Antivirals Linked to Lower Risk of Liver Cancer Return

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Long-Term Effectiveness Questioned

The researchers show that nucleoside analogues may reduce short-term mortality after liver resection, but "given the long interval between cell damage, malignant transformation, and tumor development, it is unrealistic to expect that administration of antiviral therapy for 1-2 years can prevent HCC recurrence," said Dr. Anna S. F. Lok.

"Further studies with longer duration of treatment and better characterization of HBV replication status and liver disease are needed to determine the magnitude of benefit" from taking the drugs, she said.

Dr. Lok is in the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor. She reported serving as an adviser for Arrowhead, Bayer, and other companies, and receiving research grants from Bristol-Myers Squibb, Gilead, and GlaxoSmithKline. These remarks were taken from her editorial accompanying Dr. Wu’s report (JAMA 2012;308:1922-24 [doi: 10.1001/jama.2012.12971]).



Using antiviral drugs after "curative" surgery for hepatitis B–related liver cancer may lower the risk of cancer recurrence, according to a Taiwanese study presented at the annual meeting of the American Association for the Study of Liver Diseases and simultaneously published online in JAMA.

The cumulative 6-year incidence of hepatocellular carcinoma (HCC) recurrence was significantly lower for patients who were treated with the nucleoside analogues lamivudine, entecavir, or telbivudine than it was for patients who weren’t given these agents.

Accordingly, overall 6-year mortality and disease-related mortality also were significantly lower, said Dr. Chun-Ying Wu of National Yang-Ming University, Taipei, and his associates (JAMA 2012;308:1906-13 [doi: 10.1001/2012.jama.11975]).

The investigators noted that their study could not definitively establish that these antiviral drugs caused the reductions in cancer recurrence and mortality, because no retrospective observational study can prove causality. But nucleoside analogues are known to be effective at suppressing hepatitis B virus (HBV) replication, ameliorating other HBV-related liver diseases, and reducing the risk of HCC in patients with chronic hepatitis or cirrhosis.

"Although it is generally accepted that HBV viral load plays an important role in HCC recurrence, studies regarding the effectiveness of nucleoside analogues in HCC recurrence have been very limited and have produced conflicting results," they said.

The investigators examined the issue using data from Taiwan’s National Health Insurance Research Database, which covers more than 99% of the country’s population of approximately 25 million. They identified all 4,569 inpatients with newly diagnosed HBV-related HCC who underwent "curative" liver resection during a 6-year period.

A total of 518 of these patients received lamivudine (159 patients), entecavir (292 patients), telbivudine (36 patients), or a combination of these antivirals (31 patients) for at least 90 days. The remaining 4,051 patients never received any nucleoside analogues.

The mean duration of antiviral therapy with these nucleoside analogues was 1.5 years. The patients were followed up until HCC recurrence, death, or the end of the 6-year study period.

After the data were adjusted to account for competing mortality, the cumulative rate of HCC recurrence was significantly lower for patients who received the nucleoside analogues (45.6%) than for those who did not (54.6%), the researchers said.

The unadjusted number needed to treat to achieve 1 less HCC recurrence within 6 years was 12. "This implies that use of nucleoside analogues in 12 HCC patients after liver resection is associated with 1 less HCC recurrence within 6 years," the investigators explained.

The overall cumulative 6-year mortality rate also was significantly lower (29.0%) in patients who received the nucleoside analogues than in those who did not (42.4%).

The unadjusted number needed to treat associated with 1 less death within 6 years was 8. "This implies that use of nucleoside analogues in 8 HCC patients after liver resection is associated with 1 less death within 6 years," Dr. Wu and his colleagues said.

Treatment with nucleoside analogues also was associated with improved disease-free survival.

These results were unchanged when the data were analyzed according to the use or nonuse of NSAIDs and the presence or absence of comorbid diabetes.

However, the use of nucleoside analogues was associated with a lower risk of HCC recurrence in patients who didn’t have concomitant cirrhosis but not in those who did have cirrhosis, they noted.

This study was supported by Taiwan’s National Health Research Institute. No financial conflicts of interest were reported.

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