Antiviral treatment reduces the risk of
hepatocellular carcinoma (HCC) in people with hepatitis C-related fibrosis or
cirrhosis, according to the results of a meta-analysis published in British Medical Journal Open. The risk
was reduced irrespective of the virological outcome of therapy, but the
benefits were most pronounced in people when therapy cleared the infection.
“This review found that antiviral therapy
may prevent HCC in patients with hepatitis C-related fibrosis or cirrhosis,”
write the authors. “Our subgroup analyses suggest that the antiviral therapy
may have beneficial effects on the risk of developing HCC that are unrelated to
the virological response.”
Hepatitis C-related cirrhosis is a major
risk factor for the development of HCC, the most common form of liver cancer.
The annual incidence of HCC in hepatitis C-infected people with cirrhosis
ranges between 1 and 4%.
Antiviral treatment can clear hepatitis C.
A cure is defined as an undetectable viral load six months after the completion
of therapy, often called a sustained virologicial response (SVR).
A team of investigators wanted to see if
antiviral treatment with interferons – with or without ribavirin – reduced the risk of HCC in hepatitis
C-infected people with fibrosis or cirrhosis.
They therefore conducted a meta-analysis of
published randomised, controlled trials and observational studies that reported
on the risk of HCC in people who received antiviral treatment, compared to
rates of the cancer in individuals who received a placebo or no treatment.
A total of eight randomised trials and five
observational studies met the investigators' inclusion criteria.
A variety of treatment regimens were used
in these studies. One randomised trial assessed pegylated interferon and
ribavirin – the current standard of care; two studies assessed monotherapy with
pegylated interferon; all the remaining studies assessed interferon
Duration of treatment in the randomised
studies ranged between one and five years, and total follow-up in these studies
was between two and nine years. In the observational studies, treatment lasted
for between six and 18 months, and follow-up was for between five and
A total of 81 of the 1156 participants in the
randomised trials who received antiviral treatment developed HCC. This compared
to 129 of the 1074 participants in the control groups.
The investigators therefore calculated that
antiviral treatment reduced the risk of HCC by 47% (RR = 0.53; 95% CI,
One case of liver cancer was prevented per
eight patients who received therapy.
Subgroup analysis showed that antiviral
treatment had benefits, irrespective of its virological outcomes.
However, its effect was most pronounced in
people who achieved a sustained virological response, who had an 85%
reduction on their risk of HCC (RR = 0.15; 95% CI, 0.05-0.45). The risk of HCC
was reduced by 43% for people whose therapy did not clear the infection (RR =
0.57; 95% CI, 0.37-0.85).
Restricting analysis to the observational
studies showed that antiviral treatment reduced the risk of HCC by 71% (RR =
0.29; 95% CI, 0.12-0.69).
“The combined evidence suggests that
interferon may have other beneficial effects than the direct antiviral
activity,” comment the authors.
However, there was little evidence that
antiviral treatment had any benefit in terms of all-cause mortality (RR = 0.81;
95% CI, 0.33-2.03).
The authors believe that the benefits of
antiviral treatment for the prevention of liver cancer are likely to be less
pronounced in hepatitis C-infected people without cirrhosis or fibrosis.
“Patients with cirrhosis or fibrosis are likely to have a higher degree of
inflammation than those patients without histological changes.”
They also caution that their results are
not definitive. “Based on duration of follow-up and lack of clear evidence
concerning morbidity and mortality, we cannot exclude that interferon delays
rather than prevents carcinogenesis. Additional randomised trials with longer
follow-up are still warranted to determine whether this is the case.”