Adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma: a systematic review and a meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and liver transplantation (LT) is considered as the best therapeutic option for patients with HCC combined with cirrhosis. However, tumor recurrence after LT for HCC remains the major obstacle for long-term survival. The present study was to evaluate the efficacy and necessity of adjuvant chemotherapy in patients with HCC who had undergone LT. DATA SOURCES: Several databases were searched to identify comparative studies fulfilling the predefined selection criteria before October 2014. Suitable studies were chosen and data extracted for meta-analysis. Three authors independently evaluated the bias of each study according to the Cochrane Handbook for Systematic Review of Intervention. Stata 12 was used for statistical analysis. Hazard ratio (HR) was considered as a summary statistic for overall survival, disease-free survival and recurrence rate. RESULTS: Three prospective studies and 5 retrospective studies including 360 patients (166 in the adjuvant chemotherapy group, and 194 in the control group) were included. Compared with the control group, post-LT adjuvant chemotherapy conferred significant benefit for overall survival (HR: 0.34; 95% CI: 0.22-0.52; P=0.000). Meanwhile, the results showed an improvement for disease-free survival on favoring adjuvant chemotherapy (HR: 0.87; 95% CI: 0.78-0.95; P=0.004). However, no significant difference in HCC recurrence rate was observed between the two groups (HR: 1.26; 95% CI: 0.40-4.00; P=0.696). Descriptions of adverse events were of anecdotal nature and did not allow meta-analytic calculations. CONCLUSIONS: Adjuvant chemotherapy after LT for HCC can significantly prolong patient's survival and delay the recurrence of HCC. For advanced HCC with poor differentiation, patients may perhaps benefit from the early implantation of adjuvant chemotherapy after LT.

[The change of intestinal microecology in rats after orthotopic liver transplantation].

OBJECTIVE: To investigate the intestinal microflora status and bacterial translocation in rats after liver transplantation. METHODS: Male Brown-Norway (BN) rats were randomly divided into 4 groups: group I (n = 8) for liver transplantation; group II (n = 8) for simulated liver transplantation; group III (n = 8) for sham operation and group IV (n = 8) for normal group. Caecal bacterial counts, plasma endotoxin, intestinal mucosal ultrastructure and bacterial translocation to liver, spleen, kidney, and mesenteric lymph node were studied 24 h after surgery. RESULTS: The numbers of Bifidobacterium and Lactobacillus per gram of wet feces were significantly decreased in group I compare with those in the group III and group IV, while Enterobacteriaceae and Enterococcus counts were increased markedly compare with those in the group III and group IV, but no different was found between group I and group II. Impaired intestinal mucosa integrity were found in the group I and group II. In group I, the levels of plasma endotoxin increased after the transplantation when compare with group III and group IV. Increased incidence of bacterial translocation to liver, spleen and mesenteric lymph node were also observed after the transplantation (compare with those in the group IV, P < 0.01; compare with those in the group III, P < 0.01, P < 0.01, P < 0.05, separately). The increased rate of the bacterial translocation in liver was also found in transplantation group as compare with group II (P < 0.05). CONCLUSIONS: Liver transplantation may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function, and this dysfunction might be caused by the process of intestinal ischemia-reperfusion injury in transplantation.

Increased expression of non-interleukin-2 T cell growth factors and their implications during liver allograft rejection in rats.

BACKGROUND AND AIM: Rejection remains a problem in the transplantation field. The aim of this study was to establish acute and chronic rejection models in rats and to investigate the roles of non-interleukin (IL)-2 T cell growth factors such as IL-15, IL-7 and IL-13 during rejection. METHODS: A liver transplant model was established using Dark Agouti and Brown Norway rats. The rats were divided into group A, left without treatment; group B, received cyclosporinee (1 mg/kg/day); and group C, cyclosporinee (4 mg/kg/day). Histopathological, reverse transcriptase-polymerase chain reaction and western blot were performed in liver specimens obtained from different time-points after transplantation in the three groups. RESULTS: In group A, the livers showed irreversible acute cellular rejection with cell infiltration. In group B, chronic liver rejection was found, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy and liver fibrosis. No apparent histological alterations were observed in group C. IL-15, IL-7 and IL-13 messenger RNA and their protein were all highly expressed in the liver specimens of groups A and B. Upregulated expression was found in IL-15 since the first day after transplantation and in IL-7 and IL-13 since day 6. The extent of IL-15 upregulation was more than that of IL-7 and IL-13. CONCLUSIONS: Liver transplantation in Dark Agouti to Brown Norway rats with low-dose immunosuppression can induce chronic rejection. In the process of acute and chronic allograft rejections, non-IL-2 T cell growth factors such as IL-15, IL-7 and IL-13 play roles. Strategies should pay more attention to regulating these cytokines after liver transplantation.

Enteral feeding of glycyl-glutamine dipeptide improves the structure and absorptive function of the small intestine after allogenetic liver transplantation in rats.

BACKGROUND: Recipients of liver transplantation could have postoperative structural injury and declined absorptive function in the gastrointestinal tract. Glutamine (Gln) is a special nutrient of small intestinal mucosa and of various kinds of cells proliferating rapidly. But Gln could form a kind of poisonous pyroglutamic acid in water solution, which is the limitation of Gln in clinical practice. Glycyl-glutamine (Gly-Gln) is highly soluble and can be hydrolyzed to release glutamine. This study was undertaken to observe the effect of Gly-Gln dipeptide by enteral feeding on the intestinal structure and absorptive function after allogenetic liver transplantation in rats. METHODS: Twelve male inbred Lewis rats were selected randomly as donors, and 24 male inbred BN rats as recipients of allogenetic liver transplantation. The recipients were also randomly divided into two groups: control group (ALA group, n=12) and experimental group (GLN group, n=12). In each group, 6 normal BN rats were sampled as the normal parameter on the 3rd preoperative day. The 6 recipients in the control group received alanine 0.6 g/kg daily for 3 days before operation and 7 days after operation by gastric perfusion, and the 6 recipients in the experimental group were given Gly-Gln 0.6 g/kg daily the same way. The 12 BN recipients underwent 3-day fasting (free access to water with 0.23% sodium chloride) and orthotopic liver transplantation in aseptic conditions and were given subcutaneous injection of CsA 2 mg/kg daily after the operation. The 12 BN recipients were sampled on the 8th postoperative day. All of the 24 BN rats were subjected to examination of mucosal structure, activities of Na+-K+-ATP and disaccharidase, and D-xylose absorption test. RESULTS: The 12 BN recipients were alive after liver transplantation. On the 3rd preoperative day, mucosal structure, activities of Na+-K+-ATP and disaccharidase and D-xylose absorption in the two groups were not significantly different. On the 8th postoperative day, the parameters of the two groups were markedly changed compared with those on the 3rd preoperative day. However, the parameters of GLN group were remarkably higher than those of ALA group. CONCLUSION: Enteral feeding of Gly-Gln could improve the structure and absorptive function of the small intestine after liver transplantation in rats.

Cytomegalovirus and chronic allograft rejection in liver transplantation.

Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain. This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.