Information for the Public

Because the Center’s members include some of the nation’s leading experts in the area of alcohol-associated liver and pancreatic diseases, we are committed to utilizing their knowledge and expertise to provide its intellectual and technical expertise to the community.

Alcohol Misuse and Alcohol-Associated Liver Disease
Alcohol is part of our culture—it helps us celebrate and socialize, and it enhances our religious ceremonies. But drinking too much—on a single occasion or over time—can have serious consequences for our health. Read More.

What is Cirrhosis?
Cirrhosis is a chronic liver disease in which normal liver cells are damaged and replaced by scar tissue. This scar tissue prevents the liver from performing important functions. Read More.

Pathogenesis of ALD
Chronic liver disease continues to be one of the leading medical causes of mortality in the United States. Every half hour, one person dies in the this nation from complications associated with irreversible chronic liver disease. Read More.

Alcohol-related Pancreatic Damage
National Institute on Alcohol Abuse and Alcoholism
Pancreatitis Association International
This article discusses the mechanisms and treatment of alcoholic pancreatitis.

Alcohol’s Risk to Women
National Institute on Alcohol Abuse and Alcoholism No. 46 December 1999
This article discusses some of the gender differences in the effects of alcohol and risks specific to women who drink.

Alcohol and the Liver
National Institute on Alcohol Abuse and Alcoholism No. 42 October 1998
This article discusses the research on the mechanisms and treatment of Alcoholic Liver Disease.

Alcohol and Minorities
National Institute on Alcohol Abuse and Alcoholism No. 23 PH 347 January 1994
This article considers why some minorities have more medical problems than others and whether minorities receive adequate treatment and prevention services. It examines genetic and environmental factors that may put minorities at risk for or protect them from alcohol problems. It also reviews research on screening to identify those at risk for alcoholism or alcohol abuse.

Alcohol and Nutrition
National Institute on Alcohol Abuse and Alcoholism No. 22 PH 346 October 1993
This article discusses how alcohol and nutrition work together in your body.

Viral Hepatitis C
Centers for Disease Control and Prevention
A plethora of information on Hepatitis C, including a web-based training course for health professionals.

Cirrhosis is a chronic liver disease in which normal liver cells are damaged and replaced by scar tissue. This scar tissue prevents the liver from performing important functions such as processing nutrients, hormones, and detoxifying drugs and poisons, including alcohol. Excessive alcohol intake is the most common cause of cirrhosis.

Liver cirrhosis is ranked as the 5th to 7th leading cause of death among adults 25-60 years old. It is responsible for approximately 25,000 deaths per year in the United States, a mortality rate which is roughly equivalent to that caused by stroke, HIV or type I diabetes.

Approximately 90% of deaths attributed to cirrhosis are estimated to be preventable since excessive alcohol intake is the most common cause of cirrhosis. However, it is also estimated that 40-60% of chronic liver disease is related to hepatitis C virus (HCV) infection, the most common chronic bloodborne infection in the United States, with approximately 4 million people infected. About 20% of the HCV infected individuals develop chronic liver disease and cirrhosis. Chronic liver disease often shows no symptoms, and many patients are found to have the disease during the course of physical examination for an unrelated illness.

No curative therapy is currently available for cirrhosis except for liver transplantation. Due to an insufficient pool of donors, many patients die while they are on the donor waiting list.

Scientists of the Cirrhosis Research Program are working to find new ways to treat cirrhosis. Their goals are to develop gene therapies for the treatment of liver cirrhosis, to develop a new generation of bioartificial liver systems, and to promote cutting-edge science in non-parenchymal liver cell biology.

Alcohol is part of our culture—it helps us celebrate and socialize, and it enhances our religious ceremonies. But drinking too much—on a single occasion or over time—can have serious consequences for our health. Most Americans recognize that drinking too much can lead to accidents and dependence.  However, in addition to these serious problems, alcohol misuse and abuse can damage organs, weaken the immune system, and contribute to cancers.

Globally, alcohol misuse was the fifth leading risk factor for premature death and disability in 2010. Among people between the ages of 15 and 49, it is the first.  Among people between the ages of 20 and 39, approximately 25% of the total deaths are alcohol attributable.

Considering this prevalent use of alcohol, its misuse is expected to have a global impact.   Indeed, 3.3 million deaths were caused by alcohol misuse in 2012, corresponding to 5.9% of all deaths in the world.  Excessive alcohol intake which causes more than 200 diseases including alcohol use disorder (AUD) and liver cirrhosis, was the 5^th leading risk factor for premature death and disability and responsible for 5.1% of the burden of disease and injury around the globe in 2010.  This means alcohol misuse reduced healthy life years of people by 5.1% worldwide. In the U.S., 15.1 million adults aged 18 and older (6.2% of this age group population), have AUD with the male to female gender ratio of 2:1.

