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Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To investigate liver transplantation patients who survived for more than 5 years for the occurrences of their various long-term complications, prevention and treatment., Methods: By May 31, 2010, totally 69 patients who had received liver transplantation from July 2000 to May 2005 in Peking University People's Hospital were still alive. We reviewed the clinical data of these patients and the recent records of their liver and kidney functions, blood pressure, blood sugar and blood fat, etc. The occurrences of their various long-term complications were summarized and the status of treatment was studied., Results: In these 69 patients, 39.1% (27/69) of them were overweight or obese, 33.3% (23/69) had post transplantation diabetes mellitus (PTDM), 26.1% (18/69) had hyperlipemia, 20.3% (14/69) suffered from renal insufficiency, 15.9% (11/69) had hypertension and 23.2% (16/69) had hyperuricemia. Interestingly, the occurrences of PTDM and hyperlipemia in overweight or obese patients were higher than those in normal weight patients (48.2% vs. 23.8% and 40.7% vs. 16.7%, P<0.05). In addition, hepatitis B virus (HBV) infection recurred in 4 patients out of the 61 patients who had HBV related liver disease pre-operation, and liver cancer relapsed in 3 patients out of the 19 patients who had hepatocellular carcinoma (HCC) pre-operation. Totally 4 patients received re-transplant during the follow-up., Conclusion: The occurrences of long-term complications in liver transplantation patients who survived for more than 5 years were rather high, so the follow-up should be strengthened and procedures done to avoid the exacerbation of these complications.

Objective: To explore the experience of hepatic arterial reconstruction and management of its complications., Methods: The clinical data of 570 consecutive orthotopic liver transplantation patients performed from May 2001 to May 2009 in Peking University People's Hospital were analyzed retrospectively in order to summarize the key factors of hepatic arterial reconstruction and the experience of management of its complications., Results: Arterial complications developed in 18 (3.1%) of the 570 patients including 11 cases of hepatic artery thrombosis, 5 cases of hepatic artery stenosis and 2 cases of hepatic artery rupture. Of the 11 cases with early complication (within 4 weeks), 7 patients died, including 2 due to the rupture of hepatic artery and 5 due to acute liver failure and sepsis of hepatic artery thrombosis. Of the 7 cases with late complication, 4 patients died, including 1 due to graft failure and 3 due to ischemic-type biliary complications., Conclusion: Good quality of donor artery and proper choice of microsurgical anastomosis technique in hepatic artery reconstruction could significantly reduce the incidence of its complication. Early detection and diagnosis with active early interventional therapy can improve prognosis of the patients.

In documenting clinical experience in the diagnosis and treatment of graft versus host disease (GVHD), we retrospectively analyzed data of one case that has developed GVHD after liver transplantation. This patient exhibited fever, skin rash, and diarrhea on day 9 after liver transplantation. His liver function was normal. Skin biopsy showed scattered keratinocytes accompanied by satellite-like lymphocyte infiltration and basal cell liquefaction degeneration. After carefully analyzing the complications, we took the strategy of decreasing the dose of tacrolimus. Thereafter, the patient's temperature decreased to normal, his skin rashes subsided, and his diarrhea was relieved. This case suggests that reducing the dosage of immunosuppressive agents can be an effective strategy for GVHD after liver transplantation.

Objective: To investigate the outcome of liver transplantation(LT) for end stage liver disease with portal vein thrombosis (PVT) in different processes., Methods: Data from 308 patients who underwent LT from July 2004 to February 2008 were retrospectively assessed. The processes of varies grades of PVT during LT were analyzed and estimated for whether the outcome of LT was different between patients with or without PVT., Results: There were 46 patients with PVT, including 11 of grade 1, 14 of grade 2, 18 of grade 3 and 3 of grade 4. LT performed in grade 1 and 2 PVT patients without special intervention. LT was performed in 16 patients with grade 3 PVT after simple thrombectomy or thrombus-extraction. The other 2 patients with grade 3 PVT received the donor superior mesenteric vein to act as a bridge between the donor portal vein and host superior mesenteric vein. Two cases with grade 4 PVT received a cavo-portal hemitransposition, and the other one anastomosis between graft portal vein and varicose coronary vein. The postoperative 1-year survival rates of patients without PVT and patients with PVT were 91.6%(240/262), 80.5%(211/262)vs 86.9%(40/46), 76.1%(35/46), respectively. The patients with PVT had a recurrence rate of 4.3%(2/46)., Conclusion: Most patients suffering from end stage liver disease with PVT can be successfully treated by LT. However, the result of the patients with diffused PVT undergoing LT is relatively poor.

Objective: To determine the preventative and curative strategies after liver transplantation by investigating the risk factors on prognosis., Methods: The data of 565 consecutive patients who underwent orthotopic liver transplantation were retrospectively analyzed with the survival rate and complication morbidity., Results: The follow-up time ranges from 3 to 104 months of all the 565 patients after liver transplantation. From January 2004 to January 2009, the patient survival rates were 91.2% after 1 month, 84.9% after 1 year, 69.2% after 3 years, and 66.1% after 5 years, while they were 87.8%, 73.2%, 60.2%, and 57.7% from May 2000 to December 2003. The patient survival rates were 83.3% after 1 year, 79.8% after 3 years, and 78.5% after 5 years in non-hepatocellular carcimoma (non-HCC) group, while they were 78.4%, 49.1%, and 45.1% in HCC group. In early stage after surgery, the morbidities of re-operation due to intra-abdominal hemorrage, vascular complication, severe infection, acute renal failure and primary graft dysfunction were 1.1%, 1.6%, 13.6%, 7.4%, and 1.2%, while in late stage, the morbidities of HCC recurrence, biliary complications, HBV recurrence, de novo malignancy, chronic graft dysfunction were 40.3%, 6.7%, 2.1%, 0.9%, 0.9%, and 1.1%, respectively. The HCC recurrent rates were 8.1% versus 62.5% in matching Milan criteria group or exceeding Milan criteria group and the median survival time was 19.6 months of all recurrent patients., Conclusion: Liver transplantation has been the effective treatment for end stage liver disease. Due to the shortage of graft,we prefer to do operations for the patients without HCC or the patients with HCC but matching Milan Criteria.

