Indikationen zur Lebertransplantation beim chronischen Leberversagen

Zusammenfassung

Durch die operative Entfernung einer chronisch geschädigten Leber und die Implantation einer gesunden Spenderleber können das Überleben und die Lebensqualität der betroffenen Patienten wesentlich gebessert werden. Die Lebertransplantation ist für das lebensbedrohliche akute und chronische Leberversagen derzeit die einzig langfristig erfolgreiche therapeutische Option. Dies gilt auch für einige genetisch bedingte Stoffwechselerkrankungen. Die 5-Jahres-Überlebenszeit liegt bei 70 % und führt bei drei von vier Transplantierten zu einem weitgehend normalen Leben mit Wiedereingliederung in den Arbeitsprozess. Nachteile dieses Verfahrens sind die lebenslange Abhängigkeit von Medikamenten und ärztlicher Betreuung sowie das mit der Transplantation und der dauerhaften Immunsuppression verbundene Risiko von Komplikationen oder Nebenwirkungen. Insbesondere in den ersten drei Monaten nach Operation sind eine erhöhte Mortalität und Morbidität gegeben. Diese Nachteile und die limitierte Verfügbarkeit von Spenderorganen erfordern die Ausschöpfung aller konservativer Maßnahmen, bevor bei deren Versagen die Indikation zur Lebertransplantation gestellt werden sollte. Umgekehrt darf die Indikation nicht zu spät gestellt werden, um die Erfolgsaussichten der Operation nicht zu schmälern. Genaue Kenntnisse der Prognose einer chronischen Lebererkrankung und ihre Beeinflussung durch konservative Therapiemaßnahmen sind erforderlich, die korrekte Indikation zur Lebertransplantation und deren Zeitpunkt festzulegen.

Abstract

Surgical resection of the diseased liver together with the implantation of a new donor organ allows patients with chronic liver failure to survive longer as well as to achieve a better quality of life. In life-threatening acute and chronic hepatic failure liver transplantation represents the only causal and long-term therapeutic option. This is also true for several genetically defined liver diseases. Five-year survival approaches 70 % in most cases. Three of four patients regain a nearly normal life with complete reintegration into their professional work. Drawbacks of this therapeutic option relate to a life-long dependence on drugs and medical services as well as to the risks associated with the surgical procedure and the side-effects of a continuous drug-induced immunosuppression. Mortality and morbidity are considerably increased during the first three months after operation. These limitations and the dramatically low availability of donor organs necessitate the application of all conservative measures before a transplantation procedure should be performed. However, the surgical option should be evaluated early enough to allow for a good chance of success. Profound knowledge of prognosis and medical treatment of each individual liver disease is a prerequisite for correct indication and timing of liver transplantation.

Schlüsselwörter

Lebertransplantation - chronische Leberkrankheiten - Leberversagen - chronische Hepatitis - Leberzirrhose - Indikation zur Lebertransplantation

Key words

Liver transplantation - chronic liver disease - liver failure - chronic hepatitis - liver cirrhosis - indication for liver transplantation

Literatur

• 1 Adam R, Cailliez V, Majno P. et al . Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study.  Lancet. 2000;  356 621-627
• 2 Adams P C, Ghent C N, Grant D R. et al . Employment after liver transplantation.  Hepatology. 1995;  21 140-144
• 3 Reich D J, Fiel I, Guarrera J V. et al . Liver transplantation for autoimmune hepatitis.  Hepatology. 2000;  32 693-700
• 4 Ratziu V, Samuel D, Sebagh M. et al . Long-term follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease.  J Hepatol. 1999;  30 131-141
• 5 Manns M P, Bahr M J. Recurrent autoimmune hepatitis after liver transplantation - when non-self becomes self.  Hepatology. 2000;  32 868-70
• 6 Bresson-Hadni S, Koch S, Beurton I. et al . Primary disease recurrence after liver transplantation for alveolar echinococcosis: long-term evaluation in 15 patients.  Hepatology. 1999;  30 857-64
• 7 Washburn W K, Johnson L B, Lewis W D. et al . Liver transplantation for adult polycystic liver disease.  Liver Transpl Surg. 1996;  2 17-22
