Hepatitis B Virus Reactivation Rate Is Considerably High during Sorafenib Therapy without Antiviral Treatment in Patients with Advanced Hepatocellular Carcinoma = Hepatitis B Virus Reactivation Rate Is Considerably High during Sorafenib Therapy without Antiviral Treatment in Patients with Advanced Hepatocellular Carcinoma

다국어 초록 (Multilingual Abstract)

Aims: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC). However, the influence of sorafenib on the replication of HBV remains unknown. Herein, we evaluated the rate of HBV reactivation during sorafenib therapy in chronic hepatitis B (CHB) patients with advanced HCC.
Methods: Four hundreds thirty five advanced HCC patients who visited three hospitals affiliated with Korea University from January 2004 to December 2012 were retrospectively reviewed. Among them, 327 patients were HBsAg positive. Two hundred sixty four received antiviral therapy before initiation of sorafenib therapy, and 64 patients were treatment naive with regard to anti-HBV therapy. Patients who received sorafenib less than 4 weeks, those who had not follow-up HBV DNA value, and patients who received other treatment than sorafenib were excluded. Finally, 133 and 28 patients were analyzed, respectively in each group. HBV reactivation were defined as increase of HBV DNA >10 times of baselines or ≥ 2000 IU/mL in patients with baselines HBV DNA < 2000 IU/mL. We further investigated reactivation rates in propensity score matched liver cirrhosis patients without HCC.
Results: Mean age was 54.87±9.34 and 83.2% were male. All patients were Barcelona Clinic of Liver Cancer Stage C and the sum of tumor diameter was 10.42±5.78 cm. Mean baseline HBV DNA level was 2.84±1.60 log IU/mL. Median survival was 5.97 months. At 12, 24, and 48 weeks of the sorafenib therapy, HBV reactivation occurred in 5.26%, 12.0%, 14.3% of antiviral therapy group while it developed in 28.6%, 39.3%, and 42.9% of HBV therapy naïve group, respectively. The reactivation rates was significantly higher in patient who didn’t received antiviral therapy (p = 0.001). The antiviral therapy (HR 0.250, C.I. 0.104-0.604, p = 0.002) was independent factor related to HBV reactivation by logistic regression analysis. When the 28 HBV therapy naive HCC patients who received sorafenib were compared with propensity score matched 84 HBV therapy naïve liver cirrhosis patients without HCC, the cumulative reactivation rates were also significantly higher in the former group by log-rank test (p <0.001).
Conclusions: The risk of HBV reactivation is high in CHB patients receiving sorafenib due to advanced HCC. It would be necessary to administer pre-emptive antiviral therapy before sorafenib initiation.