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Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B

  • Lung-Yi Mak
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
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  • Rex Wan-Hin Hui
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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  • James Fung
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
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  • Fen Liu
    Affiliations
    Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Danny Ka-Ho Wong
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
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  • Ka-Shing Cheung
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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  • Man-Fung Yuen
    Correspondence
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road 102, Hong Kong. Tel.: +852 22553984; fax: +852 28162863
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
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  • Wai-Kay Seto
    Correspondence
    Corresponding authors. Address: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road 102, Hong Kong. Tel.: +852 22553994; fax: +852 28725828
    Affiliations
    Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong

    State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong

    Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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      Highlights

      • Hepatic steatosis was associated with a 3-fold increase in likelihood of HBsAg seroclearance in quiescent CHB infection.
      • Cumulative probability of HBsAg seroclearance at 3 years was 18.4% in those with steatosis and low serum HBV DNA (<200 IU/ml).
      • Fibrosis progression was still observed in 25.2% patients despite virological quiescence.
      • Persistent severe hepatic steatosis was associated with a 2-fold increased risk of fibrosis progression at 36 months.
      • Routine CAP measurement in patients with apparently low-risk CHB has prognostic value.

      Background & Aims

      Concomitant non-alcoholic fatty liver disease is common in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to study the effect of hepatic steatosis on the risk of fibrosis progression and the likelihood of HBsAg seroclearance.

      Methods

      Treatment-naïve patients with CHB, normal alanine aminotransferase and low viraemia (serum HBV DNA <2,000 IU/ml) were prospectively recruited for baseline and 3-year transient elastography assessment. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1 stage increment of fibrosis. Hepatic steatosis and severe hepatic steatosis were defined as controlled attenuation parameter (CAP) ≥248 dB/m and ≥280 dB/m, respectively.

      Results

      A total of 330 patients (median age 50.5 years, 41.2% male, median HBV DNA 189 IU/ml) were recruited. Twenty-two patients (6.7%) achieved HBsAg seroclearance during follow-up, and the presence of hepatic steatosis was associated with a significantly higher chance of HBsAg seroclearance (hazard ratio 3.246; 95% CI 1.278–8.243; p = 0.013). At baseline, 48.8% and 28.8% of patients had steatosis and severe steatosis, respectively, while 4.2% had F3/F4 fibrosis at baseline, increasing to 8.7% at 3 years. The rate of liver fibrosis progression in patients with persistent severe steatosis was higher than in those without steatosis (41.3% vs. 23%; p = 0.05). Persistent severe hepatic steatosis was independently associated with fibrosis progression (odds ratio 2.379; 95% CI 1.231–4.597; p = 0.01).

      Conclusions

      CAP measurements have predictive value in patients with virologically quiescent CHB. The presence of hepatic steatosis was associated with a higher risk of fibrosis progression but, paradoxically, a 3-fold increase in HBsAg seroclearance rate.

      Lay summary

      Co-existing fatty liver disease in patients with chronic viral hepatitis B infection leads to worsening liver fibrosis, but also increases the chance of cure from hepatitis B virus. Routine bedside assessment of liver fat content is important for risk assessment in treatment-naïve patients with chronic hepatitis B.

      Graphical abstract

      Keywords

      Linked Article

      • Dynamics of liver stiffness in chronic hepatitis B patients with concurrent metabolic-associated fatty liver disease
        Journal of HepatologyVol. 75Issue 1
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          We read with interest the article by Mak et al.1 and commend their work exploring the diverse relationship between hepatic steatosis and chronic hepatitis B (CHB). Through prospective follow-up of 330 patients with normal alanine aminotransferase (ALT) and low viraemia, Mak et al. showed persistent severe steatosis (controlled attenuation parameter ≥280 dB/m) was associated with progression of fibrosis category after 3 years. As modern nucleos(t)ide analogues are able to achieve effective long-term viral/biochemical suppression and attenuate fibrosis development,2 the focus of CHB management has shifted to address non-viral risk factors such as concurrent steatosis – with approximately 30% prevalence amongst patients with CHB3 – and metabolic dysfunction-associated fatty liver disease (MAFLD).
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