Research ArticleModest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)
Introduction
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States (US) affecting as many as one third of adults [1]. Only a small subset of patients with NAFLD, namely those with a more severe subtype known as steatohepatitis (NASH), which is characterized by inflammatory infiltrates, ballooning hepatocellular injury, and fibrosis in addition to steatosis, are thought to be at risk for cirrhosis-related mortality.
The metabolic risk factors for NAFLD are also closely associated with coronary heart disease (CHD) [2]. Patients with NAFLD [3], and especially those with NASH [4], are at risk for coronary heart disease. Patients with NAFLD are approximately two times more likely to die from coronary heart disease than liver disease [5]. Therefore, management of CHD risk in patients with NAFLD is imperative. CHD risk can be modified through lifestyle changes, including diet, exercise, and smoking cessation. In addition, modest alcohol consumption has been shown to reduce the risk of coronary heart disease mortality and improve metabolic risk factors related to both coronary heart disease and NAFLD [6], [7]. As many as 50% of the adults in the United States regularly consume a modest amount of alcohol [8]. Excessive alcohol, however, can cause alcoholic liver disease [9]. In the general population, the daily threshold [10], [11], [12] of alcohol for liver injury is thought to be between 1–3 drinks per day in women and 2–3 in men. In patients with metabolic risk factors for NAFLD, the threshold may be lower [13]. Despite this, cross-sectional studies have suggested that modest alcohol consumption may protect the liver from NASH and NAFLD [14], [15]. The relationship between modest alcohol consumption and NAFLD severity has not been analyzed in detail. Whether patients with NAFLD should abstain from alcohol or be allowed modest alcohol consumption remains an important question. In practice, physicians often recommend abstinence from alcohol for patients with NAFLD, although the data to support this approach are lacking.
To provide counseling on alcohol consumption for patients with NAFLD, it is important to know whether modest alcohol consumption is associated with NAFLD disease severity. We hypothesize that modest alcohol consumption is associated with lower prevalence of NASH in patients with NAFLD. The primary aim of this study was to investigate a potential association between modest alcohol drinking and steatohepatitis in patients with NAFLD. Secondary aim was to test the association between modest alcohol drinking and the individual histological features of NAFLD including fibrosis.
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Study sample
This was a cross-sectional study of the association between modest alcohol consumption and histological presence and/or severity of recognized lesions in NAFLD. We included baseline data from participants 21 years or older enrolled in two recently published NASH Clinical Research Network (CRN) studies: (1) a cohort study, the NAFLD Database [16]; and (2) a clinical trial, Pioglitazone versus Vitamin E versus Placebo for the Treatment of Non-diabetic Patients with Non-alcoholic Steatohepatitis
Study sample
The study sample included 252 lifetime non-drinkers and 331 modest drinkers enrolled in the NASH CRN studies with central pathology readings. The social, demographical, lifestyle, and metabolic characteristics of the two groups are presented in Table 1. As compared to lifetime non-drinkers, modest drinkers were more likely to be male, have higher income and education, have higher insulin sensitivity and HDL, and less likely to have diabetes.
Prevalence of histological features in lifetime non-drinkers and modest drinkers
The frequency and adjusted odds ratio for each
Discussion
We studied the association of modest alcohol consumption and steatohepatitis in a sample of well-characterized study participants with biopsy-proven NAFLD from referral centers across the US These data suggest that among subjects with biopsy-proven NAFLD, modest alcohol consumption up to two drinks per day was associated with half the odds of steatohepatitis. Modest drinkers also had a lesser severity of fibrosis and ballooning hepatocellular injury. Notably, a dose response was observed; among
Conclusions
In a large, well-characterized population with NAFLD, modest alcohol consumption was associated with significantly lower odds of biopsy-diagnosed NASH. Speculation regarding the role of modest alcohol consumption in prevention or treatment of NASH is tempting but premature. It is likely, however, that most non-cirrhotic patients with NAFLD who already drink modestly are not at risk for aggravating their liver disease. Whether a person with NAFLD should be abstinent or consume alcohol modestly
Conflict of interest
The underlying research reported in this study was funded by the NIH Institutes of Health.
Financial support
The Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development (NICHD). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of
Acknowledgements
Members of the Non-alcoholic Steatohepatitis Clinical Research Network.
Baylor College of Medicine, Houston, TX:
Stephanie H. Abrams, MD, MS; Leanel Angeli Fairly, RN.
Case Western Reserve University Clinical Centers:
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MetroHealth Medical Center, Cleveland, OH: Arthur J. McCullough, MD; Patricia Brandt; Diane Bringman, RN (2004–2008); Srinivasan Dasarathy, MD; Jaividhya Dasarathy, MD; Carol Hawkins, RN; Yao-Chang Liu, MD (2004–2009); Nicholette Rogers, PhD, PA-C (2004–2008); Margaret Stager, MD
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For the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN): NASH CRN Roster in Acknowledgements section.