Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients.

Lukas Denkmayr,Bernhard Paulweber,Ursula Huber-Schönauer,Sebastian Eder,Carolin Lackner,Michael Schranz,Karl Sotlar,Stephan Buch,Michael Strasser,Elmar Aigner,Alexandra Feldman,Jochen Hampe,Lars Stechemesser,Christian Datz,Stephan Zandanell,Heike Haufe

doi:10.3390/jcm7120562

Lukas Denkmayr, Bernhard Paulweber + Show 14 more

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https://doi.org/10.3390/jcm7120562

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Abstract

A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², n confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², n = 242) and obese (BMI > 30.0 kg/m², n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010) and obese patients (3/150; 2.0% p = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% p = 0.01) and obese (26/150; 17.3%; p = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients.

Highlights

Non-alcoholic fatty liver disease (NAFLD) has become a severe socioeconomic burden in Western societies, affecting approximately one third of the population in most countries [1]
NAFLD is closely linked to the complications of excess adipose tissue on the population level; it has been reported in lean patients with a body mass index (BMI)
The disease spectrum of NAFLD ranges from non-alcoholic fatty liver (NAFL) which is characterized by simple steatosis without inflammation or fibrosis to non-alcoholic steatohepatitis (NASH) that can progress further to cirrhosis, end-stage liver disease or hepatocellular carcinoma [7,8,9]

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) has become a severe socioeconomic burden in Western societies, affecting approximately one third of the population in most countries [1]. According to the NHANES III (National Health and Nutrition Examination Survey) data, approximately 7% of lean individuals may have evidence of NAFLD. The risk of significant fibrosis was approximately one in four in the NHANES III NAFLD population [4,5]. Insulin resistance plays a critical role in the development of NAFLD as it does in all other components of the metabolic syndrome, among which are obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia [6]. Age, advanced insulin resistance or T2DM have repeatedly been reported as risk factors for progression from NAFLD to NASH [5,10]

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