Prophylactic Strategy Against De Novo Hepatitis B Virus Infection for Pediatric Recipients Who Receive Hepatitis B Core Antibody-Positive Liver Grafts.

The goal of this study was to evaluate the efficacy of a perioperative prophylactic strategy against de novo hepatitis B virus (HBV) infection in pediatric liver transplantation (LT) recipients with hepatitis B core antibody (HBcAb)-positive grafts. A total of 482 pediatric recipients transplanted between 2013 and 2017 were enrolled, and 170 recipients received HBcAb-positive liver grafts. The overall graft and recipient survival rates in HBcAb-positive and HBcAb-negative graft recipients were 91.8% versus 91.3% and 95.3% versus 94.2% at the end of follow-up. Preoperative hepatitis B surface antibody (HBsAb) titer ≥ 1000 IU/L and postoperative HBsAb titer ≥200 IU/L were our prophylactic targets for recipients receiving HBcAb-positive grafts. While 11 recipients developed de novo HBV infection, 10 received HBcAb-positive grafts. Both the preoperative and postoperative HBsAb targets were achieved in 78 recipients, the infection rate of de novo HBV was 1.3%; 24 recipients met the preoperative target, the infection rate was 4.2%; 52 recipients met the postoperative target, the infection rate was 1.9%; and 16 recipients met neither the preoperative nor postoperative HBsAb target, 43.8% of the recipients were infected with de novo HBV, which was significantly higher than the recipients who met both or either of the preoperative and postoperative targets. Split-liver grafts positive for HBcAb showed higher risk of de novo HBV infection. Postoperative application of lamivudine to recipients whose preoperative HBsAb titer < 1000 IU/L did not show preventive effect. Out of 11 infected recipients, 3 showed seroconversion under entecavir treatment. In conclusion, the graft and recipient survival rates were similar in pediatric LT recipients receiving HBcAb-positive or HBcAb-negative grafts. Our prophylactic strategy was effective for preventing de novo HBV infection in HBcAb-positive liver graft recipients.

Successful living donor liver transplantation plus domino-auxiliary partial orthotopic liver transplantation for pediatric patients with metabolic disorders.

PURPOSE: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders. METHODS: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. RESULTS: The mean follow-up was 26.6 months. The liver function and ammonia remained in the normal range at the end of the follow-up in all recipients. One D-APOLT patient experienced portal vein thrombosis 2 days after transplantation and required reoperation, this patient presented an imbalance of portal blood perfusion between the native and the domino liver at 8 months after liver transplant. The imbalance was improved by interventional radiology treatment. Two LDLT patients experienced early mild acute rejection. CONCLUSIONS: The non-cirrhotic livers from pediatric patients with metabolic liver disease can be used as domino donor grafts for selected pediatric patients with different metabolic liver disease. D-APOLT achieves ideal recipient outcomes and provides a strategy to expand donor source for children.

Bibliometric Analysis of Pediatric Liver Transplantation Research in PubMed from 2014 to 2018.

BACKGROUND Pediatric liver transplantation is used to treat children with end-stage liver disease. This study explored the research hotspots and bibliometric characteristics of pediatric liver transplantation through a variety of bibliometric analysis software. We conducted hotspot analysis to help determine important directions for future scientific research. MATERIAL AND METHODS The study samples were articles related to pediatric liver transplantation published in PubMed in the past 5 years. The high-frequency keywords are extracted by BICOMB software, and then a binary matrix and a common word matrix were constructed. Gcluto software was used to perform double-clustering and visual analysis on high-frequency words, and then we obtained hot area classification. Strategic coordinates are constructed using Excel. Citespace and VOSviewer software are used for further analysis and bibliometric data visualization. RESULTS A total of 36 high-frequency words were found in the 4118 studies. A peak map was drawn through double-cluster analysis. Biclustering analysis was used to calculate the concentricity and density of each hotspot. We obtained the top 10 countries/regions engaged in pediatric liver transplantation research. VOSviewer was used to visualize the co-author map. CONCLUSIONS We found 5 clusters and 7 aspects for pediatric liver transplantation. Additionally, calculation results showed that post-transplant lymphoproliferative disorder in pediatric patients and outcomes of multivisceral transplantation seem very promising. This conclusion is of great value for future exploratory research.

The management and outcomes of ABO-incompatible pediatric liver transplantation: Experience of a single Chinese center.

