Download PDF
Gastroenterologie up2date 2007; 3(2): 115-132
DOI: 10.1055/s-2007-966621
Leber/Galle/Pankreas

© Georg Thieme Verlag Stuttgart · New York

Aktuelle Diagnostik und Therapie des hepatozellulären Karzinoms

Christa-Maria  Behrens, Wolfgang  E.  Fleig
Further Information

Publication History

Publication Date:
06 July 2007 (online)

Also available at
    Permissions and Reprints All articles of this category

Kernaussagen

Epidemiologie

  • Das hepatozelluläre Karzinom gehört weltweit zu den häufigsten malignen Tumorerkrankungen und gewinnt durch steigende Inzidenzraten auch in den westlichen Industrieländern an Bedeutung.

Risikofaktoren und Früherkennung

  • In den Risikogruppen der Patienten mit hochaktiver Virushepatitis B und C sowie mit einer Leberzirrhose jedweder Genese führt eine Überwachung durch halbjährliche Bestimmung des AFP und abdominellen Ultraschall zur frühzeitigeren Entdeckung kleiner HCC-Knoten und damit zu besseren Therapieoptionen.

Therapie

  • Die potenziell kurativen Therapieoptionen mit guter Prognose - wie chirurgische Resektion, Lebertransplantation und lokal ablative Therapie wie RFTA, PEI und TACE - stehen für den überwiegenden Teil der Patienten, bei denen die Erkrankung erst in einem fortgeschrittenen Stadium diagnostiziert wird, nicht mehr zur Verfügung.

  • Unter einem palliativen Aspekt kann bei nicht zu großem Tumor, fehlenden Hinweisen für eine Gefäßinvasion sowie guter Leberfunktion die TACE lebensverlängernd wirken.

  • Darüber hinaus gibt es für Patienten mit lokal fortgeschrittenem, multifokalem oder metastasiertem HCC trotz zahlreicher Studien zur systemischen Chemotherapie, Hormontherapie und Immunmodulation bisher keine etablierte Therapie mit gesicherter Wirksamkeit.

  • Eine besondere Herausforderung und Hoffnung liegt deshalb in der weiteren Erforschung der molekularen Pathogenese und entsprechender zielgerichteter Therapien, um auch Patienten in fortgeschrittenen Tumorstadien eine effiziente und verträgliche Behandlungsoption bieten zu können.

  • Grundsätzlich sollten Patienten mit HCC in allen Stadien wegen der Komplexität der oft interdisziplinären Therapieentscheidungen in Zentren vorgestellt und möglichst in Studien behandelt werden.