Objective: To investigate principal surgical techniques of living donor liver transplantation (LDLT) ., Methods: A retrospective analysis was made in 4 cases undergoing living donor liver transplantation from Feb. 2003 to Nov. 2006., Results: All the living donors of 4 cases were adults, including the right lobe transplanted in 3 patients (not including the middle hepatic vein in 2, including the middle hepatic vein in one), the extended left lateral lobe (not including the middle hepatic vein) in one. The graft-to-recipient weight ratio (GRWR) was 0.85%-1.44%. The right hepatic vein reconstructions were performed in end to end anastomoses in 3 patients. The left and middle hepatic vein reconstruction was performed in end to end left hepatic vein of graft anastomosis in one. The arterial anastomoses were performed in end to end, including the right hepatic arteria of the graft to the hepatic proprial arteria in 2 patients, the branch of the right hepatic arteria of the graft through the radialis arteria to the hepatic proprial arteria in one, the left hepatic arteria of the graft to the hepatic proprial arteria in one. Biliary reconstructions were made by using duct to duct anastomoses, and placement of a T tube in 2 patients. All 4 donors were uneventfully discharged after operation. Four recipients were without vascular complication, and the stoma of bile duct was light stegnosis in a child recipient without "T" tube. They have been surviving 58 months, 32 months, 20 months and 14 months respectively., Conclusion: The process of LDLT was complicated, and the surgical technique was difficult. Choosing suitable donors and flexible mastering of the principal surgical techniques can achieve favorable prognosis of LDLT.

Objective: To investigate the variations type of hepatic artery and discuss the method of how to protect hepatic artery from injury during the quick harvest of the donor liver., Methods: A retrospective review of the variations of hepatic arteries of the donor livers and the course of excision and reconstruction of 200 donor livers was performed, and the aberrance and reconstruction method of hepatic arteries were summarized., Results: 37 out of 200 hepatic arteries varied and 2 patients suffered biliary complications because of improper preservation of aberrant hepatic arteries., Conclusions: Most aberrant liver arteries come from superior mesenteric artery or left gastric artery. Proper quick harvest of multiple organs is the basis of the integrity of hepatic arteries, and all the aberrance must be reconstructed.

Objective: To study the risk factors of renal failure in the early post-liver transplantation period., Methods: 92 consecutive liver transplantation cases were reviewed and a multi-factor analysis of presumed risk factors of early post-transplantation period renal failure was conducted. The factors analyzed were total bilirubin level, prothrombin activity, onset of structural renal disease, onset of gastrointestinal hemorrhage, whether the patient underwent large-volume paracentesis, or underwent plasmapheresis therapy, needed renal replacement therapy, the operation method used, the bleeding volume during operation and the immunosuppressive agents used., Results: Of the 92 patients, 29 (31.5%) developed acute renal failure (ARF) in the early postoperative period. Multi-factor analysis revealed a high pre-transplantation serum creatinine level and low prothrombin activity as risk factors for development of ARF., Conclusion: ARF is a frequent medical complication after liver transplantation. A high pre-transplantation serum creatinine level and low prothrombin activity are risk factors of its development.

Objective: To investigate the diagnosis and managements of hepatic artery complications in orthotopic liver transplantation., Methods: The clinical data of 107 consecutive orthotopic liver transplantation patients was reviewed retrospectively to assess the risk factors and the diagnosis and treatment of the vascular complications., Results: The incidence of the artery related complications in orthotopic liver transplantation was associated with the quality of the donor organ artery and the reconstruction way of donor-recipient artery intimately. The main hepatic artery related complications were hepatic artery thrombosis and stenosis. The incidence of the vascular complications was 6.54%, and the mortality rate was 85.7%., Conclusions: The main influence factors of vascular complications were the quality of the donor organ artery and the reconstruction way of donor-recipient artery. The key steps of organ salvaging and the patients' life saving were early diagnosis and treatment of those complications.

Objectives: To summarize hemodynamic and metabolic changes during bypass, and to evaluate the bypass in liver transplantation., Methods: Fifty-four patients underwent orthotopic liver transplantation with venovenous bypass from May 2000 to May 2002. Their clinical features were analysed., Results: SHR, MAP, CVP, CO, PaO(2), PaCO(2), serum K(+), Na(+), Ca(2+), BUN values were not significantly changed during bypass. Compared to the pre-bypass stage, pH was decreased in the post-bypass stage (P < 0.05), serum lactic acid value was increased in the bypass and post-bypass stage (P < 0.05), active clotting time was increased in the bypass stage (P < 0.05), serum creatinine value was increased on first postoperative day (P < 0.05)., Conclusions: Venovenous bypass could improve hemodynamic and metabolic stability in the anhepatic phase, but it also could increase operation duration, liver ischemic time and cost.