• 8 Swenson K, Seu P, Kinkhabwala M. et al . Liver transplantation for adult polycystic liver disease.  Hepatology. 1998;  28 412-415
• 9 Kugelmas M. Budd-Chiari syndrome. Treatment options and the value of liver transplantation.  Hepatogastroenterology. 1998;  45 1381-1386
• 10 Hemming A W, Langer B, Greig P. et al . Treatment of Budd-Chiari syndrome with portosystemic shunt or liver transplantation.  Am J Surg. 1996;  171 176-180
• 11 Vennarecci G, Gunson B K, Ismail T. et al . Transplantation for end stage liver disease related to alpha 1 antitrypsin.  Transplantation. 1996;  61 1488-1495
• 12 Bloomer J R, Rank J M, Payne W D. et al . Follow-up after liver transplantation for protoporphyric liver disease.  Liver Transpl Surg. 1996;  2 269-275
• 13 Lock G, Holstege A, Mueller A R. et al . Liver failure in erythropoietic protoporphyria associated with choledocholithiasis and severe post-transplantation polyneuropathy.  Liver. 1996;  16 211-217
• 14 Consensus statement on indications for liver transplantation: Paris, June 22-23.1993.  Hepatology. 1994;  20 (Suppl.) 63S-68S
• 15 Springer J, Cauch-Dudek K, O’Rourke K. et al . Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis.  Am J Gastroenterol. 1999;  94 47-53
• 16 Nijhawan P K, Therneau T M, Dickson E R. et al . Incidence of cancer in primary biliary cirrhosis: the Mayo experience.  Hepatology. 1999;  29 1396-1398
• 17 Floreani A, Baragiotta A, Baldo V. et al . Hepatic and extrahepatic malignancies in primary biliary cirrhosis.  Hepatology. 1999;  29 1425-1428
• 18 Leuschner M, Dietrich C F, You T. et al . Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment.  Gut. 2000;  46 121-126
• 19 Jorgensen R A, Dickson E R, Hofmann A F. et al . Characterisation of patients with a complete biochemical response to ursodeoxycholic acid.  Gut. 1995;  36 935-938
• 20 Lindor K D, Jorgensen R A, Therneau T M. et al . Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis.  Mayo Clin Proc. 1997;  72 1137-1140
• 21 Angulo P, Batts K P, Therneau T M. et al . Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis.  Hepatology. 1999;  29 644-647
• 22 Degott C Zafrani ES, Callard P. et al . Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression.  Hepatology. 1999;  29 1007-1012
• 23 Combes B, Markin R S, Wheeler D E. et al . The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis.  Hepatology. 1999;  30 602-605
• 24 Poupon R E Lindor KD, Cauch-Dudek K. et al . Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis.  Gastroenterology. 1997;  113 884-890
• 25 Poupon R E Bonnand AM, Chretien Y. et al . Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group.  Hepatology. 1999;  29 1668-1671
• 26 Böker K HW, Holstege A, Manns M. et al .Leberkrankheiten. Classen M, Dierkesmann R, Heimpel H et al Rationelle Diagnostik und Therapie in der Inneren Medizin, Leitlinien 2001 München, Jena; Verlag Urban & Fischer 2001 Kapitel A7: 1-22
• 27 Angulo P, Dickson E R. The timing of liver transplantation in primary biliary cirrhosis.  Baillieres Best Pract Res Clin Gastroenterol. 2000;  14 657-668
• 28 Benhamou J P. Indications for liver transplantation in primary biliary cirrhosis.  Hepatology. 1994;  20 (Suppl.) 11S-13S
• 29 Gross C R, Malinchoc M, Kim W R. et al . Quality of life before and after liver transplantation for cholestatic liver disease.  Hepatology. 1999;  29 356-364
• 30 Eastell R, Dickson E R, Hodgson S F. et al . Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.  Hepatology. 1991;  14 296-300
• 31 Jones D E, James O F, Portmann B. et al . Development of autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.  Hepatology. 1999;  30 53-57
• 32 Balan V, Batts K P, Porayko M K. et al . Histological evidence for recurrence of primary biliary cirrhosis after liver transplantation.  Hepatology. 1993;  18 1392-1398
• 33 Gouw A S, Haagsma E B, Manns M. et al . Is there recurrence of primary biliary cirrhosis after liver transplantation? A clinicopathologic study in long-term survivors.  J Hepatol. 1994;  20 500-507
