Long-term outcomes in patients with non-alcoholic fatty liver disease: further evidence that a multidisciplinary and patient-centred approach to treatment is needed.

| https://dx.doi. org/10.21037/hbsn-21-528 The prevalence of non-alcoholic fatty liver disease (NAFLD) is thought to be on the rise globally (1). An updated meta-analysis reported that in 2019 the pooled global prevalence of NAFLD was 29.8% [95% confidence interval (CI): 28.6–31.1%] with the highest NAFLD prevalence observed in South America and North America (2). From 1991–2019, trend analysis also showed that NAFLD prevalence increased from ~22% to 37% (with yearly increase of 0.7%), with South America showing the most rapid change of 2.7% per year followed by the Europe at 1.1% (2). To date, our knowledge(s) of NAFLD-related long-term clinical outcomes is based largely on retrospective analyses of population-based or hospital-based cohort studies that are limited by the absence of histological confirmation of NAFLD, whereas the few published retrospective studies with liver biopsy data are limited by their relatively small sample size, short duration of follow-up, and variable assessments of disease status and outcomes (3). Thus, there is currently a paucity of good quality data on the rates and types of long-term clinical outcomes among patients with NAFLD. In a prospective observational study recently published in the New England Journal of Medicine, Prof. Sanyal and colleagues provided interesting data on the long-term clinical outcomes in adults with NAFLD (4). Using the NAFLD Database Study phase 2 that is a prospective, noninterventional registry of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN), these researchers prospectively followed for a median of 4 years a carefully selected cohort of 1,773 United States adults with biopsy-proven NAFLD (1,141 women and 632 men with a mean age of 52 years, most of whom were White and of European ancestry) (4). The clinical and laboratory data were obtained at enrollment and then at 48-week intervals in a prospective, protocol-mandated approach and at the time of any liver biopsies performed as local standard care. The principal outcomes of the study included all-cause death, hepatic decompensation, a Model for End-stage Liver Disease (MELD) score of 15 or greater, hepatocellular carcinoma, extra-hepatic cancers, cardiovascular events (including myocardial infarction, unstable angina, sudden death, revascularization interventions, and hospitalization for heart failure), and cerebrovascular events (including transient ischemic attack and ischemic stroke). New onsets of coexisting conditions such as type 2 diabetes, hypertension and chronic kidney disease were defined by standard criteria and also tracked as clinical outcomes of interest. At baseline, from a histological point of view, 75% of the 1,773 patients had borderline or definite NASH, and 25% had fatty liver without NASH. A total of 536 patients (30%) had ‘bridging’ fibrosis [stage F3 (369 patients)] or cirrhosis [stage F4 (167 patients)]. In their study the researchers found that during a median follow-up of 4 years, 47 of the 1,773 patients with NAFLD (2.7%) died, an event rate of 0.57 per 100 person-years. The main causes of death among these patients were liverEditorial