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The concept of MAFLD gathers patients with distinct disease progression trajectories.

  • Pierre Deltenre
    Affiliations
    Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium

    Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
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  • Eric Trépo
    Affiliations
    Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
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  • Christophe Moreno
    Correspondence
    Corresponding author. Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology. Université libre de Bruxelles. Route de Lennik 808 1070 Brussels, Belgium. Tel: +3225553712, Fax:+3225554697.
    Affiliations
    Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
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Published:November 16, 2022DOI:https://doi.org/10.1016/j.jhep.2022.11.009

      Linked Article

      To the Editor,
      We read with great interest the article of Staufer et al. on the rate of alcohol consumption in patients with presumed non-alcoholic liver disease (NAFLD)
      • Staufer K.
      • Huber-Schonauer U.
      • Strebinger G.
      • Pimingstorfer P.
      • Suesse S.
      • Scherzer T.M.
      • et al.
      Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.
      . The authors made a substantial effort to reclassify patients according to the recent definition of metabolic-associated liver disease (MAFLD). The findings of this study further illustrate the wide heterogeneity that this nomenclature englobes.
      The concept of MAFLD was introduced in 2020 by Eslam et al. as an alternative to describing liver disease associated with an underlying metabolic dysfunction for several reasons that will not be developed here
      • Eslam M.
      • Newsome P.N.
      • Sarin S.K.
      • Anstee Q.M.
      • Targher G.
      • Romero-Gomez M.
      • et al.
      A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement.
      . As a result, this definition includes all patients with hepatic steatosis and metabolic abnormalities regardless of alcohol intake. Hence, a significant proportion of patients with alcohol-related liver disease (ALD) now falls into this category
      • Moreno C.
      • Sheron N.
      • Tiniakos D.
      • Lackner C.
      • Mathurin P.
      Europe ECftSoA-rLdi
      "Dual aetiology fatty liver disease": A recently proposed term associated with potential pitfalls.
      .
      In their study, Staufer et al. included 184 patients, 114 with presumed NAFLD and 70 with ALD, and made important observations. First, more than 90% of their population that could be reclassified according to MAFLD criteria belong to this category. This result is not surprising as the median BMI was 30, and 68% of patients had type 2 diabetes or glucose intolerance. Second, ALD patients differed from a clinical point of view on age, sex ratio, BMI, and prevalence of glucose metabolism abnormalities from presumed NAFLD patients. This indicates that the MAFLD nomenclature gathers patients with distinct clinical profiles. Third, considerable differences in rates of cirrhosis were observed between presumed NAFLD and ALD patients (11% vs. 87%, respectively). Although NAFLD and ALD have similar pathogenic features and patients share common clinical risk factors for disease progression, the natural history of the disease differs. In addition, this discrepancy in cirrhosis rate also shows that NAFLD and ALD patients have different progression trajectories.
      The discrepancy in the natural history of ALD and NAFLD has already been documented. Previous studies indicated that the risk of cirrhosis differs between ALD and NAFLD patients. In a study including 106 ALD patients and 109 NAFLD patients, the incidence of cirrhosis was 21% in the first group of patients and 1% in the latter
      • Dam-Larsen S.
      • Franzmann M.
      • Andersen I.B.
      • Christoffersen P.
      • Jensen L.B.
      • Sorensen T.I.
      • et al.
      Long term prognosis of fatty liver: risk of chronic liver disease and death.
      . In addition, the risk of liver-related mortality is known to be low in patients with NAFLD and conversely high in patients with ALD. In a large study enrolling more than 3000 individuals with biopsy-proven ALD, 5-year mortality was 41%
      • Hagstrom H.
      • Thiele M.
      • Roelstraete B.
      • Soderling J.
      • Ludvigsson J.F.
      Mortality in biopsy-proven alcohol-related liver disease: a population-based nationwide cohort study of 3453 patients.
      . In contrast, this rate was less than 5% in patients without fibrosis and around 10% in those with fibrosis in another study population with biopsy-proven NAFLD
      • Orman E.S.
      • Roberts A.
      • Ghabril M.
      • Nephew L.
      • Desai A.P.
      • Patidar K.
      • et al.
      Trends in Characteristics, Mortality, and Other Outcomes of Patients With Newly Diagnosed Cirrhosis.
      .
      Overall, there is no doubt that ALD and NAFLD share similar pathogenic pathways, that excessive alcohol consumption and features of the metabolic syndrome are frequently associated in a significant proportion of patients seen in daily clinical practice and have a synergistic effect on disease progression. However, several lines of evidence indicate that liver-related morbidity and mortality are mainly driven by alcohol use. The article by Staufer et al. brings additional evidence that ALD and NAFLD patients should not be gathered in a unique set of patients under the current MAFLD definition.

      Competing interests

      The authors have no competing interests to declare

      Funding

      The authors did not receive any funding for this study

      Author contributions

      Pierre Deltenre: study concept and design; drafting of the manuscript; critical revision of the manuscript for important intellectual content; study supervision.
      Eric Trépo: drafting of the manuscript; critical revision of the manuscript for important intellectual content.
      Christophe Moreno: study concept and design; drafting of the manuscript; critical revision of the manuscript for important intellectual content; study supervision.

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        Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.
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