• 34 Klion F M, Fabry T L, Palmer M. et al . Prediction of survival of patients with primary biliary cirrhosis. Examination of the Mayo Clinic model on a group of patients with known endpoint.  Gastroenterology. 1992;  102 310-313
• 35 Dickson E R, Grambsch P M, Fleming T R. et al . Prognosis in primary biliary cirrhosis: model for decision making.  Hepatology. 1989;  10 846-850
• 36 Kilmurry M R, Heathcote E J, Cauch-Dudek K. et al . Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis?.  Hepatology. 1996;  23 1148-1153
• 37 Murtaugh P A, Dickson E R, Van Dam G M. et al . Primary biliary cirrhosis: prediction of short-term survival based on repeated patient visits.  Hepatology. 1994;  20 126-134
• 38 Markus B H, Dickson E R, Grambsch P M. et al . Efficiency of liver transplantation in patients with primary biliary cirrhosis.  N Engl. J Med. 1989;  320 1709-1713
• 39 Kim W R, Wiesner R H, Therneau T M. et al . Optimal timing of liver transplantation for primary biliary cirrhosis.  Hepatology. 1998;  28 33-38
• 40 Chalasani N, Baluyut A, Ismail A. et al . Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.  Hepatology. 2000;  31 7-11
• 41 Harnois D M, Gores G J, Ludwig J. et al . Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer?.  J Hepatol. 1997;  27 512-516
• 42 Bergquist A, Glaumann H, Persson B. et al . Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study.  Hepatology. 1998;  27 311-316
• 43 Marchesa P, Lashner B A, Lavery I C. et al . The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis.  Am J Gastroenterol. 1997;  92 1285-1288
• 44 Shetty K, Rybicki L, Brzezinski A. et al . The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis.  Am J Gastroenterol. 1999;  94 1643-1649
• 45 Lindor K D. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group.  N Engl J. 1997;  336 691-695
• 46 Lee J G, Schutz S M, England R E. et al . Endoscopic therapy of sclerosing cholangitis.  Hepatology. 1995;  21 661-667
• 47 Stiehl A, Rudolph G, Sauer P. et al . Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study.  J Hepatol. 1997;  26 560-566
• 48 Graziadei I W, Wiesner R H, Batts K P. et al . Recurrence of primary sclerosing cholangitis following liver transplantation.  Hepatology. 1999;  30 1121-1127
• 49 Papatheodoridis G V, Hamilton M, Mistry P K. et al . Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis.  Gut. 1998;  43 639-644
• 50 Mitchell S A, Chapman R WG. The management of primary sclerosing cholangitis.  lin Liver Dis. 1998;  2 353-372
• 51 Loftus E V Jr, Aguilar H I, Sandborn W J. et al . Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation.  Hepatology. 1998;  27 685-690
• 52 Dickson E R, Murtaugh P A, Wiesner R H. et al . Primary sclerosing cholangitis: refinement and validation of survival models.  Gastroenterology. 1992;  103 1893-1901
• 53 Kim W R, Lindor K D, Poterucha J J. et al . The Mayo risk score increases rapidly in the terminal phase of primary sclerosing cholangitis.  Gastroenterology. 1998;  114 A1274
• 54 Kim W R, Poterucha J J, Wiesner R H. et al . The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis.  Hepatology. 1999;  29 1643-1648
• 55 Neuberger J, Gunson B, Komolmit P. et al . Pretransplant prediction of prognosis after liver transplantation in primary sclerosing cholangitis using a Cox regression model.  Hepatology. 1999;  29 1375-1379
• 56 Jilg W, Hottentrager B, Weinberger K. et al . Prevalence of markers of hepatitis B in the adult German population.  J Med Virol. 2001;  63 96-102
• 57 Garcia G, Petrovic L M, Vierling J M. Overview of hepatitis B and transplantation in the hepatitis B patient.  Sem Liver Dis. 2000;  20 (Suppl. 1) 3-6
• 58 de Jongh F E, Janssen H L, de Man R A. et al . Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver.  Gastroenterology. 1992;  103 1630-1635
• 59 Villeneuve J P, Condreay L D, Willems B. et al . Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.  Hepatology. 2000;  31 207-210
• 60 Honkoop P, de Man R A, Niesters H G. et al . Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy.  Hepatology. 2000;  32 635-639
• 61 Grellier L, Mutimer D, Ahmed M. et al . Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis.  Lancet. 1996;  348 1212-1215
