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Abstract
Background To evaluate the long-term risk of hepatocellular carcinoma (HCC) and hepatic decompensation in chronic hepatitis B (CHB) patients who cleared hepatitis B surface antigen (HBsAg).
Methods All adult CHB monoinfected patients who achieved HBsAg seroclearance between January 2000 and June 2021 were identified using a territory-wide electronic healthcare database managed by Hospital Authority, Hong Kong. Patients with liver transplantation and/or HCC before HBsAg loss or follow-up less than 6 months were excluded. Hepatic decompensation included ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, liver transplantation, and liver-related mortality. The comparison of patients before and after year 7 of HBsAg loss was handled by clustered data in the Fine-Gray model.
Results 9,769 CHB patients who cleared HBsAg at a mean age of 57 years (60.0% male, 5.7% cirrhosis) were identified; most patients had compensated liver function at HBsAg seroclearance. At a mean follow-up of 5.4 ± 3.7 years, 106 (1.1%) patients developed HCC. Patients who developed HCC were older, more likely to be male and cirrhotic, and had higher alanine aminotransferase, and lower platelets than patients without HCC development. The cumulative incidence of HCC remained steady in 0–7 and 8–12 years after HBsAg loss (P=0.898) (crude annual incidence reduction: -0.04%, 95% CI -0.13%–0.04%, P=0.265) (IDDF2022-ABS-0226 Figures 1A. Cumulative incidence of hepatocellular carcinoma, IDDF2022-ABS-0226 Figure 1B. Crude annual incidence of hepatocellular carcinoma). Meanwhile, 124/9,640 (1.3%) patients without prior hepatic decompensation developed hepatic decompensation. The cumulative incidence of hepatic decompensation decelerated in 8–12 years after the first 7 years of HBsAg seroclearance (P=0.009) (crude annual incidence reduction: -0.23%, 95% CI -0.40% – -0.06%, P=0.012) (IDDF2022-ABS-0226 Figures 1C. Cumulative incidence of hepatic decompensation in chronic hepatitis B patients who achieved hepatitis B surface antigen (HSbAg) loss, IDDF2022-ABS-0226 Figure 1D. Crude annual incidence of hepatic decompensation in chronic hepatitis B patients who achieved hepatitis B surface antigen (HSbAg) loss). HBsAg loss for over 7 years was found to be associated with a reduced risk of hepatic decompensation (adjusted subdistribution hazard ratio [aSHR] 0.53, 95% CI 0.30–0.94, P=0.029) but not HCC (aSHR 1.38, 95% CI 0.85–2.23, P=0.193) after adjusting for age, gender, presence of cirrhosis and diabetes, platelet, and liver biochemistry.
Conclusions The risk of HCC persists up to 12 years in patients after HBsAg loss, whereas the risk of hepatic decompensation reduces after 7 years.