The needs of surveillance of metabolic associated fatty liver disease in Taiwan

Taiwan is an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Liver-related diseases are the leading cause of death in Taiwan. Contributing to the first vaccination program of HBV in the world since 1984 in Taiwan, the prevalence of HBV infection drops to as low as 1% of the vaccinated population. In addition, anti-HBV therapy could effectively suppress HBV replication, regress liver histology, and reduce the incidence of cirrhotic complications and hepatocellular carcinoma. Similarly, by the advent of direct-acting antiviral therapy, World Health Organization announces the goal of HCV elimination by 2030. In Taiwan, combining coverage of HCV treatment by National Health Insurance and efforts to treat and screen high-risk population drive the goal to achieve as early as 2025. Therefore, the question raises in every hepatologist is what is the next liver disease we should focus on in Taiwan? Among liver diseases, metabolic (dysfunction) associated fatty liver disease (MAFLD) will be the next important public health issue. MAFLD is defined as the presence of hepatic steatosis detected by either image, liver histology, or blood biomarkers, in addition to one or more of the following metabolic features: overweight/obesity, diabetes mellitus, or evidence of metabolic dysregulation (MD) in lean subjects. MD is defined as the presence of at least two of the following criteria: abnormal waist circumference; arterial hypertension; hypertriglyceridemia; low HDL-cholesterol; pre-diabetes; insulin resistance; and subclinical systemic inflammatory state (highsensitivity C-Reactive Protein). It is different from the old nomenclature named nonalcoholic fatty liver disease (NAFLD) in that MAFLD does not need to exclude other etiologies of liver diseases. Based on the criteria, subjects with presence of liver steatosis from various etiologies are under the umbrella term of MAFLD. In Taiwan, the reported prevalence of NAFLD was 21.8% (18.6%-25.0%) in 2019, while the prevalence of MAFLD needs to be clearly defined. By definition, the prevalence of MAFLD from two small community-based studies using sonography survey is estimated to be as high as 54.9% (659/1201). These results implied that MAFLD is a common liver disease in Taiwan. Although there is a different definition, a recent report demonstrates that NAFLD and MAFLD seem to share similar outcomes in both new-onset metabolic and cardiovascular events. Hence, the disease burden of MAFLD is supposed quite heavier than that of NAFLD in Taiwan. In the study of Chien et al of this issue, they conducted a community-based study to survey the prevalence of elevated aspartate (AST) or alanine (ALT) aminotransferase levels and their associated risk factors in northeastern Taiwan. Of MAFLD subjects, 12.5% has elevated AST and 27.4% has elevated ALT in community. In the other community-based study from southern Taiwan shows that 12.4% and 13.1% of MAFLD subjects have elevated AST and ALT, respectively. Another report also demonstrates that the prevalence of ALT elevation in checkup subjects is 33.6% of MAFLD, which is higher than 28.5% of HBV, 21.8% of unexplained cause, 13.2% of HCV, 2.2% of HBV/HCV co-infection, and 0.8% of excess alcohol consumption. It should be noted that only a minor proportion of MAFLD subjects present with elevated liver enzymes. However, once elevated AST or ALT is present, it would imply the link to liver injury. Indeed, MAFLD subjects with significant fibrosis have significantly higher proportion of elevated AST (46.4% vs 8.6%, P < .0010) and ALT (42.9% vs 9.8%, P < .001) than those without significant fibrosis. On the other hand, more than half of MAFLD subjects with liver stiffness more than 7 kPa exhibit normal ALT and AST levels. The presumed liver injury is probably underestimated because liver injury is not necessarily presented with elevated AST or ALT in MAFLD subjects. Taking these results together, a substantial proportion of MAFLD subjects in community are at risk of progression of liver injury and may not have elevated aminotransferase levels. Hence, how to survey and how to determine the severity of MAFLD are the important issues following control of viral hepatitis in Taiwan. For the purpose of surveillance, the first step is to identify the population who are at high risk of developing or having MAFLD. The population are those subjects Received: 4 May 2021 Accepted: 9 May 2021