Higher mortality among lean patients with non‐alcoholic fatty liver disease despite fewer metabolic comorbidities

Abstract

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) can develop in individuals who are not overweight. Whether lean persons with NAFLD have lower mortality and lower incidence of cirrhosis, cardiovascular diseases (CVD), diabetes mellitus (DM) and cancer than overweight/obese persons with NAFLD remains inconclusive. We compared mortality and incidence of cirrhosis, CVD, DM and cancer between lean versus non-lean persons with NAFLD.Methods: This is a retrospective study of adults with NAFLD in a single centre from 2012 to 2021. Primary outcomes were mortality and new diagnosis of cirrhosis, CVD, DM and cancer. Outcomes were modelled using competing risk analysis and Cox proportional hazards regression analysis.Results: A total of 18,594 and 13,420 patients were identified for cross-sectional and longitudinal analysis respectively: approximately 11% lean, 25% overweight, 28% class 1 obesity and 35% class 2-3 obesity. The median age was 51.0 years, 54.6% were women. The median follow-up was 49.3 months. Lean patients had lower prevalence of metabolic diseases at baseline and lower incidence of cirrhosis and DM than non-lean patients and no difference in CVD, any cancer or obesity-related cancer during follow-up. However, lean patients had significantly higher mortality with incidence per 1000 person-years of 16.67, 10.11, 7.37 and 8.99, respectively, in lean, overweight, obesity class 1 and obesity class 2-3 groups respectively.Conclusions: Lean patients with NAFLD had higher mortality despite lower incidence of cirrhosis and DM, and similar incidence of CVD and cancer and merit similar if not more attention as non-lean patients with NAFLD.| 1015 WIJARNPREECHA et al. | INTRODUC TI ONNon-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, affecting 25% of the population worldwide, and its clinical burden is expected to rise. 1 NAFLD is strongly associated with obesity and its comorbidities but can also develop in individuals who are not overweight ('lean NAFLD'). 2 The prevalence of NAFLD among lean individuals in the general population is 10%-20% with most studies reported from Asian countries, and the highest prevalence reported in Mexico (37%). [3][4][5][6] NAFLD is associated with a wide spectrum of extrahepatic diseases, such as cardiovascular diseases (CVD), metabolic diseases (diabetes mellitus [DM], hypertension, dyslipidaemia), chronic kidney diseases (CKD) or cancers. 7,8 Several cross-sectional studies have evaluated prevalence of hepatic and extra-hepatic diseases among lean versus obese individuals with NAFLD. A cross-sectional analysis of the TARGET-NASH study cohort with 3386 NAFLD patients in the United States found a lower prevalence of cirrhosis, DM and CVD in lean individuals compared to overweight/obese individuals. 2 Another study from Austria with 4091 NAFLD participants had similar findings with lower prevalence of metabolic diseases (DM, metabolic syndrome, hypertension, dyslipidaemia) and lower Framingham risk score for CVD but no significant differen...

Editorial: clinical outcomes in lean NAFLD—the devil is in the details

“…Recently, a meta-analysis by Ha et al reported that lean NAFLD had comparable risks of all-cause mortality, cardiovascular mortality and liver events, but had higher risk of liver diseasespecific mortality. 9 Karn and colleagues 10 have compared the baseline characteristics between lean and non-lean NAFLD patients and also analysed longitudinally the mortality and clinical outcomes between these two groups of patients. They utilised a validated natural language processing algorithm, which identified >13,000 patients with NAFLD through ultrasonographic, transient elastography or biopsy reports.…”

“…Karn and colleagues 10 have compared the baseline characteristics between lean and non‐lean NAFLD patients and also analysed longitudinally the mortality and clinical outcomes between these two groups of patients. They utilised a validated natural language processing algorithm, which identified >13,000 patients with NAFLD through ultrasonographic, transient elastography or biopsy reports.…”

Editorial: clinical outcomes in lean NAFLD – the devil is in the details. Authors' reply

“…The authors' declarations of personal conflicts of interest are unchanged from those in the original article 2 …”

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We read with great interest the editorial by Tan et al 1 on our recent study on clinical outcomes in patients with lean non-alcoholic fatty liver disease (NAFLD), where we found that lean patients with NAFLD experienced higher mortality than patients with overweight or obesity, despite lower prevalence of baseline metabolic disease and lower incidence of cirrhosis and diabetes.We would like to clarify how our cohort was generated and the rationale for this approach. 2 We identified patients with hepatic steatosis based on simple natural language processing algorithms applied to imaging, biopsy, and vibration-controlled transient elastography re-Medicine

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“…We would like to clarify how our cohort was generated and the rationale for this approach. 2 We identified patients with hepatic steatosis based on simple natural language processing algorithms applied to imaging, biopsy, and vibration-controlled transient elastography re-Medicine…”