Literatur

  • 1 Bosch F X, Ribes J, Diaz M. et al . Primary liver cancer: Worldwide incidence and trends.  Gastroenterology. 2004;  127 5-16
    PubMedSearch in Google Scholar
  • 2 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
    CrossrefPubMedSearch in Google Scholar
  • 3 Benvegnù L, Gios M, Boccato S. et al . Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications.  Gut. 2004;  53 744-749
    CrossrefPubMedSearch in Google Scholar
  • 4 Davila J A, Morgan R O, Shaib Y. et al . Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study.  Gastroenterology. 2004;  127 1372-1380
    CrossrefPubMedSearch in Google Scholar
  • 5 Donato F, Bofetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma.  Int J Cancer. 1998;  75 347-354
    CrossrefPubMedSearch in Google Scholar
  • 6 Fattovich G, Stroffolini T, Zagni I. et al . Hepatocellular carcinoma in cirrhosis: incidence and risk factors.  Gastroenterology. 2004;  127 (Suppl. 1) 35-50
    PubMedSearch in Google Scholar
  • 7 Morgan T R, Mandayam S, Jamal M M. Alcohol and hepatocellular carcinoma.  Gastroenterology. 2004;  127 87-96
    CrossrefPubMedSearch in Google Scholar
  • 8 Yuan J M, Govindarajan S, Arakawa K. et al . Synergism of alcohol, diabetes and viral hepatitis on risk of hepatocellular carcinoma in US blacks and whites.  Cancer. 2004;  101 1009-1017
    CrossrefPubMedSearch in Google Scholar
  • 9 Grando-Lemaire V, Guettier C, Chevret S. et al . Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver. Groupe d’Etude et de traitement du carcinome hepatocellulaire.  J Hepatol. 1999;  31 508-513
    CrossrefPubMedSearch in Google Scholar
  • 10 El-Serag H B, Tran T, Everhart J E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.  Gastroenterology. 2004;  126 460-468
    CrossrefPubMedSearch in Google Scholar
  • 11 Neuschwander-Tetri B A, Caldwell S H. Nonalcoholic steatohepatitis: summary of a AASLD single topic conference.  Hepatology. 2003;  37 1202-1219
    CrossrefPubMedSearch in Google Scholar
  • 12 Marrero J A, Fontana R J, Fu S. et al . Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma.  J Hepatology. 2005;  42 218-224
    PubMedSearch in Google Scholar
  • 13 Falize L, Guillygomarc’h A, Perrin M. et al . Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases.  Hepatology. 2006;  44 472-477
    CrossrefPubMedSearch in Google Scholar
  • 14 Ming L, Thorgeirsson S S, Gail M H. et al . Dominant role of hepatitis B virus ans cofactor role of aflatoxin in hepatocarcinogenesis in Quidong, China.  Hepatology. 2002;  36 1214-1220
    CrossrefPubMedSearch in Google Scholar
  • 15 Bréchot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms.  Gastroenterology. 2004;  127 (Suppl. 1) S56-S61
    CrossrefPubMedSearch in Google Scholar
  • 16 Liang T J, Heller T. Pathogenesis of hepatitis C-associated hepatocellular carcinoma.  Gastroenterology. 2004;  127 (Suppl. 1) S62-S71
    CrossrefPubMedSearch in Google Scholar
  • 17 Wu T. Cyclooxygenase-2 in hepatocellular carcinoma.  Cancer Treat Rev. 2006;  32 28-44
    CrossrefPubMedSearch in Google Scholar
  • 18 El-Serag H B. Hepatocellular carcinoma: recent trends in the United States.  Gastroenterology. 2004;  127 27-34
    CrossrefPubMedSearch in Google Scholar
  • 19 Zhang B H, Yang B H, Tang Z Y. et al . Randomized controlled trial of screening for hepatocellular carcinoma.  J Cancer Res Clin Oncol. 2004;  130 417-422
    PubMedSearch in Google Scholar
  • 20 Sangiovanni A, Del Ninno E, Fasani P. et al . Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance.  Gastroenterology. 2004;  126 1005-1014
    CrossrefPubMedSearch in Google Scholar
  • 21 Spangenberg H C, Thimme R, Blum H E. Serum markers of hepatocellular carcinoma.  Semin Liver Dis. 2006;  26 385-390
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Bruix J, Sherman M, Llovet J M. et al . Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.  J Hepatol. 2001;  35 421-430
    CrossrefPubMedSearch in Google Scholar
  • 23 Bolondi L, Gaiani S, Celli N. et al . Characterisation of small nodules in cirrhosis by assessment of hypervascularity.  Hepatology. 2005;  42 27-34
    CrossrefPubMedSearch in Google Scholar
  • 24 Caturelli E, Solmi L, Anti M. et al . Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study.  Gut. 2004;  53 1356-1362
    CrossrefPubMedSearch in Google Scholar
  • 25 Llovet J M, Chen Y, Wurmbach E. et al . A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis.  Gastroenterology. 2006;  131 1758-1767
    CrossrefPubMedSearch in Google Scholar
  • 26 Ishii H, Okada S, Okusaka T. et al . Needle tract implantation of hepatocellular carcinoma after percutaneous ethanol injection.  Cancer. 1998;  82 1638-1642
    CrossrefPubMedSearch in Google Scholar
  • 27 Villa E, Colantoni A, Camma C. et al . Estrogen receptor classification for hepatocellular carcinoma: comparison with clinical staging systems.  J Clin Oncol. 2003;  21 441-446
    PubMedSearch in Google Scholar
  • 28 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
    CrossrefPubMedSearch in Google Scholar
  • 29 Gallo . et al . A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients.  Hepatology. 1998;  28 751-755
    CrossrefPubMedSearch in Google Scholar
  • 30 Marrero J A, Fontana R J, Barrat A. et al . Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort.  Hepatology. 2005;  41 707-716
    CrossrefPubMedSearch in Google Scholar
  • 31 Bruix J, Llovet J M. Prognostic prediction and treatment strategy in hepatocellular carcinoma.  Hepatology. 2002;  35 519-524
    CrossrefPubMedSearch in Google Scholar
  • 32 Mazzaferro V, Regalia E, Doci R. et al . Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis.  N Engl J Med. 1996;  334 693-699
    CrossrefPubMedSearch in Google Scholar
