The excessive consumption of alcohol is one of the most frequent causes of cirrhosis of the liver.
Alcoholic liver disease consists of a broad range of conditions in a broad spectrum, which range from asymptomatic fatty liver to alcoholic hepatitis and decompensated cirrhosis of the liver with ascites, digestive haemorrhage caused by esophageal varices, or encephalopathy.
While the majority of people consume alcohol in some quantity, only some develop liver damage. Epidemiological studies have defined that a minimum quantity of alcohol consumption is necessary for the development of liver disease. The most-mentioned limit is 80 g of alcohol daily over a period 10 to 20 years. This is equivalent to a liter of wine, 300 ml of spirits (whiskey, vodka, etc.) or eight beers.
Alcoholism is a complex chronic disease, in which genetic, psychosocial and environmental factors interact. It is characterised by the loss of control over alcohol consumption, alcohol abuse in spite of the negative consequences and frequently the denial of consumption. Alcoholism is a serious illness that can be progressive and lead to death.
In clinical practice there is a brief questionnaire that can help the doctor to detect alcoholism:
1. Have you tried to stop or reduce alcohol consumption?
2. Have you been offended by comments about your drinking habits?
3. Have you had any feeling of guilt related to your drinking habits?
4. Have you ever drunk ‘the hair of the dog’ in the morning (to avoid the effects of excess alcohol consumption)?
Two or more positive replies strongly suggest the diagnosis of alcoholism.
Physical examination is frequently normal in alcoholics. The so-called stigmas of cirrhosis (telangiectasias, paratidomegaly, liver palm, gynecomastia and gynecoid distribution of pubic hair, among others) may be found in the advanced stages of the disease. Some findings may be a little more suggestive of alcoholic etiology, such as Dupuytren’s contraction and partidomegaly.
There is no laboratory examination that is sensitive enough to give a specific diagnosis of alcoholism; nevertheless, there exist some abnormalities that when present, can help to establish a diagnosis:
In alcoholic liver disease there is disproportionately high elevation of SGOT in relation to SGPT, with a ratio greater than 2. The absolute values of transaminase are habitually lower than 300 U/L.
There are frequently elevations of gamma-glutamyl transpeptidase (GGT) in people that drink heavily. Nevertheless, the findings are not specific, given that other hepatic disease may produce elevations of GGT (cholestatic disease in particular), the same as the consumption of many medicines.
Mean corpuscular volume (MCV)
Macrocitosis, expressed as an increase in the MCV of the erythrocytes is another marker of excessive alcohol intake, nevertheless its sensitivity is low (40%).
Triglycerides are frequently elevated in people who have consumed alcohol in excess during previous days. Carbohydrate-deficient transferrin has been used as a marker of alcohol consumption; nevertheless, its efficiency is not superior to the measure of GGT levels. Its availability in laboratories is limited.
Hepatic steatosis or fatty liver is more frequent in persons who drink alcohol in excess and may occur later after one heavy intake. It may me diagnosed through ultrasound scan imaging of the abdomen. Most of the time patients do not show symptoms. The condition is reversible if the patient stops drinking.
Alcoholic hepatitis is an important complication resulting from excessive alcohol consumption, which can have a high mortality rate when the criteria of severity are fulfilled. It is suspected in a person with a history of alcohol abuse. The presentation usually includes slight fever (‹38º), anorexia, dark urine, jaundice and hepatomegaly. There may be ascites even in patients who are not cirrhotic. Laboratory analysis shows elevations of transaminase usually under 500, with the characteristic ratio of SGOT/SGPT >2. The bilirubin rises in relation to the severity of the hepatitis. The prothrombine time also becomes prolonged, in relation to the severity of the hepatitis. The appearance of hepatic encephalopathy is always a symptom of severity in patients with alcoholic cirrhosis. A liver biopsy may be necessary in some cases.
Hepatic cirrhosis caused by alcohol presents itself in a clinically similar fashion to that of any other type of cirrhosis.
Liver histology is one of the fundamental pillars of the diagnosis and the evaluation of any hepatic disease. In alcoholic liver disease there are elements of hepatic histology that permit the suspicion of the diagnosis when there are doubts or the patient minimizes alcohol intake. The liver biopsy permits, in addition, the staging of the disease, allowing the doctor to distinguish between simple steatosis and cirrhosis of the liver, or make a straight diagnosis of alcoholic hepatitis.
