Liver Transplantation and the Epidemic of Hepatocellular Carcinoma

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Liver Transplantation and the Epidemic of
Hepatocellular Carcinoma
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Trends in SEER Incidence US Death Rates by
Primary Cancer Site 1995-2004
Surveillance, Epidemiology, and End Results
(SEER) database. lthttp//seer.cancer.gov/gt
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Features of HCC in the U.S.

• 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)
• gt98 with fibrosis or cirrhosis

El-Serag et al. Gastroenterology 2004 127, Vol
5. S27-34
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Risk Factors in the U.S.

• HCV
• HBV
• Alcohol
• Other
• Hemochromatosis
• Cryptogenic
• NAFLD
• Alpha-1 antitrypsin deficiency
• Wilsons Disease
• PBC/PSC/AIH

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HCV Disease Progression
Time 20-30 years
HCV infection
60-851
Chronic HCV
Cirrhosis
Hepatic Failure
203
20-502
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Liver Transplant Candidates
Liver Cancer
1. NIH Consensus Development Conference
Statement March 24-26, 1997. 2. Davis GL et al.
Gastroenterol Clin North Am. 199423603-613. 3.
Koretz RL et al. Ann Intern Med.
1993119110-115. 4. Takahashi M et al. Am J
Gastroenterol. 199388240-243.
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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
?
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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 (gt 3 cm) lesions
with three or more nodules and should be
restricted to small lesions (lt 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.
MDMeeting of the American Surgical
AssociationVolume 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. 121201-212, 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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UCSF
CONCLUSION

• 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.

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Role of LDLT

• Todo
• Tanaka
• Miller
• Kam

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Unfavorable characteristics

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

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MiamiTransplant Institute
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HCC / CIRRHOSIS
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RFA TACE/TACI RESECTION OLT CHEMO EXP
PROTOCOLS
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• T1 one lesion lt 2cm

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• T2 Milan, one lesion lt 5cm, or up to 3 all lt 3
  cm

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• T3 SF one lesion lt 6.5cm, up to 3 all lt 4.5 cm,
  total diameter lt 8cm

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

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MELD

• T Bili
• Creat
• PT
• Patients receive Liver Grafts with MELDgt15
• T2 MELD 22

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