May/June 2016 

France – Events after cure of HCV

Chronic hepatitis C virus (HCV) infection increases the risk of serious liver injury. If left untreated, this can lead to serious complications, including increasing dysfunction of the liver, increased risk of bacterial infections, liver failure and liver cancer.

Direct-acting antivirals (DAAs) are relatively new in the history of HCV treatment. They are highly effective at curing HCV and the duration of treatment is relatively short, usually about 12 weeks (though longer courses of treatment may be necessary in cases of severe liver injury).

Long-term monitoring of people who have been cured with DAAs is essential to understand what happens to the health of such patients. For instance, by how much is their risk for liver-related complications, including liver cancer, reduced?

Researchers in France reviewed health-related data collected from 2,156 patients who received treatment with at least one DAA in 2013 and 2014. Prior to entering the study none of these participants had received a liver transplant or developed liver cancer.

Key results

The findings from the French observational study show that the vast majority of patients who are treated with DAAs see their health improve and this improvement is sustained. In total, 3.5% of participants developed liver cancer after they were cured. It is highly likely that these cancers were already present when they started HCV treatment. Some people with cirrhosis who are cured of HCV may become at risk for liver-related complications; therefore, close and regular monitoring may be necessary.

Study details

The average profile of participants upon entering the study was as follows:

  • age – 58 years
  • 62% men, 38% women
  • 63% of participants had cirrhosis (severe scarring of the liver)

The distribution of genotypes was as follows:

  • genotype 1 – 65%
  • genotype 2 – 6%
  • genotype 3 – 13%
  • genotype 4 – 14%
  • genotype 5 or 6 – 1%

(Percentages do not total 100 due to rounding.)

Therapies used were as follows:

  • sofosbuvir + ribavirin – 283 people
  • sofosbuvir + peginterferon + ribavirin – 228 people
  • sofosbuvir + daclatasvir with or without ribavirin – 1,048 people
  • sofosbuvir + simeprevir with or without ribavirin – 597 people


Participants were monitored for an average of two years after they were cured.

Liver cancer

Cases of liver cancer significantly declined over time. They were most commonly diagnosed during the first 12 months after treatment cessation and were very uncommon two years after treatment cessation. Rates of liver cancer were greater among people with cirrhosis. Here is the distribution of cases of liver cancer:

Liver cancer diagnosed within 12 months of treatment cessation

  • among people with cirrhosis – 66 cases
  • among people without cirrhosis – 6 cases

Liver cancer diagnosed 18 to 24 months after treatment cessation

  • among people with cirrhosis – 4 cases
  • among people without cirrhosis – 1 cases

The data should not be misinterpreted to imply that therapy with DAAs somehow resulted in liver cancer. Screening for liver cancer in some participants may have been irregular (details were not provided) but previous French reports suggest that within research programs such screening tends to occur every six months. Given that the majority of participants had cirrhosis, they would have been at elevated risk for liver cancer. In general, tumours tend to form slowly and usually take years to grow. Overall, there were 77 cases of liver cancer after treatment cessation. That figure is equivalent to 3.5% of participants developing liver cancer, a relatively low overall rate.

DAAs can cure HCV, but the immune system has to recover (from HCV infection) and attack the tumour. Such recovery takes time. It is reassuring that over time there were fewer cases of liver cancer. Overall, the findings from the French study underscore the need for intensive monitoring of people with cirrhosis so that any cancers that develop can be detected and treated early.

Deaths from liver-related causes

As mentioned earlier, DAAs are very effective at curing HCV. However, many underlying health problems need time to resolve as the liver slowly repairs itself once HCV has been cured. People who are very ill with liver-related health issues will need close monitoring to maximize their chances of survival after being cured.

Deaths due to liver-related complications were most common in the first 18 months after cessation of therapy. (In the final six months of the study there were no liver-related deaths.) These deaths were distributed as follows:

Liver-related deaths within the first 18 months after treatment cessation

  • among people with cirrhosis – 10 people
  • among people without cirrhosis – 10 people

Serious symptoms of cirrhosis

When severe scarring of the liver occurs (cirrhosis), the dysfunction of the liver increasingly affects other parts of the body, leading to further complications. This is called decompensated cirrhosis.

In the first six months after treatment cessation there were cases of decompensated cirrhosis but these quickly fell and remained low. All cases of decompensation occurred only among people with cirrhosis. Such cases of decompensated cirrhosis were distributed as follows:

The first six months after treatment cessation

  • 33 cases of decompensation

During months 6 to 12 after treatment cessation

  • 8 cases of decompensation

During months 12 to 18 after treatment cessation

  • 6 cases of decompensation

During months 18 to 24 after treatment cessation

  • 1 case of decompensation

—Sean R. Hosein


Carat F. Clinical outcomes in HCV-infected patients treated with direct-acting antivirals—18 months post-treatment follow-up in the French ANRS CO22 Hepather cohort study. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract LBP 505.