Inherited metabolic liver disease (IMLD) is a category of liver metabolic diseases caused by genetic disorders. The pathogenesis of IMLD is complex, which primarily comprises the accumulation of harmful metabolic substrates or products caused by specific enzyme defects and energy defects or abnormal deposition caused by abnormal metabolism of glucose, fat and other substances. In recent years, liver transplantation has played an increasingly critical role in the treatment of IMLD with the development of liver transplantation. At present, IMLD has become the second most important indication after biliary atresia in pediatric liver transplantation. Currently, IMLD patients receiving liver transplantation can be divided into two categories: the first category is IMLD complicated with liver disease; Category 2 patients have a normal liver structure but are deficient in related metabolic enzymes. It can not only replace the liver with abnormal structure and function, but also provide normal enzymes required for patients' metabolism, which may improve their quality of life and even save their lives. In this article, common feasible liver transplantation for IMLD, clinical prognosis and surgical procedures of liver transplantation for IMLD were reviewed, aiming to provide reference for liver transplantation for IMLD.

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Objective:To explore the effect of pre-transplant immunotherapy on the prognosis of transplant recipients with hepatocellular carcinoma(HCC).Methods:From June 2018 to September 2021, retrospective analysis was conducted for clinical data of 19 HCC-liver transplant recipients receiving pre-transplant immunotherapy in affiliated Huashan Hospital of Fudan University. Pre-transplant immunotherapy regimen, adverse reactions, post-transplant acute rejection, tumor recurrence and metastasis and other complications were recorded. According to the preoperative tumor imaging and the changes of alpha-fetoprotein level, tumor change during recipient waiting period was judged by the mRECIST standard. According to whether or not there was partial tumor remission, they were divided into two groups of non-remission( n=13)and remission( n=6). Postoperative conditions of two groups were compared. Kaplan-Meier method was used for calculating the survival rate of recipients after transplantation and survival curve and Log-rank test utilized for comparing the recurrence-free and overall survival rates of recipients at 1 and 2 years post-operation. Results:A total of 19 liver transplant recipients received immunotherapy plus targeted and transcatheter arterial chemoembolization(TACE) before transplant. In non-remission group, tumor was stable( n=9)and progressive( n=4); 6 cases in remission group had tumor partial remission. Two recipients in non-remission group were pathologically confirmed by liver biopsy to have acute rejection(2/19, 10.5%)and both recovered after glucocorticoid + rATG and glucocorticoid therapy. In non-remission group, 2 patients died from septic shock post-operation. Among 3 patients of tumor recurrence and metastasis post-operation, 2 cases survived with tumor and 1 died after tumor recurrence and metastasis. In remission group( n=6), none had postoperative tumor recurrence and metastasis. The recurrence-free survival rates of non-remission group recipients at 1 and 2 years post-operation were 76.9% and 76.9% and recurrence-free survival rates in remission group were 100% and 100% respectively and inter-group difference in RFS was not statistically significant( χ2=1.468, P=0.226). The overall survival rates of recipients in non-remission group at 1 and 2 years post-operation were 76.9% and 76.9% respectively. And recipients in remission group were 100% and 100% respectively and no statistically significant inter-group difference existed in OS( χ2=1.292, P=0.256). Conclusions:Without a significantly higher risk of acute rejection after transplant, immunotherapy may be an effective option for bridging treatment before liver transplantation for HCC. And it remains necessary to expand the sample size for verifications and supports.

Objective:To explore the clinicopathological characteristics, treatments and outcomes of posttransplant lymphoproliferative disorder(PTLD)in pediatric liver transplant recipients.Methods:From October 2016 to October 2021, retrospective data analysis was performed for 11 pediatric liver transplant recipients with PTLD. There were 5 males and 6 females with a diagnostic age of 1-8 years. Living donor liver transplantation(LDLT, n=9)and deceased donor liver transplantation(DDLT, n=2)were performed. All recipients received tacrolimus plus methylprednisolone. The major clinical manifestations included lymphadenopathy, splenomegaly, anemia, fever and digestive system symptoms(diarrhea, abdominal pain, ascites, hematochezia & intussusception, etc.). Laboratory tests hinted at hypoproteinemia, elevated transaminases and serum positivity of EBV-DNA. Positron emission tomography and computed tomography(PET-CT)revealed PTLD( n=9). Ten children were diagnosed by pathology, including lymphoid hyperplasia( n=3), plasmacytic hyperplasia PTLD( n=1), polymorphic PTLD( n=2), diffuse large B-cell lymphoma( n=2), infectious mononucleosis PTLD( n=1)and Burkitt lymphoma( n=1). Results:After a definite diagnosis of PTLD, tacrolimus was tapered or discontinued. And rituximab was prescribed. Two patients received chemotherapy(R-COP & R-CHOP)while 2 cases of local masses were operated. Up until February 2022, 10 cases survived and their conditions improved. One patient died of infection.Conclusions:PTLD is one of the most serious and fatal complications after liver transplantation in children. Clinical manifestations are diverse and an early diagnosis is difficult. The changes of EBV-DNA load should be closely monitored after liver transplantation. Imaging and pathological examinations may aid in an early diagnosis of PTLD. A treatment regimen based on immunosuppression reduction and rituximab improves the prognosis of PTLD in pediatric liver transplant recipients.

