POSITION PfiPER DIGEST LIVER OIS 2000;32:249-56

Liver transljlantation in Italy: current status

l? Burra A. Smedilel M. Angelico* A. Ascione3 M. Rizzettol on behalf of the Study Group on Liver Transplantation of the Italian Association for the Study of the Liver [A.I.S.F.)

Front Chair of Gastroenterology, University of Pedua; 1 Chair of Gastroenterology, University of Turin; 2 Chair of Gastroenterology, University of Tor Vergata, Rome; 3 G. 1. Unit, Cardarelli Hospital, Naples, Italy.

Addn?88 for uomwpoodonco: Dr. P. Burra, Sezione di Gestroenterologia, Dipartimentddi Scienze Chirurgiche e Gastroenterologiche, University degli Studi, via Giustiniani 2, 35 128 Padova, Italy. Fax: +39-049-8760820 E-mail: burra@ux I. unipd it

Submitted February 28, 2000. Accepted March 16, 2000.

The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the in- dications for liver transplantation have expanded and have raised the need for more organized structures where patients can be re- ferred for evaluation and transplantation. Indications and con- traindications to liver transplantation in Italy the role of retrans- plantation, paediatric liver transplantation, waiting list manage- ment, liver transplantation outside Italy and the new Italian laws on organ donation are discussed. The multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver [AISF] has collected information from all the Italian centres to ascertain the degree of consistency in their methods.

Digest liver Dis 2000;32:249-56

Key words: contraindications; indications; liver transplantation

Introduction

The first liver transplant in Italy was performed in 1982. At the present time liver transplantation is performed in 18 centres (Table I). Organs are allo-

Table I. Liver transplantation activity at liver transplant centras in Italy las at 31 .I 2.19981.

Centrv Mdiver Me. liw MO. trensplonts rew dwltlw

I. Bari 2 0 2. Bergamo” 42 5 9 3. Bologna 49 100 4. Genoa 202 57 5. Milan Ospedale Niguarda 422

E 135

6. Milan Policlinico 412 47 114 7. Milan lstituto Nazionale Tumori 123 19 8. Naples Ospedale Cardarelli E 9. Naples Policlinico Faderico II ;: 1 E

10. Padua I 219 11. Padua II ’ 142 ii 25: 12. Palermo

13. Pisa 97 14. Rome Policlinico Gemelli 122 E :: 15. Rome S. Eugenio Tor Vergata 136 6 16. Rome Policlinico Llmberto I, La Sapianza 200 ;ls 17. Turin 497 4: 92 18. Udine 69 6 13

* Paediatric Liver Transplantation.

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Cnperience of liver transplant centres in Italy -__1 -___I_--

cated by 3 regional agencies (North Italy Transplant, NITp; Inter-regional Transplant Association, AIRT; Centre-South Transplant Organization, OCST). In ad- dition, there is a Permanent Technical Consultation Group for Organ Transplantation, a branch of the Su- perior Institute for Public Health in Rome. Liver transplant centres have developed their own strategies in the absence of a national programme, in compliance with national laws on organ donations. With the improvement in results, the number of pa- tients followed has substantially increased, at all cen- tres, in recent years. In parallel, the indications for liv- er transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Due to the shortage of organ donors in Italy it is impossible to transplant all patients with end-stage liver disease and, therefore, a strict selection of candidates on the basis of medical and ethical aspects has become mandatory. In 1998, a multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF) collected information from all Ital- ian centres to identify the degree of consistency in their methods. These issues are the object of this report.

The maximum age for considering a candidate for liv- er transplantation has been arbitrarily set at 60 years in all Italian transplant centres. This is not an absolute rule, not based on medical reasons, but is dictated by the shortage of donors. Thus, transplant limitation, on the basis of age, is an ethical, not a medical criterion. Liver transplantation has, nonetheless, been performed in patients over 60 years old. Decisions overriding this rule have been taken at single transplant centres de- pending on organ availability, local lists and logistics. Patients over 60 years old have occasionally been sent abroad and transplanted at other European or Ameri- can centres.

