Letter regarding “A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement”

We read with great interest the paper published in Journal of Hepatology by Eslam et al.,[1]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.J Hepatol. 2020; 73: 202-209Abstract Full Text Full Text PDF PubMed Scopus (906) Google Scholar which we feel is particularly relevant to hepatologists who manage patients with non-alcoholic fatty liver disease (NAFLD), a disease now advocated to be redefined as metabolic dysfunction-associated fatty liver disease (MAFLD). With the rising prevalence of MAFLD, we increasingly encounter patients with heterogeneous clinical profiles – from simple excessive hepatic fat detected on imaging, to steatohepatitis or even cirrhosis. Some patients present with concomitant metabolic risk factors such as diabetes mellitus (DM) or obesity, and some patients suffer from other chronic liver diseases apart from MAFLD. In Hong Kong, the prevalence of chronic hepatitis B infection (CHB) is 7.8%[2]Liu K.S.H. Seto W.K. Lau E.H.Y. Wong D.K. Lam Y.F. Cheung K.S. et al.A territorywide prevalence study on blood-borne and enteric viral hepatitis in Hong Kong.J Infect Dis. 2019; 219: 1924-1933Crossref PubMed Scopus (18) Google Scholar and the prevalence of NAFLD is reported to be 27–42%.[3]Fung J. Lee C.K. Chan M. Seto W.K. Lai C.L. Yuen M.F. et al.High prevalence of non-alcoholic fatty liver disease in the Chinese - results from the Hong Kong liver health census.Liver Int. 2015; 35: 542-549Crossref PubMed Scopus (55) Google Scholar,[4]Wong V.W. Chu W.C. Wong G.L. Chan R.S. Chim A.M. Ong A. et al.Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography.Gut. 2012; 61: 409-415Crossref PubMed Scopus (338) Google Scholar In our previously published study[5]Seto W.K. Hui R.W.H. Mak L.Y. Fung J. Cheung K.S. Liu K.S.H. et al.Association between hepatic steatosis, measured by controlled attenuation parameter, and fibrosis burden in chronic hepatitis B.Clin Gastroenterol Hepatol. 2018; 16: 575-583.e2Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar that assessed 1,606 Asian patients with CHB between 2015 and 2016 using transient elastography, we found severe steatosis, defined as controlled attenuation parameter (CAP) ≥280 dB/m,[6]Karlas T. Petroff D. Sasso M. Fan J.G. Mi Y.Q. de Ledinghen V. et al.Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol. 2017; 66: 1022-1030Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar to be associated with the development of severe liver fibrosis in CHB. In our expanded cohort of 2,370 consecutively recruited Asian patients with CHB, the prevalence of dual CHB + NAFLD, with NAFLD defined as CAP ≥248 dB/m[6]Karlas T. Petroff D. Sasso M. Fan J.G. Mi Y.Q. de Ledinghen V. et al.Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol. 2017; 66: 1022-1030Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar without a significant alcohol history, was 47.8% (1,134/2,370). Among these 1,134 patients (male 58.6%, median age 56.6 [IQR 49.6–64.2] years old), severe steatosis was present in 689 (60.8%). According to the recommended positive diagnostic criteria for MAFLD in the expert consensus statement,[1]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.J Hepatol. 2020; 73: 202-209Abstract Full Text Full Text PDF PubMed Scopus (906) Google Scholar 84.1%, 85.7% and 42.9% patients were overweight/obese, had ≥2/5 metabolic risk abnormalities (including 76.5% with central obesity, 55.7% with reduced high-density lipoprotein cholesterol, 46% with increased triglyceride, 77.2% with increased blood pressure, and 55.1% with raised fasting glucose), and type 2 DM, respectively. To our surprise, 1,083 out of these 2,370 patients (45.7%), or 95.5% of patients with concomitant CHB + NAFLD fulfilled the criteria of CHB + MAFLD, with only 4.5% (n = 51) of CHB + NAFLD patients not within the recommended MAFLD criteria. Compared to these 51 patients, patients with CHB + MAFLD were older (51.5 vs. 57.5 years old, p <0.001), and more often male (41.2% vs. 59.5%, p = 0.008). The distribution of severity of steatosis in both groups is shown in Fig. 1. Severe steatosis was significantly more common in patients with CHB + MAFLD (62.0% vs. 35.3%, p <0.001). Patients with CHB + MAFLD also had a higher median alanine aminotransferase level (30 vs. 22 U/L, p = 0.001) and a greater proportion had advanced fibrosis/cirrhosis (22.6% vs. 11.8%, p = 0.043) compared to patients with CHB + NAFLD outside the MAFLD criteria. There were no differences in the proportion receiving anti-HBV treatment in either group (54.1% vs. 52.9%, p = 0.491), nor the risk of hepatocellular carcinoma (HCC) (1.1% vs. 0%, p = 0.586), respectively. With these findings, we feel that the diagnostic criteria for MAFLD are highly relevant to our daily practice in view of the high prevalence of MAFLD in patients with CHB. The implications of MAFLD on the clinical outcomes of patients with CHB, such as the risk of fibrosis progression and HCC, remain unknown. Our recent work[7]Mak L.Y. Wan-Hin Hui R. Fung J. Liu F. Ka-Ho Wong D. Cheung K.S. et al.Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B.J Hepatol. 2020; Abstract Full Text Full Text PDF Scopus (31) Google Scholar showed that the presence of hepatic steatosis was associated with 3-fold increased probability of hepatitis B surface antigen seroclearance, but the presence of persistent severe hepatic steatosis was also associated with more than 2-fold increase in risk of fibrosis progression. Further studies should investigate the interaction between CHB and MAFLD, incorporating the new diagnostic criteria, and dissect the driver mechanisms for both favorable and unfavorable clinical outcomes. The authors received no financial support to produce this manuscript. The authors declare they have participated in the preparation of the manuscript and have seen and approved the final version. LY Mak was involved in acquisition of data, analysis and interpretation of data and drafting of manuscript. MF Yuen was involved in study design and critical revision of manuscript. WK Seto was involved in study concept and design, analysis and interpretation of data, critical revision of manuscript and overall study supervision. MF Yuen is an Associate Editor of Journal of Hepatology. All other authors: none to declare. Please refer to the accompanying ICMJE disclosure forms for further details. Download .pdf (.16 MB) Help with pdf files disclosures.pdf A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statementJournal of HepatologyVol. 73Issue 1PreviewThe exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. Full-Text PDF Reply to: correspondence regarding “A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement”: Bringing evidence to the NAFLD-MAFLD debateJournal of HepatologyVol. 73Issue 6PreviewWe thank Mak et al.,1 and Zheng et al.,2 for their interest and comments on our work.3 Mak et al. suggest that the diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) are highly relevant to daily clinical practice. This is because of clear evidence of the high prevalence of MAFLD in patients with chronic hepatitis B (CHB) reported in their study using the new MAFLD criteria. Importantly, the new definition was superior to the old non-alcoholic fatty liver disease (NAFLD) criteria for identifying patients with more severe liver injury (steatosis, fibrosis and elevated liver enzymes). Full-Text PDF