Changing Nomenclature from Nonalcoholic Fatty Liver Disease to Metabolic Dysfunction-Associated Fatty Liver Disease – Not Only Premature But Also Confusing

Abstract

We read with great interest the article by Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar published in a recent issue of ‘Hepatology’ regarding the change in nomenclature of nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and completely agree with the views of the authors that it is premature to change this terminology.1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google ScholarIn addition to the issues raised by Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar regarding the disease awareness, research development, drug development and biomarker development all of which may be affected by this change, we would like to add few more reasons as to why it is not only premature but also confusing to change this nomenclature at this stage.Nomenclatures are scientifically validated hierarchic systems that primarily evolve to accommodate new knowledge in a disease with objective of bringing clarity, objectivity targeting improved management and outcome. Terminology of metabolic liver disease has been used conventionally for either paediatric metabolic liver diseases such as glycogen storage disease, hereditary fructosemia, tyrosinemia and so on or for diseases such as Wilson's disease and haemochromatosis where there is an inherited genetic defect in metabolism. Not denying the fact that NAFLD as a terminology has had its own inadequacies and has endured the limitations of a syndromic nomenclature for long and does require a more suitable terminology.2Eslam M. Sanyal A.J. George J. International consensus panel. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology. 2020; 158 (e1): 1999-2014Abstract Full Text Full Text PDF PubMed Scopus (992) Google Scholar But we also have to admit that over the years, there has been a progressive refinement in our understanding of pathogenesis, assessment and treatment approach, and NAFLD is a much better understood terminology today than when conceived. Hence, the change in terminology could only be welcome when path breaking research studies surface that clear the mist around with a paradigm shift. In that sense, MAFLD is an equally inappropriate terminology as it classifies it to be a metabolically driven disease and to that list there can be so many other liver diseases including alcohol-associated liver disease which is also metabolically driven. Hence, without a compelling need for change in nomenclature and changing from one inadequate term to another inappropriate term is not only premature but also confusing.3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google ScholarLiver disease is one of the most dynamic templates that have witnessed nomenclature change from chronic hepatitis to primary biliary cholangitis. All these happened after widespread scientific deliberations where most concurred on a unifying theme. The result was more clarity on the subject with improved clinical management. However, we are still short of that in the NAFLD context. The spectrum of NAFLD comprises nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and NASH-related hepatocellular carcinoma. Over the years, the importance of distinction between NAFL and NASH has been well understood, finding its place in international classification of diseases. Hence, it is highly likely that abandoning the terminology of NAFLD/NASH3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google Scholar and on the path of an unfolding story, a new term for NAFLD will not only create confusion for the researchers, public health professionals, policy makers, regulatory and funding agencies but most importantly for the patients and patient-driven organizations.As mentioned by Younossi et al,1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar not only hepatologists but nonhepatologists (physicians, endocrinologists, cardiologists, gynaecologists, radiologists and so on) now have better insight into understanding the terminology of NAFLD and NASH. In fact, within the community of endocrinologists, subgroups have emerged exploring the relationship between NAFLD with not only diabetes mellitus but also other endocrine disorders such as hypothyroidism, hypogonadism, growth hormone deficiency, and hypercortisolism and are testing various antidiabetic drugs such as Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose transport protein 2 (SGLT2) inhibitors in patients with NAFLD/NASH. Because of the close association of polycystic ovarian syndrome (PCOS) with insulin resistance, gynaecologists have become more familiar with NAFLD/NASH. In fact, new drugs such as saroglitazar (PPAR-α/γ dual agonist) which have been approved for the treatment of diabetic dyslipidemia and NASH in India are being explored in patients with PCOS. Similarly, radiologists today are well versed with the nomenclature of NAFLD/NASH with so many advances happening in the radiological diagnosis of NAFLD. Changing nomenclature from NAFLD to MAFLD thus may cause potential clouding of the diagnostics and drug development endeavours that will be left to lurch with further delay in getting a pharmacological solution that we earnestly seek.We also feel that the propositions for changing the terminology also fell short of accommodating the context of Asian and Indian dilemma and have conceived a unipolar Western world definition with global extrapolations that are avoidable.3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google Scholar This disease is not limited to Europe and America but has become a global disease and is equally common in Asia and India contributing to significant liver disease.4Duseja A. Najmy S. Sachdev S. et al.High prevalence of non-alcoholic fatty liver disease among healthy male blood donors of urban India.JGH Open. 2019; 3: 133-139Crossref PubMed Scopus (18) Google Scholar, 5Das K. Das K. Mukherjee P.S. et al.Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease.Hepatology. 2010; 51: 1593-1602Crossref PubMed Scopus (308) Google Scholar, 6Duseja A. Sharma B. Kumar A. et al.Nonalcoholic fatty liver in a developing country is responsible for significant liver disease.Hepatology. 2010; 52: 2248-2249Crossref PubMed Scopus (38) Google Scholar Various scientific societies, working parties and consortia in Asia and India have been contributing significantly towards the understanding of NAFLD/NASH.7Wong V.W. Chan W.K. Chitturi S. et al.Asia-pacific working party on non-alcoholic fatty liver disease guidelines 2017-Part 1: definition, risk factors and assessment.J Gastroenterol Hepatol. 2018; 33: 70-85Crossref PubMed Scopus (231) Google Scholar, 8Duseja A. Singh S.P. Saraswat V.A. et al.Non-alcoholic fatty liver disease and metabolic syndrome-position paper of the Indian National Association for the Study of the Liver, Endocrine society of India, Indian college of Cardiology and Indian society of Gastroenterology.J Clin Exp Hepatol. 2015; 5: 51-68Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 9Jonathan Lee W.J. Tan X.X.E. Chan W.K. et al.Characterizing and predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-obese non-alcoholic fatty liver disease (NAFLD) in Asia – the GOASIA initiative.Hepatology. 2019; 70 (suppl l): 25APubMed Google Scholar, 10Duseja A. Mehta M. Singh S.P. Parmar D. Sanyal A. Nationwide registry on nonalcoholic fatty liver disease (NAFLD) - the ICON-D (Indian consortium on NAFLD) study.J Gastroenterol Hepatol. 2019; 34 (suppl 3): 46Google Scholar Therefore, we agree with Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar that stakeholders across the globe need to discuss and exchange ideas rather than taking a premature decision of changing the nomenclature from NAFLD to MAFLD.CRediT authorship contribution statementAjay Duseja: Conceptualization, Writing - original draft. Sunil Taneja: Writing - review & editing.Conflicts of interestThe authors have none to declare. We read with great interest the article by Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar published in a recent issue of ‘Hepatology’ regarding the change in nomenclature of nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and completely agree with the views of the authors that it is premature to change this terminology.1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar In addition to the issues raised by Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar regarding the disease awareness, research development, drug development and biomarker development all of which may be affected by this change, we would like to add few more reasons as to why it is not only premature but also confusing to change this nomenclature at this stage. Nomenclatures are scientifically validated hierarchic systems that primarily evolve to accommodate new knowledge in a disease with objective of bringing clarity, objectivity targeting improved management and outcome. Terminology of metabolic liver disease has been used conventionally for either paediatric metabolic liver diseases such as glycogen storage disease, hereditary fructosemia, tyrosinemia and so on or for diseases such as Wilson's disease and haemochromatosis where there is an inherited genetic defect in metabolism. Not denying the fact that NAFLD as a terminology has had its own inadequacies and has endured the limitations of a syndromic nomenclature for long and does require a more suitable terminology.2Eslam M. Sanyal A.J. George J. International consensus panel. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology. 2020; 158 (e1): 1999-2014Abstract Full Text Full Text PDF PubMed Scopus (992) Google Scholar But we also have to admit that over the years, there has been a progressive refinement in our understanding of pathogenesis, assessment and treatment approach, and NAFLD is a much better understood terminology today than when conceived. Hence, the change in terminology could only be welcome when path breaking research studies surface that clear the mist around with a paradigm shift. In that sense, MAFLD is an equally inappropriate terminology as it classifies it to be a metabolically driven disease and to that list there can be so many other liver diseases including alcohol-associated liver disease which is also metabolically driven. Hence, without a compelling need for change in nomenclature and changing from one inadequate term to another inappropriate term is not only premature but also confusing.3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google Scholar Liver disease is one of the most dynamic templates that have witnessed nomenclature change from chronic hepatitis to primary biliary cholangitis. All these happened after widespread scientific deliberations where most concurred on a unifying theme. The result was more clarity on the subject