Liver Transplantation in Patients with Hepatocellular Carcinoma

Gi-Won Song; Shin Hwang; Sung-Gyu Lee

doi:10.4166/kjg.2010.55.6.350

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Song, Hwang, and Lee: Liver Transplantation in Patients with Hepatocellular Carcinoma

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Korean J Gastroenterol 2010;55(6):350-360.

Published online: 21 February 2010

DOI: https://doi.org/10.4166/kjg.2010.55.6.350

Liver Transplantation in Patients with Hepatocellular Carcinoma

Gi-Won Song, M.D., Shin Hwang, M.D., Sung-Gyu Lee, M.D.

Department of Surgery, Division of Liver Transplantation and Hepatobiliary Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Sung-Gyu Lee, M.D. Department of Surgery, Asan Medical Center, 388-1, Asan-byungwongil, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-3485, Fax: +82-2-474-9027 E-mail: sglee2@amc.seoul.kr

Abstract

Hepatocellular carcinoma (HCC) is the third most common malignancy, with a new incidence of more than 11,000 cases per year and the second most common cause of malignancy-related death in Korean males. In Korea, more than 80% of all HCCs have developed from hepatitis B virus (HBV)-related cirrhotic livers. Liver transplantation (LT) is the only treatment that offers a chance of cure for HCC and the underlying liver cirrhosis simultaneously, but the availability of liver grafts and the aggressiveness of tumor recurrence are critical limiting factors of LT for HCC patients. The serious shortage of deceased-donors on strong demand for LT leads to the development of living-donor LT (LDLT) as a practical alternative replacing deceased-donor LT. Considering that HCC recurrence is the most common cause of posttransplant patient death, recipient candidates should be pru-dently selected through objectively established criteria. Uniquely, some Asian major LDLT centers challenged the Milan criteria, accepting a much higher number of HCC nodules instead of tumor size expansion. The eligibility criteria of LDLT for HCC are likely to be expanded more than before, but it still requires further qualified risk-benefit analyses. The development of new effective treatment modalities for HCC recurrence will reasonably expand the selection criteria further wide without the expense of recurrence rate. This article is mainly focused on the role of LT for HCC and discussed on the validity of currently available indication criteria.

Keywords: Hepatocellular carcinoma, Liver transplantation, Indication criteria

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Fig. 1.

Liver resection and transplantation for hepatocellular carcinoma at Asan Medical Center from June 1989 to December 2008.

Fig. 2.

Annual changes in the proportion of hepatocellular carcinoma patients in adult living-donor liver transplantation at Asan Medical Center.

Fig. 3.

Comparison of the hepatocellular carcinoma (HCC) recurrence curves of 206 patients who underwent living-donor liver transplantation from February 1997 to December 2004 at Asan Medical Center based on explant pathology. (A) HCC recurrence curves of the patients beyond the Milan criteria but within UCSF criteria showed 1-year, 3-year, and 5-year recurrence rates of 0%, 20.0%, and 20.0%, respectively. There was no statistically significant difference in recurrence rates between the patient group beyond the Milan criteria but within the UCSF criteria and the patient group within the Milan criteria (p=0.626). (B) HCC recurrence curves of the patients beyond the Milan criteria but within the Asan criteria showed 1-year, 3-year, and 5-year recurrence rates of 0%, 9.1%, and 9.1%, respectively. There was no statistically significant recurrence difference between the patient group beyond the Milan criteria but within the Asan criteria and that within the Milan criteria (p=0.554).⁶

Fig. 4.

Comparison of the patient survival curves of 206 patients who underwent living-donor liver transplantation from February 1997 to December 2004 at Asan Medical Center based on explant pathology. (A) Patient survival curves of the patients beyond the Milan criteria but within UCSF criteria showed 1-year, 3-year, and 5-year survival rates of 100%, 90.0%, and 78.8%, respectively. There was no statistically significant difference in survival rates between the patient group beyond the Milan criteria but within the UCSF criteria and the patient group within the Milan criteria (p=0.923). (B) Patient survival curves of patients beyond the Milan criteria but within the Asan criteria showed 1-year, 3-year, and 5-year recurrence rates of 100%, 88.9%, and 80.0%, respectively. There was no statistically significant survival difference between the patient group beyond the Milan criteria but within the Asan criteria and that within the Milan criteria ⁶

Fig. 5.