Youth drinking is becoming an important issue worldwide, and in the U.S. approximately 0.6 million adolescents aged 12-17, have AUD with the gender ratio of roughly 1:1. This is an alarming statistic because youth drinking is closely associated with eventual addiction to alcohol.  Alcohol is the 3^rd leading preventable cause of death and responsible for 88,000 deaths in the U.S. with 11% caused by drunk driving.  In 2010, alcohol misuse cost the U.S. $249 billion. More specifically for liver disease, in 2015, 78,529 deaths were caused by liver disease, and 47% were due to alcohol. Similarly, 47.9% of cirrhosis deaths were alcohol-related. In 2009, one third of liver transplantations performed in the U.S. was due to alcohol-related liver disease.

Tsukamoto H, Kaplowitz N.
In: Kaplowitz N, ed. Liver and Biliary Diseases, 2nd Edition, Williams & Wilkins, Baltimore, p121-138, 1996.

Overview

Chronic liver disease continues to be one of the leading medical causes of mortality in the United States. Every half hour, one person dies in this nation from complications associated with irreversible chronic liver disease. Liver cirrhosis and hepatocellular carcinoma are the two most common and devastating sequela responsible for this mortality, and chronic alcohol abuse is the single most important etiologic factor for cirrhosis. This fact is well-illustrated by a historical observation that the number of deaths from cirrhosis decreased by more than 50% during Prohibition, while the mortality from all other causes remained unchanged. Even though a positive correlation exists between per capita consumption of alcohol and the incidence of cirrhosis, only 15-30% of heavy drinkers acquire clinical or histologic signs of alcohol-associated hepatitis and develop cirrhosis. This trend is confirmed even in animal models of alcohol-associated liver disease (ALD) which have minimal variability in the contribution of various intrinsic and extrinsic factors to the development of the experimental disease. Why does the liver possess such a heterogeneous response to consumption of alcohol? This question reflects the complexity of the problem, and is in large part due to the fact there are at least seven proposed underlying mechanisms of ALD (Table 1), which can potentially have profound influences over any one of the primary mechanisms. In search of the underlying primary factors and cofactors for ALD, the past 25 years saw the most impressive advances in our knowledge of biochemical, cellular, and molecular basis for the pathogenesis of ALD. Hence, we devote a large portion of this chapter to these areas.

The complexities of the pathogenesis of ALD are underscored by its epidemiology. Although studies have correlated per capita ethanol consumption with the incidence of cirrhosis in comparing different nations or states, and the duration and dose of ethanol with the incidence of cirrhosis in a given population, the relationship remains controversial. Leibach’s studies demonstrating linear relationship between the incidence of cirrhosis and the product of dose and duration of ethanol consumption, have been interpreted to show that the cumulative dose of ethanol determines the development of cirrhosis. However, these data are strongly influenced by the time factor, i.e., duration, suggesting that there may be a constant rate of developing cirrhosis (a linear slope). Such an interpretation would indicate fixed annual rate of developing cirrhosis rather than a cumulative dose-related effect. Indeed, studies of Sorensen and colleagues support the fixed rate interpretation. They prospectively followed a group of chronic people with alcohol use disorder who initially did not have cirrhosis and found that 2-3% developed cirrhosis per year, regardless of the preceding duration of drinking. Furthermore, although a threshold dose of 80 g/day of ethanol was found, consumption above the threshold to very high doses did not predict who would develop cirrhosis. These data have lead to the view that ethanol “conditions” the liver, i.e., it makes the liver susceptible to injury, but the development of cirrhosis may involve the random interplay of sufficient group of primary and cofactors (Table 1) and/or other unidentified factors. Currently, the issue of epidemiology is unsettled as to whether ethanol simply damages the liver, predisposes the liver to damage caused by other factors, or damages the liver when it is sensitized by cofactors.

In considering the pathogenesis of ALD, it is important to bear in mind that two distinct pathologic processes are seen in the liver: alcoholic hepatitis, characterized by necrosis and inflammation, and liver cirrhosis, which results from progression of liver fibrogenesis from perivenular and perisinusoidal fibrosis to bridging fibrosis. Here again, controversy exists. The bulk of patients with alcoholic hepatitis who continue to ingest alcohol develop cirrhosis. However, the vast majority of patients also develop alcoholic cirrhosis without evidence of preceding alcoholic hepatitis. The question is whether the hepatitis was not clinically apparent and missed, or never existed. Much evidence favors the latter and supports the view that alcohol can promote fibrosis without a necroinflammatory response. The important point for our discussion is to bear in mind, as we consider various pathogenetic mechanisms, that different factors may be responsible for the two pathologic processes, or that the same factor may cause both processes in an independent of interdependent fashion.

Table 1. Primary Factors and Cofactors for the Pathogenesis of Alcoholic Liver Disease

Primary Factors

1. Acetaldehyde
2. Reactive oxygen species
3. Decreased antioxidants
4. Endotoxin, cytokines, and immune responses
5. Centrilobular
6. hypoxia
7. Membrane alterations
8. Redox shift

Cofactors

1. Nutrition
   1. Malnutrition
   2. Dietary Fat
   3. Vitamin A
   4. Iron
2. Genotypes of alcohol dehydrogenase, aldehyde dehydrogenase and CYP2E1
3. Viral hepatitis
4. Gender