器官移植

Abstract:
Objective To investigate the effect of Immutol on inducing the immune tolerance of cardiac grafts in rat models. Methods A rat model of heterotopic abdominal heart transplantation was established. The recipient rats were divided into 5 groups: blank control group (n=6); dimethyl sulfoxide (DMSO) group (n=6), in which DMSO was administered until the cardiac graft arrest; Immutol group (n=6), in which Immutol was administered until the cardiac graft arrest; ciclosporin (CsA) group (n=10), in which CsA was administered for 20 d; combined group (n=13), in which Immutol was given for 60 d combined with CsA for 20 d. The survival time and pathological changes of cardiac grafts in each group were observed. The contents of serum interleukin (IL)-10 and interferon (IFN)-γ were detected. The expression levels of indoleamine 2, 3-dioxygenase (IDO) and fibrinogen-like protein 2(Fgl2) messenger RNA(mRNA) in heart tissues of rats in each group were measured. Results In the combined group, the cardiac grafts survived for >180 d and immune tolerance was induced. The pathological score of cardiac grafts in the combined group was significantly lower than that in the CsA group at postoperative 39 d (P < 0.05). The levels of serum IL-10 and IFN-γ in the combined group were significantly higher than those in the CsA group at 9 d and 39 d after operation (both P < 0.05). The content of serum IL-10 and IFN-γ in the combined group were gradually increased over time. At postoperative 39 d, the expression levels of IDO and Fgl2 mRNA in the combined group were significantly higher than those in the CsA group (both P < 0.05). The expression level of IDO mRNA in the combined group tended to gradually elevate after operation. In the combined group, the expression level of Fgl2 mRNA at postoperative 180 d was significantly higher than those at 9 d and 39 d after operation (both P < 0.05). Conclusions Combined administration of Immutol and CsA can effectively inhibit the incidence of acute rejection, and maintain the long-term survival of the cardiac grafts and induce immune tolerance after drug withdrawal.

MiR-494 alleviates hepatic ischemia-reperfusion injury in rats by activating PI3K/AKT signaling pathway

Chen Xinpei, Su Song, Zhou Pengcheng, Luo De, Liu Xiangdong, Liu Anding, Li Bo

2019, 10(3): 295-301. doi: 10.3969/j.issn.1674-7445.2019.03.012

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Abstract:
Objective To investigate the effect and related mechanism of microRNA (miR)-494 on the hepatic ischemia-reperfusion injury (HIRI). Methods Twenty-four male SD rats were randomly divided into four groups (n=6 in each group). In the sham operation group, abdominal surgery without hepatic ischemia-reperfusion was performed. In the HIRI group, partial liver ischemia was performed for 60 min, followed by 6 h perfusion. In the HIRI+agomir-miR-494 group, intraperitoneal injection of agomir-miR-494 (20 μL) was daily given within preoperative 7 d. In HIRI+agomir-NC group, an equivalent quantity of agomir-NC was daily injected intraperitoneally within preoperative 7 d. The expression level of miR-494 messenger RNA(mRNA) in the liver tissues in each group was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression levels of liver injury and oxidative stress related indexes were measured by relevant kits. The histopathological changes of the liver in each group were observed. The quantity of apoptotic cells and cytoplasmic histone-related DNA fragments in the liver tissues of rats was detected by relevant kits. The expression levels of the proteins related to the phosphatidylinositol-3-kinase(PI3K)/protein kinase(AKT) signaling pathway were measured by Western blot. Results The expression level of miR-494 mRNA in the rat liver tissues in the HIRI+agomir-miR-494 group was significantly higher than that in the HIRI+agomir-NC group (P < 0.01). The levels of the serum liver injury and oxidative stress related indexes in the HIRI+agomir-miR-494 group were significantly lower than those in the HIRI+agomir-NC group (all P < 0.01). Compared with those in the HIRI+agomir-NC group, the quantity of cellular necrosis was significantly reduced, the cell integrity was considerably increased and the quantity of TUNELpositive cells was evidently decreased in the HIRI+agomir-miR-494 group (all P < 0.05). The expression levels of poly ADP-ribose polymerase(PARP), cysteinyl aspartate specific proteinase-3(Caspase-3) and Bax in the HIRI+agomirmiR-494 group were significantly lower than those in the HIRI+agomir-NC group (all P < 0.05). The quantity of DNA fragments in the HIRI+agomir-miR-494 group was significantly less than that in the HIRI+agomir-NC group (P < 0.01). The expression levels of p-AKT, p-mammalian target of rapamycin(mTOR) and p-p70S6K in the HIRI+agomir-miR-494 group were significantly higher than those in the HIRI+agomir-NC group (all P < 0.05). Conclusions miR-494 can alleviate the severity of HIRI in rats by activating the PI3K/AKT signaling pathway.

