Screening for NAFLD and its severity in type 2 diabetic patients: Value of magnetic resonance imaging and outstanding issues

A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetesJournal of HepatologyVol. 78Issue 3PreviewThere are limited prospective data on patients with type 2 diabetes mellitus (T2DM) specifically enrolled and systematically assessed for advanced fibrosis or cirrhosis due to non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to evaluate the prevalence of advanced fibrosis and cirrhosis in a prospectively recruited cohort of adults with T2DM. Full-Text PDF Reply to: “Screening for NAFLD and its severity in type 2 diabetic patients: Value of magnetic resonance imaging and outstanding issues”Journal of HepatologyVol. 78Issue 5PreviewWe thank Binet et al. for their comments regarding our recently published manuscript characterizing the prevalence of NAFLD, advanced fibrosis and cirrhosis in a prospectively recruited cohort of older adults with type 2 diabetes mellitus (T2DM).1,2 Binet and colleagues raise a few points which we seek to clarify. First, recruitment occurred through primary care and endocrinology clinics as well as IRB-approved advertisements directed at patients. Collaborators in primary care and endocrinology throughout the greater San Diego area were contacted and educated about the study. Full-Text PDF We read Ajmera et al.'s original manuscript[1]Ajmera V. Cepin S. Tesfai K. Hofflich H. Cadman K. Lopez S. et al.A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes.J Hepatol. 2023; 78: P471-P478https://doi.org/10.1016/j.jhep.2022.11.010Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar with great interest. Screening for non-alcoholic fatty liver disease (NAFLD) is indeed crucial in the type 2 diabetes population because of the intricate links between insulin resistance and hepatic steatosis.[2]Binet Q. Loumaye A. Preumont V. Thissen J.P. Hermans M.P. Lanthier N. Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far?.Acta Gastroenterol Belg. 2022; 85: 346-357https://doi.org/10.51821/85.2.9775Crossref PubMed Scopus (9) Google Scholar We were therefore looking forward to prospective studies in this area.[2]Binet Q. Loumaye A. Preumont V. Thissen J.P. Hermans M.P. Lanthier N. Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far?.Acta Gastroenterol Belg. 2022; 85: 346-357https://doi.org/10.51821/85.2.9775Crossref PubMed Scopus (9) Google Scholar The great value of their analysis was the use of MRI-proton density fat fraction (PDFF) and elastography in the vast majority of patients, which allowed for optimal non-invasive assessment of the degree of steatosis and fibrosis[3]Park C.C. Nguyen P. Hernandez C. Bettencourt R. Ramirez K. Fortney L. et al.Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease.Gastroenterology. 2017; 152https://doi.org/10.1053/j.gastro.2016.10.026Abstract Full Text Full Text PDF Scopus (419) Google Scholar and to highlight advanced fibrosis (and even hepatocellular carcinoma) in patients with a low fibrosis-4 (FIB-4) score, for example.[1]Ajmera V. Cepin S. Tesfai K. Hofflich H. Cadman K. Lopez S. et al.A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes.J Hepatol. 2023; 78: P471-P478https://doi.org/10.1016/j.jhep.2022.11.010Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Although best suited for easy, large-scale screening, the FIB-4 score should indeed be used with caution in patients with diabetes.[4]Gracen L. Hayward K.L. Irvine K.M. Valery P.C. Powell E.E. Low accuracy of FIB-4 test to identify people with diabetes at low risk of advanced fibrosis.J Hepatol. 2022; 77: 1219-1221https://doi.org/10.1016/j.jhep.2022.06.016Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar However, these results raise additional questions. First, did the selected patients represent a full sample of patients with type 2 diabetes? Over 7 years, with recruitment in primary care and endocrinology clinics, the authors only screened 524 patients. We therefore wonder whether study participation was proposed to all patients with type 2 diabetes seen during this period who met inclusion criteria. Secondly, the presence of one of the following criteria compatible with newly diagnosed diabetes was required as inclusion criteria (diabetes symptoms and plasma glucose ≥200 mg/dl or fasting plasma glucose ≥126 mg/dl or plasma glucose ≥200 mg/dl during a 75-g oral glucose tolerance test on two separate tests or HbA1c ≥6.5%). However, in the results section, 72% of patients were already treated with glucose-lowering drug(s). We therefore wonder