Objective:To explore the relationship between CD24 expression in preoperative peripheral blood as well as cancer tissue and clinical parameters and prognosis in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).Methods:From November 2018 to November 2019, clinical data were collected for 65 HCC patients and 41 patients with benign liver disease.The preoperative peripheral blood level of CD24 was detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CD24 in cancerous foci and adjacent tissues examined by immunohistochemistry.Kaplan-Meier survival curves of differential CD24 expression were plotted and survival differences compared by Log-rank method.One-way ANOVA was utilized for examining the relationship between the expression level of CD24 and various clinicopathological parameters and multivariate Cox analysis for screening independent risk factors affecting patient prognosis.Results:The concentration of CD24 in preoperative peripheral blood (p-CD24) of HCC patients (6.51±2.33 μg/L) was significantly higher than that of patients with benign liver disease (4.10±0.91) μg/L, P<0.05.The positive rate of CD24 was obviously higher in cancerous tissues than that in adjacent tissues (87.7% vs. 4.6%, P<0.05). The peripheral blood level of CD24 was positively correlated with the expression intensity of CD24 in tumor tissues (t-CD24, r=0.570, P<0.001). The expression of CD24 (both in blood and cancer foci) was significantly correlated with preoperative level of gamma-glutamyl transferase (GGT), maximal tumor diameter, microvascular invasion, portal vein tumor thrombus, vessel carcinoma embolus and satellite focus ( P<0.05). The expression of CD24 in patients exceeding the Milan/UCSF criteria was higher than those fulfilling the criteria ( P<0.005). Patients with a higher expression of CD24 had worse overall survival and recurrence-free survival rates as compared to those a lower expression of CD24 ( P<0.05). Multivariate Cox analysis indicated that t-CD24 [OS: HR=3.661(1.005-13.333)], P=0.049; recurrence-free survival (RFS): [HR=4.331(1.887-9.942), P=0.001] and preoperative level of alpha fetoprotein (AFP) [OS: HR=4.900(1.590-15.097), P=0.006]; RFS: [HR=3.414(1.614-7.221), P=0.001] were independent risk factors for overall survival and recurrence-free survival in HCC patients undergoing LT. Conclusions:The preoperative peripheral blood level of CD24 in HCC patients undergoing LT indirectly reflects the expression of CD24 in cancerous tissues to a certain extent.And the expression of CD24 in cancerous tissue is one of the independent risk factors affecting OS and RFS of LT patients.

