Alcoholic Liver Disease

What is Alcoholic Liver Disease?

Alcoholic liver disease is a general term used to designate the hepatic manifestations of alcohol overconsumption. It encompasses alcoholic steatosis ("fatty liver", with or without significant fibrosis), alcoholic steatohepatitis and cirrhosis. These conditions are usually considered as progressive stages of the same general syndrome. Although fatty liver develops in most people who abuse alcohol for a period of days, it is generally asymptomatic and entirely reversible with abstinence. However, approximately 15% to 20% of people who abuse alcohol for an extended period of time develop alcoholic hepatitis and/or cirrhosis, either at the same time or in succession. It has been estimated that a level of alcohol intake equivalent to six to eight daily drinks for several years is necessary for the development of these advanced forms of alcoholic liver disease.

Alcoholic liver disease is a major source of alcohol-related morbidity and mortality. The per capita consumption of alcohol within populations has been shown to be a strong determinant of mortality rates. Important declines in the number of deaths related to alcoholic liver disease have been observed in recent years and these declines have been in part attributed to changes in alcohol consumption rates.

What Causes Alcoholic Liver Disease?

The immediate cause of the spectrum of disorders collectively known as alcoholic liver disease is excessive alcohol consumption. However, the threshold of alcohol necessary for the development of the advanced forms of the disease varies substantially among individuals, suggesting that factors other than absolute alcohol consumption clearly have an important role in determining who will develop alcoholic liver disease and who will not. For example, specific polymorphisms that may confer genetic susceptibility to the disease have been identified. Obesity and infection with the hepatitis C virus have also been associated with an enhanced risk.

At a cellular level, hepatic stellate cells in the liver respond to alcohol, leading to the deposition of collagen that ultimately causes fibrosis. Programmed cell death (apoptosis) triggered by the local release of pro-inflammatory cytokines plays an important role in the pathogenesis of chronic liver disease. When alcohol is consumed, reactive oxygen species are generated as a by-product in the cytosol of liver cells, leading to an increase in the harmful condition known as oxidative stress. Ethanol can also induce and/or activate the inducible enzyme nitric oxide synthase (iNOS), which plays a key role in worsening alcohol-mediated hepatotoxicity.

Symptoms of Alcoholic Liver Disease

Alcoholic steatosis, the milder form of alcoholic liver disease, is generally asymptomatic. If the disease progresses to later stages, the following symptoms are usually observed:

• Jaundice (yellowish pigmentation of the skin and eyes)
• Fever
• Nausea
• Vomiting
• Anorexia
• Weight loss
• Fatigue
• Abdominal pain
• Swollen liver
• Palmar erythema (reddening of the palms)
• Contractures in the finger muscles
• White nails
• Fatty infiltration

Diagnosis of Alcoholic Liver Disease

The major clinical assessment necessary for diagnosis is determining alcohol abuse by the patient. This is not always straightforward, as alcoholic patients and even their family members tend to minimize or conceal alcohol use. Interrogation of multiple family members and the use of standardized questionnaires such as CAGE can be used by the clinician to overcome patient deception.

Steatosis can be determined with a good level of accuracy by using non-invasive imaging techniques. Liver biopsy is generally unnecessary for diagnosis because the condition is benign and reversible. However, in some patients, biopsy may be performed to determine the degree of advancement of alcoholic liver disease and to exclude the presence of cirrhosis. Alcoholic hepatitis is often diagnosed on clinical and laboratory findings, although some diagnostic uncertainty may remain in the absence of histological confirmation. A biopsy of the liver is often useful to secure the diagnosis and to determine the extent of injury to the organ, but since this procedure is associated with risk to the patient, the cost-benefit ratio should be considered by the clinician on an individual basis according to the degree of diagnostic certainty required. A biopsy also helps to exclude other coexisting conditions, such as hepatitis C, hemochromatosis, or Wilson disease.

Treatment of Alcoholic Liver Disease

Management of alcoholic liver disease depends on the degree of damage to the organ at the time of diagnosis. An isolated episode of steatosis requires no management other than abstinence. In more advanced stages, therapy focuses predominantly on supportive care.

The most important factor in the management of patients with alcoholic liver disease is abstinence from alcohol. This may require treatment of addiction using a multidisciplinary approach that includes an addiction specialist, a primary care physician, psychiatrist and a social worker. Malnourishment in patients with progressive disease may make nutritional support necessary to maintain a positive nitrogen balance and provide the adequate energy requirements.

Since alcoholic liver disease clearly has an inflammatory component and patients often exhibit a high incidence of autoimmune markers, corticosteroids have been proposed as a treatment tool, but there is currently a lack of consensus on their actual effectiveness.

