Carelli Francesco , Professor for Family Medicine, University  of Milan

Censabella Federica,  intern trainee FM, University of Milan 

Colosimo Valentina , intern trainee FM , University of Milan

Ferrario Guido, intern doctor, University of Milan

Inzoli Irene, intern doctor trainee FM, University of Milan

 

 

 

A patient of our Family Medicine clinic, a 56 years old man with history of heavy alcohol drinking (> 100 g/day) until three year , was hospitalized for umbilical hernioplasty.

 

Shortly after hospital discharge he came to us presenting massive abdominal ascites. Suspecting a possible liver damage from alcoholism we sent  him to  emergency department.

Abundant ascites due to alcoholic liver cirrhosis was confirmed and a  drug therapy associated with a low-sodium diet was introduced.

Nine months later the patient presented an episode of ascitic decompensation with a porto-systemic encephalopathy, and was re-admitted to the hepatology department where an paracentesis was performed with the drainage of 4700 cc of clear ascitic fluid.

The patient was therefore included in the liver transplant list of that hospital.  Eight months later he was contacted by the same hospital and the transplant was successfully performed there.

Currently, fourteen months after the transplant, the patient is significantly improved both physically and psychologically, thanks to the joint work of the transplant center, of his family and of our Family Medicine practice. 

Considering the particular cause having produced the cirrhosis and the subsequent need for transplantation, we think it is useful to investigate the correlation between alcoholism and liver damage. In fact, the ethyl alcohol (or ethanol) is a widespread consumer staple, is found in many beverages and for this reason is also considered an aliment. Very often people abuse of it and its toxicity in these cases is considerable. We note that the potential energy capacity of alcohol cannot, in contrast to other substances, be stored in the form of reserve, and then alcohol, once absorbed in the small intestine, is mainly metabolized by the liver due to enzyme systems (alcohol dehydrogenase). The remaining part is metabolized in the digestive tract (especially in the stomach), in kidneys and in the lungs.

Liver damage is the most common result from alcohol abuse being the liver precisely the primary site of alcohol metabolism. The risk of developing hepatopathy is linked to the consumption of alcohol in large quantities for many years; however there are small differences according individual susceptibility, gender (women are exposed to a greater risk of alcoholic hepatopathy),  BMI (malnutrition is a synergistic factor  with alcohol in causing liver damage),  simultaneous presence of other liver damaging factors (for example HCV and HBV).

So metabolism of alcohol itself is the main cause of liver damage: whatever the enzyme system used (alcohol dehydrogenase, microsomal and peroxisomal catalase), the result is the production of acetaldehyde, a highly reactive compound, which in chronic intake tends to a considerable increase. The acetaldehyde by its electrophilic nature is able to react with several molecules, particularly proteins, with nucleophilic groups, giving rise to the formation of stable adducts with serious effects on hepatocyte physiology, bringing it to degeneration and necrosis.

Furthermore during the various stages of ethanol oxidation, free radicals may form, that hepatocyte is not able to eliminate, thus triggering lipid peroxidation that in addition to damage the membrane can activate synthesis of various components of the extracellular matrix.

Liver diseases resulting from these processes are essentially steatosis, liver fibrosis, alcoholic hepatitis and cirrhosis, which often coexist in the same patient. Note that in some patients cirrhosis may progress to hepatocellular carcinoma.

Liver transplantation is often the only viable therapy for many terminal liver diseases, for acute liver failure and for certain metabolic or congenital diseases, of adult or pediatric interest, implying the involvement of the liver.

In Italy liver transplantation has progressively been increasing in recent years. In the period 2000-2005, 4892 transplants were performed (official data of the Italian National Center for Transplantation). Despite the increase in the number of liver transplantations, also the number of patients on the waiting lists for it has grown in the same time, reaching 1,499 patients on the waiting list on 10/31/2007. The average waiting time for a liver transplantation in 2007 was 1.82 years and the mortality rate of patients on the waiting list of 7.2%.

 

Alcoholic liver cirrhosis is an established indication for liver transplantation. The survival of patients with alcoholic cirrhosis is 82% in the 1st year, 72% at 5 years, comparable with the results obtained for other indications for intervention.

The indication for liver transplantation for this disease requires a careful assessment of the suitability of the recipient, for both ethical and clinical reasons, given the high incidence of alcohol abuse resumption after surgery, reported up to 95% of cases. The recurrence of alcoholic liver disease is the commonest cause of death after liver transplantation (87.5%), while malignancies, cardiovascular diseases and infections, represent the greatest risk of mortality in patients who remain abstinent. Most of the international transplantation centers consider indispensable for   inclusion in the waiting list, at least six months of documented alcohol abstinence. In this context it is important to note that some factors such as age, socio-economic stability,  absence of cohabiting people with habitual assumption of alcohol, no abuse of other substances, result  positive prognostic factors for the post-transplant maintenance of abstinence.

From a strictly clinical point of view, furthermore, you have to carefully exclude various factors of co morbidity from chronic alcohol abuse that can adversely affect the prognosis both in the short and in the long term, such as:

 

• organic brain damage

 

• cardiomyopathy

• chronic pancreatitis

• protein malnutrition.

• malignancies (of esophagus, oropharynx, etc..)

• coexistence of viral infections (HCV, up to 38% of cases).

The presence of specialized personnel in this issue is desirable, to improve the selection criteria and to prepare specific protocols for the selection and the clinical follow-up in the pre-and post-transplant period.

Acute alcoholic hepatitis is still a controversial indication for liver transplantation. This condition is associated with an adverse prognosis with the only use of medical support therapy, with a reported mortality variable between 35% and 46%. Some authors have shown that, in the absence of a tangible clinical improvement of acute alcoholic hepatitis after 3 months of total abstinence from alcohol, it is very unlikely a further recovery for liver function, and therefore this class of patients may be considered for liver transplantation after only 3 months of certified abstinence from alcohol.

Currently there is no justification to extend the indication for liver transplantation in patients with cirrhosis associated with acute alcoholic hepatitis, except as part of an experimental protocol, shared by most transplant centers.