BACKGROUND: To investigate the safety of using ABO incompatible (ABO-i) liver grafts in pediatric patients under our prophylactic strategies. METHODS: A total number of 544 pediatric liver transplantations between January 2013 and December 2017 performed in Organ Transplant Center, Tianjin First Central Hospital were included in this study. The recipients were divided into 3 groups based on the compatibility of donor-recipient blood type matching (ABO-identical group, n = 352, ABO-compatible group, n = 121 and ABO-incompatible group, n = 71). Recipient characteristics, perioperative data, postoperative complications and recipient survival rate were compared. The recipient outcomes between living-related and non-living-related ABO-incompatible liver graft recipients were also compared. RESULTS: The median follow-up time in three groups were 3.4 (1.8, 6.4) years, 3.2 (1.8, 6.1) years and 2.8 (1.8, 6.2) years, without statistical difference. The cumulative 1-year and 3-year graft survival rate were 94.3% and 94.0% in ABO-id group, 93.1% and 93.1% in ABO-c group and 97.1% and 97.1% in ABO-i group. The cumulative 1-year and 3-year recipient survival rate were 96.1% and 95.5% in ABO-id group, 94.8% and 94.8% in ABO-c group and 97.1% and 97.1% in ABO-i group, respectively. No significant difference was seen among three groups. The recipient characteristics and perioperative data were similar among three groups. The recipients in ABO-i group showed significantly lower incidence of portal vein stenosis. Apart from that, three groups shared equal incidence of other surgical complications and acute rejection. Among ABO-i liver graft recipients, the cumulative 1-year and 3-year recipient survival rate were 98.2% and 98.2% in living donor liver transplant (LDLT) recipients and 92.9% and 92.9% in deceased donor liver transplant (DDLT) recipients, without significant difference. The incidence of hepatic artery thrombosis was significantly higher in DDLT group compared with LDLT group, while the other complications were similar between two groups. CONCLUSION: Our data revealed that the application of ABO-i liver grafts in pediatric liver transplantation under rational peri-operative management strategy is a safe measure to increase donor availability for pediatric patients in Chinese population. LEVELS OF EVIDENCE: III.

Risk factors of de novo hepatitis B virus infection in pediatric hepatitis B core antibody positive liver graft recipients under prophylactic therapy.

BACKGROUND AND AIM: We aim to investigate the risk factors of de novo hepatitis B virus (HBV) infection in pediatric liver transplantation recipients receiving hepatitis B core antibody positive grafts and to evaluate the efficacy of our prophylactic strategies. METHODS: One hundred thirty-nine pediatric recipients receiving hepatitis B core antibody positive grafts operated from September 2016 to September 2018 were retrospectively enrolled, and all the patients received prophylactic treatment to prevent de novo HBV infection. Donor and recipient features, operative information along with graft, and recipient outcomes were compared between recipients with or without de novo HBV infection. Univariate and multivariate analyses were applied to identify the risk factors of de novo HBV infection. RESULTS: The mean follow-up time was 23.5 ± 15.7 months, and the overall incidence of de novo HBV infection was 3.6%. Recipients with de novo HBV infection showed equal graft and recipient outcome compared with the recipients without de novo HBV infection during the follow-up time. Recipient preoperative hepatitis B surface antibody titer of < 1000 IU/L (odds ratio [OR] = 9.652, P = 0.024), graft HBV DNA of > 1000 copies (OR = 9.050, P = 0.032), and intraoperative fresh-frozen plasma transfusion of > 400 mL (OR = 10.462, P = 0.023) were identified as independent risk factors for de novo HBV infection. CONCLUSION: Hepatitis B core antibody positive grafts can safely be used in pediatric liver transplantation under rational prophylactic therapy.

Application of pediatric donors in split liver transplantation: Is there an age limit?

The experience of using pediatric donors in split liver transplant is exceedingly rare. We aim to investigate the outcomes of recipients receiving split pediatric grafts. Sixteen pediatric recipients receiving split liver grafts from 8 pediatric donors < 7 years were enrolled. The donor and recipient characteristics, perioperative course, postoperative complications, and graft and recipient survival rates were evaluated. The mean follow-up time was 8.0 ± 2.3 months. The graft and recipient survival rates were 100%. The liver function remained in the normal range at the end of the follow-up time in all recipients. No life-threatening complications were seen in these recipients, and the only surgery-related complication was portal vein stenosis in 1 recipient. Cytomegalovirus infection was the most common complication (62.5%). The transaminase level was significant higher in extended right lobe recipients in the early postoperative days, but the difference vanished at the end of first week; postoperative complications and graft and recipient survival rates did not differ between left and right graft recipients. Notably, the youngest split donor graft (2.7 years old) was associated with ideal recipient outcomes. Split liver transplant using well-selected pediatric donors is a promising strategy to expand pediatric donor source in well-matched recipients.

Risk factors of hepatic artery thrombosis in pediatric deceased donor liver transplantation.

