain these findings.”


Barreiro P et al. Influence of interleukin-28B single nucleotide polymorphisms on progression to liver cirrhosis in human immunodeficiency virus-hepatitis C virus-coinfected patients receiving antiretroviral therapy. J Infect Dis 203: 1629-36, 2011 (click here for the free abstract).