Hepatitis G virus ~HCUI

Liver cirrhosis due to HCV is the major indication at all transplant centres, reflecting the high prevalence of this infection in Italy. The early optimistic views on HCV disease recurrence after liver transplantation, based on short- and medium-term follow-up studies are now under debate. With longer virological and his- tological monitoring, lasting 7-8 years in many cen- tres, it has been recognized that reinfection occurs in almost 90-100% of transplants and hepatitis recurs in many reinfected patients, though its severity varies.

These findings have been the object of concern and discussion. Uncertainty as to post-transplantation out- come in HCV transplants is reflected in different local management policies of this condition.

Prophylaxis and therapy Any therapeutic strategy aimed at combatting HCV in- fection and disease recurrence is, at best, controversial. Experience with interferon (IFN) is limited and has usually been disappointing, as no clear benefit has emerged in terms of biochemical and virological dis- ease remission. Combination therapy with IFN plus ribavirine appears to be promising as a means of pro- phylaxis when given soon after liver transplantation or at the time of hepatitis recurrence, as advocated by most centres. A prospective multicentre Italian study is underway to assess the role of this combination in pa- tients with recurrent HCV disease.

Immunosuppression In patients transplanted for HCV-related cirrhosis, ear- ly recurrence of hepatitis often coincides with acute re- jection, sepsis or biliary complications. These events may occur simultaneously in the early months after surgery, sharing similar histological features, thus the early diagnosis of hepatitis C recurrence is often diffi- cult. Some centres recommend that steroids should be tapered as soon as possible and, in any case, within three months of liver transplantation, or not used at all.

Retransplantation There was no consensus on the indication of retrans- plantation for liver failure after HCV recurrence. Some centres are reluctant to retransplant patients over 50 years of age presenting with a rapid and progressive course.

Hepatitis B virus IHBUI

Liver transplantation for liver disease due to HBV re- mains one of the major indications in Italy. Early on, patients with HBV were considered poor candidates because of the high rate of reinfection and disease re- currence after surgery. The availability of anti-HBs antibodies (HBIg) for long-term passive immunopro- phylaxis after orthotopic liver transplantation has led to an increased enrolment of these patients. Since the use of HBIg improved the post-transplant outcome, particularly, in patients negative at the pre-transplant HBV-DNA test, the policy currently applied in many centres is to transplant only candidates who are nega- tive by standard hybridization at the HBV-DNA test. There are some discrepancies on the rate of HBV re- currence among Italian transplant centres possibly ex-

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plained by differences in patient selection and in im- munoprophylaxis.

Candidate selection Since the risk of HBV reinfection has been related to the viral load before transplantation, all centres test for HBV-DNA concentration in the serum. To avoid mis- leading results due to different methods for measuring serum HBV-DNA, all centres have called for the use of a standard method for HBV-DNA detection and quan- tification. Most centres use commercial reagents. A few centres have their own experience with home- made polymerase chain reaction (PCR)-based assays. Recent reports confirm good results in the control of HBV reinfection with a combination of pre- and post- transplantation therapy with lamivudine and post- transplantation immunoprophylaxis with HBIg. The centres agreed that with this strategy highly viraemic patients (who are currently not considered suitable) could become eligible for transplantation.

Immunoprophylaxis Long-term passive immunoprophylaxis with HBIg is used in all centres. Albeit, there are differences in the dosage, the administration schedule and the titre of an- ti-HBs considered to be optimal. The range varies be- tween 200 and 400 mlU/ml. Well-designed studies on this aspect are warranted in view of the high cost of HBIg therapy.

Post-transplant therapy The antivirals used include the nucleoside analogues ganciclovir, famciclovir, ARA-AMP and lamivudine. The latter is now preferred not only on account of its rapidity in reducing HBV-DNA levels in serum but al- so its tolerability. Long-term lamivudine is used in many centres with encouraging reductions in the rate of reinfection and HBV recurrence, despite the possi- ble emergence of mutants in the DNA polymerase gene.

