Direct-Acting Antivirals Tied to Lower Risk of Liver Cancer in HCV

A new study has found that direct-acting antivirals (DAAs) may decrease the risk of liver cancer and death in hepatitis C virus (HCV) infection. The findings were published online in the February issue of Lancet.¹

The study is the first large analysis to compare DAAs to no treatment over time and to use a rigorous approach that controlled for a broad range of potential biases, including factors related to HCV-related liver disease.

“Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection,” wrote researchers led by Fabrice Carrat, PhD, of the Sorbonne Université in Paris, France.

Research has shown that combining 2 or 3 DAAs can lead to sustained virologic response in >95% of cases. Treatment duration is generally shorter with DAAs than with interferon-based regimens. And patients with cirrhosis may better tolerate DAAs.

However, the impact of DAAs on liver cancer is controversial. Some studies have suggested increased risk for liver cancer with DAAs. In contrast, a recent study has suggested decreased liver cancer recurrence with DAA therapy.²

A closer look at benefits vs harms

A closer look at benefits vs harms

To assess the benefits vs harms of DAAs, researchers conducted an observational study at 32 liver specialty clinics in France. The study included 9895 adults with chronic HCV that were treated according to European guidelines. Of these, 7344 received DAAs and 2551 went untreated (control group). Follow-up occurred for almost 3 years.

Compared to untreated patients, those treated with DAAs had more severe liver disease, longer duration of HCV infection, higher prevalence of cirrhosis, and were more likely to have received prior HCV treatment. They were also more likely to be older men, have a higher body mass index (BMI), and have past excessive alcohol intake.

Nevertheless, results adjusted for age, sex, BMI, geographical origin, alcohol, diabetes, and HCV-related factors showed that DAAs were significantly associated with 34% decreased risk of liver cancer, 61% decreased risk of liver-related death, and 52% decreased risk of all-cause death.

Even in patients with cirrhosis before treatment, DAAs were linked to significantly decreased risk for liver cancer, liver-related mortality, and all-cause mortality.

Adjusted analysis also showed no significant association between DAAs and decompensated cirrhosis.

Results confirm past studies suggesting significantly decreased mortality with DAA therapy, according to the authors.

“Direct-acting antivirals induce a sustained virological response, reducing liver damage and inflammation. This effect causes liver regeneration, decreasing risk for progression to liver-related complications or hepatocellular carcinoma,” they explained.

However, they cautioned that the long-term effects of DAAs on liver decompensation still need further study.

References:

1. Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study [published ahead of print February 11, 2019]. Lancet. doi: 10.1016/S0140-6736(18)32111-1. 
2. Singal AG, Rich NE, Mehta N, et al. Direct-acting antiviral therapy not associated with recurrence of hepatocellular carcinoma in a multicenter North American cohort study [published ahead of print January 17, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2019.01.027.