Lower Risk of Recurrence in Patients with HBV-related Liver Cancer Receiving Nucleoside Analogs

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Patients with hepatitis B virus (HBV)-related hepatocellular carcinoma who received nucleoside analogs after curative liver resection had an associated lower risk of hepatocellular carcinoma in a nationwide cohort study using data from the Taiwan National Health Research Data Base. The study was reported in the Journal of the American Medical Association and presented at the Annual Meeting of the American Association for the Study of Liver Diseases.

Study Rationale

Higher HBV viral load is an independent risk factor for recurrence of HBV-related hepatocellular carcinoma, and nucleoside analogs are effective in suppressing HBV replication and ameliorating HBV-related liver disease, the researchers explained. Nevertheless, studies of nucleoside analog use in hepatocellular carcinoma recurrence “have been relatively limited and have yielded conflicting results,” they noted.

The researchers identified 4,569 patients with HBV-related hepatocellular carcinoma who received curative liver resection. The primary outcome measure for the study was the risk of first tumor recurrence between patients not taking nucleoside analogs (untreated group, n = 4,051) and patients taking nucleoside analogs (treated group, n = 518). The median age of patients was 54 years, and more than 80% of the patients in both groups were men.

The researchers found that the treated group had a higher prevalence of liver cirrhosis when compared with the untreated group (48.6% vs 38.7%; P < .001) but a lower risk of hepatocellular carcinoma recurrence (20.5% vs 43.6%), and lower overall death rate (10.6% vs 28.3%).

“After adjusting for competing mortality, the treated cohort had a significantly lower 6-year [hepatocellular carcinoma] recurrence rate,” the researchers reported, 45.6% vs 54.6% for untreated patients (P < .001). The risk of overall mortality was also significantly lower in patients in the treated vs untreated group (6-year cumulative incidence, 29% vs 42.4% (P < .001).

Multivariate analysis revealed that use of statins, nonsteroidal anti-inflammatory drugs (NSAIDs), or aspirin was associated with a lower risk of hepatocellular carcinoma recurrence, the investigators noted. While the protective role of statins in HBV-infected hepatocellular carcinoma has been previously reported, the “association between the use of NSAIDs or aspirin and a lower risk of [hepatocellular carcinoma] recurrence is a novel finding,” they wrote.

Interpreting the Data

“The results of this study support findings from multiple smaller studies but are by no means definitive enough to answer the question of whether antiviral therapy after curative resection of hepatitis B-related [hepatocellular carcinoma] will prevent disease recurrence,” Anna S. F. Lok, MD, of the University of Michigan in Ann Arbor, stated in an accompanying editorial. “Given the long interval between cell damage, malignant transformation, and tumor development, it is unrealistic to expect that administration of antiviral therapy for 1 to 2 years can prevent [hepatocellular carcinoma] recurrence, particularly because early recurrence is likely due to previously undiscovered metastasis from the primary tumor.”

Nevertheless, Dr. Lok continued, nucleoside/nucleotide analogs “may decrease short-term mortality after liver resection, particularly among patients with underlying cirrhosis, high levels of HBV replication, or active hepatic inflammation.” For patients who do not show early hepatocellular carcinoma recurrence, continued therapy with these agents may prevent new primary tumors and further disease progression, thereby decreasing late recurrence and long-term mortality.

“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 and to clarify whether nucleoside/nucleotide analogs should be administered to all or a subset of patients after curative treatment for HBV-related [hepatocellular carcinoma],” she concluded. ■

Wu C-Y, et al: JAMA 308:1906-1914, 2012.

Lok ASF: JAMA 308:1922-1924, 2012.