Immunosuppression While it is generally agreed that steroids must be ta- pered and completely withdrawn three months after transplantation, not all centres comply with this policy.

Retransplantation The feasibility of retransplantation for HBV recur- rence is controversial. However, with the availability of new potent antiviral drugs, it now seems possible to rapidly control HBV-DNA replication before re- transplantation also in these patients. Confidence in this strategy, in association with a standard HBIg cov- erage after retransplantation, was expressed by all centres.

Hepatitis D virus (HDV) Patients undergoing liver transplantation for HDV cir- rhosis have a better long-term prognosis than those with other viral indications. The same strategy as that used to control HDV in hepatitis B patients is applica- ble in those few patients with hepatitis D who have concomitant active HBV infection (i.e., antivirals, in particular lamivudine, to inhibit concomitant HBV synthesis).

Alcoholic liver disease

Many transplant centres are reluctant to transplant pa- tients with end-stage alcoholic liver diseases (ALD) because of the likelihood of being unable to refrain from alcohol intake and of poor compliance with im- munosuppressive therapy. ALD patients may also have other serious medical problems that increase morbidi- ty and mortality after transplantation. However, the survival rates of Italian patients transplanted for ALD are comparable to those of patients transplanted for other indications.

Candidate selection It was agreed that a subset of highly-motivated ALD patients, likely to remain abstinent, can be identified before liver transplantation. These patients profess a strong tendency to comply with medical advice, dis- play no overt psychopathology and usually have a good social support system. Careful medical and psy- chiatric evaluation is thus mandatory before listing for transplantation. Potential candidates should be classi- tied as having a diagnosis of alcohol dependence or abuse, as defined in the Diagnostic and Statistical Manual 4th (DSM-IV). Willingness to join a rehabilita- tion programme is also considered a favourable factor for transplantation. In a few centres where a specific programme for alcohol-related problems has been de- veloped, a multidisciplinary approach is used. In all Italian centres a mandatory 6-month period of absti- nence from alcohol is required prior to evaluation for transplantation.

Follow-up after liver transplantation No specific programme has been developed in many centres. In a few with a particular interest in alcohol- related problems, a more stringent follow-up con- tributes to being better able to avoid drinking episodes and better recognition of overt recidivism.

Recidivism to alcohol abuse The recidivism rates reported by Italian centres do not differ from those of European and American centres and range between 10 and 30%.

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Retransplantation No retransplantation has been done in Italy. The gen- eral opinion is not in favour of retransplantation for re- current alcohol-related liver cirrhosis.

Neoplasms

Cholangiocarcinoma is not considered an indication for liver transplantation in any of the Italian transplant centres because of the unacceptable risk of recurrence and mortality following surgery. In a few centres even patients with hepatocellular carcinoma (HCC) are not considered for transplantation due to the long waiting time. In some centres, only patients who develop HCC after joining the waiting list remain eligible for trans- plantation.

Candidate selection Common eligibility criteria for transplantation are gen- erally accepted by most centres, i.e., the presence of a single tumour no more than 5 cm in diameter or no more than 3 tumour nodules, each no more than 3 cm in diameter, with no evidence of vascular, lymph node or extrahepatic spread. Pre-transplant trans-arterial chemo-embolization (TACE) using doxorubicin, lipiodol and gelfoam is of- ten performed. Systemic chemotherapy including 5- fluorouracil, doxorubicin and cisplatin has occasional- ly been used. Percutaneous ethanol injection (PEI) therapy is also used before transplantation in some pa- tients with HCC.

Waiting list Candidates with HCC are not given priority on the wait- ing list in Italian centres. Priority criteria are only based on the severity of the underlying liver disease and on the time of listing. Patients with HCC are usually re-evalu- ated every 3 months while on the waiting list using ab- dominal ultrasound/echo-Doppler examination to ex- clude any new feature which may be considered a con- traindication for transplantation.

