This section gives the pathology and clinical features of liver disease. The amounts needed to produce liver damage, alcohol metabolism, and other clinical effects of alcohol are described. Ethanol is metabolized in the liver by two pathways resulting in an increase in the NADH/NAD ratio. The altered redox potential results in increased hepatic fatty acid synthesis with decreased fatty acid oxidation, both events leading to accumulation of fatty acid that is then esterified to glycerides.
The changes in oxidation-reduction also impair carbohydrate and protein metabolism and are also the cause of the centrilobular necrosis of the hepatic acinus typical of alcohol damage. Acetaldehyde is formed by the oxidation of ethanol and its effect on hepatic proteins may well be an important factor in producing liver cell damage. The exact mechanism of alcoholic hepatitis and cirrhosis is unknown, but since only 10-20% of people who drink excessively will suffer from cirrhosis, a genetic predisposition is proposed. Immunological mechanisms have also been proposed. Alcohol can enhance the effects of toxic metabolites of drugs, e.g. paracetarnol, on the liver, as it induces microsomal metabolism via the microsomal ethanol oxidizing system (MEOS).
Alcohol can produce a wide spectrum of liver disease from fatty change to hepatitis and cirrhosis. Fatty change The metabolism of alcohol invariably produces fat in the liver, mainly in zone 3. This is minimal with small amounts of alcohol, but with larger amounts the cells become swollen with fat (steatosis) giving, eventually, a Swiss-cheese effect on haematoxylin and eosin stain. Steatosis can also be seen in obesity, diabetes, starvation and occasionally in chronic illness. There is no liver cell damage and therefore in general this is not precirrhotic. The fat disappears on stopping alcohol.
In some cases collagen is laid down around the central hepatic veins (perivenular fibrosis) and this can sometimes progress to cirrhosis without a preceding hepatitis. Alcoholic hepatitis Here there is necrosis of liver cells and infiltration with polymorphonuclear leucocytes mainly in zone 3. A dense cytoplasmic material called a Mallory body is sometimes seen in hepatocytes. Steatosis is also frequently present and an established cirrhosis is often seen. Mallory bodies are suggestive of but not specific for alcoholic damage as they can also be found in other liver diseases, such as Wilson’s disease and PBC. Alcoholic hepatitis usually goes on to become cirrhosis if alcohol consumption continues. Alcoholic cirrhosis Destruction and fibrosis with regenerating nodules produces classically a micronodular cirrhosis; in later stages a macro nodular pattern may be seen. There is bridging fibrosis between portal tracts and terminal hepatic veins. Fat may be present with the additional features of alcoholic hepatitis.
There are often no symptoms or signs. Vague abdominal symptoms of nausea, vomiting and diarrhoea are due to the more general effects of alcohol on the gastrointestinal tract. Hepatomegaly, sometimes huge, can occur together with other features of chronic liver disease.
The clinical features vary in degree:
THE PATIENT MAY BE WELL, with few symptoms, the hepatitis only being apparent on the liver biopsy in addition to fatty change.
MILD TO MODERATE SYMPTOMS OF ILL-HEALTH, occasionally with mild jaundice, may occur. Signs include all the features of chronic liver disease. Liver biochemistry is deranged and the diagnosis is made on liver histology.
IN THE SEVERE CASE, usually superimposed on patients with alcoholic cirrhosis, the patient is ill, with jaundice and ascites. Abdominal pain is frequently present, with a high fever associated with the liver necrosis. On examination there is deep jaundice, hepatomegaly, sometimes splenomegaly, and ascites with ankle oedema. The signs of chronic liver disease are also present.
This represents the final stage of liver disease from alcohol abuse. Nevertheless, patients can be very well with few symptoms.On examination, there are usually signs of chronic liver disease. The diagnosis is confirmed by liver biopsy.
Usually the patient presents with one of the complications of cirrhosis. In many cases there are features of alcohol dependency (see p.983) as well as evidence of involvement of other symptoms, e.g. polyneuropathy.
An elevated MCV often indicates heavy drinking. Liver biochemistry shows mild abnormalities with elevation of both serum aminotransferase enzymes. The y-GT level is a sensitive test for determining whether the patient is taking alcohol. With severe fatty infiltration, marked changes in all liver biochemical parameters can occur. Ultrasound or CT will demonstrate fatty infiltration as will liver histology.
Investigations show a leucocytosis with markedly deranged liver biochemistry with elevated:
• Serum bilirubin
• Serum AST and ALT
• Serum alkaline phosphatase
• Prothrombin time
A low serum albumin may also be found. Rarely, hyperlipidaemiawith haemolysis (Zieve’s syndrome) may occur. The prolonged PT makes liver biopsy impossible in the severe form. In these severe cases the mortality is at least50%, and with a PT twice the normal, progressive encephalopathy and renal failure, the mortality approaches 90%.
Investigations are as for cirrhosis in general.
MANAGEMENT AND PROGNOSIS
Patients should be advised to stop drinking. Delirium tremens (withdrawal symptoms) should be treated with diazepam or chlormethiazole. Bed rest with a diet high in protein and vitamin supplements is given. Dietary protein may have to be limited because of encephalopathy. Follow-up of patients with alcoholic liver disease show that apart from highly motivated groups, most patients continue to abuse alcohol.
In all but the mildest cases the patient is advised to stop drinking; the fat will disappear and the liver biochemistry usually returns to normal. Small amounts of alcohol can be drunk subsequently as long as patients are aware of the problems and can control their consumption.
In severe cases the patient is confined to bed. Treatment for encephalopathy and ascites is commenced. Patients should be fed preferably via a fine-bore nasogastric tube or sometimes intravenously. Nitrogen solutions enriched with branched-chain amino acids, e.g. leucine, isoleucine and valine, may be helpful. Vitamins Band C should be given by injection. Corticosteroids are often given, but controlled trials have shown them to be of little benefit. Patients are advised to stop drinking for life, as this is undoubtedly a precirrhotic condition. The prognosis is variable and, despite abstinence, the liver disease is progressive in many patients. Conversely, a few patients continue to drink heavily without developing cirrhosis.
The management of cirrhosis is described Again, all patients are advised to stop drinking for life. Abstinence from alcohol results in an improvement in prognosis, with a 5-year survival of 90%, but with continued drinking this falls to 60%. With advanced disease (i.e. jaundice, ascites and haematemesis) the 5-year survival rate falls to 35%, with most of the deaths occurring in the first year. Liver transplantation is being widely used in some countries with good survival figures. Patients must demonstrate their ability to abstain from alcohol. HCC is a complication in men in approximately 10- 15% of cases.