PURPOSE: Hepatic artery thrombosis (HAT) remains a life-threatening complication in liver transplantation. We aim to investigate the risk factors of HAT in deceased donor pediatric liver transplantation. METHODS: 104 recipients from 2014 to 2016 were enrolled; donor and recipient characteristics, surgical variables, graft and recipient survival rate were compared between recipients with or without HAT. Univariate and multivariate analysis were applied to identify the risk factors of HAT. RESULTS: The recipient survival rate was 87.0% and 96.3% at 1 year, and 87.0% and 96.3% at 3 years in HAT and non-HAT groups without significant difference. The graft survival rate was 73.9% and 96.3% at 1 year, and 73.9% and 95.1% at 3 years in HAT and non-HAT groups; significant difference was observed between two groups at both 1 and 3 years. Donor age less than 8.5 months, graft weight less than 190 g and GRWR less than 2.2% were identified as independent risk factors for HAT. Recipients with HAT were associated with higher incidence of post-operative biliary complications. CONCLUSIONS: Young donor age and small liver graft are risk factors for HAT in deceased donor pediatric liver transplantation.

Utility of neonatal donors in pediatric liver transplantation: A single-center experience.

BACKGROUND: The lack of age- and size-matched organs result in higher waiting list mortality in pediatric recipients than adults. Organs from deceased newborns and infants are a valuable source to increase donor pool in pediatric liver transplantation. However, the feasibility and safety of using neonatal donors have not been well evaluated. METHODS: From 2014 to 2016, 48 deceased donor pediatric liver transplantations with donor age younger than 1 year old in our center were enrolled in this study. The recipients were divided into three groups based on the donor age (<1 month, 1 month ≤ to <3 months, and 3 months ≤ to <1 year). Recipient's characteristics, perioperative data, and postoperative complications were compared. RESULTS: Two-year patient survival rates were 87.5%, 94.4%, and 95.5%, and 2-year graft survival rates were 75%, 94.4%, and 95.5%, respectively, without significant difference. The liver grafts from donors younger than 3 months were more advantageous in terms of acute rejection and virus infection, while the young grafts were related to slight higher incidence of hepatic artery thrombosis and SFSS. Those complications could be effectively prevented or treated by our perioperative care strategies. In addition, eight recipients who received neonatal livers achieved comparable outcomes with recipients with older livers. CONCLUSION: Our data revealed that the application of liver grafts from donors younger than 1 year old could achieve excellent outcome. In particular, neonatal donors could be safely used in well-selected patients.

Feasibility and safety of using low-body-weight donors in pediatric liver transplantation.

BACKGROUND: Donors with low-body-weight were previously reported to be related to inferior recipient outcomes in pediatric liver transplantation. However, the scarce availability of age and size-matched organs has encouraged us to re-evaluate the feasibility and safety of using low-body-weight donors. METHODS: We retrospectively analyzed 91 deceased donor pediatric liver transplantation between January 2014 and December 2016, donor weight less than 5 kg was defined as low-body-weight donors. The recipients were divided into two groups according to donor weight. (≤5 kg and 5 kg < to ≤20 kg). Donor and recipient characteristics, perioperative data, postoperative complications as well as graft and recipient survival rate were compared RESULTS: The recipients and grafts recovery after transplantation were comparable between two groups. The recipients receiving low-body-weight donors showed higher risk of hepatic artery thrombosis and small-for-size syndrome, however, these complications can effectively be treated by our strategies. The 2-year patient survival rates were 92.9% and 95.2%, 2-year graft survival rates were 92.9% and 93.7% in Groups 1 and 2, without significant difference. CONCLUSIONS: Our finding suggested that the utility of livers from low-body-weight donors is a potential strategy to increase donor availability in well-selected pediatric recipients. LEVEL OF EVIDENCE: III.

The effects of Kasai procedure on living donor liver transplantation for children with biliary atresia.

OBJECTIVE: To evaluate the effects of Kasai procedure (hepatic portoenterostomy) on living donor liver transplantation (LDLT) for children with biliary atresia (BA). METHODS: From January 2006 to January 2014, 150 children with BA were treated with LDLT in China. The children were categorized into pre-Kasai and non-Kasai groups, based on whether they had previously undergone Kasai procedure. Clinical data were retrospectively analyzed, and the difference in postoperative survival was compared between the groups. Preoperative data, including height, weight, serum bilirubin, and pediatric end-stage liver disease score, and perioperative blood loss, operation duration, incidence of postoperative surgical complications including vascular complications, bile duct complications, lymphatic fluid leakage, and digestive tract fistula were compared between the groups. RESULTS: In total, 89 and 61 children were categorized in the pre-Kasai and non-Kasai groups, respectively. The 1-, 6-, and 12-month survival was 97.8%, 95.4%, and 95.4% for the Kasai group, and 98.4%, 96.7%, and 96.7% for the non-Kasai group, respectively (P > 0.05). The differences in mean operation duration and mean blood loss, and the incidences of outflow tract obstruction, portal vein stenosis, hepatic artery thrombosis, bile duct complications, lymphatic fluid leakage, and digestive tract fistula were not statistically significant between the groups (P > 0.05). CONCLUSION: Kasai procedure could effectively delay the requirement of liver transplantation. In light of previous findings that Kasai procedure could significantly improve the liver transplantation-free survival of children with BA, we suggest that Kasai procedure should be used as a first-line treatment method for this condition. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

Adherence to medical regimen after pediatric liver transplantation: a systematic review and meta-analysis.

