Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

Eun Young Park,Mi Jin Bae,Min Kyung Lim,Heeyoun Cho,E Hwa Yun,Dong-Il Kim,Hai-Rim Shin,Jin-Kyoung Oh,Anna Alisi

doi:10.1371/journal.pone.0063439

Abstract

We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20–4.67]; GGT, 1.91 [1.17–3.13]). Only GGT level (odds ratio 6.04 [3.68–9.94], SI 2.33 [1.24–4.41]) was significantly elevated when the effect of moderate drinking (<24 g/day) and metabolic syndrome was combined. The combined effect of any level of alcohol consumption and cigarette smoking was also supra-additive on the elevation of GGT level with SIs of 5.57 for drinking <24 g/day and smoking ≤20 pack years, 5.12 for <24 g/day and >20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12–6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

Highlights

The prevalence of unexplained elevated serum liver enzyme levels ranged from 2.8% to 5.4% of the general population in previous reports from the United States [1,2]
Between 80% and 90% of the unexplained hypertransaminasemia are assumed to be representative of non-alcoholic fatty liver disease (NAFLD), which refers to a broad spectrum of disorders, from simple fatty liver disease to non-alcoholic steatohepatitis (NASH) with various degrees of fibrosis or intrahepatic necroinflammation
A supra-additive effect of alcohol consumption and both cigarette smoking and metabolic syndrome was observed on serum liver enzyme levels

Summary

Introduction

The prevalence of unexplained elevated serum liver enzyme levels ranged from 2.8% to 5.4% of the general population in previous reports from the United States [1,2]. Previous studies have suggested that increased liver enzymes levels may predict type 2 diabetes and cardiovascular disease independent of other potential risk factors, such as obesity and alcohol consumption [8,9,10]. A prospective Japanese study suggested that NAFLD might be a better predictor of cardiovascular disease than metabolic syndrome [11]. Features of metabolic syndrome, such as adiposity, NAFLD, hypertension, hyperglycemia and dyslipidemia may modulate liver fibrosis (i.e., NASH) through hepatic stellate cell activation stimulated by advanced glycation end product, macrophage infiltration, promotion of inflammation, leptin, angiotensin II, and oxidative stress [14]. NAFLD and NASH have attracted attention for their associations with end-stage liver disease and hepatocellular carcinoma [15]

Methods

Results

Conclusion