Nucleos(t)ide Analogues Associated With a Reduced Risk of Hepatocellular Carcinoma in Hepatitis B Patients: A Population-Based Cohort Study

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Hepatocellular carcinoma (HCC) is a major complication of hepatitis B virus (HBV) infection. This study investigated the association between nucleos(t)ide analogue (NA) use and the risk of HCC and mortality in HBV carriers on the basis of the Taiwan National Health Insurance Database.


In all, 1544 HBV carriers taking NAs (treated cohort) who were identified between October 1, 2003 and December 31, 2011 were examined for their risk of HCC and mortality; 1544 patients not receiving NA treatment (untreated cohort) were selected via propensity score matching as the comparison group. The risks of first tumor occurrence and mortality were compared.


The treated cohort had a significantly lower HCC occurrence rate (6.0%; 95% confidence interval [CI], 4.4%-7.9%) in comparison with the untreated cohort (8.5%; 95% CI, 6.6%-10.6%; P = .0025). The overall mortality rates for the treated and untreated cohorts were 6.9% (95% CI, 5.3%-8.7%) and 9.4% (95% CI, 7.7%-11.3%), respectively (P = .0003). After adjustments for competing confounders, Cox regression analyses showed that NA use significantly reduced the risk of HCC (hazard ratio [HR], 0.64; 95% CI, 0.45-0.93; P = .017) and overall mortality (HR, 0.58; 95% CI, 0.43-0.79; P < .001). There was a dose-response relationship between NA use and the risk of HCC in the treated cohort. With respect to no NA use, the adjusted HRs were 0.93 (95% CI, 0.58-1.48), 0.67 (95% CI, 0.42-1.06), and 0.35 (95% CI, 0.17-0.70) for 90 to 365, 366 to 730, and >730 cumulative defined daily doses of NAs, respectively.


NA use reduced the risk of HCC and overall mortality in HBV carriers. Cancer2015;121:1446–1455. © 2014 American Cancer Society.

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