barcelona . spain - European Association for the Study of the Liver
barcelona . spain - European Association for the Study of the Liver
barcelona . spain - European Association for the Study of the Liver
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BARCELONA . SPAIN<br />
142 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 143<br />
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012<br />
In a recent study based on ELTR (<strong>European</strong> <strong>Liver</strong> Transplant Registry) database, it has been demonstrated<br />
that patient survival at 1, 3, 5 and 10 years from first transplantation was 84%, 78%, 73%, 58%, significantly<br />
higher in alcoholic liver disease patients compared to HCV and HBV-relate liver disease recipients (82%,<br />
74%, 70%, 60%) and cryptogenic cirrhosis patients (78%, 73%, 69%, 61%) (log rank p = 0.04 and p = 0.05,<br />
respectively). When alcoholic liver disease patients were analysed according to HCV or HBV infection,<br />
patient survival at 1, 3, 5 and 10 years from first transplantation was 84%, 75%, 65%, 52%, respectively,<br />
in alcoholic liver disease with concomitant HCV infection group, significantly lower than 89%, 85%, 81%,<br />
64%, respectively, observed in alcoholic liver disease with concomitant HBV infection patients (log rank p =<br />
0.0002). The incidence <strong>of</strong> deaths due to all social causes was double in patients with an alcoholic etiology<br />
<strong>of</strong> liver disease with or without viral infection, compared to o<strong>the</strong>r etiologies (1.3% alcoholic liver disease and<br />
alcoholic liver disease with concomitant HCV or HBV infection vs. 0.7% HCV or HBV and 0.4% cryptogenic<br />
cirrhosis, respectively; p = 0.03). In detail, transplanted patients or previous alcoholic liver disease had<br />
double <strong>the</strong> incidence <strong>of</strong> deaths <strong>for</strong> suicide compared to viral etiology, p = 0.02 [24].<br />
Alcohol relapse after liver transplantation<br />
With <strong>the</strong> term “relapse” is generally defined any alcohol intake occurring after liver transplantation. Studies<br />
which have evaluated alcohol relapse after liver transplantation <strong>for</strong> alcoholic cirrhosis have reported a wide<br />
range <strong>of</strong> frequencies ranging from 10% to 50% in up to 5 years follow up [21, 25]. However most <strong>of</strong> <strong>the</strong><br />
studies evaluating alcohol relapse after liver transplantation are based on retrospective analysis <strong>of</strong> routine<br />
screening tests, questionnaires or interviews with patients and/or family during routine follow-up, with a<br />
consequent potential underestimate <strong>of</strong> patients’ real drinking habits.<br />
In a study based on 51 patients with alcoholic liver disease who underwent strictly medical and psychological<br />
evaluation be<strong>for</strong>e and after liver transplantation, alcohol abuse was recorder in 60% and alcohol dependence<br />
in 40% <strong>of</strong> <strong>the</strong>m be<strong>for</strong>e transplantation. Alcohol relapse was observed in 33% <strong>of</strong> transplanted patients, 64%<br />
<strong>of</strong> who were occasional and 36% were heavy drinkers. The admission <strong>of</strong> alcoholism by <strong>the</strong> patient and his/<br />
her family prior to transplantation significantly predicted abstinence after transplantation [26].<br />
Combining results from many studies is evident that from a third to half <strong>of</strong> <strong>the</strong> alcoholic transplant recipients<br />
start drinking again after transplantation <strong>of</strong>ten within <strong>the</strong> first year after surgery; amongst <strong>the</strong>se nearly 10%<br />
resume drinking in an abusive or dependent fashion [27].<br />
Acute and chronic rejection<br />
Patients transplanted <strong>for</strong> alcoholic cirrhosis experience fewer episodes <strong>of</strong> acute cellular rejection after<br />
liver transplantation compared to patients transplanted <strong>for</strong> o<strong>the</strong>r reasons [28, 29]. Histologically-proven<br />
acute cellular rejection was reported in 14% <strong>of</strong> patients 23-180 days after liver transplantation <strong>for</strong> alcoholic<br />
cirrhosis [23].<br />
Chronic ductopenic rejection is also very uncommon in alcoholics receiving liver transplants. In Padua <strong>Liver</strong><br />
Transplant Centre, since November 1990, 415 patients have undergone 480 liver transplantations. Eighty<br />
<strong>of</strong> whom were transplanted <strong>for</strong> alcoholic liver disease ei<strong>the</strong>r alone or in combination with viral hepatitis or<br />
hepatocellular cancer. Among 312 long-term survivors, chronic rejection was seen in 6 (5%).<br />
Medical complications following liver transplantation<br />
Infections are common after liver transplantation <strong>for</strong> alcoholic liver disease. Bacterial infections seem to be<br />
more frequent than in patients transplanted <strong>for</strong> o<strong>the</strong>r causes. The incidence <strong>of</strong> cytomegalovirus infection<br />
