Metabolic-Associated Fatty Liver Disease, Hepatitis B Surface Antigen Seroclearance, and Long-Term Risk of Hepatocellular Carcinoma in Chronic Hepatitis B

Ming Whei Yu, Chih Lin Lin, Chun Jen Liu, Wan Jung Wu, Jui Ting Hu, Yi Wen Huang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989–1992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD–HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p < 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and ≥ 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities.

Original languageEnglish
Article number6012
JournalCancers
Volume14
Issue number23
DOIs
Publication statusPublished - Dec 2022

Keywords

  • all-cause mortality
  • diabetes
  • extrahepatic mortality
  • hepatic steatosis
  • MBOAT7
  • metabolic dysfunction
  • obesity
  • PNPLA3
  • TM6SF2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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