BACKGROUND: The established procedure for ABO-incompatible liver transplantation(ABO-I LT) was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin(IVIG) for ABO-I LT in patients with acute liver failure(ALF).METHODS: The data from 101 patients who had undergone liver transplantation(LT) for ALF were retrospectively analyzed.The patients were divided into two groups: ABO-compatible liver transplantation group(ABO-C LT, n=66) and ABO-I LT group(n=35). All the patients in the ABO-I LT group received a single dose of rituximab(375 mg/m2) and IVIG(0.4 g/kg per day) at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS: The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively(P>0.05), and the graft survival rates were 80.0%and 86.3%, respectively(P>0.05). Two patients(5.7%) suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS: The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.
BACKGROUND: Living donor liver transplantation(LDLT)has been widely accepted over the past decade, and hepatic dysfunction often occurs in the donor in the early stage after liver donation. The present study aimed to evaluate the effect of intraoperative cholangiography(IOC) and parenchymal resection on liver function of donors in LDLT, and to assess the role of IOC in influencing the biliary complications and improving the overall outcome.METHODS: Data from 40 patients who had donated their right lobes for LDLT were analyzed. Total bilirubin(TB), alanine aminotransferase(ALT), aspartate aminotransferase(AST),alkaline phosphatase(ALP) and γ-glutamyl transpeptidase(GGT)at different time points were compared, and the follow-up data and the biliary complications were also analyzed.RESULTS: The ALT and AST values were significantly increased after IOC(P<0.001) and parenchymal resection(P<0.001).However, the median values of TB, ALP and GGT were not significantly influenced by IOC(P>0.05) or parenchymal resection(P>0.05). The biochemical changes caused by IOC or parenchymal resection were not correlated with the degree of post-operative liver injury or the recovery of liver function. The liver functions of the donors after operation were stable, and none of the donors suffered from biliary stenosis or leakage during the follow-up.CONCLUSIONS: IOC and parenchymal resection may induce a transient increase in liver enzymes of donors in LDLT, but do not affect the recovery of liver function after operation. Moreover,the routine IOC is helpful to clarify the division line of the hepatic duct, thus reducing the biliary complication rate.
BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells. DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the Key words such as liver failure bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed. RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines the incorporation of BAL with GS-HepG2 cells or alginate encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved. CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functionalhepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver failure in the near future.
Xiao-Ping Pan , Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.