Objective:To investigate the imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinical data of 39 living donor liver transplantation (LDLT) donors who were admitted to Huashan Hospital Affiliated to Fudan University between October 2016 and December 2018 were collected. There were 10 males and 29 females, aged (31±7)years. The clinical data of 39 LDLT recipients were collected. There were 26 males and 13 females, aged 8 months (range, 4-68 months). Abdominal enhanced computed tomography and three-dimensional vascular reconstruction were performed on donors to evaluate the anatomical characteristics of hepatic vessels. All the donors underwent laparoscopic left lateral donor liver acquisition. Observation indicators: (1) three-dimensional vascular reconstruction of preoperative imaging; (2) surgical conditions; (3) follow-up. Follow-up was performed using outpatient examination to detect complications of recipients after LDLT up to October 2019. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Three-dimensional vascular reconstruction of preoperative imaging: the anatomical characteristics of hepatic artery and hepatic vein revealed by three-dimensional vascular reconstruction of preoperative imaging of 39 donors included ① middle hepatic artery was present in 11 donors, among which 5 started from the right hepatic artery, 3 from the confluence of the right and left hepatic artery, and 3 from the left hepatic artery. Two donors had anatomical variation in the left hepatic artery which was presentation of left accessory hepatic artery originated from the left gastric artery. The other 26 donors had no middle hepatic artery or anatomical variation in the left hepatic artery. ② The left hepatic vein and the middle hepatic vein of 9 donors were respectively drained into the inferior vena cava. Seven donors had the left upper branch of the left hepatic vein, and 23 donors had a joint trunk of the left hepatic vein and the middle hepatic vein which drained into the inferior vena cava. (2) Surgical conditions: ① all the 39 donors successfully underwent laparoscopic left lateral donor liver acquisition. The operation time and volume of intraoperative blood loss were (160±32)minutes and (142±74)mL. ② Of 11 donors with middle hepatic artery, left hepatic artery was the dominant artery in 8 donors and was used for hepatic artery anastomosis and reconstruction in liver transplantation, middle hepatic artery started from left hepatic artery in 3 donors and the joint trunk of left and middle hepatic artery was used for hepatic artery anastomosis and reconstruction in liver transplantation. Of 2 donors with anatomical variation in the left hepatic artery, one had left accessory hepatic artery as the dominant artery and the other had left hepatic artery as the dominant artery. Left accessory hepatic artery and left hepatic artery were respectively used for hepatic artery anastomosis and reconstruction in liver transplantation. The other 26 donors had left hepatic artery for hepatic artery anastomosis and reconstruction in liver transplantation. ③ Among the 39 donors, 11 received intraoperative left hepatic vein preferred approach and 28 received intraoperative non-left hepatic vein preferred approach. The operation time and volume of intraoperative blood loss of donors with left hepatic vein preferred approach were (147±22)minutes and (110±44)mL, respectively, versus (169±33)minutes and (154±81)mL of donors with non-left hepatic vein preferred approach, showing significant differences in the above indicators between the two groups ( t=4.19, 2.81, P<0.05). (3) Follow-up: 39 donors were followed up for 10 months. During the follow-up, there was no hepatic artery anastomotic bleeding, stenosis, ischemic bile duct injury and biliary stenosis caused by poor hepatic arterial blood supply, or any complications related to hepatic venous outflow tract stenosis. Conclusions:Three-dimensional vascular reconstruction before laparoscopic left lateral donor liver acquisition can reveal the anatomical variation of middle hepatic artery and left hepatic artery, which can guide the selection of surgical approach. The left hepatic vein preferred approach is recommended for the qualified donor in the laparoscopic left lateral donor liver acquisition, which can shorten the operation time and reduce the volume of intraoperative blood loss.

Objective To summarize the screening Methods for human parvovirus (HPV) B19 infection after liver transplantation and analyze the related risk factors. Methods Clinical data of 86 recipients were retrospectively analyzed. According to the Results of next generation sequencing (NGS), all recipients were divided into the HPV B19 infection group and control group. Clinical characteristics, treatment regime and clinical prognosis of patients infected with HPV B19 were analyzed. The risk factors of HPV B19 infection were analyzed using univariate and multivariate Logistic regression model by forward LR step method. Results Nine of the 86 recipients developed fever and progressive anemia with unexplained reasons at approximately 2 weeks after liver transplantation. NGS detection demonstrated that HPV B19 was positive and they were diagnosed with pure red cell aplasia (PRCA) caused by HPV B19 infection. After intravenous immunoglobulins (IVIG) was given and the immunosuppressant therapy was adjusted, the hemoglobin levels in all patients were significantly increased. The Results of multivariate analysis revealed that low serum globulin level in peripheral blood at postoperative 7 d [odds ratio (OR) =0.749, P=0.040] and young age (OR=0.937, P=0.038) were the independent risk factors of HPV B19 infection after liver transplantation. Conclusions HPV B19 infection should be considered in relatively young patients with unexplained hemoglobin decline early after liver transplantation. NGS screening is an effective method for early diagnosis of HPV B19 infection. Low serum globulin level in peripheral blood at postoperative 7 d and young age may be independent risk factors of the incidence of HPV B19 infection.