PURPOSE: Adherence to the medical regimen after pediatric liver transplantation is crucial for good clinical outcomes. However, the existing literature provides inconsistent evidence regarding the prevalence of and risk factors for nonadherence to the medical regimen after pediatric liver transplantation. This study aimed to investigate such nonadherence after pediatric liver transplantation and risk factors associated with this nonadherence using findings of reported studies. METHODS: The electronic databases of Excerpta Medica, Ovid Technologies, PubMed and WanFang Data were searched using the keywords "adherence", "liver transplant" and "paediatric". Additionally, relevant references cited in related studies were used to obtain original articles. Using 22 original articles, data regarding nonadherence to the medical regimen after pediatric liver transplantation were quantitatively combined, and risk factors associated with nonadherence were qualitatively identified. Average rates of nonadherence in four areas of medical regimens were calculated. The heterogeneity of the included original articles was also analyzed. When I 2>50 and P<0.05, a random effects model was used; otherwise, a fixed effects model was used. Moreover, Egger's and Begg's tests were used to evaluate publication bias, if any, and original articles with P>0.05 were considered to have no publication bias. RESULTS: The clinical attendance nonadherence rate was 45% (95% confidence interval [CI]: 39-51), global nonadherence rate was 17% (95% CI: 13-21) and immunosuppression non-adherence rates were 39% (95% CI: 26-52) and 34% (95% CI: 30-39) for cyclosporine and tacrolimus, respectively. Risk factors included older age of the pediatric patient, low family cohesion, poor social functioning, poor mental health and single-parent family. CONCLUSIONS: The nonadherence rate in pediatric liver transplantation is high. Therefore, intervention on the basis of risk factors, such as mental health and family function, may be necessary. Moreover, a standard technique for assessing nonadherence to the medical regimen after pediatric liver transplantation, comprising as many dimensions as possible, is required in order to be more objective and comprehensive when assessing nonadherence.

Acquired diaphragmatic hernia in pediatrics after living donor liver transplantation: Three cases report and review of literature.

RATIONALE: Diaphragmatic hernia (DH) in pediatrics following living donor liver transplantation (LDLT) has been seldom reported in the past. PATIENT CONCERNS: We report successful diagnosis and treatment of three pediatric cases with DH secondary to LDLT, discuss the possible etiology, and review the relevant literature. DIAGNOSES: The primary disease was biliary atresia and DH was diagnosed by computed tomography scan or x-ray of chest. INTERVENTIONS: Laparotomy was performed successfully to repair the DH. OUTCOMES: The respiratory and digestive function was gradually recovered in 1 to 2 weeks after repair operation. In 2 to 8 months follow-up, patients were asymptomatic without any respiratory or digestive complications. LESSONS: DH post-LDLT should be recognized as a possible complication when a left lateral segment graft is used. Careful clinical examination and prompt surgery could minimize complications.

Alterations of Serum IP-10 and TARC in Patients with Early Acute Rejection after Liver Transplantation.

BACKGROUND/AIMS: To analyze alterations of interferon-γ-induced protein 10 (IP-10) and thymus and activation-regulated chemokine (TARC) levels in early acute liver transplantation rejection. METHODS: Thirty-six patients with early acute liver transplantation rejection were classified as non-, mild, moderate, and severe rejection groups. The levels of serum IP-10 and TARC were determined on days 3, 2, 1, and 0 before biopsy. RESULTS: The IP-10 activities in all rejection groups were significantly higher (p < 0.05) than those in the non-rejection group at all time points and correlated with the extent of rejection (p < 0.05). The differences in TARC among the three rejection groups were significant (p < 0.05), and its highest level was found in the mild rejection group at all observed time points, whereas its lowest level was detected in the severe rejection group. The analysis of the TARC/IP-10 ratio revealed that the volume was correlated with the rejection degree. This ratio in the moderate and severe rejection groups on days 2, 1, and 0 before biopsy were 20% lower than that before transplantation. CONCLUSION: Serum IP-10 showed an increasing trend during early acute liver transplantation rejection. IP-10 increase or TARC/IP-10 ratio decrease combining with abnormal hepatic enzymatic alteration could be a valuable and specific sign for early rejection of the transplanted liver.