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.
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.
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
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
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).
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.”