Sustained response to direct-acting HCV antivirals tied to lower HCC risk

By Marilynn Larkin

NEW YORK (Reuters Health) - A sustained virologic response to direct-acting antiviral treatment of hepatitis C (HCV) is associated with a “considerable” reduction in the risk of hepatocellular carcinoma (HCC), researchers say.

Dr. Fasiha Kanwal of Baylor College of Medicine in Houston, Texas and colleagues analyzed data on 22,500 HCV patients (mean age 62) from 129 Veterans Health Administration hospitals who filled more than one prescription of sofosbuvir, simeprevir, ledipasvir, a combination of paritaprevir/ritonavir or ombitasvir and dasabuvir, and daclatasvir in 2015.

Follow-up continued through September 2016; this time frame allowed more than six months for treatment completion and testing for a sustained virologic response (SVR).

The date of the first filled prescription was considered treatment initiation, and the last date covered by the final prescription as the treatment completion date. For patients on multiple courses of DAAs, the authors used the first course and ended their followup before another course was initiated.

Patients had an SVR if all HCV RNA tests were negative after DAA treatment ended, with one test given at least three months after treatment completion.

As reported online June 19 in Gastroenterology, 19,518 HCV patients had an SVR and 2,982 did not.

There were 271 new HCCs during follow-up, including 183 in patients with an SVR. Close to 45% of cases were classified as stage I. In more than 75%, the maximum size of the largest lesion was no greater than 5 cm.

Patients with an SVR had a significantly reduced risk of HCC (adjusted hazard ratio, 0.28).

Overall, 39.0% of patients had cirrhosis; this group had the highest annual incidence of HCC after SVR (adjusted HR, 4.73).

Summing up, Dr. Kanwal told Reuters Health by email, “We found that the risk of hepatocellular cancer is lower in patients who achieved cure after receiving the new direct acting antiviral agents than in those who failed to achieve cure. However, the risk remains high enough in patients with cirrhosis to warrant ongoing surveillance and monitoring.”

“The risk of hepatocellular cancer was higher in our study than expected based on older studies of patients treated with interferon treatment, and this is likely due to different types of patients who are eligible for and receive the new therapies,” she explained.

“Future studies will need to monitor this risk to see if it diminishes as time since treatment elapses,” she said.

Dr. Scott Friedman, chief of the division of liver diseases at Icahn School of Medicine at Mount Sinai in New York City, said, “The treatment landscape of chronic HCV has recently undergone an exhilarating transformation in which direct acting antivirals have consistently achieved cures of >90%, compared to 50% to 65% cure rates for regimens in which patients received alpha interferon combined with ribavirin.”

“Moreover,” he told Reuters Health by email, “these astonishing results using any one of several different DAA regimens are also extremely well-tolerated and cure disease in as little as 12 weeks, (without) the difficult side effects induced by the older interferon-based regimens, which were typically administered for one year.”

“However, in 2016 a sobering report appeared from Spain suggesting that once patients were cured of HCV with DAAs, their risk of developing hepatocellular carcinoma was greater than when cures were achieved using interferon regimens, especially in patients who had previously been cured of small hepatocellular carcinomas,” said Dr. Friedman, who was not involved in the study.

The current study “refutes the suggestion that cure of HCV with DAA confers a high risk of hepatocellular carcinoma,” he noted. “While the data are very solid, the findings are limited somewhat by the retrospective study design, and because the patients were only from a government health system.”

“Moreover, the findings do not compare the relative risk of carcinoma based on the type of the curative treatment – i.e., interferon-based regimens versus DAAs.”

Nonetheless,” he concluded, “the data conclusively establish the value of curing HCV in reducing the risk of hepatocellular carcinoma, (and) other studies have shown a marked improvement in liver function and regression of scar in many patients following HCV cure using these DAA drugs.”


Gastroenterology 2017.

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