Alcoholic liver disease cirrhosis

Cirrhosis is the result of long-term insult to the liver, so damage is typically not evident clinically until the fourth decade of life. Chronic liver disease and cirrhosis combined were the 12th leading cause of death in the United States in 2002. In patients between the ages of 25 and 64, damage from excessive alcohol use accounted for over one-half of the deaths.2 Alcoholic liver disease and viral hepatitis are the most common causes of cirrhosis in the United States and worldwide. 

Progression of alcoholic liver disease moves through several distinct phases from development of fatty liver to the development of alcoholic hepatitis and cirrhosis. Fatty liver and alcoholic hepatitis may be reversible with cessation of alcohol intake, but cirrhosis itself is irreversible. Although the scarring of cirrhosis is permanent, maintaining abstinence from alcohol can still decrease complications and slow development to end-stage liver disease.22 Continuing to imbibe speeds the advancement of liver dysfunction and its complications. 

Lifestyle modifications can limit disease complications and slow further liver damage. Avoidance of additional hepatic insult is critical for successful cirrhosis treatment. The only proven treatment for alcoholic liver disease is the immediate cessation of alcohol consumption. Patients who have cirrhosis from etiologies other than alcoholic liver disease should also abstain from alcohol consumption to prevent further liver damage. 

The main indications for liver transplantation include chronic hepatitis C, alcoholic liver disease, nonalcoholic fatty liver disease, and cryptogenic cirrhosis. 

Liver disease is the most common medical complication of alcohol abuse it is estimated that 15-30% of chronic heavy drinkers eventually develop severe liver disease. Clinically significant alcoholic liver disease may be insidious in onset and progress without evidence of overt nutritional abnormalities. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the USA, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Another factor that increases the risk of severe liver disease is concurrent infection with hepatitis B or C virus. 

Milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver disease, and toxin-induced liver injury in human patients. Milk thistle has most often been studied in the treatment of alcoholic hepatitis and cirrhosis. In both of these disorders, outcomes have been mixed and reports include significant reductions in markers of liver dysfunction and in mortality, as well as no effect. In acute viral hepatitis, studies have generally involved small sample sizes and have shown mixed outcomes of improved liver function (eg, aminotransferase values, bilirubin, prothrombin time) or no effect. Studies in chronic viral hepatitis and toxin-induced injury have also been of small size but have reported mostly favorable results. Parenteral silybin is marketed and used in Europe as an antidote in Amanitaphalloides mushroom poisoning, based on favorable outcomes reported in case-control studies. 

In this chapter Case studies levels 1-3 explore the management of a patient with alcoholic liver disease. The patient has alcoholic liver cirrhosis and first presents with alcohol withdrawal (Case study level 1), then the patient s risk of bleeding and treatment for the maintenance of alcohol abstinence are considered (Case study level 2). The patient then goes on to develop encephalopathy (Case study level 3). Case studies levels Ma and Mb consider two patients one presents with TB and the other liver failure. 

Causes of cirrhosis can usually be identified by the patient s history combined with serological and histological investigation. Alcoholic liver disease and hepatitis C and B are the most common causes of cirrhosis. The association of excessive alcohol consumption with liver disease has been recognised for centuries. After the identification of the hepatitis C vims and of non-alcoholic steatohepatitis in obese patients with diabetes, the diagnosis of cirrhosis without an apparent cause (cryptogenic cirrhosis) is rarely made. Genetic causes of cirrhosis include haemochromatosis and Wilson s disease. 

There are three main histological stages of alcoholic liver disease, as highlighted in Figure 3.3 stage 1, steatosis (fatty infiltration of the hepatocyte) stage 2, alcoholic hepatitis and stage 3, fibrosis and cirrhosis. 

Liver disease is now recognised as a major complication of type 2 diabetes. Diabetes mellitus can lead to metabolic changes that alter normal hepatic and biliary function and structure. Type 2 diabetes is associated with an increased risk of a range of hepatobiliary diseases, including non-alcoholic fatty liver disease, cirrhosis, acute liver failure, hepatocellular carcinoma and cholelithiasis [22]. 

Patient 4 Alcoholic liver disease Decompensated cirrhosis... 

Steatohepatitis is the accumulation of lipids and the presence of inflammatory cells within hepatic parenchyma. Steatohepatitis is usually the next stage of steatosis if untreated (Bautista, 2002 French, 2003 Lieber, 1994). The inflammatory cells are usually neutrophils and mononuclear leukocytes. Conditions usually associated with steatohepatitis are alcoholic liver disease, NAFLD, and endotoxemia secondary to intestinal disease. Any toxic compounds that cause steatosis can also result in steatohepatitis if the condition is left untreated. Steatohepatitis may progress to flbrosis/cirrhosis and hepatocellular carcinoma if the inciting cause is not removed or treated (Diehl, 2002). 

Cirrhosis occurs most frequently in the setting of alcoholic liver disease and represents the final common pathway of a number of chronic liver diseases. The development of cirrhosis is characterized by the appearance of fibroblasts and collagen deposition. This is accompanied by a reduction in liver size and the formation of nodules of regenerated hepatocytes. As a result, total liver content of cytochrome P450 is reduced in these patients. Initially, fibroblasts deposit collagen fibrils in the sinusoidal space, including the... 

Lieber, C.S. Hepatic and metabolic effects of ethanol pathogenesis and prevention. Ann. Med. 1994 26 325-330 Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta 1997 257 59-84 Role of oxidative stress and antioxidant therapy in alcoholic and non-alcoholic liver diseases. Adv. Pharmacol. 1997 38 601-628... 

The prognosis of alcoholic liver disease is better than that for other forms of liver disease, with only 10% to 15% developing cirrhosis and a much smaller fraction developing Both hepatitis B and hepatitis C appear to accelerate the course of alcoholic liver disease. The 5-y survival rate in patients with cirrhosis, jaundice, and ascites is 40% if the patient continues drinking and 60% if the patient abstains. " ... 

While cirrhosis has many causes (Table 37-1), in the United States excessive alcohol intake and chronic viral hepatitis (types B and C) are the most common causes. A breakdown of the indications for liver transplantation (Table 37-2) provides an estimate of the clinical frequency for each of the potential causes of cirrhosis, as transplant represents the deflnitive therapeutic strategy for cirrhosis. These data underestimate alcoholic liver disease, as these patients are often not considered suitable transplant candidates. 

It has been claimed that alcohol can increase the hepatotoxic effects of methotrexate. Two reports of patients treated for psoriasis indicate that this may be so in one, 3 out of 5 patients with methotrexate-induced cirrhosis were reported to have taken alcohol concurrently (2 patients greater than 85 g, one patient 25 to 85 g of alcohol per week), and in the other, the subject was known to drink excessively. The evidence is by no means conclusive and no direct causal relationship has been established. However, the manufacturers of methotrexate advise the avoidance of drugs, including alcohol, which have hepatotoxic potential, and contraindicate its use in patients with alcoholism or alcoholic liver disease. ... 

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