Alcoholic hepatic disease can be classified histologically in three forms.
An accumulation of macro or microvesicular fat in the cytoplasm of the hepatocytes. Megamitochondrias may also be observed which reflect mitochondrial damage produced by ethanol.
2. Alcoholic hepatitis
Alcoholic hepatitis produces histological symptoms indistinguishable from those of non-alcoholic steatohepatitis. Apart from the steatosis, swelling and hepatocitic necrosis, neutrophile infiltration of the lobule, Mallory bodies and central perivenular inflammation, with a variable degree of fibrosis in this part of the lobule can be observed
Cirrhosis, with regenerated nodule formation delimited by bands of collagen tissue, is a progression of the fibrosis that starts in the central perivenular zone. When formed, its histological appearance is similar to that of cirrhosis; nevertheless, the presence of steatosis or Mallory bodies may strongly suggest etiology.
The treatment of alcoholic hepatitis disease is complete and permanent abstinence from alcohol. The benefits of not drinking are evident in patients who have advanced liver disease (cirrhosis).
Alcoholic fatty liver
Patients with alcoholic hepatic steatosis may progress towards more important degrees of fibrosis or cirrhosis, thus permanent abstinence from alcohol consumption is applied.
The treatment of alcoholic liver disease includes the prevention and handling of each one of the specific complications of cirrhosis, in a similar way to any other type of cirrhosis. A liver transplant is a treatment option for those patients who have stopped drinking. The use of colchine, which is disputed, may be an option, given that it is reasonably tolerated. Propylthiouracil and metadoxin are not normally used in the treatment of alcoholic liver disease.
With alcoholic hepatitis it is fundamental to determine the gravity of the episodes in deciding the therapy. The seriousness is usually determined via a formula known as the discriminant function or Maddrey score:
Discriminant function =[4.6 x prothrombin time - prothrombin control] + bilirubin
(Prothrombin time in seconds and bilirrubin in mg/dl)
A discriminate function > 32 is associated with high mortality within 30 days (35% without encephalopathy, and 45% in patients with encephalopathy). This cut off point is normally used to decide on therapy with corticoids.
Recently it has been demonstrated that the application of MELD in patients with alcoholic hepatitis has a prognosis value comparable with discriminate function. A MELD score > 11 is equivalent to a Maddrey score of > 32.
Treatment measures of alcoholic hepatitis include:
1. General support
The patient with alcoholic hepatitis has frequently drunk heavily the previous days and weeks, thus when admitted to hospital a premature diagnosis of alcoholic deprivation syndrome should be avoided, normally with the use of benzodiazepines. Vitamin K should be given, vitamin B complex and folate, minerals (Mg and P) and hydration. Nevertheless, overhydration should be avoided as it can precipitate ascetes or even increase the portal pression and the risk of varicose vein bleeding. Nutritional therapy, with a hypercaloric and normoproteic nutrition seem to lead to recovery. In case of the oral intake not being sufficient, we consider the use of enteral intake to provide the nutritional requirements.
Treatment with corticoids is the most accepted for acute alcoholic hepatitis (Maddrey score> 32 , MELD score >11 or the presence of encephalopathy), in spite of there still being controversy as to its benefits). It is the treatment chosen by our centre, provided that there are no contraindications such as active infection and digestive haemorrhage. The corticoid of choice is prednisolone in doses of 40 mg/per day for 4 weeks, followed by its gradual withdrawal. A reduction of bilirubin serum levels a week after treatment is an indicator of response to the treatment.
The use of pentoxifilline, which should act via the blocking of TNF alpha, seems to be an attractive option, given the risks of corticoids (for example, infections). Until now there is only one study that has demonstrated the benefits of pentoxifilline in doses of 400 mg taken orally three times a day, which reduces mortality from 46 to 25% in 4 weeks, fundamentally at the expense of avoiding hepatorenal syndrome. More affirmative studies are required before it can be considered a first line therapy. Nevertheless, it is the therapy used when there are contraindications in the use of corticoids.
Other therapies aimed at blocking inflammatory cytokines (TNF alpha), such as infliximab and etanercept are at the evaluation stage. The possibility of increasing the risk of serious infections in preliminary studies has put a hold on the enthusiasm for these biological therapies.