Post-operative treatment Postoperative prophylactic chemotherapy is used in a few centres; it is administered for at least six months after transplantation. However, the influence of post- operative chemotherapy on patient survival and recur- rence is admittedly uncertain.

Other indications

Other indications for adult liver transplantation are: cholestatic liver diseases (primary biliary cirrhosis,

primary or secondary sclerosing cholangitis), autoim- mune chronic active hepatitis, metabolic liver disease (haemochromatosis, Wilson’s disease, amyloidosis), and the Budd-Chiari syndrome.

Primary biliary cirrhosis (PBC) Clusters of clinical or histological variables are com- monly used to predict survival of PBC patients before transplantation. In Italy, many centres adopt the “Mayo risk score”, which allows survival to be estimated based on patients’ age, bilirubin, albumin, oedema and prothrombin time. If there have been no complications, PBC patients are usually referred to a transplant centre when the bilirubin levels exceed 100 nmol/l. A few pa- tients are occasionally listed earlier because of severe pruritus and fatigue which have a significant impact on their quality of life.

Primary sclerosing cholangitis (PSC) Patients with PSC may develop disease-specific com- plications (recurrent bacterial cholangitis, pruritus, he- patic osteodystrophy, inflammatory bowel disease, risk of cholangiocarcinoma) which often represent a prompt consideration for transplantation. The pro- posed scores to predict patient survival (based on clin- ical, biochemical and histological data) are not rou- tinely used, since they are considered useless. Thus, the final decision regarding transplantation is usually made case by case.

Autoimmune chronic active hepatitis (ACAH) The indications for liver transplantation in ACAH are similar to those for other forms of cirrhosis. The onset of recurrent hepatic encephalopathy, variceal haemor- rhage or intractable ascites, despite apparently ade- quate immunosuppression, usually prompts evaluation for transplantation. ACAH patients, in all centres in Italy, are referred for transplantation when they have hypo-albuminaemia (~2.5 g/dl), markedly impaired prothrombin time (prolonged by more than 5 seconds) or encephalopathy.

Haemochromatosis It is agreed that patients with haemochromatosis re- questing liver transplantation should undergo thorough clinical scrutiny due to the possible effects of wide- spread iron deposition in other organs, leading to car- diomyopathy and arrhythmia, diabetes mellitus, en- docrine failure and arthropathy. Only a very few of pa- tients with haemochromatosis have undergone trans- plantation in Italy.

Wilson’s disease Medical treatment is the first option and patients with Wilson’s disease should not be considered as candi-

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dates for transplantation unless medical treatment has failed. The indications for liver transplantation, in all centres, include failure of medical treatment, fulminant liver failure and decompensated cirrhosis.

Budd-Chiari syndrome Budd-Chiari syndrome has been referred for liver transplantation in Italy in the presence of severe bio- chemical abnormalities (albumin ~3.0 g/dl, prothrom- bin time over 3 seconds longer than controls, conjugat- ed bilirubin >60 umol/l) and encephalopathy. All cen- tres stressed the need to assess the primary disease ac- curately in order to rule out locally-invasive tumours or metastatic extrahepatic malignancies which may be re- sponsible for hepatic vein obstruction. Most centres recommend that patients with the fulminant form of Budd-Chiari syndrome or cirrhosis should undergo liv- er transplantation while those with acute or subacute forms of the disease may undergo portosystemic de- compressive procedures.

Fulminant hepatic failure

Although the need for transplantation can be identified by specific scoring systems, the usefulness of these pa- rameters is debatable and they are not always strictly and uniformly applied by the centres. Only a few centres monitor the intracranial pressure as a prognostic index.

Zndications In Italy, liver transplantation for fulminant hepatic liv- er failure is reserved for patients under 55 years of age. Currently, all centres follow the policy of performing liver transplantation for fulminant hepatic failure in no more than 5 cases a year and obtaining the best possi- ble match between donor and recipient. However, it was suggested that patients with fulminant hepatic fail- ure should preferably be sent to one or a few transplant centres particularly qualified to deal with this particu- lar clinical situation. There is general agreement to in- dicate liver transplantation for most forms of fulminant hepatic, e.g. viral, autoimmune, Wilson disease, toxic damage (drugs, Amanita phalloides), with the exclu- sion of active drug-addicts.

