Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.

Up to now, a variety of immune checkpoint inhibitors (ICIs) have been proved to have good therapeutic effects in the treatment of hepatocellular carcinoma (HCC). However, the effects of their applications in liver transplant (LT) recipients are still unclear. In this analysis report, the clinical applications and therapeutic effects of ICIs on LT recipients with hepatic tumor recurrence or de novo carcinoma based on eight databases, including PubMed, EMBASE, Web of Science, Google Scholar, China National Knowledge Infrastructure, Wanfang Data, and CQVIP, were investigated. And the prior treatment, disease response, adverse reactions, and prognosis of patients with malignant tumors after LT and receiving ICI treatments were analyzed. After screening, a total of 28 articles with 47 recipients on the application of ICIs after LT were included. In these patients, their median age was 57 (14-71) years and the main type of tumor after LT was HCC (59.6%). The overall remission rate following ICI treatment was 29.8% (14/47) and the disease progression rate was 68.1% (32/47). Among all these patients, 31.9% (15/47) of patients had immune rejection; the median survival time was 6.5 (0.3-48) months, and the fatality rate was 61.7% (29/47). Considering that the therapeutic effect of ICIs in LT recipients with HCC recurrence or de novo carcinoma is not ideal, ICI treatment should be carefully considered for LT patients, and further research is needed.

Liver transplantation is an effective treatment for patients with various end-stage liver diseases, and the demand of graft livers is increasing. Non-alcoholic fatty liver disease (NAFLD) is getting more and more attention as a chronic liver disease. Recently, the international expert consensus has proposed a new name for NAFLD-metabolic associated fatty liver disease. With the increasing number of liver transplantation, the problems of NAFLD after transplantation have attracted more and more attention. This paper reviews the occurrence, risk factors, measures of prevention and treatment in NAFLD after liver transplantation.

本综述介绍了免疫检查点抑制剂在肝癌肝移植中的研究进展，总结了近几年国内外对肝癌肝移植术后免疫检查点抑制剂药物应用的临床报道，分别从免疫检查点抑制剂的作用机制、临床应用、发生排斥反应的相关因素及机制等方面做了详细描述，以期为临床管理人员制定肝癌肝移植术后诊疗计划提供参考。

近年来,免疫检查点抑制剂(Immune Checkpoint Inhibitors,ICIs)药物作为一类新型的抗肿瘤药物,已在黑色素瘤、非小细胞肺癌和肾细胞癌等多种肿瘤中显示了生存益处.免疫检查点是指调节免疫系统平衡的负性调控因子所对应的抑制性信号通路,其受体包括程序性死亡受体(PD-1)和抗细胞毒性T淋巴细胞相关抗原-4(CTLA-4),均可下调免疫细胞介导的免疫应答.而ICIs则可阻断对淋巴细胞的免疫抑制通路,使淋巴细胞发挥正常功能,从而抑制肿瘤细胞生长,达到肿瘤免疫治疗效果.

红皮病(Erythroderma)是一种病因复杂、 病死率高的全身性皮肤病,表现为全身皮肤广泛的红斑和脱屑,体表受累面积可超过90％[1].红皮病的年发病率约为0.0001％～0.0002％[2].肝移植术后红皮病的临床报道并不多见,且该症的临床诊疗具有其特殊性及一定难度,本文回顾了1例少见的肝移植后新发重度红皮病的临床诊疗经验,报道如下.

Objective:To investigate the clinical efficacy and safety of sorafenib sequential regorafenib in the treatment of recurrence of hepatocellular carcinoma after liver transplantation.Methods:The clinical data of 14 patients with hepatocellular carcinoma who had tumor recurrence after liver transplantation and received sorafenib and regorafenib were collected from the Affiliated Hospital of Qingdao University from February 2014 to September 2020. After the clinical diagnosis of recurrence of liver cancer, sorafenib (400 mg/time, twice a day, oral) was added for treatment. When the disease progressed or the adverse events of sorafenib was not tolerated, sequentially treated with regorafenib (160 mg/time, once a day, oral, continuous medication for 21 days, stop medication for 7 days, every 28 days is a cycle) treatment. The medication was supplemented with symptomatic support treatment, followed up regularly, alpha-fetoprotein (AFP), liver function, immunosuppressive blood concentration, ultrasound or CT and other imaging examinations were monitored, and adverse events were recorded.Results:Among the 14 patients who finally met the inclusion criteria, 12 were males and 2 were females; the median age was 56.5 (40.0-65.0) years. The median interval from tumor recurrence after liver transplantation to initiation of sorafenib was 1.0 (0.1-6.4) months. The median treatment time for sorafenib was 2.7 (0.9-9.2) months, and the median time to progression (mTTP) was 4.4 (0.9-14.1) months. The median time between cessation of sorafenib and initiation of regorafenib was 16.5 (1-366) d; the median treatment time of regorafenib was 9.3 (1.3-20.4) months, the mTTP was 2.8 (1.0-9.7) months, and the median overall survival (mOS) was 20.1 (95%CI 0.7-39.5) months. There were no significant differences in AFP and liver function indexes before and after sorafenib treatment (all P>0.05). AFP increased and serum albumin decreased after treatment, with statistical significance (all P<0.05). ALT, AST and total bilirubin changes had no statistical difference (all P>0.05). Adverse events during the treatment of sorafenib and regofinib included: diarrhea (9 cases and 10 cases), fatigue (9 cases and 6 cases), decreased body mass (3 cases and 2 cases), and hand-foot skin reactions (1 case and 2 cases), respectively. Among them, sorafenib treatment was terminated in 2 cases due to severe diarrhea, and the dosage of regogafenib was reduced in 1 case, and the treatment of regogafenib was discontinued in 1 case due to hand and foot skin reaction, respectively. The other patients had adverse reactions and were tolerated after symptomatic treatment. By September 2020, the median follow-up time was 12.4 (5.6-34.2) months, and a total of 7 patients died, all due to tumor progression after liver cancer recurrence. Of the 7 patients who survived, 3 were discontinued due to lung tumor progression, and 4 were continued with regofinib. The mOS was 14.4 (95%CI 3.4-25.4) months for 14 patients who received sorafenib sequential regolfinib, and the 1-year and 2-year cumulative survival rates were 67.7% and 48.4%, respectively.Conclusion:Sorafenib sequential regorafenib for the treatment of tumor recurrence after liver transplantation of hepatocellular carcinoma has good clinical efficacy and safety, but a larger sample size of research support is still needed.