Antiviral treatment reduces risk of liver cancer in people with hepatitis C-related cirrhosis and fibrosis

Michael Carter
Published: 29 October 2012

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 monotherapy.

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 seven years.

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, 0.34-0.81).

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.”

Hepatitis information

For more information on hepatitis visit

Infohep is a project we're working on with the World Hepatitis Alliance and the European Liver Patients Association.

Visit >
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.