Drug addiction

Active drug addiction is an absolute contraindication to liver transplantation due to lack of compliance and the risk of HIV infection. HIV infection is currently re- garded by all Italian centres as an absolute contraindi- cation. Although there was some controversy as to whether patients who are asymptomatic and have nor-

mal T cell subsets can be listed for transplantation, in practice the shortage of donors excludes these patients. Those patients who are no longer drug-addicts and are HIV seronegative may be considered for liver trans- plantation. Selection, in this case, is based primarily on psychiatric evaluation, to exclude primary psychiatric disorders or latent dependence.

Candidate selection Abstinence from drugs for at least one year is required in the majority of centres. In a few centres, the required duration of abstinence is longer, i.e., at least two years. It is considered important for the patient to take an ac- tive part in self-help groups or join specific drug ad- diction centres. It is also considered important to have a report from psychiatric and social workers involved in the psycho-social treatment of the patient, to estab- lish the likelihood of long-term abstinence and ade- quate compliance.

Post-transplantation follow-up In the majority of centres, there are no specific follow- up programmes for patients who were drug-dependent before transplantation. In a few centres attention is paid to the use of structured interviews to monitor patients after liver transplantation. These centres reported a pos- itive outcome of transplantation in patients selected on the basis of strict medical and psychiatric criteria.

Retransplantation

Retransplantation has only been carried out in the fol- lowing indications: 1) primary non-function of the graft; 2) hyperacute rejection; 3) vascular thrombosis, 4) chronic rejection; and 5) selected disease recur- rence, as specified below.

Recurrence of cholestatic liver disease The rare recurrence of cholestatic liver diseases (PBC, PSC, ACAH) is not a contraindication for liver re- transplantation.

Alcohol recidivism and recurrent neoplasm Retransplantation is not considered in either of these conditions.

Recurrence of Budd-Chiari syndrome The experience in this setting is very limited.

Paediatric liver transplantation

The indications for paediatric liver transplantation have continued to expand in all Italian centres and are

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usually divided into the following categories: chronic cholestatic liver disease (which accounts for at least two-thirds of the indications); inborn metabolic errors; acute hepatocellular injury; space-occupying lesions; miscellaneous. The transplantation of a donor liver to two recipients (split transplantation) is a new application in the fur- ther development of liver transplantation in children and adults in our Country. Chronic cholestatic liver disease In Italy, more than 60% of paediatric liver transplants have been per- formed in children with biliary atresia. The onset of primary liver malignancy is an important consideration in determining the best timing for transplantation. Alagille’s syndrome accounts for about 2% of the cas- es in which paediatric liver transplantation is indicated in Italy; Caroli’s disease accounts for less than 1% of paediatric liver transplantations in Italy, while PSC is responsible for about 2% of cases. Inborn errors of the metabolism In Italian centres, 3% of liver transplants performed in children are due to in- born metabolic errors. Acute hepatocellular injury Less than 5% of the liver transplants performed in children, in Italy, are for ful- minant hepatic failure. Space-occupying lesions In a very few cases, benign and malignant lesions of the liver have prompted liver transplantation in children. Miscellaneous Patients with end-stage liver disease due to cystic fibrosis are considered suitable candi- dates for liver transplantation provided the degree of pulmonary involvement is minimum.

Candidate selection protocol

Each transplant centre usually follows its own protocol in evaluating patients for liver transplantation. Most of the stages involved are the same at the various centres and differences depend on the specific interest of the single centre or on its cooperation with specialized units which have developed more sophisticated diagnostic techniques that are not available all over the Country.

