Association of Chronic Hepatitis B Virus Infection and Antiviral Treatment With Risk of Extrahepatic Malignancies

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In a Korean nationwide cohort study reported in the Journal of Clinical Oncology, Lee et al found that patients with chronic hepatitis B infection were at increased risk of extrahepatic malignancies, with risk being reduced among those receiving nucleoside/nucleotide analog antiviral treatment for chronic hepatitis B.

Study Details

The 18-month landmark analysis used nationwide claims data from the National Health Insurance Service of South Korea. The study cohort included 90,944 patients diagnosed with chronic hepatitis B from 2012 to 2014 and 685,436 matched controls without chronic hepatitis B infection who had a hospital visit for any reason during 2012 to 2014.

Among patients with chronic hepatitis B, 6,539 were nucleoside/nucleotide analog–treated (CHB/NA+) and 84,405 were not (CHB/NA–). Nucleoside/nucleotide analog users were defined as patients who received nucleoside/nucleotide analog treatment for at least 72 days consecutively within the first 90 days of the 18-month exposure period. The median cumulative defined daily dose of nucleoside/nucleotide analogs during the 18-month exposure period was 443 days (interquartile range [IQR] = 260–520 days) after inverse probability of treatment weighting.

Key Findings

During a median follow-up of 47.4 months (IQR = 38.1–57.1 months), a total of 30,413 individuals (3.9%) developed any extrahepatic malignancy.

In the 18-month landmark analysis, the rate of development of extrahepatic malignancy per 100 person-years was 1.21 in the CHB/NA– group, 0.99 in the CHB/NA+ group, and 0.98 in the control group. The CHB/NA– group had a higher risk of extrahepatic malignancy vs the CHB/NA+ group (adjusted subdistribution hazard ratio [aSHR] = 1.28, 95% confidence interval [CI] = 1.12–1.45, P < .001) and vs controls (aSHR = 1.22, 95% CI = 1.18–1.26, P < .001). No difference in the risk was observed for the CHB/NA+ group vs controls (aSHR = 0.96, 95% CI = 0.84–1.08, P = .48).

In a time-varying Cox analysis, CHB/NA– patients had a higher risk of extrahepatic malignancy vs CHB/NA+ patients (aSHR = 1.37, 95% CI = 1.23–1.52, P < .001).

The investigators concluded, “Patients with chronic hepatitis B infection have an elevated risk of developing primary extrahepatic malignancy. Long-term nucleoside/nucleotide analog treatment was associated with a lower risk of extrahepatic malignancy development among patients with chronic hepatitis B.”

Jeong-Hoon Lee, MD, PhD, of the Department of Internal Medicine, Seoul National University Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Korea Ministry of Science and ICT, Liver Research Foundation of Korea, Yuhan Pharmaceutical Company, and others. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.