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Chapter 7: Alcoholic Liver Disease in the Transplant Setting

Jeanne Morley; Joseph Conigliaro

BACKGROUND

The Spectrum of Alcohol Use Disorders

Alcohol use disorder (AUD), defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress with at least 2 symptoms over a 12-month period,1 affects over 17 million people in the United States. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) stratifies the severity of AUD into mild (2 to 3 symptoms), moderate (4 to 5 symptoms), and severe (6 to 11 symptoms) based on 11 criteria. Nearly 88,000 people die from alcohol-related causes annually, making it the third leading preventable cause of death in the United States.2 In 2013, driving while intoxicated resulted in 10,076 deaths, 30.8% of all motor vehicle fatalities that year.

In 2013, among the 16.6 million adults ages 18 and older who had an AUD, only 1.3 million, or 7.8%, of those who needed treatment actually received it.3 Based on a 2011 national survey, 22% of Americans over the age of 12 reported binge drinking in the past 30 days, and 6% report binge drinking more than 5 times per month.4

Alcoholic liver disease (ALD) is the second most common indication for liver transplant and the leading cause of end-stage liver disease in the United States.1,3 In 2013, 71,713 total deaths were due to liver disease in patients 12 years and older, and 46.4% involved alcohol. Among all cirrhosis deaths in 2011, 48% were alcohol related.2 Nearly 8 per 100,000 of patients with AUD will eventually die from ALD.

Despite the morbidity and mortality associated with AUDs, the concept of low-risk drinking has been identified as a level of consumption where the benefits of alcohol use may outweigh the dangers. For women and the elderly, low-risk drinking is defined as no more than 7 drinks per week or 3 drinks per day. For men, this is no more than 14 drinks per week or 4 drinks per day. Only 2% of people who drink within these limits have an AUD.2

Alcohol and Liver Injury

Typically, alcoholic-related liver injury spans a spectrum of 3 major lesions: steatosis (fatty liver), steatohepatitis (formerly alcoholic hepatitis), and cirrhosis (Fig. 7-1).

FIGURE 7-1

Spectrum of alcoholic liver disease. Heavy ethanol consumption produces a wide spectrum of hepatic lesions. Fatty liver (i.e., steatosis) is the earliest, most common response that develops in more than 90 percent of problem drinkers who consume 4 to 5 standard drinks per day. With continued drinking, alcoholic liver disease can proceed to liver inflammation (i.e., steatohepatitis), fibrosis, cirrhosis, and even liver cancer (i.e., hepatocellular carcinoma). Reproduced with permission from ARCR.

A figure shows the spectrum of 3 major lesions spanning over 5 to 50 years in alcoholic-related liver injury: steatosis (fatty liver), steatohepatitis, and cirrhosis. The figure shows the spectrum of 3 major lesions spanning over 5 to 50 years in alcoholic-related liver injury: steatosis (fatty liver), steatohepatitis (formerly alcoholic hepatitis), and cirrhosis. Genetic polymorphism, epigenetic markers and cofactors (such as obesity and alcohol) result in portal hypertension or liver failure. Chronic liver injury such as viral infection, alcohol, NASH, autoimmune disorders, cholestatic disorders and metabolic diseases cause inflammatory damage; matrix deposition; parenchymal cell death and angiogenesis in liver and result in early fibrosis. Removal of underlying cause and anti-fibrotic drug or cell therapy causes resolution to normal liver. If early fibrosis does not resolve, then disrupted liver architecture, loss of function, aberrant hepatocyte regeneration results in cirrhosis. Removal of underlying cause and anti-fibrotic drug or cell therapy causes regression to early fibrosis stage. If cirrhosis does not resolve, it can cause hepatocellular carcinoma or generate need for liver transplant.
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The pathogenesis of ALD is multifactorial and still incompletely understood, with genetics, consumption patterns, ethnicity, ...

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