Role of alcohol in nonalcoholic steatohepatitis: Rush university (Con) patients with nonalcoholic steatohepatitis should be abstinent from alcohol use

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Abbreviations

ASH

alcoholic steatohepatitis

FFA

free fatty acid

GI

gastrointestinal

IL

interleukin

MAC

moderate alcohol consumption

NASH

nonalcoholic steatohepatitis

T2DM

type 2 diabetes mellitus

TNF

tumor necrosis factor

On March 2nd, the American Liver Foundation's (ALF) Great Lakes Division (GLD) hosted the 14th annual Academic Debates, a CME accredited educational program for the medical community of the Great Lakes region. The program addresses controversial yet clinically relevant topics on issues pertaining to liver disease treatment, best practices and new research in hepatology. Fellows representing six premier Liver Centers are selected by a highly‐regarded mentor from each of their respective institutions. Dr Michael Lucey, University of Wisconsin, moderated the 2017 debates.

During the program fellows present their pro or con position followed by a rebuttal of the opposing team's position. A panel of judges score the debators based on their research, presentation skills, and their knowledge of the topic.

This article presents the Con: Patients With Nonalcoholic Steatohepatitis Should Be Abstinent From Alcohol Use

Key Points

• There is significant synergy between alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH).

• There is an increased risk for hepatocellular carcinoma (HCC) with alcohol use.

• Moderate alcohol consumption (MAC) is poorly defined, which may lead to miscommunication between patient and provider.

• Overall, there is a lack of robust data to support the recommendation of MAC in NASH.

• Miscommunication between provider and patient will lead to nonadherence.

Nonalcoholic fatty liver disease (NAFLD) and, in turn, nonalcoholic steatohepatitis (NASH) are rapidly becoming more prevalent1 due to the epidemic of obesity, diabetes mellitus, and metabolic syndrome. MAC has been reported to have cardioprotective effects in the general population2; however, the role of alcohol consumption in NASH remains unclear. There have been retrospective observational studies suggesting benefits of MAC in NAFLD; however, we argue that complete abstinence is essential.

Alcohol has largely been discouraged in patients with concomitant liver disease because of the risk for synergistic hepatic injury. The pathogenesis of NASH lies in dysregulation of free fatty acid (FFA) metabolism, which leads to oxidative injury, influx of inflammatory changes, and progression to fibrosis (Fig. 1). Alcoholic steatohepatitis (ASH) follows the same central dysregulation of FFA metabolism, again leading to oxidative injury and fibrosis.3 Adding alcohol injury to underlying metabolic injury can exaggerate and accelerate the progression of fibrosis. It is likely due to this pathophysiology that NASH and ASH are virtually indistinguishable histologically, and it is important to recognize that they are not mutually exclusive among patients. In fact, Ajmera et al.4 concluded, in a cross‐sectional study, that MAC was associated with significantly less improvement in steatosis grade as compared with nondrinkers.

Figure 1.

Pathogenesis of NASH. Abbreviations: IL, interleukin; TNF, tumor necrosis factor.

With the pandemic of NAFLD and the prevalence of cirrhosis approaching 25% of the NASH population,5 there is already an expected increase in cirrhosis‐related morbidity and mortality6 without alcohol in the mix. In addition, Ascha et al.7 demonstrated that patients with NASH cirrhosis who consumed any amount of alcohol had a dramatically increased risk for development of HCC. Adding a recommendation to consume alcohol, even in moderation, to such a large population will be detrimental.

Retrospective observational data do suggest that an association between MAC and less severe liver‐related outcomes such as histological steatosis, inflammation, and fibrosis8, 9, 10, 11, 12 and non‐liver‐related outcomes such as diabetes.10 In addition, one study by Sinn et al.13 concluded that MAC use in subjects with NAFLD was associated with less cardiovascular disease (carotid plaque and stenosis). VanWagner et al.14 conducted a prospective population‐based study of individuals with NAFLD and found no significant difference in cardiovascular disease among drinkers and nondrinkers.

The effects of alcohol and liver disease have been described as a J‐shaped curve (Fig. 2A).15 The benefits begin with minor amounts of alcohol intake, and the harms accumulate exponentially as intake increases. However, the point at which this curve turns (theoretically known as MAC) is not well understood or defined.16 The definition of MAC is not standardized in the currently published literature (Table 1). In addition, the convexity of the curve may vary depending on intake pattern, genetics, beverage type, and lifetime consumption, further altering the effect of alcohol (Fig. 2B). The boundaries of alcohol consumption are unclear and leave room for detrimental variability.

Figure 2.

(A) Effects of alcohol J‐shaped curve. (B) Variable convexity of J‐shaped curve. Abbreviations: GI, gastrointestinal; T2DM, type 2 diabetes mellitus. (A) Adapted with permission.

Table 1.

Varied Definitions of MAC

First Author, Year	Definition of MAC	Conversion to g/day	Conversion to Standard Drinks/Day (Standard Drink = 14 g)
M.S. Ascha, 20107	<2 drinks/day OR 3‐6 drinks/day on weekends	<28	<2
W. Dunn, 20128	<20 g/day	<20	<1.4
H.P. Cotrim, 20099	<40 g/day OR <280 g/week	<40	<2.9
J.B. Dixon, 200110	<200 g/week	<28.5	<2
M. Ekstedt, 200911	<140 g/week	<20	<1.4
H.K. Kwon, 201412	<40 g/week	<5.7	<0.4
D.H. Sinn, 201413	<20 g/day	<20	<1.4

Moreover, interpersonal communication surrounding alcohol consumption is notoriously poor between healthcare providers and patients. Physician interviews have been found to be less accurate in discovering underlying alcoholic liver disease than cognitive lifetime drinking histories.17 Less than a quarter of patients can accurately quantify a unit of alcohol, and their accuracy declines as risky drinking behavior increases.18 Not to mention that patients underreport their drink consumption by 50% to 66%.19 With unclear definitions of MAC, inaccurate alcohol ascertainment methods, and well‐known morbidity and mortality surrounding alcohol consumption, the risks are too high to confidently recommend alcohol consumption even in moderation.

Patients with NASH should be abstinent from alcohol. At the center of the argument is synergy between the pathophysiology of liver damage due to alcohol and nonalcoholic liver disease. Alcohol in patients with NASH is detrimental and has been shown to lead to HCC when consumed at any quantity. Permissive alcohol use is not a benign intervention, and boundaries in clinical practice should be clearly defined; however, even among the limited retrospective observational studies available, the definition of MAC varies. If such a recommendation for moderate alcohol intake were made, history and data suggest that there is high risk for miscommunication and a likelihood that our patients will not safely adhere.