was reportedly 14.3% in patients transplanted <strong>for</strong> alcoholic cirrhosis, which is no different from <strong>the</strong> 25%<br />
incidence observed in patients transplanted <strong>for</strong> o<strong>the</strong>r causes. The incidence <strong>of</strong> new-onset insulin-dependent<br />
diabetes is reportedly less than 10%, while <strong>for</strong> hypertension it is around 33%, again much <strong>the</strong> same as in<br />
patients transplanted <strong>for</strong> non-alcoholic liver disease [30].<br />
Patients transplanted <strong>for</strong> alcoholic liver disease may have an higher incidence <strong>of</strong> cardiovascular events<br />
compared to patients transplanted <strong>for</strong> o<strong>the</strong>r causes <strong>of</strong> liver disease. It was recently demonstrated that<br />
cardiovascular events were <strong>the</strong> cause <strong>of</strong> death in 8% <strong>of</strong> patients transplanted <strong>for</strong> alcoholic liver disease with<br />
and without associated viral infection and in 5.3% <strong>of</strong> patients transplanted <strong>for</strong> HCV or HBV cirrhosis, and<br />
<strong>the</strong> difference was statistically significant [24].<br />
The prevalence <strong>of</strong> diabetes mellitus (10%), and hypertension (33%) are comparable with patients<br />
transplanted <strong>for</strong> o<strong>the</strong>r aetiologies [30].<br />
Te cerebral blood flow may also be impaired after liver transplantation since many functional alterations<br />
in brain physiology are seen in alcoholic cirrhotic patients. Usually <strong>the</strong>se abnormalities are reversed after<br />
liver transplantation, but a reduction in <strong>the</strong> frontal cerebral blood flow may persist <strong>for</strong> up to 12 months after<br />
surgery [31].<br />
De novo neoplasms<br />
An increased risk <strong>of</strong> de novo malignancies after liver transplantation has been reported to rise from 6%<br />
to 55% at 15 years after liver transplantation and to account <strong>for</strong> a significant risk <strong>of</strong> late death [32]. An<br />
overall incidence <strong>of</strong> oropharyngeal squamous cell carcinoma <strong>of</strong> 17% in alcohol-induced cirrhosis transplant<br />
patients was reported [33]. In ano<strong>the</strong>r series <strong>of</strong> patients who underwent liver transplantation <strong>for</strong> alcoholic<br />
liver disease, an incidence <strong>of</strong> 4.2% <strong>of</strong> oropharyngeal and esophageal malignancies were seen between<br />
8-40 months after surgery [34].<br />
The incidence <strong>of</strong> <strong>the</strong> de novo tumors as cause <strong>of</strong> death was significantly higher in alcoholic compared with<br />
non-alcoholic etiology <strong>of</strong> <strong>the</strong> primary liver disease. Among solid organ tumors, 2% <strong>of</strong> patients with viral<br />
cirrhosis developed oral or upper GI tract tumors compared to 5.4% <strong>of</strong> patients with alcoholic liver disease<br />
and <strong>the</strong> difference was statistically significant [24].<br />
Quality <strong>of</strong> life and adherence to medical prescriptions<br />
Whatever <strong>the</strong> reason <strong>for</strong> liver transplantation, quality <strong>of</strong> life improves after surgery in most domains [35].<br />
Overall quality <strong>of</strong> life and employment levels appear similar between patients transplanted <strong>for</strong> alcoholic and<br />
non-alcoholic liver disease [36].<br />
Adherence <strong>of</strong> patients suffering from alcoholic cirrhosis is still under discussion. After liver transplantation<br />
no difference between patients with or without alcohol relapse concerning compliance with medication,<br />
incidence <strong>of</strong> rejection or adherence to check-ups were reported [37]. They appear to return to society to<br />
lead active and productive lives, despite <strong>the</strong>y seem less likely to be involved in structured social activities<br />
than patients transplanted <strong>for</strong> non-alcoholic liver disease [38].<br />
CONCLUSION<br />
In conclusion, alcoholic cirrhosis is a widely accepted indication <strong>for</strong> liver transplantation, whereas <strong>the</strong><br />
experience <strong>of</strong> transplantation in patients with acute alcoholic hepatitis is limited to a restricted number <strong>of</strong><br />
patients with specific slection criteria.<br />
Literature data showed that, despite alcohol relapse is ranging between 10% and 50% at 5 years after liver<br />
transplantation, graft and patient survival is comparable with patients transplanted <strong>for</strong> different aetiology.<br />
A psycho-social assessment to establish <strong>the</strong> likelihood <strong>of</strong> long-term abstinence after liver transplantation<br />
and a psychiatric evaluation should be per<strong>for</strong>med in all patients with alcoholic liver disease. The role <strong>of</strong> <strong>the</strong><br />
length <strong>of</strong> pretransplantation abstinence, <strong>the</strong> so called “6-month rule”, as predictor <strong>of</strong> posttransplantation<br />
abstinence is still controversial.