Liver transplantation has become an important method for radical treatment of hepatocellular carcinoma (HCC), but postoperative recurrence and metastasis severely limit the efficacy of liver transplantation for HCC. In recent years, scholars in China and globally have conducted a series of studies on the association of the application of immunosuppressants after liver transplantation with the recurrence and metastasis of HCC. This article briefly introduces the strategies and suggestions for the clinical application of immunosuppressants after liver transplantation for HCC, in order to provide guidance for clinical practice.

Immune induction therapy with antibodies has been widely applied in liver transplantation. This paper introduces common antibodies for immune induction and their application in liver transplantation, and points out that immune induction therapy with antibodies reduces the dosage of hormones and calcineurin inhibitors (cyclosporine and tacrolimus), reduces infections effectively, protects renal function, prevents acute rejection reaction, and finally improves the prognosis of transplant recipients. The effect of immune induction therapy with antibodies on hepatitis and liver cancer still needs further investigation.Key words：liver transplantation；immunity induction；therapy

Objective To explore the features of peripheral blood immune cells in long-term survival recipients after liver transplantation.Methods The expression of T subsets (Th1,Th2,Th17,Th22,Tregs),NK cells,NKt cells,Bregs,MDSC in long-term survival recipients (postoperative follow-up time ≥5 years,30 cases),short-term survival recipients(postoperative follow-up time ≤1 year,15 cases) and healthy control (15 cases) were determined by flowcytometry.Results Th17 cells were significantly higher in the long-term group compared with short-term group and healthy control group(P ＜0.01).Tregs in long-term group compared with short-term group were significantly higher (P ＜ 0.01),but the difference was not statistically significant compared with healthy control group (P ＞ 0.05).NK cells were significantly higher in long-term group compared with short-term group and healthy control group (P ＜ 0.01).MDSC were significantly higher in long-term group compared with short-term group and healthy control group (P ＜0.01).Conclusions Th17,Tregs,NK cells and MDSC were significantly higher in long-term survival of liver recipients,which may be related to immune tolerance.

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Objective To evaluate the clinical efficacy of application of hepatitis B surface antigen (HBsAg)-positive donor liver in adult liver transplantation. Methods Clinical efficacy of 28 recipients with liver diseases induced by virus B hepatitis (hepatitis B) undergoing liver transplantation using HBsAg-positive donor liver from July 2012 to October 2015 was retrospectively analyzed. Clinical prognosis and postoperative complications of the recipients were summarized. The changing features of serum levels of HBsAg and hepatitis B virus (HBV) DNA was investigated. Results After liver transplantation, 28 recipients were orally administered with entecavir to prevent the recurrence of hepatitis B. During perioperative period, 2 recipients died from sepsis and acute heart failure. During postoperative follow-up, 2 cases died from the recurrence of hepatocellular carcinoma (liver cancer). The remaining 24 patients were followed up for 12-26 months. Throughout the follow-up, 24 recipients were positive for serum HBsAg. After treatment, the titre of HBV DNA was significantly declined to <1×102 copies/mL at postoperative 12 months. No graft dysfunction induced by hepatitis B recurrence occurred in 24 recipients alive. Conclusions As a marginal donor liver, HBsAg-positive liver graft is safe for liver transplantation in the recipients with hepatitis B-related liver diseases. Postoperatively, anti-HBV treatment should be strengthened and intimate follow-up should be delivered.

Objective:To explore the safety and efficacy of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma with PD-L1 negativity in transplanted liver tissue.Methods:From May 2020 to December 2020, retrospective analysis was performed for 3 cases of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma recipients with PD-L1 negative in transplanted liver tissue.Three recipients with extrahepatic recurrence progressed after first/second-line targeted drug therapy.Camrelizumab was given as salvage therapy after normal tissue of ransplanted liver was confirmed as negative for PD-L1 by immunohistochemistry.The safety and efficacy of treatment were observed by monitoring the changes in the levels of alanine aminotransferase, aspartate aminotransferase and bilirubin, the occurrence of complications and the outcome of treatment before and after dosing.Results:During a follow-up period of 1.5 to 15.5 months, no recipients showed acute rejection symptoms such as sharp elevations of transaminase and bilirubin.Headache ( n=1), vomiting ( n=1) and fatigue & hypertension ( n=1) became relieved after treatment.As of February 28, 2022, there were one survivor and two deaths.The fatal causes were tumor progression ( n=1) and thoracic aortic rupture due to esophageal perforation ( n=1). The survival time of recipients was (11-15.5) months and the progression-free survival time (4-6) months. Conclusions:For extrahepatic recurrent hepatocellular carcinoma with PD-L1-negative liver transplantation in normal liver tissue, camrelizumab salvage therapy can control tumor progression to a certain extent and prolong the survival time of recipients.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.