Waiting list management

A better and more transparent management of the wait- ing list has emerged as a critical issue; the need for a common approach is approved by all centres. At pre- sent, there are several differences between Italian cen- tres in the way they manage their waiting list, due, in part, to the use of different admission criteria. The ma- jor issue concerns the definition of standardized crite- ria to determine the priority of patients listed for liver

transplantation. This implies ethical, deontological and legal aspects. It is necessary to establish guidelines to be used in all centres and a computerized data base to provide clinical data on all patients listed in Italy in re- al time, enabling rapid connections and the exchange of information. Italian patients are too often evaluated by more than one transplant centre and it is not rare for them to be placed on more than one list. It was sug- gested that listed patients should be provided with a listing certificate considered as valid all over the Coun- try, to avoid useless duplications and wasting of time and resources. The following specific recommendations were made: 1) A plausible length of each waiting list should be de-

termined in order to offer all these patients joining a list a genuine chance of being transplanted. Most waiting lists in Italy currently vary between 20 and 50 patients, but there are a few much lengthier ex- ceptions. It is recommended that the length of each list, at any time, be related to (and be a function of) the actual number of transplants performed by the centre concerned each year.

2) In most, but not all, Italian centres the waiting list is managed in close conjunction, both by transplant surgeons and hepatologists. However, their respec- tive roles need to be better defined, together with their individual responsibilities and the criteria adopted in list management, in order to guarantee respect for ethical issues and the legal rights of pa- tients and doctors.

3) At present, there is a considerable lack of homo- geneity nationwide in the definition of priority for transplantation. Some centres give priority to pa- tients presenting in the worst clinical conditions, others to patients in the conditions most likely to ensure the best results, and a few to those who rapidly develop life-threatening complications, such as HCC. Clearly, all centres must use common disease severity scores in the follow-up of listed pa- tients. Though many centres have adopted the Unit- ed Network for Organ Sharing (UNOS) scoring system, the development of an Italian Priority Score, better suited to the specific situation in Italy, seems advisable. In addition, minimal criteria for listing, specific for the situation in Italy, should be defined.

4) Mortality rates and the average time spent on the waiting list vary considerably between Italian liver transplant centres. Mortality is reported by most centres to vary from 10 to 20%, largely reflecting the patients’ Child-Pugh score at the time of listing, but no precise data are available. The average wait- ing time is often stated to be approximately one year, but there are considerable variations between centres. This again strongly supports the need to

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adopt common rules in defining criteria for listing and for attributing priority.

Liver transplantation outside Italy

The current national laws regulating the possible ad- mission of Italian patients to transplant-related health services in other countries in the European Commu- nity appear to be largely inadequate today, due to the growing number of transplant candidates in Italy and the other European countries, the dramatic reduction in the willingness of most foreign centres to accept patients from Italy and the greater costs involved in liver transplantation outside Italy. The present laws came into force years ago, when the number of transplants performed each year in Italy was far lower than it is now. The law essentially states that any patient who has been on an Italian waiting list for liver transplant for more than 3 months (one month in the case of HCC) has the right, at his/her own request, to obtain a transplant abroad (within the European Community) at the expense of the National Health Service. The Regional Referral Centre should check the existence of the essential requirements for each candidate. Since the average waiting time in Italy is far longer than three months, most Italian pa- tients listed for transplant will ask to go abroad, while fewer and fewer European centres are currently ac- cepting them. A proposal to update this law is clearly needed. Another complicating issue is that, until re- cently, the Regional Referral Centre was not always coincident with an authorized transplant centre.

The new Italian laws on organ donation

Despite the considerable differences from one region to another, the number of organ donations is current- ly much lower in Italy, as a whole, than in most West- ern European countries. The average number of donors is approximately 12 per million inhabitants, compared with a European average of 15 per million. To overcome this important problem, which prevents the proper development of organ transplantation pro- grammes, a new law governing organ donation has re- cently been passed by the Italian Parliament (April 1999). In the past, the explantation of organs was not allowed, in Italy, without explicit permission from the close relatives of any potential donor. This rule has been modified by the new law, with the introduction of a so-called “presumed consent”, already adopted in many European countries. This enables the explan- tation of organs from any deceased person who has not specifically manifested his/her dissent in life. Ac-