Experimental study of compound BAM15 alleviating cryopreservation-induced primary hepatocyte injury in rats

Zhang Yi, Zhang Xiaomei, Chen Liang, Zheng Jun, Yang Qing, Fu Binsheng, Liu Wei, Chen Guihua

2019, 10(3): 302-307. doi: 10.3969/j.issn.1674-7445.2019.03.013

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Abstract:
Objective To investigate the effect of compound BAM15 on the primary hepatocyte injury induced by cold storage in rats. Methods The primary rat hepatocytes were extracted by collagenase perfusion method. According to different cell culture conditions, the cells were divided into 4 groups: group A (Hibernate cell culture solution containing 250 nmol/L BAM15), group B (Hibernate cell culture solution containing 500 nmol/L BAM15), group C (Hibernate cell culture solution containing 1 000 nmol/ L BAM15), control group (Hibernate cell culture solution). The cells of each group were cryopreserved for 12 h. The purity of primary hepatocytes was observed under fluorescence microscope. The changes in the cell proliferation ability, cell apoptosis rate and mitochondrial reactive oxygen species (ROS) were measured in each group. Results The cell proliferation ability in groups B and C was significantly higher than that in the control group (both P < 0.05). The apoptosis rates in groups A, B and C were (33.7±2.2)%, (19.7±1.1)% and (28.7±1.2)%, which were significantly lower than (82.7±4.2)% in the control group (all P < 0.05). The positive rates of intracellular ROS in groups A, B and C were (11.8±4.0)%, (7.6±1.3)% and (8.9±1.6)%, remarkably lower than (27.4±4.5)% in the control group (all P < 0.05). Conclusions Compound BAM15 can effectively mitigate the primary hepatocyte injury in rats induced by cryopreservation. The underlying mechanism is probably associated with the role of BAM15 in reducing ROS generation during cold ischemia.

Clinical Researches

Effect of different liver function Child-Pugh classification on clinical prognosis of hepatocellular carcinoma recipients after liver transplantation

Lin Guozhen, Dai Tianxing, Liu Rongqiang, Deng Mingbin, Wang Guoying, Yi Shuhong, Li Hua, Yang Yang, Chen Guihua

2019, 10(3): 308-312. doi: 10.3969/j.issn.1674-7445.2019.03.014

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Abstract:
Objective To evaluate the effect of the different Child-Pugh classification on the recurrence and survival of hepatocellular carcinoma (HCC) recipients after liver transplantation. Methods Clinical data of 125 HCC recipients undergoing liver transplantation were retrospectively analyzed. The 3-year disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival curve. The independent risk factors probably affecting the recurrence and survival of HCC recipients after liver transplantation were identified by using Cox's proportional hazards regression model. Results The median follow-up time was 25.6 months. The 3-year DFS and OS rates were 68.4% and 65.7% for all patients. The 3-year DFS and OS rates in 113 patients with Child-Pugh class A/B HCC were 68.6% and 66.2%, whereas 66.7% and 65.6% for 12 patients with Child-Pugh class C HCC with no statistical significance (all P>0.05). Cox's proportional hazards regression model demonstrated that vascular invasion (P=0.001)and the number of tumors>3 (P=0.025) were the independent risk factors for the postoperative recurrence of HCC in recipients undergoing liver transplantation. Alpha fetoprotein (AFP)>400μg/L (P=0.035), vascular invasion (P=0.031) and number of tumors>3 (P=0.008) were the independent risk factors affecting the survival of HCC patients. Conclusions The postoperative prognosis does not significantly differ between Child-Pugh class C and A/B HCC patients after liver transplantation. AFP, vascular invasion and number of tumors are the risk factors affecting the clinical prognosis of HCC patients after liver transplantation. Liver transplantation is an efficacious treatment for HCC patients with Child-Pugh class C.

Effect of hypernatremia in donors on perioperative liver function of recipients undergoing liver transplantation

Wang Bo, Li Xiao, Zhang Pengcheng, Zhang Ruohan, Tao Kaishan

2019, 10(3): 313-317. doi: 10.3969/j.issn.1674-7445.2019.03.015

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Abstract:
Objective To evaluate the effect of hypernatremia in donors on perioperative recovery of liver function in the recipients undergoing liver transplantation. Methods Clinical data of 73 liver transplant recipients were analyzed retrospectively. According to the serum levels of sodium in donors, all recipients were divided into hypernatremia group (donor serum sodium ≥150 mmol/L, n=19) and non-hypernatremia group (donor serum sodium < 150 mmol/L, n=54). Serum alanine aminotransferase(ALT), aspartate aminotransferase (AST), model for end-stage liver disease (MELD) score, albumin, total bilirubin (TB), serum creatinine, prothrombin time and hepatocyte growth factor (HGF) in the recipients were detected at 1, 3, 7, 14 and 21 d after liver transplantation. The time of postoperative use of liver-protecting drugs in the recipients, the length of intensive care unit (ICU) stay, the average length of hospital stay and the incidence rate of postoperative complications were statistically compared and analyzed. Results Compared with the non-hypernatremia group, the serum levels of TB, ALT, AST, HGF and MELD scores of the recipients in the hypernatremia group at the postoperative 1, 3 and 7 d were significantly higher (all P < 0.05), whereas the serum albumin level was significantly decreased (P < 0.05). The prothrombin time in the hypernatremia group was significantly longer than that in the non-hypernatremia group at 3 and 7 d after operation (both P < 0.05). In the hypernatremia group, the time of postoperative use of liver-protecting drugs and the length of ICU stay were 9 (7-13) d and 11 (8-13) d, significantly longer than 4 (3-9) d and 7 (3-9) d in the non-hypernatremia group (both P < 0.05). The average length of hospital stay, serum creatinine level and incidence rate of postoperative complications did not significantly differ between two groups (all P>0.05). All recipients were recovered and discharged. Conclusions The hypernatremia in donors exert no significant effect on the perioperative liver function of the recipients, whereas it can prolong the postoperative recovery time of liver function of the recipients.

