@article {Kimgutjnl-2017-314904, author = {Gi-Ae Kim and Young-Suk Lim and Seungbong Han and Jonggi Choi and Ju Hyun Shim and Kang Mo Kim and Han Chu Lee and Yung Sang Lee}, title = {High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B}, elocation-id = {gutjnl-2017-314904}, year = {2017}, doi = {10.1136/gutjnl-2017-314904}, publisher = {BMJ Publishing Group}, abstract = {Objective High serum HBV DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B (CHB). Although the immune-tolerant (IT) phase is characterised by high circulating HBV DNA levels, it remains unknown whether antiviral treatment reduces risks of HCC and mortality.Design This historical cohort study included HBeAg-positive patients with CHB with high HBV DNA levels (>=20 000 IU/mL) and no evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013. The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, \<19 IU/mL; males, \<30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT >=80 IU/mL) treated with nucleos(t)ide analogues.Results The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7\% vs 6.1\%; p=0.001) and death/transplantation (9.7\% vs 3.4\%; p\<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95\% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95\% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.Conclusions Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients.}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/early/2017/11/09/gutjnl-2017-314904}, eprint = {https://gut.bmj.com/content/early/2017/11/09/gutjnl-2017-314904.full.pdf}, journal = {Gut} }