cording to this principle, the Italian central adminis- tration will invite all citizens to declare in writing whether they consent to their organs being donated after their death. The lack of any written reply will be considered as a declaration of consent. The law has also designed a better system for coordinating Italian transplantation programmes, introducing regional re- ferral centres and a Transplant Centre at the Superior Institute of Health, which should define common guidelines for implementation nationwide and exert a quality control on single local centres. This is partic- ularly important in Italy due to the vast differences in the efficiency of transplant centres, which only par- tially reflects the different organ donation rates around the country. In fact, there are too many differ- ences in the actual evaluation to be listed, waiting times, mortality and morbidity on the waiting list, and post-transplantation management and outcome. The new law, which, unfortunately, has yet to be put into effect, is expected to contribute towards raising the number of organ donations and thus overcome some of the above problems.

Conclusions

The aim of the multidisciplinary AISF Study Group on Liver Transplantation was to compare the experi- ence of liver transplant centres in Italy. This effort has brought to light concordant attitudes on some issues, but also revealed many discordant aspects in the poli- cies adopted in the different centres. There is widespread agreement concerning the age of candidates and the indications for and management of patients with alcoholic, HBV-related, cholestatic and metabolic liver diseases, or fulminant hepatic failure, and the paediatric indications for transplanta- tion. On the other hand, there is no consensus con- cerning liver transplantation in HCV-related, end- stage liver disease, particularly as regards the man- agement of post-transplant disease recurrence. Nor was any consensus found concerning the manage- ment of patients with HCC. The work of the Study Group also brought to light a number of problems regarding the organization, pro- gramming and management of transplantation activi- ties. These problems stress the need to improve the global organ donation system in many parts of the country - particularly in the South and also, to some degree, in Central Italy - and to achieve a better mod- el of organization at many centres and adopt an effi- cient system for monitoring the quality of each liver transplant centre. It is hoped that the implementation of the new law on organ donations will contribute to- wards overcoming at least some of these problems.

Eqm-ience of liver transplant centres in Italy

Italian Association for the Study of the Liver - Study Group on Liver Transplantation

Bat-i: A. Francavilla, V. Memeo, M. Rendina, L. Lupo

Bergamo: B. Gridelli

Bologna: C. Sama, C. Morelli, G.L. Grazi, G. Ercolani, B. Begliomini, l? Andreone, P Caraceni, S. De Notariis

Brescia: D. Alberti

Genoa: G. Dardano, E. Andorno, M. Bertocchi, G. Ardizzone

Milan Ospedale Niguarda: G. Ideo, D. Forti, G. Bellati, L. Belli, A.B. Alberti, S.A. Omar, G. Colella, G.F. Rondinara, A. De Gasperi, G. Pinzello

Milan Policlinico: L.R. Fassati, L. Caccamo

Milan Istituto Tumori: V. Mazzaferro, E. Regalia, A. Pulvirenti, R. Romito

Naples Ospedale Cardarelli: F. Calise, E. Di Florio,

F. P. Picciotto, G.G. Di Costanzo

Naples Policlinico Federico II: G. Belli, P. Amoroso

Padua: U. Tedeschi, G. Gerunda, F. Fagiuoli, R.M. Iemmolo, U. Cillo, R. Merenda, G. Guariso

Pisa: F. Filipponi, F. Cellai, G. Biancofiore

Rome Policlinico Gemelli: S. Agnes, M. Foco, A. Avo- lio, S. Magalini, A. Gasbarrini, M. Pompili, G.L. Ra- paccini, L. Sollazzi

Rome S. Eugenio Tor Vergata: G. Tisone, M. Dauri

Rome Policlinico Umberto I: R. Cortesini, D. Alfani*, M. Rossi

Turin: M. Salizzoni, A. Franchello, A. Marzano, E. Cerutti, F. Zamboni, F. Gennari

Udine: A. Risaliti, A. Uzzau, M. Pirisi, G. Soardo

* Professor Dario Alfani unfortunately passed away on January 4, 1999.

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