A good prognostic predictor for liver transplantation recipients with benign end-stage liver cirrhosis.

BACKGROUND: Post-transplant model for predicting mortality (PMPM, calculated as -5.359+1.988Xln (serum creatinine [mg/dL])+1.089Xln (total bilirubin [mg/dL])) score has been proved to be a simple and accurate model for predicting the prognosis after liver transplantation (LT) in a single center study. Here we aim to verify this model in a large cohort of patients. METHODS: A total of 2727 patients undergoing LT with end-stage liver cirrhosis from January 2003 to December 2010 were included in this retrospective study. Data were collected from the China Liver Transplant Registry (CLTR). PMPM score was calculated at 24-h and 7-d following LT. According to the PMPM score at 24-h, all patients were divided into the low-risk group (PMPM score ≤-1.4, n=2509) and the high-risk group (PMPM score >-1.4, n=218). The area under receiver operator characteristic curve (AUROC) was calculated for evaluating the prognostic accuracy. RESULTS: The 1-, 3-, and 5-year patient survival rates in the low-risk group were significantly higher than those in the high-risk group (90.23%, 88.01%, and 86.03% vs 63.16%, 59.62%, and 56.43%, respectively, P<0.001). In the high-risk group, 131 patients had a decreased PMPM score (≤-1.4) at 7-d, and their cumulative survival rate was significantly higher than the other 87 patients with sustained high PMPM score (>-1.4) (P<0.001). For predicting 3-month mortality, PMPM score showed a much higher AUROC than post-transplant MELD score (P<0.05). CONCLUSION: PMPM score is a simple and effective tool to predict short-term mortality after liver transplantation in patients with benign liver diseases, and an indicator for prompt salvaging treatment as well.

ZIP4, a novel determinant of tumor invasion in hepatocellular carcinoma, contributes to tumor recurrence after liver transplantation.

BACKGROUND AND PURPOSE: Recently, evidence that Zinc transporter ZRT/IRT-like protein 4 (ZIP4) is involved in invasiveness and apoptosis has emerged in pancreatic cancer and prostate cancer. Our aim was to assess the role of ZIP4 in invasiveness, migration and apoptosis of hepatocellular carcinoma (HCC). The prognostic value of ZIP4 in HCC after liver transplantation was evaluated. METHODS: The role of ZIP4 in HCC was investigated by overexpressing ZIP4 in BEL7402 and HepG2 cells and inhibiting ZIP4 in HuH-7 and HepG2 cells, using overexpression and shRNA plasmids in vitro studies. Immunohistochemical analysis was used to evaluate ZIP4 expression in HCC tissues from 60 patients undergoing liver transplantation, 36 cirrhotic tissue samples, and 6 normal tissue samples. Prognostic significance was assessed using the Kaplan-Meier method and the log-rank test. RESULTS: Specific suppression of ZIP4 reduced cell migration and invasiveness, whereas ZIP4 overexpression caused increases in cell migration and invasiveness. Furthermore, overexpression of ZIP4 resulted in increased expression of pro-metastatic genes (MMP-2, MMP-9) and decreased expression of pro-apoptotic genes (caspase-3, caspase-9, Bax). In contrast, suppression of ZIP4 resulted in an opposite effect. ZIP4 was more highly expressed in tumor tissues than non-tumor tissues (P < 0.0001). ZIP4 expression was significantly associated with tumor recurrence (P = 0.002), tumor node metastasis stage (P = 0.044), Child-Turcotte-Pugh score (P = 0.042), and tumor size (P = 0.022). Univariate analysis showed that ZIP4 expression was significantly associated with overall survival (P = 0.020) and tumor-free survival (P = 0.049). Multivariate analysis revealed that ZIP4 was an independent predictor of overall survival (P = 0.037) after liver transplantation. CONCLUSIONS: ZIP4 could promote migration, invasiveness, and suppress apoptosis in hepatocellular carcinoma, and represent a novel predictor of poor prognosis and therapeutic target for patients with HCC who undergo liver transplantation.