Recurrence of hepatocellular carcinoma in recipients having positive positron emission tomography (PET) scans. LDLT, living-donor liver transplantation.

Table 1.

Eligibility Criteria of Liver Transplantation for Hepatocellular Carcinoma

Institution	Selection criteria
Milan University, Italy⁴	Single, ϕ≤5 cm; or 2 to 3, Max ϕ≤3 cm
UCSF University, USA⁵	Single, ϕ≤6.5 cm; or 2 to 3, Max ϕ≤4.5 cm, Sum ϕ≤8 cm
Asan Medical Center, Korea⁶	Max ϕ≤5 cm, number ≤6, no gross vascular invasion
Samsung Medical Center, Korea⁷	Max ϕ≤5 cm, any number, AFP ≤400 ng/dL
Seoul University Hospital, Korea⁸	Max ϕ≤5 cm, number ≤10, PIVKA-II ≤400 mAU/mL
Kyoto University, Japan⁹	Max ϕ≤5 cm, number ≤10, PIVKA-II ≤400 mAU/mL
Tokyo University, Japan¹⁰	Max ϕ≤5 cm, number ≤5
Kyushu University, Japan¹¹	Max ϕ≤5 cm, any number, DCP ≤300 ng/dL

AFP, alphafetoprotein; DCP, des-gamma-carboxy prothrombin; PIVKA-II, protein induced by vitamin K absence or antagonist-II.

Table 2.

Comparison of Data and Outcomes of the HCC Patients Who Underwent Deceased-donor and Living-donor Liver Transplantations (DDLT and LDLT) at 4 Centers of Korea from August 1992 to December 2002²²

Parameter	DDLT	LDLT	p-value
Number of patients	75 (24%)	237 (76%)
Age (years, mean± SD)	49±7	50±8	0.599
Sex, n (%)			0.595
Male	60 (79.0)	196 (82.7)
Female	15 (21.0)	41 (17.3)
Serology, n (%)			0.458
Hepatitis B	68 (90.7)	215 (90.7)
Hepatitis C	6 (8.0)	13 (5.5)
Hepatitis B and C	0	8 (3.4)
None	1 (1.3)	1 (0.4)
Child-Pugh classification, n (%)			0.005
Class A	4 (5.3)	29 (12.2)
Class B	13 (17.3)	70 (29.5)
Class C	55 (73.4)	138 (58.3)
Pathologic tumor staging, n (%)			0.767
T1	34 (45.3)	116 (49.0)
T2	25 (33.3)	96 (40.5)
T3	16 (21.3)	25 (10.5)
T4	0	0
Milan criteria			0.694
Within	53 (70.7)	173 (73.0)
Beyond	22 (29.3)	64 (27.0)
Perioperative mortality, n (%)	14 (18.7)	24 (10.1)	0.048
Overall 3-year survival rate (%)	61.3	73.2	0.043
2-year recurrence-free survival rate (%)	81.6	79.7	0.884

Table 3.

Risk Factors for Hepatocellular Carcinoma Recurrence and Patient Survival in 206 Patients Who Underwent Living-donor Liver Transplants from February 1997 to December 2004 at Asan Medical Center⁶

Risk factors	Hepatocellular carcinoma recurrence			Patient survival
Risk factors	Hazard ratio	95% CI	p-value	Hazard ratio	95% CI	p-value
Largest tumor diameter＞5 cm	6.08	2.720-13.59	＜0.001	4.63	2.11-10.19	＜0.001
Tumor number＞6	6.65	3.02-14.63	＜0.001	6.22	2.96-13.08	＜0.001
Gross vascular invasion present	2.53	1.39-6.28	0.042	2.63	1.07-6.48	0.035

CI, confidence interval

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