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. 2021 Aug 8;3(5):100350.
doi: 10.1016/j.jhepr.2021.100350. eCollection 2021 Oct.

Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B

Laurens A van Kleef  1 , Hannah S J Choi  2 , Willem P Brouwer  1 , Bettina E Hansen  2 , Keyur Patel  2 , Robert A de Man  1 , Harry L A Janssen  2 , Robert J de Knegt  1 , Milan J Sonneveld  1
Affiliations

Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B

Laurens A van Kleef et al. JHEP Rep. .

Abstract

Background & aims: A recent consensus document has defined metabolic dysfunction-associated fatty liver disease (MAFLD) as hepatic steatosis together with overweight, diabetes, and/or a combination of other metabolic risk factors. The clinical relevance of this novel diagnosis is unknown among patients with chronic hepatitis B (CHB). We studied the association between MAFLD (with or without steatohepatitis) and adverse clinical outcomes in patients with CHB.

Methods: We performed a retrospective long-term follow-up cohort study at 2 tertiary hospitals in patients with CHB who underwent liver biopsy. Biopsies were reassessed for steatosis, degree of fibrosis, and presence of steatohepatitis. Associations with event-free hepatocellular carcinoma (HCC)-free and transplant-free survival were explored.

Results: In our cohort, 1076 patients were included, median follow-up was 9.8 years (25th-75th percentile: 6.6-14.0), and 107 events occurred in 78 patients, comprising death (n = 43), HCC (n = 36), liver decompensation (n = 21), and/or liver transplantation (n = 7). MAFLD was present in 296 (27.5%) patients and was associated with reduced event-free (adjusted hazard ratio [aHR] 2.00, 95% CI 1.26-3.19), HCC-free (aHR 1.93, 95% CI 1.17-3.21), and transplant-free survival (aHR 1.80, 95% CI 0.98-3.29) in multivariable analysis. Among patients with MAFLD, the presence of steatohepatitis (p = 0.95, log-rank test) was not associated with adverse outcomes.

Conclusions: The presence of MAFLD in patients with CHB was associated with an increased risk for liver-related clinical events and death. Among patients with MAFLD, steatohepatitis did not increase the risk of adverse outcomes. Our findings highlight the importance of metabolic dysfunction in patients with CHB.

Lay summary: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been defined as fatty liver disease with signs of metabolic dysfunction. Among patients with chronic hepatitis B, MAFLD was associated with liver-related events and death. Metabolic health assessment should be encouraged among patients with chronic hepatitis B, especially in those with fatty liver disease.

Keywords: ALT, alanine aminotransferase; Adverse clinical outcomes; CHB; CHB, chronic hepatitis B; Chronic hepatitis B; FLD, fatty liver disease; HBV; HCC; HCC, hepatocellular carcinoma; HR, hazard rate; Hepatitis B; Hepatocellular carcinoma; MAFLD; MAFLD, metabolic dysfunction-associated fatty liver disease; Metabolic dysfunction-associated fatty liver disease; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; NASH, non-alcoholic steatohepatitis; NHANES, National Health and Nutrition Examination Survey; P25–P75, 25th–75th percentile; Steatohepatitis; Survival; ULN, upper limit of normal; aHR, adjusted hazard rate.

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Conflict of interest statement

MJS has received speaker's fees and research support from Fujirebio and has received grants from Gilead. KP consults for, advises, and received grants from Gilead. HLAJ received grants from Abbvie, Arbutus, Bristol Myers, Squibb, Gilead Sciences, Janssen, Merck, and Roche and is a consultant for Aligos, Arbutus, Arena, Eiger, Enyo, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Regulus, Roche, VBI Vaccines (Variation Biotechnologies), Vir Biotechnology Inc., and Viroclinics. RdK is a speaker for Echosens, consultant for AbbVie, and received grants from Abbvie, Gilead, and Janssen. The remaining authors report no relevant conflicts. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Flowchart study population. FLD, fatty liver disease; MAFLD, metabolic dysfunction-associated fatty liver disease.
Fig. 2
Fig. 2
Association of MAFLD with (A) event-, (B) HCC-, and (C) transplant-free survival. Results were obtained with Kaplan–Meier analysis with log-rank statistics. HCC, hepatocellular carcinoma; MAFLD, metabolic dysfunction-associated fatty liver disease.
Fig. 3
Fig. 3
Association of MAFLD for event-free survival in (A) patients without and (B) with advanced fibrosis. Results were obtained with Kaplan–Meier analysis with log-rank statistics. Advanced fibrosis: METAVIR F3–F4. MAFLD, metabolic dysfunction-associated fatty liver disease.
Fig. 4
Fig. 4
Event-free survival in patients with MAFLD according to presence of (A) steatohepatitis and (B) NAS ≥3. Results were obtained with Kaplan–Meier analysis with log-rank statistics. MAFLD, metabolic dysfunction-associated fatty liver disease; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score.
See this image and copyright information in PMC

References

    1. Razavi-Shearer D., Gamkrelidze I., Nguyen M.H., Chen D.-S., Van Damme P., Abbas Z. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3:383–403. - PubMed
    1. World Health Organization . World Health Organization; Geneva: 2017. Global Hepatitis Report 2017.
    1. Arends P., Sonneveld M.J., Zoutendijk R., Carey I., Brown A., Fasano M. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians. Gut. 2015;64:1289–1295. - PubMed
    1. Younossi Z.M., Koenig A.B., Abdelatif D., Fazel Y., Henry L., Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84. - PubMed
    1. Li J., Zou B., Yeo Y.H., Feng Y., Xie X., Lee D.H. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2019;4:389–398. - PubMed