Infection is one of the most common causes of death in patients suffering from alcoholic liver disease due to malnutrition, underlying cirrhosis and aggressive in-hospital medical procedures. Alcohol also increases gut permeability to microbes, leading to additional risk. Spontaneous bacterial peritonitis, aspiration pneumonia and lower extremity cellulitis are among the most common infections in this patient population. Patients should be evaluated carefully and treated aggressively with antibiotics in the event of an infection.

Liver transplantation is an option considered in those cases with extensive organ damage, with excellent survival rates after the procedure. However, the well-documented organ shortage for liver transplantation means that not every patient with end-stage disease can be considered a candidate. Alcohol abuse after liver transplantation can result in a rapid development of cirrhosis in the graft, making it necessary to identify candidates with a low risk of recidivism as a first step. At present, most transplant centers require patients to have six months of abstinence and appropriate addiction treatment before being considered.

Prognosis of Alcoholic Liver Disease

The prognosis for alcoholic liver disease depends on the degree of pathological injury, the nutritional status of the patient, the presence of complications of advanced disease, other comorbid conditions such as hepatitis C virus infection, and the ability to eliminate destructive patterns of drinking.

The average survival rate after one year for all patients affected by alcoholic liver disease is 80%, and this number falls to 50% after five years. Patients with fatty liver have the best outcome, with total remission in the majority of cases after alcohol intake has been reduced. The prognosis of individual patients with alcoholic hepatitis can vary dramatically. Those with severe disease have an extremely high mortality, approaching that of patients with fulminant hepatic failure. If the heavy drinking pattern continues, 40% will develop cirrhosis. Complications such as spontaneous hepatic encephalopathy and hepatorenal syndrome can severely affect the prognosis for these patients: One-month mortality in patients with spontaneous hepatic encephalopathy can be approximately 50%, and as high as 75% in those with hepatorenal syndrome.

The prognosis of patients presenting cirrhosis of the liver is usually determined using the Child-Turcotte-Pugh (CTP) classification. Five-year survival rates of patients with alcoholic cirrhosis have a wide variation according to this classification. Patients with cirrhosis and superimposed alcoholic hepatitis have a four-year mortality greater than 60%. Ascites (build-up of fluid), variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis and hepatorenal syndrome are common complications at this stage, and only between 20% and 50% of patients who develop any of these complications survives after five years. Alcoholic cirrhosis also appears to be an independent risk factor for hepatocellular carcinoma.

Preventing Alcoholic Liver Disease

Excessive alcohol consumption is the trigger for the development of alcoholic liver disease, and therefore prevention measures are aimed primarily to discourage patterns of heavy drinking. Men should not drink more than 3 to 4 units of alcohol per day, and women no more than 2 to 3, in order to avoid progressive health risks.

Alcohol dependency is a complex addictive disorder that involves multiple factors, and therefore the preventive approach should be multidisciplinary and consider the social environment (parents, family, friends, peers, community, society) as well as possible social co-determinants such as poverty, social inequality, and easy availability of alcoholic beverages.

Living with Alcoholic Liver Disease

The most important aspect of living with alcoholic liver disease is to stop alcohol consumption immediately after diagnosis and maintain the abstinence in order to arrest the progression of the condition.

Patients should eat a well-balanced diet, rich in proteins and carbohydrates. Since the capacity of the diseased liver to store glycogen is compromised, the extra energy is necessary to prevent muscle wasting and weakness resulting from the metabolization of muscle tissue. Healthy snacking between meals can also improve nourishment and make the patient feel better. Eating regularly every two to three hours is recommended.

In the event of abnormal accumulation of fluid in the abdomen (ascites), the amount of sodium intake in the diet should be reduced to 500-1,000mg a day. Caffeine consumption should be limited as well, since a diseased liver has a lower capacity to process it. This can result in a higher concentration of caffeine in the blood, causing headaches, fatigue, insomnia and anxiety.

Current Research of Alcoholic Liver Disease

Recent experimental work has led to the identification of new molecular mechanisms and mediators of alcoholic liver disease. These include plasminogen activator inhibitor 1, which was shown to play a central role for steatosis, and the anti-inflammatory adipokine adiponectin, which regulates macrophage function in the liver. Excessive hepatic deposition of iron resulting from alcohol consumption has been shown to be important for the development of hepatocellular carcinoma.

Because of the lack of effective therapies and high mortality rate of patients with advanced alcoholic liver disease, novel treatment options are being investigated. Investigators have studied the role of antibodies to TNF-α in suppressing liver injury caused by chronic exposure to alcohol, based on the hypothesis that this signaling molecule is an important mediator of the process. Preliminary data seems to indicate that this therapeutic strategy offers some short-term survival advantages. Antioxidant compounds such as propylthiouracil are also being evaluated as potential therapeutic agents.