Patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC; liver cancer) who received nucleoside analogues (antiviral therapy) after cancer surgery had an associated lower risk of HCC recurrence compared to patients who did not receive antiviral therapy, according to a study appearing in the November 14 issue of JAMA.1 The study is being released early online to coincide with its presentation at the annual meeting of the American Association for the Study of Liver Diseases.
“Surgery is considered the standard curative treatment option for HCC. However, the rate of long-term disease-free survival after liver resection remains unsatisfactory due to persistent high incidences of HCC recurrence,” according to background information in the article. “Higher HBV viral load has been reported to be an independent risk factor for HCC recurrence in patients with HBV-related HCC. Nucleoside analogues are effective in suppressing HBV replication and in ameliorating [make better] HBV-related liver disease. They have been shown to be associated with a lower risk of HCC and other cirrhosis-related complications in those with chronic hepatitis and cirrhosis. However, studies on the effectiveness of nucleoside analogue use in HCC recurrence have been relatively limited and have yielded conflicting results.”
Chun-Ying Wu, M.D., Ph.D., M.P.H., of National Yang-Ming University, Taipei, Taiwan, and colleagues conducted a study to examine the association between use of nucleoside analogues and risk of HCC recurrence among patients with HBV-related HCC after curative liver resection. The study included data from the Taiwan National Health Insurance Research Database. Among 100,938 patients newly diagnosed with HCC, the researchers identified 4,569 patients with HBV-related HCC who received curative liver resection for HCC between October 2003 and September 2010. The primary outcome measure for the study was the risk of first tumor recurrence between patients not taking nucleoside analogues (untreated group, n = 4,051) and patients taking nucleoside analogues (treated group, n = 518).
The researchers found that the treated group had a higher prevalence of liver cirrhosis when compared with the untreated group (48.6 percent vs. 38.7 percent), but lower risk of HCC recurrence (n = 106 [20.5 percent] vs. n = 1,765 [43.6 percent]), and lower overall death (n = 55 [10.6 percent] vs. n = 1,145 [28.3 percent]). After adjusting for competing mortality, the risk of HCC recurrence was significantly lower for patients in the treated group (6-year cumulative incidence, 45.6 percent) than for patients in the untreated cohort (54.6 percent). The risk of overall mortality was significantly lower in patients in the treated vs. untreated group (6-year cumulative incidence, 29.0 percent vs. 42.4 percent, respectively).
After analysis, nucleoside analogue use was associated with a 33 percent reduced risk of HCC recurrence; statin use, a 32 percent reduced risk; and nonsteroidal anti-inflammatory drugs or aspirin use a 20 percent reduced risk of HCC recurrence. Further analyses verified the association in all subgroups of patients, including those who were noncirrhotic and diabetic.
“In conclusion, nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection,” the authors write.
Anna S. F. Lok, M.D., of the University of Michigan, Ann Arbor, Mich., writes in an accompanying editorial 2that “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 HCC will prevent disease recurrence.”
“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 HCC recurrence, particularly because early recurrence is likely due to previously undiscovered metastasis from the primary tumor. However, nucleoside/nucleotide analogues 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 experience early HCC recurrence, continued therapy with nucleoside/nucleotide analogues may prevent de novo primary tumors and further progression of liver disease, thereby decreasing late HCC recurrence and long-term mortality.”
1. (JAMA. 2012;308(18):1906-1913
2. (JAMA. 2012;308(18):1922-1924;