In the second study, described in the August 2013 Journal of Hepatology,
Alessandra Mangia from IRCCS Casa Sollievo della Sofferenza Hospital
and colleagues in Italy explored whether IL28B rs12979860 – alone or in
combination with human leukocyte antigen (HLA) class 2 alleles, or
genetic variants – could both predict spontaneous HCV clearance and
help individualize treatment for people with persistent hepatitis C.
Most people with acute hepatitis C have no symptoms, or only general
flu-like symptoms, so infection is not usually diagnosed at this early
stage in typical clinical practice. A majority of people who undergo
treatment have been infected for at least a year, and often much longer.
Studies have shown that interferon-based therapy is very effective if
started during acute infection, but clinicians do not want to start too
early and unnecessarily treat people who would have cleared the virus on
This analysis included 178 participants with acute HCV infection who
were treated with interferon alone or interferon plus ribavirin starting
either within or after 48 weeks from the time of acute hepatitis C
diagnosis; 169 patients had data available for genetic testing.
In this study, 28% of participants achieved spontaneous HCV clearance.
Factors associated with natural clearance included development of
jaundice, or yellowing of the skin due to elevated bilirubin levels
(odds ratio 2.75, or nearly three times more likely) and having the IL28B CC
pattern (odds ratio 3.87, or nearly four times more likely). HLA alleles,
however, were not a significant predictor.
Among people with the IL28B CT or TT patterns who did not have
jaundice, the negative predictive value for HCV persistence was 98%,
meaning they had only a 2% likelihood of spontaneous clearance.
Among CT or TT patients, those who started treatment within 48 weeks
of diagnosis had a much higher likelihood of sustained virological
response than those who started treatment after 48 weeks (100 vs 28%,
respectively). In contrast, the difference in response rates between
people with the CC pattern who were treated early or late did not reach
statistical significance (85 vs 65%, respectively).
Based on these findings, the study authors concluded, "In patients
with acute HCV hepatitis, lack of viral clearance may be predicted by
absence of jaundice and IL28B [CT or TT] genotype; in patients with
these characteristics, treatment needs to be started immediately."