• 62 Bain V G, Kneteman N M, Ma M M. et al . Efficacy of lamivudine in chronic hepatitis B patients with active viral replication and decompensated cirrhosis undergoing liver transplantation.  Transplantation. 1996;  27; 62 1456-1462
• 63 Marcellin P, Samuel D, Areias J. et al . Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease.  Hepatology. 1994;  19 6-12
• 64 Colquhoun S D, Belle S H, Samuel D. et al . Transplantation in the Hepatitis B patient and current therapies to prevent recurrence.  Sem Liver Dis. 2000;  20 (Suppl. 1) 7-12
• 65 Samuel D, Müller R, Alexander G. et al . Liver transplantation in European patients with the hepatitis B surface antigen.  N Engl J Med. 1993;  329 1842-1847
• 66 Müller R, Samuel D, Fassati L R. et al . ‘EUROHEP’ consensus report on the management of liver transplantation for hepatitis B virus infection. European Concerted Action on Viral Hepatitis.  J Hepatol. 1994;  21 1140-1143
• 67 Samuel D, Zignego A L, Reynes M. et al . Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis.  Hepatology. 1995;  21 333-339
• 68 Palitzsch K D, Hottentrager B, Schlottmann K. et al . Prevalence of antibodies against hepatitis C virus in the adult German population.  Eur J Gastroenterol Hepatol. 1999;  11 1215-1220
• 69 Seeff L B. The natural history of chronic hepatitis C virus infection.  Clin Liver Dis. 1997;  1 587-602
• 70 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.  Lancet. 1997;  349 825-832
• 71 Consensus statement . EASL international consensus conference on hepatitis C.  J Hepatol. 1999;  30 956-961
• 72 Fattovich G, Giustina G, Degos F. et al . Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.  Gastroenterology. 1997;  112 463-472
• 73 Manns M P, McHutchison J G, Gordon S C. et al . Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.  Lancet. 2001;  358 958-965
• 74 Zeuzem S, Feinman S V, Rasenack J. et al . Peginterferon alfa-2a in patients with chronic hepatitis C.  N Engl J Med. 2000;  343 1666-1672
• 75 Heathcote E J, Shiffman M L, Cooksley W G. et al . Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.  N Engl J Med. 2000;  343 1673-1680
• 76 Poynard T, McHutchison J, Davis G L. et al . Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C.  Hepatology. 2000;  32 1131-1137
• 77 Shiratori Y, Imazeki F, Moriyama M. et al . Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy.  Ann Intern Med. 2000;  132 517-524
• 78 Prieto M, Berenguer M, Rayon J M. et al . High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes.  Hepatology. 1999;  29 250-259
• 79 Berenguer M, Prieto M, Rayon J M. et al . Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation.  Hepatology. 2000;  32 635-639
• 80 Charlton M, Seaberg E, Wiesner R. et al . Predictors of patient and graft survival following liver transplantation for hepatitis C.  Hepatology. 1998;  28 852-858
• 81 Sreekumar R, Gonzalez-Koch A, Maor-Kendler Y. et al . Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation.  Hepatology. 2000;  32 1125-1130
• 82 Pelletier S J, Raymond D P, Crabtree T D. et al . Hepatitis C-induced hepatic allograft injury is associated with a pretransplantation elevated viral replication rate.  Hepatology. 2000;  32 418-426
• 83 Pelletier S J, Raymond D P, Crabtree T D. et al . Pretransplantation hepatitis C virus quasispecies may be predictive of outcome after liver transplantation.  Hepatology. 2000;  32 375-381
• 84 Gane E J, Portmann B C, Naoumov N V. et al . Long-term outcome of hepatitis C infection after liver transplantation.  N Engl J Med. 1996;  334 815-820
• 85 Younoussi Z M. Epidemiology of alcohol-induced liver disease.  Clin Liver Dis. 1998;  2 661-671
• 86 Mullen K D, Dasarathy S. Potential new therapies for alcoholic liver disease.  Clin Liver Dis. 1998;  2 851-881
• 87 Pares A, Caballeria J, Bruguera M. et al . Histological course of alcoholic hepatitis. Influence of abstinence, sex and extent of hepatic damage.  J Hepatol. 1986;  2 33-42
• 88 Höckerstedt K. Liver transplantation in alcohol liver disease.  EASL-Meeting, Prague. 2001; 
• 89 Poynard T, Barthelemy P, Fratte S. et al . Evaluation of efficacy of liver transplantation in alcoholic cirrhosis by a case-control study and simulated controls.  Lancet. 1994;  344 502-507
