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Liver Transplantation and the Epidemic of Hepatocellular Carcinoma

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Slide 1 :

Liver Transplantation and the Epidemic of Hepatocellular Carcinoma

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Surveillance, Epidemiology, and End Results (SEER) database. Trends in SEER Incidence & US Death Rates by Primary Cancer Site: 1995-2004

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Features of HCC in the U.S. El-Serag et al. Gastroenterology 2004; 127, Vol 5. S27-34 Older Patients Mean age = 65 years Peak incidence 70-75 Unusual before 40 Men = 74% Racial Distribution 48% White 15% Hispanic 13% African American 24% Other (predominantly Asian) >98% with fibrosis or cirrhosis

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Risk Factors in the U.S. HCV HBV Alcohol Other: Hemochromatosis Cryptogenic NAFLD Alpha-1 antitrypsin deficiency Wilson’s Disease PBC/PSC/AIH

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1. NIH Consensus Development Conference Statement; March 24-26, 1997. 2. Davis GL et al. Gastroenterol Clin North Am. 1994;23:603-613. 3. Koretz RL et al. Ann Intern Med. 1993;119:110-115. 4. Takahashi M et al. Am J Gastroenterol. 1993;88:240-243. HCV infection Chronic HCV Cirrhosis Hepatic Failure Liver Cancer Liver Transplant Candidates 60-85%1 ~20%4 ~ 20%3 20%-50%2 HCV: Disease Progression Time: 20-30 years

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HBV and HCC Globally + Asia commonest underlying cause of HCC Western countries show significantly less risk in HBV carriers

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HCC / CIRRHOSIS ? RFA TACE/TACI RESECTION OLT CHEMO EXP PROTOCOLS ?

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RESECTION vs Transplantation ?

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Bismuth et al 1993 “…We believe that hepatic transplantation for HCC should be avoided for large (> 3 cm) lesions with three or more nodules and should be restricted to small lesions (< 3 cm) with one or two nodules, the group which until now was thought to be the most suitable for resection…”

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Cha, Charles H. MD*; Ruo, Leyo MD*; Fong, Yuman MD*; Jarnagin, William R. MD*; Shia, Jinru MD†; Blumgart, Leslie H. MD*; DeMatteo, Ronald P. MD*Meeting of the American Surgical Association:Volume 1212003pp 9-17 Resection should be considered the standard therapy for patients with HCC who have adequate liver reserve.

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Resection as a bridge?

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Adam et alMeeting of the American Surgical Association. 121:201-212, 2003. …liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.

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Transplantation as the treatment of choice

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Milan

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Mazzaferro et al ….Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis…..

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What about patients with larger tumors?

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Yao et al ….solitary tumor 6.5 cm, or 3 nodules with the largest lesion 4.5 cm and total tumor diameter 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years…

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Options for Management Ablative Radiofrequency Transarterial chemoembolization Alcohol injection Radiation Yttrium-90 Microspheres Image-guided radiotherapy

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Bridging? 90% of patients in US receive a LT within 3 months Drop out 5-10% at 5 months Regional variation No hard data available Judgment call…

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Yamashiki et al …AFP = 100 ng/mL was the only factor that significantly influenced the probability of delisting…

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Successful down-staging can be achieved in the majority of carefully selected patients with HCC exceeding conventional T2 criteria, and is associated with excellent post-transplant outcome. Down-staging allows selection of a subgroup of tumors with more favorable biology that are more likely to respond and do well after liver transplantation. CONCLUSION UCSF

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Role of LDLT Todo Tanaka Miller Kam

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Unfavorable characteristics T4 tumors AFP level > 1,000 ng/mL total tumor diameter > 8 cm Vascular invasion poorly differentiated histologic grade Older individuals

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MiamiTransplant Institute

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HCC / CIRRHOSIS ? RFA TACE/TACI RESECTION OLT CHEMO EXP PROTOCOLS ?

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T1 – one lesion < 2cm

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T2 – Milan, one lesion < 5cm, or up to 3 all < 3 cm

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T3 SF – one lesion < 6.5cm, up to 3 all < 4.5 cm, total diameter < 8cm

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T3 beyond SF -- > > T4 – multifocal HCC, or major vascular invasion (PV or HV/cava) Tx and AFP > 500

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MELD T Bili Creat PT Patients receive Liver Grafts with MELD>15 T2: MELD 22

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HCC / CIRRHOSIS ? RFA TACE/TACI RESECTION OLT CHEMO EXP PROTOCOLS ?

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Takahashi M et al. Am J Gastroenterol. 1993;88:240-243. HCV infection. Chronic HCV. Cirrhosis. Hepa more Takahashi M et al. Am J Gastroenterol. 1993;88:240-243. HCV infection. Chronic HCV. Cirrhosis. Hepatic Failure. Liver Cancer. Liver Transplant. Candidates … less