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. 2023 Mar;78(3):524-533.
doi: 10.1016/j.jhep.2022.11.020. Epub 2022 Dec 2.

Risk of hepatic decompensation but not hepatocellular carcinoma decreases over time in patients with hepatitis B surface antigen loss

Terry Cheuk-Fung Yip  1 , Vincent Wai-Sun Wong  1 , Mandy Sze-Man Lai  2 , Jimmy Che-To Lai  1 , Vicki Wing-Ki Hui  2 , Lilian Yan Liang  2 , Yee-Kit Tse  1 , Henry Lik-Yuen Chan  3 , Grace Lai-Hung Wong  4
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Risk of hepatic decompensation but not hepatocellular carcinoma decreases over time in patients with hepatitis B surface antigen loss

Terry Cheuk-Fung Yip et al. J Hepatol. 2023 Mar.

Abstract

Background & aims: We examined the long-term incidence of hepatocellular carcinoma (HCC) and hepatic decompensation among chronic hepatitis B (CHB) patients who have achieved hepatitis B surface antigen (HBsAg) seroclearance.

Methods: All adult CHB-monoinfected patients who cleared HBsAg between January 2000 and December 2020 were identified using a territory-wide database in Hong Kong. Patients who underwent liver transplantation and/or developed HCC before HBsAg seroclearance or less than 6 months follow-up were excluded. The primary and secondary endpoints were HCC and hepatic decompensation respectively.

Results: We identified 9,769 patients with CHB who achieved HBsAg seroclearance (mean age 57 years, 60.0% male, 13.2% cirrhosis); most had compensated liver function at HBsAg loss. At a median (25th-75th percentile) follow-up of 4.6 (2.2-8.4) years, 106 (1.1%) patients developed HCC. Patients who developed HCC were older, more likely to be male and have cirrhosis, and had higher alanine aminotransferase and lower platelets at the time of HBsAg loss than patients without HCC. The cumulative incidence of HCC remained steady 0-7 and 8-12 years after HBsAg loss (p = 0.898) (crude annual incidence drop: -0.04%, 95% CI -0.13% to 0.04%, p = 0.265). Moreover, 124/9,640 (1.3%) patients developed hepatic decompensation. The growth in cumulative incidence of hepatic decompensation decelerated 8-12 years after HBsAg loss (p = 0.009) (crude annual incidence drop: -0.23%, 95% CI -0.40% to -0.06%, p = 0.012). In multivariable analysis, HBsAg loss for over 7 years was associated with a reduced risk of hepatic decompensation (adjusted subdistribution hazard ratio [aSHR] 0.55, 95% CI 0.31-0.97, p = 0.039) but not HCC (aSHR 1.35, 95% CI 0.83-2.19, p = 0.230).

Conclusion: HCC risk persists in patients after HBsAg loss, whereas the risk of hepatic decompensation decreases over time.

Impact and implications: Patients with chronic hepatitis B (CHB) still have a non-negligible risk of hepatocellular carcinoma (HCC) after 12 years of HBsAg seroclearance, especially among those with cirrhosis. The risk of developing hepatic decompensation decreases over time after HBsAg seroclearance. In clinical practice, although patients with CHB who cleared HBsAg have a more favourable clinical outcome than those who remain chronically infected, long-term HCC surveillance would still be necessary for patients with cirrhosis and other high-risk subgroups after HBsAg seroclearance.

Keywords: HBsAg seroclearance; hepatic decompensation; hepatitis B virus; liver cancer.

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Conflict of interest statement

Conflict of interest Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences. Vincent Wong has served as a consultant or advisory committee member for AbbVie, Boehringer Ingelheim, Echosens, Intercept, Inventiva, Novo Nordisk, Pfizer, and TARGET PharmaSolutions; and a speaker for Abbott, AbbVie, Gilead Sciences, and Novo Nordisk. He has received a research grant from Gilead Sciences, and is a cofounder of Illuminatio Medical Technology Limited. Henry Chan has served as an Independent Non-Executive Director for Shanghai Henlius Biotech Inc; as an advisory board member for Aligos, Aptorum, Arbutus, Hepion, Janssen, Gilead, Glaxo-Smith-Kline, Roche, Vaccitech, Virion Therapeutics, and Vir Biotechnology; and as a speaker for Gilead, Roche, and Viatris. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, AbbVie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche. She has also received a research grant from Gilead Sciences. The other authors declare that they have no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details.

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