Liver Cancer Recurrence Not Linked to Hepatitis Treatment

A study published in 2016 raised concerns that patients with liver cancer related to hepatitis C virus (HCV) may have a higher risk for recurrence if they are treated with direct-acting antiviral (DAA) therapies directed against HCV.

A new multicenter study allays these concerns. It found that there was no significant difference in the risk for overall or early hepatocellular carcinoma (HCC) recurrence or degree of tumor aggressiveness between patients who received DAA therapies for HCV infection and those who did not.

The retrospective cohort study in 793 patients with HCV-related HCC showed that during a median follow-up of 10.4 months, 128 of 304 treated patients (42.1%) experienced tumor recurrence, as did 288 of 489 untreated patients (58.9%).

Early recurrence, defined as recurrence 365 days after complete response, was observed in 52 treated and 277 untreated patients. In both DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23), the study found.

After variable adjustment, DAA therapy was not associated with HCC recurrence (hazard ratio [HR], 0.90) or early HCC recurrence (HR, 0.96), say Amit G. Singal, MD, associate professor of internal medicine and medical director of the Liver Tumor Program at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

The study was published online January 18 in Gastroenterology.

"Our results suggest use of direct-acting antivirals is safe and likely beneficial in hepatitis C–infected patients with a history of hepatocellular carcinoma," Singal told Medscape Medical News.

"We found no significant difference in the proportion of patients with recurrence or the aggressiveness of the recurrence between DAA-treated and untreated patients. Therefore, patients with a history of HCC who achieve complete response to cancer treatment should be referred for consideration of hepatitis C therapy," he said.

Although the findings suggest that DAA therapy is not associated with an increased risk for HCC recurrence, Singal pointed out that HCC recurrence was experienced by a high proportion of both DAA-treated and untreated patients.

"Therefore, it is critical for all patients to undergo HCC screening with CT or MRI to evaluate for recurrence before and after DAA therapy. In our center, we typically require two consecutive imaging studies to confirm the absence of HCC recurrence prior to starting DAA therapy," he said.

Contrast With Earlier Study

The new findings are in sharp contrast to results from the study published in 2016, in which researchers from the University of Barcelona reported an unexpectedly high rate of early tumor recurrence in 57 patients with HCV-related HCC. At a median follow-up of 5.7 months, 27% experienced tumor recurrence after undergoing DAA therapy.

"That study gained a lot of press and sparked fear about treating liver cancer patients for their hepatitis C," Singal said in a statement. "Based on these new data, providers can feel reassured that it is safe to treat hepatitis C in these patients and allow them to receive the known benefits of hepatitis C therapy."

Based on these new data, providers can feel reassured that it is safe to treat hepatitis C in these patients. Dr Amit Singal

As previously reported by Medscape Medical News, earlier studies have also raised theoretical concerns about the possibility of an "immune surveillance break" following DAA therapy.

It has been suggested that a rapid drop in the HCV viral load and a degree of hepatic inflammation might reduce immune surveillance of microscopic tumor clones, explained Singal. "Our results suggest that this does not appear to be the case," he said.

The investigators point out that data from the current study are consistent with findings from more recent studies "which have found most recurrences are detected at an early stage and can be treated with potentially curative treatments."

However, none of the studies have evaluated HCC-related mortality, he noted.

Hepatitis-Related Liver Cancer Increasing in US

There are more than 3.2 million HCV-infected persons in the United States, where HCV infection is the most common cause of HCC, the researchers note. Although highly effective DAA therapies could potentially decrease the incidence of HCV-related HCC, the authors predict that "suboptimal rates of HCV screening and treatment make this unlikely in the near future."

The Centers for Disease Control and Prevention estimates that 50% of adults in the United States are infected with HCV and do not know it. A recent study found that more than 25% of those diagnosed with HCC do not know they are HCV infected, as reported by Medscape Medical News.

"Therefore, HCV-related HCC incidence may continue to increase over the next decade, if not longer," Singal and colleagues warn.

Study Details

In the latest study, the investigators analyzed data from patients with HCV-related HCC who had experienced a complete response to treatment for HCC. The patients underwent treatment at 31 healthcare institutions in the United States and Canada from 2013 through December 2017.

These treatments included surgical resection, local ablative therapies, transarterial chemoembolization, bland embolization, transarterial radioembolization, and stereotactic body radiation therapy.

The median age of the patients was 61.6 years, and most were male and non-Hispanic whites. At the time of HCC diagnosis, nearly 75% had a unifocal HCC, and more than 80% were within Milan criteria, the benchmark for liver transplantation.

The analysis revealed that a larger proportion of DAA-treated patients than untreated patients underwent potentially curative HCC therapy, such as transplant, resection, or ablation (32.0% vs 24.6%). Of the 45.3% of treated patients and the 41.0% of untreated patients who achieved a complete or partial response, however, this did not reach statistical significance (P = .15), the researchers say.

Singal told Medscape Medical News that the team is currently conducting two follow-up studies. In the first, they are evaluating whether DAA therapy is associated with improvement in overall survival in patients with HCV-related HCC.

"Prior studies have suggested that liver dysfunction is a major cause of morbidity and mortality in these patients. While our current study highlights the safety of DAA therapy, this follow-up study is necessary to demonstrate its benefits," he said.

The second study will evaluate the efficacy and potential benefit of DAA therapy in patients with active HCC. "This is another group of patients in whom HCV therapy has yet to be evaluated," Singal noted.

The study was funded by the National Cancer Institute and AbbVie. Singal disclosed financial relationships with Gilead, Bayer, Bristol-Myers Squibb, AbbVie, Bayer, Eisai, Wako Diagnostics, Roche, Exact Sciences, and Glycotest. A number of coauthors also reported financial relationships with industry.

Gastroenterology. Published online on January 18, 2019. Abstract

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