with improved clinical management. However, we are still short of that in the NAFLD context. The spectrum of NAFLD comprises nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and NASH-related hepatocellular carcinoma. Over the years, the importance of distinction between NAFL and NASH has been well understood, finding its place in international classification of diseases. Hence, it is highly likely that abandoning the terminology of NAFLD/NASH3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google Scholar and on the path of an unfolding story, a new term for NAFLD will not only create confusion for the researchers, public health professionals, policy makers, regulatory and funding agencies but most importantly for the patients and patient-driven organizations. As mentioned by Younossi et al,1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar not only hepatologists but nonhepatologists (physicians, endocrinologists, cardiologists, gynaecologists, radiologists and so on) now have better insight into understanding the terminology of NAFLD and NASH. In fact, within the community of endocrinologists, subgroups have emerged exploring the relationship between NAFLD with not only diabetes mellitus but also other endocrine disorders such as hypothyroidism, hypogonadism, growth hormone deficiency, and hypercortisolism and are testing various antidiabetic drugs such as Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose transport protein 2 (SGLT2) inhibitors in patients with NAFLD/NASH. Because of the close association of polycystic ovarian syndrome (PCOS) with insulin resistance, gynaecologists have become more familiar with NAFLD/NASH. In fact, new drugs such as saroglitazar (PPAR-α/γ dual agonist) which have been approved for the treatment of diabetic dyslipidemia and NASH in India are being explored in patients with PCOS. Similarly, radiologists today are well versed with the nomenclature of NAFLD/NASH with so many advances happening in the radiological diagnosis of NAFLD. Changing nomenclature from NAFLD to MAFLD thus may cause potential clouding of the diagnostics and drug development endeavours that will be left to lurch with further delay in getting a pharmacological solution that we earnestly seek. We also feel that the propositions for changing the terminology also fell short of accommodating the context of Asian and Indian dilemma and have conceived a unipolar Western world definition with global extrapolations that are avoidable.3Eslam M. Newsome P.N. Anstee Q.M. et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020 Jul; 73 ([Epub 2020 Apr 8]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1055) Google Scholar This disease is not limited to Europe and America but has become a global disease and is equally common in Asia and India contributing to significant liver disease.4Duseja A. Najmy S. Sachdev S. et al.High prevalence of non-alcoholic fatty liver disease among healthy male blood donors of urban India.JGH Open. 2019; 3: 133-139Crossref PubMed Scopus (18) Google Scholar, 5Das K. Das K. Mukherjee P.S. et al.Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease.Hepatology. 2010; 51: 1593-1602Crossref PubMed Scopus (308) Google Scholar, 6Duseja A. Sharma B. Kumar A. et al.Nonalcoholic fatty liver in a developing country is responsible for significant liver disease.Hepatology. 2010; 52: 2248-2249Crossref PubMed Scopus (38) Google Scholar Various scientific societies, working parties and consortia in Asia and India have been contributing significantly towards the understanding of NAFLD/NASH.7Wong V.W. Chan W.K. Chitturi S. et al.Asia-pacific working party on non-alcoholic fatty liver disease guidelines 2017-Part 1: definition, risk factors and assessment.J Gastroenterol Hepatol. 2018; 33: 70-85Crossref PubMed Scopus (231) Google Scholar, 8Duseja A. Singh S.P. Saraswat V.A. et al.Non-alcoholic fatty liver disease and metabolic syndrome-position paper of the Indian National Association for the Study of the Liver, Endocrine society of India, Indian college of Cardiology and Indian society of Gastroenterology.J Clin Exp Hepatol. 2015; 5: 51-68Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 9Jonathan Lee W.J. Tan X.X.E. Chan W.K. et al.Characterizing and predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-obese non-alcoholic fatty liver disease (NAFLD) in Asia – the GOASIA initiative.Hepatology. 2019; 70 (suppl l): 25APubMed Google Scholar, 10Duseja A. Mehta M. Singh S.P. Parmar D. Sanyal A. Nationwide registry on nonalcoholic fatty liver disease (NAFLD) - the ICON-D (Indian consortium on NAFLD) study.J Gastroenterol Hepatol. 2019; 34 (suppl 3): 46Google Scholar Therefore, we agree with Younossi et al1Younossi Z.M. Rinella M.E. Sanyal A. et al.From NAFLD to MAFLD: implications of a premature change in terminology.Hepatology. 2020 Jun 16; ([Epub ahead of Print])https://doi.org/10.1002/hep.31420Crossref PubMed Scopus (139) Google Scholar that stakeholders across the globe need to discuss and exchange ideas rather than taking a premature decision of changing the nomenclature from NAFLD to MAFLD. CRediT authorship contribution statementAjay Duseja: Conceptualization, Writing - original draft. Sunil Taneja: Writing - review & editing. Ajay Duseja: Conceptualization, Writing - original draft. Sunil Taneja: Writing - review & editing. Conflicts of interestThe authors have none to declare. The authors have none to declare.