• 90 Poynard T, Naveau S, Doffoel M. et al . Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival. Multi-centre group.  J Hepatol. 1999;  30 1130-1137
• 91 Sherman D, Williams R. Liver transplantation for alcoholic liver disease.  J Hepatol. 1995;  23 474-479
• 92 Conjeevaram H S, Hart J, Lissoos T W. et al . Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients.  Transplantation. 1999;  67 1562-1568
• 93 Lucey M R, Carr K, Beresford T P. et al . Alcohol use after liver transplantation in alcoholics: a clinical cohort follow-up study.  Hepatology. 1997;  25 1223-1227
• 94 Platz K P, Mueller A R, Spree E. et al . Liver transplantation for alcoholic cirrhosis.  Transpl Int. 2000;  13 (Suppl. 1) S127-S130
• 95 Osorio R W, Ascher N L, Avery M. et al . Predicting recidivism after orthotopic liver transplantation for alcoholic liver disease.  Hepatology. 1994;  20 105-110
• 96 Foster P F, Fabrega F, Karademir S. et al . Prediction of abstinence from ethanol in alcoholic recipients following liver transplantation.  Hepatology. 1997;  25 1469-1477
• 97 Anand A C, Ferraz-Neto B H, Nightingale P. et al . Liver transplantation for alcoholic liver disease: evaluation of a selection protocol.  Hepatology. 1997;  25 1478-1484
• 98 Burke A, Lucey M R. Liver transplantation for alcoholic liver disease.  Clin Liver Dis. 1998;  2 839-850
• 99 Lucey M R, Merion R M, Henley K S. et al . Selection for and outcome of liver transplantation in alcoholic liver disease.  Gastroenterology. 1992;  102 1736-1741
• 100 Ferenci P. Wilson`s disease.  Clin Liver Dis. 1998;  1 31-49
• 101 Stremmel W, Meyerrose K W, Niederau C. et al . Wilson disease: clinical presentation, treatment, and survival.  Ann Intern Med. 1991;  115 720-726
• 102 Santos S ilva EE, Sarles J, Buts J P. et al . Successful medical treatment of severely decompensated Wilson disease.  J Pediatr. 1996;  128 285-287
• 103 Durand F, Bernuau J, Giostra E. et al . Wilson’s disease with severe hepatic insufficiency: beneficial effects of early administration of D-penicillamine.  Gut. 2001;  48 849-852
• 104 Schilsky M L, Scheinberg I H, Sternlieb I. Liver transplantation for Wilson’s disease: indications and outcome.  Hepatology. 1994;  19 583-587
• 105 Bellary S, Hassanein T, Van Thiel D H. Liver transplantation for Wilson’s disease.  J Hepatol. 1995;  23 373-381
• 106 Stracciari A, Tempestini A, Borghi A. et al . Effect of liver transplantation on neurological manifestations in Wilson disease.  Arch Neurol. 2000;  57 384-386
• 107 Niederau C, Fischer R, Purschel A. et al . Long-term survival in patients with hereditary hemochromatosis.  Gastroenterology. 1996;  110 1107-1119
• 108 Kilpe V E, Krakauer H, Wren R E. An analysis of liver transplant experience from 37 transplant centers as reported to Medicare.  Transplantation. 1993;  56 554-561
• 109 Brandhagen D J, Alvarez W, Therneau T M. et al . Iron overload in cirrhosis-HFE genotypes and outcome after liver transplantation.  Hepatology. 2000;  31 456-460
• 110 Farrell F J, Nguyen M, Woodley S. et al . Outcome of liver transplantation in patients with hemochromatosis.  Hepatology. 1994;  20 404-410
• 111 Surakomol S, Olson L J, Rastogi A. et al . Combined orthotopic heart and liver transplantation for genetic hemochromatosis.  J Heart Lung Transplant. 1997;  16 573-575
• 112 Poulos J E, Bacon B R. Liver transplantation for hereditary hemochromatosis.  Dig Dis. 1996;  14 316-322
• 113 Zoller H, Pietrangelo A, Vogel W. et al . Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis.  Lancet. 1999;  353 2120-2123
• 114 Okuda K, Ohtsuki T, Obata H. et al . Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients.  Cancer. 1985;  56 918-928
• 115 The Cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP score; a new prognostic system for patients with cirrhosil and hepatocellular carcinoma.  Hepatology. 2000;  31 840-845
• 116 Schafer D F, Sorrell M F. Hepatocellular carcinoma.  Lancet. 1999;  353 1253-1257
• 117 Yuen M F, Cheng C C, Lauder I J. et al . Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience.  Hepatology. 2000;  31 330-335
• 118 Wall W J. Liver transplantation for hepatic and biliary malignancy.  Sem Liver Dis. 2000;  20 425-436
• 119 Tanaka Y, Sasaki Y, Katayama K. et al . Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography.  Hepatology. 2000;  31 890-898
