Dataset Information

Alpha-fetoprotein-adjusted-to-HCC-size criteria are associated with favourable survival after liver transplantation for hepatocellular carcinoma.

ABSTRACT:

Background

The Milan criteria are recommended to select hepatocellular carcinoma (HCC) patients for liver transplantation (LT). The utility of other selection criteria, such as the alpha-fetoprotein-adjusted-to-HCC-size (AFP-UTS) criteria, is still unclear.

Objective

We investigated, in HCC patients who underwent LT, the survival and the recurrence after LT according to AFP-UTS and Milan criteria, the impact of early recurrence and the correlation between radiological and pathological staging.

Methods

Adult HCC patients undergoing deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed.

Results

Among 166 patients included, the number of patients who fulfilled Milan or AFP-UTS criteria was the same (139 [84%] each), although not all of them were the same individuals; 127 patients (77%) fulfilled both Milan and AFP-UTS criteria. Median overall survival of patients within AFP-UTS was 126.9 versus 34.2 months outside AFP-UTS (5-year survival rate 71% vs. 43%; p = 0.104). The 5-year recurrence rate was significantly lower in patients fulfilling the AFP-UTS criteria (18%) than in those exceeding AFP-UTS (64%; p < 0.001). Of the 139 patients within Milan criteria on imaging, 24 (17%) had microvascular invasion and 47 (34%) were outside Milan according to explant histology. Early recurrence correlated with AFP-UTS and was associated with dismal survival (median overall survival 17.2 vs. 122.1 months, p = 0.002).

Conclusions

The overall survival of patients within AFP-UTS criteria was favourable with a 5-year survival rate above 70%. Early recurrence is associated with worse survival after LT. The AFP-UTS criteria may be more suitable to exclude patients at high risk of (early) recurrence than Milan criteria.

SUBMITTER: Meischl T

PROVIDER: S-EPMC8259374 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Several attempts have been made to expand the indications of liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria. We aimed to define genomic features that enable the identification of patients with HCC beyond Milan criteria who have acceptable transplant outcomes. Methods: Among 770 consecutive HCC patients transplanted at Mount Sinai Hospital and Mayo Clinic between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study. Explant tumors were analyzed to assess genomic signatures of poor prognosis and immunohistochemical markers associated with tumor recurrence and overall survival. Results: Most of the patients were males (80%) and HCV positive (71%) with a median age of 56. HCC beyond Milan criteria was defined pre-operative in 67%. On pathology, 44% of the patients satisfied the ‘up-to-7 rule’. At a median follow-up of 88 months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. CK19 gene signature was independently associated with recurrence (HR=2.95, p<0.001), along with tumor size >5 cm (HR=3.37, p=0.023) and presence of satellite lesions (HR=2.98, p=0.001). S2 subclass signature, which is known to be associated with progenitor cell markers, was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size >5 cm (HR=5.06, p<0.001) and outside up-to-seven rule (HR=2.50, p=0.002). Using the presence of markers of progenitor cells (either CK19 or S2 subclass signatures) patients may be classified into poor-prognosis (n=58; 5-year recurrence 53%, survival 45%) and good-prognosis subgroups (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). Conclusion: Gene signatures associated with progenitor cell markers (CK19 and S2 subclass signatures) define outcome of HCC patients beyond Milan criteria after transplantation. Patients without these signatures achieve survival rates similar as those patients within Milan criteria. Once prospectively validated, these markers may provide the rationale for a limited expansion of liver transplantation indications.

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