Objective To explore the postoperative psychological status of donors during pediatric living donor liver transplantation (LDLT) to elucidate the correlation between resilience,anxiety and depression.Methods Random sampling was employed for selecting 60 pediatric LDLT donors undergoing LDLT from September 2014 to February 2019.They were requested to answer a questionnaire.The questionnaire concluded general information,self-rating anxiety scale (SAS),selfrating depression scale (SDS) and Chinese version of Resilience Scale.Results The score of anxiety was (46.06 ± 10.06) and depression was (50.32 ± 11.49).Both values were higher than those of Chinese norm.The score of resilience was (59.55 ± 14.62).And the total score of resilience and the score of each dimension were negatively correlated with anxiety and depression (P＜0.01).Conclusions The postoperative anxiety and depression level of donors during LDLT are higher than the ordinary.Resilience is negatively correlated with the level of anxiety and depression.The lower level of resilience,the higher anxiety and depression of donors during LDLT.For clinicians,appropriate intervention measures should be taken for improving the resilience,reducing negative emotions and boosting the quality-of-life of donors during LDLT.

Objective To explore the clinical features and risk factors associated with intrahepatic and hilar cholangiocarcinoma after liver transplantation .Methods Retrospective analysis of clinical data was performed for 20 hospitalized patients with intrahepatic and hilar cholangiocarcinoma from June 25 ,2014 to October 31 ,2018 .Treatments and follow-up outcomes were analyzed .The survival rate was calculated by the Kaplan-Meier method and the survival curve plotted .Cox regression model was employed for analyzing the prognostic factors .Results The cumulative recurrence rate of patients with AJCC stage Ⅰ /Ⅱ was significantly lower than that in AJCC stage Ⅲ/Ⅳ .And the cumulative recurrence rate of stageⅠ/Ⅱ Patients was 0 and that of stage Ⅲ/Ⅳ 76％ (P=0 .042) .Cox regression model showed that CA19-9 was the only prognostic factor .An elevated level of CA19-9 was associated with high recurrence post-transplantation (HR=1 .001;95％ CI:1 .000～1 .001;P=0 .035) .Conclusions During progressive stage ,the recurrence rate is higher with a worse prognosis .And an elevation of CA19-9 is an independent poor prognostic factor after intrahepatic and hilar cholangiocarcinoma transplantation .

OBJECTIVETo summarize the clinical characteristics, early diagnosis, comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.

METHODData of 6 cases with PTLD seen between January 2011 and December 2013 were retrospectively analyzed. The anti-rejection drug dose adjustments, the effect of rituximab, antiviral therapy and comprehensive treatment program after surgery were explored.

RESULT(1) The diagnosis of PTLD was confirmed by histologic findings. Six cases of PTLD including 3 males and 3 females were diagnosed as congenital biliary atresia and underwent split liver transplantation. The occurrence rate of PTLD was 2.9%. (2) The median time to the development of PTLD was less than 6 months. The initial symptom of PTLD in all patients was fever and clinical manifestations of PTLD were non-specific, depending on the involving organs. Five cases of PTLD developed gastrointestinal symptoms, including diarrhea, abdominal pain, and abdominal distension. One case developed respiratory symptoms, including cough and tachypnea. Three cases had lymph node involvement. In 2 cases pathophysiology involved polymorphic lymphocyte proliferation and in 4 cases B lymphocyte proliferation. (3) Two cases died, in whom EBV DNA was not detected and were diagnosed as PTLD by surgical pathology before death. Four survived cases had high EBV-DNA load and then were diagnosed as PTLD by biopsy pathology. (4) Of the 6 cases of PTLD, 2 cases died and 4 cases survived. The overall mortality was 33%. The dead cases were only treated with laparotomy because of intestinal obstruction or perforation and the survived cases were treated with tacrolimus at reduced doses or discontinuation and rituximab. In 2 cases antiviral therapy (acyclovir) was continued, including 1 cases of intestinal obstruction treated with surgical repair. All the survived patients were followed up for 4 months to 1 year and no evidence has been found.

CONCLUSIONEBV infection is the high risk factor for PTLD after liver transplantation. Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD. Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD. A reduction in the dose of tacrolimus is suggested. Operation therapy can also play a role in the management of local complications.

Antiviral Agents ; administration & dosage ; Biliary Atresia ; therapy ; DNA, Viral ; analysis ; Drug Therapy, Combination ; Early Diagnosis ; Epstein-Barr Virus Infections ; diagnosis ; therapy ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Infant ; Liver Transplantation ; adverse effects ; Lymphoproliferative Disorders ; diagnosis ; etiology ; mortality ; therapy ; Male ; Pediatrics ; Postoperative Complications ; Retrospective Studies ; Survival Rate ; Tacrolimus ; administration & dosage