• 120 Kawamoto C, Ido K, Isoda N. et al . Prognosis of small hepatocellular carcinoma after laparoscopic ethanol injection.  Gastrointest Endosc. 1999;  50 214-220
• 121 Bruix J, Llovet J M, Castells A. et al . Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.  Hepatology. 1998;  27 1572-1577
• 122 McPeake J R, O’Grady J G, Zaman S. et al . Liver transplantation for primary hepatocellular carcinoma: tumor size and number determine outcome.  J Hepatol. 1993;  18 226-234
• 123 Hemming A W, Cattral M S, Reed A I. et al . Liver transplantation for hepatocellular carcinoma.  Ann Surg. 2001;  233 652-658
• 124 Mazzaferro V, Regalia E, Doci R. et al . Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis.  N Engl J Med. 1996;  334 693-700
• 125 Yao F Y, Ferrell L, Bass N M. et al . Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.  Hepatology. 2001;  33 1394-1403
• 126 Arii S, Yamaoka Y, Futagawa S. et al . Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan.  Hepatology. 2000;  32 1224-1229
• 127 Llovet J M, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation.  Hepatology. 1999;  30 1434-1440
• 128 Majno P E, Sarasin F P, Mentha G. et al . Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis.  Hepatology. 2000;  31 899-906
• 129 Ikeda K, Arase Y, Saitoh S. et al . Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer.  Hepatology. 2000;  32 228-232
• 130 Takayama T, Sekine T, Makuuchi M. et al . Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.  Lancet. 2000;  356 802-807
• 131 Muto Y, Moriwaki H, Saito A. Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma.  N Engl J Med. 1999;  340 1046-1047
• 132 Oldhafer K J, Chavan A, Fruhauf N R. et al . Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?.  J Hepatol. 1998;  29 953-959
• 133 Bruix J, Llovet J M, Castells A. et al . Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.  Hepatology. 1998;  27 1578-1583
• 134 Stieber A C, Gordon R D, Galloway J R. Orthotopic liver transplantation. Zakim D, Boyer TD Hepatology. A textbook of liver disease Philadelphia; W.B. Saunders Company 1996 Kap. 60: 1759-1780
• 135 Arguedas M R, McGuire B M, Fallon M B. et al . The use of screening and preventive therapies for gastroesophageal varices in patients referred for evaluation of orthotopic liver transplantation.  Am J Gastroenterol. 2001;  96 833-837
• 136 Bayraktar Y, Bayraktar M, DeMaria N. et al . The cardiac evaluation of liver transplant recipients: a single center’s experience.  Ital J Gastroenterol Hepatol. 1997;  29 162-167
• 137 Krowka M J, Frantz R P, McGoon M D. et al . Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.  Hepatology. 1999;  30 641-648
• 138 Stoller J K, Moodie D, Schiavone W A. et al . Reduction of intrapulmonary shunt and resolution of digital clubbing associated with primary biliary cirrhosis after liver transplantation.  Hepatology. 1990;  11 54-58
• 139 Poterucha J J, Krowka M J, Dickson E R. et al . Failure of hepatopulmonary syndrome to resolve after liver transplantation and successful treatment with embolotherapy.  Hepatology. 1995;  21 96-100
• 140 Perseghin G, Mazzaferro V, Sereni L P. et al . Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: effect of liver transplantation.  Hepatology. 2000;  31 694-703
• 141 Richtlinien zur Organtransplantation gemäß § 16 Transplantationsgesetz.  Deutsch Ärzteblatt. 2000;  97 B352-B367
• 142 Infante-Rivard C, Esnaola S, Villeneuve J P. Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics.  Hepatology. 1987;  7 660-664
• 143 Oellerich M, Burdelski M, Lautz H U. et al . Predictors of one-year pretransplant survival in patients with cirrhosis.  Hepatology. 1991;  14 1029-1034
• 144 Holstege A, Staiger M, Haag K. et al . Correlation of caffeine elimination and Child’s classification in liver cirrhosis.  Klin Wochenschr. 1989;  67 6-15
• 145 D’Amico G, Morabito A, Pagliaro L. et al . Survival and prognostic indicators in compensated and decompensated cirrhosis.  Dig Dis Sci. 1986;  31 468-475
• 146 Kamath P S, Wiesner R H, Malinchoc M. et al . A model to predict survival in patients with end-stage liver disease.  Hepatology. 2001;  33 464-470