  • 33 Onaca N, Davis G L, Goldstein R M. et al . Expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a report from the International Registry of Hepatic Tumors in Liver Transplantation.  Liver Transpl. 2007;  13 391-399
    CrossrefPubMedSearch in Google Scholar
  • 34 Cillo U, Vitale A, Grigoletto F. et al . Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria.  Am J Transplant. 2007;  7 972-981
    CrossrefPubMedSearch in Google Scholar
  • 35 Lu D SK, Yu N C, Raman S S. et al . Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation.  Hepatology. 2005;  41 1130-1137
    CrossrefPubMedSearch in Google Scholar
  • 36 Porrett P M, Petermann H, Rosen M. et al . Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era.  Liver Transpl. 2006;  12 665-673
    CrossrefPubMedSearch in Google Scholar
  • 37 Millonig G, Graziadei I W, Freund M C. et al . Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma.  Liver Transpl. 2007;  13 272-279
    CrossrefPubMedSearch in Google Scholar
  • 38 Otto G, Heise M, Moench C. et al . Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma.  Transplant Proc. 2007;  39 537-539
    CrossrefPubMedSearch in Google Scholar
  • 39 Trotter J F, Adam R, Lo C M, Kenison J. Documented deaths of hepatic lobe donors for living donor liver transplantation.  Liver Transpl. 2006;  12 1485-1488
    CrossrefPubMedSearch in Google Scholar
  • 40 Knetemann N M, Oberholzer J, Al Saghier M. et al . Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma.  Liver Transpl. 2004;  10 1301-1311
    CrossrefPubMedSearch in Google Scholar
  • 41 Bismuth H, Fecteau A. Kombinationstherapie in der Onkologie - das hepatocelluläre Carcinom.  Chirurg. 1998;  69 360-365
    CrossrefPubMedSearch in Google Scholar
  • 42 Strey C W, Zapletal C, Bechstein W O. Chirurgische Therapie des hepatozellulären Karzinoms.  Gastroenterologe. 2007;  2 20-26
    CrossrefPubMedSearch in Google Scholar
  • 43 Muto Y, Moriwaki H, Ninomiya M. et al . Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.  N Engl J Med. 1996;  334 1561-1567
    CrossrefPubMedSearch in Google Scholar
  • 44 Lau W Y, Leung T W, Ho S K. et al . Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.  Lancet. 1999;  353 797-801
    CrossrefPubMedSearch in Google Scholar
  • 45 Mazzaferro V, Romito R, Schiavo M. et al . Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.  Hepatology. 2006;  44 1543-1554
    CrossrefPubMedSearch in Google Scholar
  • 46 Chen M S, Li J Q, Zheng Y. et al . A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma.  Ann Surg. 2006;  243 321-328
    CrossrefPubMedSearch in Google Scholar
  • 47 Huang G T, Lee P H, Tsang Y M. et al . Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study.  Ann Surg. 2005;  242 36-42
    CrossrefPubMedSearch in Google Scholar
  • 48 Lencioni R A, Allgaier H P, Cioni D. et al . Small hepatocellular carcinoma in cirrhosis: randomised comparison of radio-frequency thermal ablation versus percutaneous ethanol injection.  Radiology. 2003;  228 235-240
    CrossrefPubMedSearch in Google Scholar
  • 49 Shiina S, Teratani S, Obi S. et al . A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma.  Gastroenterology. 2005;  129 122-130
    CrossrefPubMedSearch in Google Scholar
  • 50 Llovet J M, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.  Hepatology. 2003;  37 429-442
    CrossrefPubMedSearch in Google Scholar
  • 51 Llovet J M, Real M I, Montana X. et al . Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.  Lancet. 2002;  359 1734-1739
    CrossrefPubMedSearch in Google Scholar
  • 52 Cammà C, Schepis F, Orlando A. et al . Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-analysis of randomized controlled trials.  Radiology. 2002;  224 47-54
    CrossrefPubMedSearch in Google Scholar
  • 53 Patt Y Z, Hassan M M, Lozano R D. et al . Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon alfa-2b for treatment of hepatocellular carcinoma.  J Clin Oncol. 2003;  21 421-427
    CrossrefPubMedSearch in Google Scholar
  • 54 Nowak A K, Stockler M R, Chow P K. et al . Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review.  Cancer. 2005;  103 1408-1414
    CrossrefPubMedSearch in Google Scholar
  • 55 Chow P K, Tai B C, Tan C K. et al . High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: A multicenter randomized controlled trial.  Hepatology. 2002;  36 1221-1226
    CrossrefPubMedSearch in Google Scholar
  • 56 Groupe d’Etude et de Traitement de Carcinome Hepatocellulaire . Randomized trial of leuprorelin and flutamide in male patients with hepatocellular carcinoma treated with tamoxifen.  Hepatology. 2004;  40 1361-1369
    CrossrefPubMedSearch in Google Scholar
  • 57 Villa E, Ferretti I, Grottola A. et al . Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors.  Br J Cancer. 2001;  84 881-885
    CrossrefPubMedSearch in Google Scholar
  • 58 Yuen M F, Poon R T, Lai C L. et al . A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma.  Hepatology. 2002;  36 687-691
    CrossrefPubMedSearch in Google Scholar
  • 59 Becker G, Allgaier H P, Olschewski M. et al . Long-acting octreotide versus placebo for treatment of advanced HCC: a randomized controlled double-blind study.  Hepatology. 2007;  45 9-15
    CrossrefPubMedSearch in Google Scholar
  • 60 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
    CrossrefPubMedSearch in Google Scholar
  • 61 Llovet J M, Sala M, Castells L. et al . Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma.  Hepatology. 2000;  31 54-58
    CrossrefPubMedSearch in Google Scholar
  • 62 Kawata S, Yamasaki E, Nagase T. et al . Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial.  Br J Cancer. 2001;  84 886-891
    CrossrefPubMedSearch in Google Scholar

Prof. Dr. med. Wolfgang E. Fleig

Universitätsklinikum Leipzig AöR

Philipp-Rosenthal-Straße 27

04103 Leipzig

Email: wolfgang.fleig@uniklinik-leipzig.de