Effect of donor risk index on early prognosis of liver transplantation for acute-on-chronic liver failure: experience of 159 cases in one single center

Zhou Zhengjun, Li Jiequn, Bin Yangyang, Chen Guangshun, Li Qiang, Qi Haizhi, Si Zhongzhou, Hu Wei

2019, 10(3): 318-322. doi: 10.3969/j.issn.1674-7445.2019.03.016

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Abstract:
Objective To evaluate the effect of donor risk index (DRI) on the early prognosis of liver transplantation for acute-on-chronic liver failure (ACLF). Methods Clinical data of 159 ACLF recipients undergoing liver transplantation were retrospectively analyzed. According to the calculation formula of DRI, all recipients were divided into DRI < 1.65 group (n=96) and DRI≥1.65 group (n=63). Based on the Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs), all recipients were divided into CLIF-C ACLFs < 48 group (n=78) and CLIF-C ACLFs≥48 group (n=81). The early prognosis indexes including the length of intensive care unit (ICU) stay and the length of postoperative hospital stay of the recipients in each group were observed after liver transplantation. The 90 dsurvival rate of the recipients after liver transplantation was analyzed by Kaplan-Meier survival curve. The risk factors affecting the early prognosis of ACLF recipients after liver transplantation were analyzed by Cox's hazards regression model. Results The length of ICU stay and the length of postoperative hospital stay did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (both P > 0.05). The length of postoperative hospital stay did not significantly differ between the CLIF-C ACLFs < 48 group and CLIF-C ACLFs≥48 group (P > 0.05). The length of ICU stay in the CLIF-C ACLFs < 48 group was 4 (3-14) d, significantly shorter than 7 (1-33) d in the CLIF-C ACLFs≥48 group (P < 0.05). The CLIF-C ACLFs was a risk factor of the early prognosis of ACLF recipients after liver transplantation (P < 0.05). The postoperative 90 d survival rate did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (P > 0.05). The postoperative 90 d survival rate in the CLIF-C ACLFs < 48 group was 94%, significantly higher than 79% in the CLIF-C ACLFs≥48 group (P < 0.05). Conclusions The early prognosis of ACLF recipients after liver transplantation is correlated with the severity of the disease rather than the DRI. Liver transplantation should be performed early and promptly.

Experience in perioperative management of liver transplantation in hepatic coma patients

Liu Huanye, Kou Jiantao, Ma Jun, Zhu Jiqiao, Yang Long, Liu Zixi, Li Xianliang, He Qiang

2019, 10(3): 323-327. doi: 10.3969/j.issn.1674-7445.2019.03.017

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Abstract:
Objective To analyse the clinical efficacy of liver transplantation and summarize the clinical experience of perioperative management in patients with hepatic coma. Methods Clinical data of 22 patients with hepatic coma undergoing liver transplantation were retrospectively analyzed. The perioperative conditions of the recipients were observed, including operation time, warm/cold ischemia time of donor liver, intraoperative anhepatic phase of the recipients, intraoperative blood loss, intraoperative blood transfusion, early postoperative blood drug concentration and incidence of postoperative complications. The survival situation of the recipients and the influencing factors of clinical prognosis were analyzed. Results The operation time of 22 recipients was 8 (6-12) h, the warm ischemia time of donor liver was 4 (2-6) min, the cold ischemia time was 7 (5-10) h, intraoperative anhepatic phase of recipients was 80 (55-120) min, intraoperative blood loss was 1 139 (400-4 000) mL and intraoperative blood transfusion was 1 440 (0-3 600) mL.The blood concentration of tacrolimus (FK506) fluctuated between 6 and 11 ng/mL at postoperative one week. Six recipients died after liver transplantation including 1 case of primary graft liver failure, 2 cases of severe infection, 1 case of severe cerebral edema caused by cerebral hemorrhage and 2 cases of multiple organ failure. The postoperative 1 month and 1 year survival rates of hepatic coma recipients were 82% and 77%. Conclusions Liver transplantation can significantly improve the survival rate of patients with hepatic coma. Preoperative decreasing blood ammonia, controlling postoperative infection, improving renal function and formulating precise individualized immunosuppression therapy according to immune status play a pivotal role in enhancing the survival rate.