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Treating ischaemia‐reperfusion injury with prostaglandin E1 reduces the risk of early hepatocellular carcinoma recurrence following liver transplantation
Author(s) -
Kornberg A.,
Witt U.,
Kornberg J.,
Friess H.,
Thrum K.
Publication year - 2015
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13380
Subject(s) - medicine , liver transplantation , hepatocellular carcinoma , milan criteria , prostaglandin e1 , gastroenterology , transplantation , population , liver injury , proportional hazards model , surgery , liver cancer , environmental health
Summary Background Surgical stress by hepatic ischaemia‐reperfusion (I/R) is supposed to promote intra‐ and extrahepatic tumour recurrence. Treatment with prostaglandin E1 ( PGE 1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti‐cancer effects have not been analysed. Aim To evaluate the impact of PGE 1 therapy on risk of hepatocellular carcinoma ( HCC ) recurrence in liver transplant patients. Methods A retrospective review of 106 liver transplant patients with HCC was conducted. Fifty‐nine patients underwent early post‐liver transplantation ( LT ) treatment with the stable PGE 1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni‐ and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging. Results Three‐ and 5‐year recurrence‐free survival rates were 87.9% and 85.7% in the PGE 1‐group, but only 65.3% and 63.1% in the non‐ PGE 1‐population ( P = 0.003). Multivariate Cox regression analysis identified absence of PGE 1‐treatment ( HR = 11.42), along with presence of poor tumour grading ( HR = 2.69) and microvascular tumour invasion ( HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out‐patients, only therapy with PGE 1 ( HR = 5.09) and well/moderate tumour differentiation ( HR = 6.51) were independent promoters of recurrence‐free survival. Conclusions Treating hepatic ischaemia‐reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT . In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE 1‐treatment. The molecular mechanisms of the anti‐tumour effects need to be further assessed.