whether this was a first diagnosis of NAFLD. Indeed, NAFLD is increasingly screened in endocrinology units, internal medicine and primary care, although progress is still needed with regard to screening. The authors provide the rate of diagnosed fibrosis and cancers, but do not mention the proportion of patients in whom NAFLD was likely already diagnosed and followed in hepatology clinic. In other words, it would be interesting to know how many new diagnoses (of NAFLD, cirrhosis and/or HCC) such a large-scale screening intervention would deliver. Third, we were surprised by the low prevalence of NAFLD in the study patients (65%), knowing the bidirectional links between NAFLD and insulin resistance.[5]Stefan N. Cusi K. A global view of the interplay between non-alcoholic fatty liver disease and diabetes.Lancet Diabetes Endocrinol. 2022; 10: 284-296https://doi.org/10.1016/S2213-8587(22)00003-1Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar We have two potential explanations for this. First, the degree of steatosis may decrease with advanced fibrosis or cirrhosis.[6]Tiniakos D.G. Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: histological diagnostic criteria and scoring systems.Eur J Gastroenterol Hepatol. 2010; 22: 643-650https://doi.org/10.1097/MEG.0b013e32832ca0cbCrossref PubMed Scopus (68) Google Scholar As elastography was performed in all patients, 38% of patients with less than 5% intrahepatic fat (thus not meeting the NAFLD criterion) had advanced fibrosis. Yet such advanced fibrosis was a late consequence of NAFLD. Secondly, an MRI-PDFF was not performed in all patients. Transient elastometry was used instead by measuring the controlled-attenuation parameter value and by choosing a cut-off of 288 dB/m, which can be considered as high, likely preventing inclusion of all patients with steatosis involving more than 5% of hepatocytes on histology.[7]de Lédinghen V. Vergniol J. Foucher J. Merrouche W. le Bail B. Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography.Liver Int. 2012; 32: 911-918https://doi.org/10.1111/j.1478-3231.2012.02820.xCrossref PubMed Scopus (292) Google Scholar Taken together, one can question the usefulness of hepatic fat quantification, which does not correlate with the complications of the disease[8]Angulo P. Kleiner D.E. Dam-Larsen S. Adams L.A. Bjornsson E.S. Charatcharoenwitthaya P. et al.Liver fibrosis, but No other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease.Gastroenterology. 2015; 149: 389-397.e10https://doi.org/10.1053/j.gastro.2015.04.043Abstract Full Text Full Text PDF PubMed Scopus (1782) Google Scholar and whose absence could falsely reassure the clinician, despite not ruling out advanced fibrosis.[1]Ajmera V. Cepin S. Tesfai K. Hofflich H. Cadman K. Lopez S. et al.A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes.J Hepatol. 2023; 78: P471-P478https://doi.org/10.1016/j.jhep.2022.11.010Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Finally, alcohol consumption can cause alcohol-related liver disease (ALD), and in real life, some patients with type 2 diabetes consume more than 20 g of alcohol per day (women) and 30 g per day (men). These patients were excluded from the study that focused on patients with NAFLD. An expert panel has proposed a definition with positive criteria for the diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD).[9]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: 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1489) Google Scholar It would be interesting to know the proportion of patients with type 2 diabetes and regular excessive alcohol consumption who were excluded (thus presenting with MAFLD and superimposed ALD) and possibly to determine the impact of such consumption on liver disease severity,[10]Ntandja Wandji L.C. Gnemmi V. Mathurin P. Louvet A. Combined alcoholic and non-alcoholic steatohepatitis.JHEP Rep. 2020; 2https://doi.org/10.1016/j.jhepr.2020.100101Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar assessed by these elegant MRI techniques. In conclusion, large prospective studies are awaited as screening for MAFLD is recommended in all patients with type 2 diabetes, whether elderly or not, or whether consuming alcohol or not. NL has a mandate as a Clinician Researcher from the FNRS, Belgium. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details. Drafting of the manuscript: NL; critical revision and approval of the final manuscript: QB, MH, NL. The following are the supplementary data to this article: Download .pdf (.17 MB) Help with pdf files Multimedia component 1