Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Development of a model to predict the risk of early graft failure after adult-to-adult living donor liver transplantation: An ELTR study.

Graft survival is a critical end point in adult-to-adult living donor liver transplantation (ALDLT), where graft procurement endangers the lives of healthy individuals. Therefore, ALDLT must be responsibly performed in the perspective of a positive harm-to-benefit ratio. This study aimed to develop a risk prediction model for early (3 months) graft failure (EGF) following ALDLT. Donor and recipient factors associated with EGF in ALDLT were studied using data from the European Liver Transplant Registry. An artificial neural network classification algorithm was trained on a set of 2073 ALDLTs, validated using cross-validation, tested on an independent random-split sample (n=518), and externally validated on United Network for Organ Sharing Standard Transplant Analysis and Research data. Model performance was assessed using the AUC, calibration plots, and decision curve analysis. Graft type, graft weight, level of hospitalization, and the severity of liver disease were associated with EGF. The model ( http://ldlt.shinyapps.io/eltr_app ) presented AUC values at cross-validation, in the independent test set, and at external validation of 0.69, 0.70, and 0.68, respectively. Model calibration was fair. The decision curve analysis indicated a positive net benefit of the model, with an estimated net reduction of 5-15 EGF per 100 ALDLTs. Estimated risks>40% and<5% had a specificity of 0.96 and sensitivity of 0.99 in predicting and excluding EGF, respectively. The model also stratified long-term graft survival ( p <0.001), which ranged from 87% in the low-risk group to 60% in the high-risk group. In conclusion, based on a panel of donor and recipient variables, an artificial neural network can contribute to decision-making in ALDLT by predicting EGF risk.

Long-term outcome after living donor liver transplantation compared to donation after brain death in autoimmune liver diseases: Experience from the European Liver Transplant Registry.

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis. In total, 29 902 individuals enrolled between 1998 and 2017 were analyzed, including 1003 with LDLT. Survival from >90 days after LDLT for AILDs in adults was 85.5%, 74.2%, and 58.0% after 5, 10, and 15 years. Adjusted for recipient age, sex, and liver transplantation era, adult PSC patients receiving LDLT showed increased mortality compared to donation after brain death (DBD) (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.36-2.80, p < .001). Pediatric PSC patients showed also increased mortality >90 days after LDLT compared to DBD (HR = 3.00, 95% CI 1.04-8.70, p = .043). Multivariate analysis identified several risk factors for death in adult PSC patients receiving LDLT including a male donor (HR = 2.49, p = .025). Adult PSC patients with LDLT versus DBD conferred increased mortality from disease recurrence (subdistribution hazard ratio [subHR] = 5.36, p = .001) and biliary complications (subHR = 4.40, p = .006) in multivariate analysis. While long-term outcome following LDLT for AILD is generally favorable, PSC patients with LDLT compared to DBD might be at increased risk of death.

Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center

Background/aim: With the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center. Material and methods: Between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed. Results: In 191 patients, one-, three- and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three- and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). Conclusion: LDLT allows us to push the limits forward and the question "Are the criteria always right?" is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.

A comparison of rates and severity of chronic kidney disease in deceased-donor and living-donor liver transplant recipients: times matter

Background/aim: The progression of chronic kidney disease (CKD) in recipients of living-donor liver transplant (LDLT) compared to deceased-donor liver transplant (DDLT) has not been studied in the literature. We hypothesize that CKD stage progression in LDLT recipients is reduced compared to that of their DDLT counterparts. Materials and methods: A retrospective study was undertaken including 999 adult, single-organ, primary liver transplant recipients (218 LDLT and 781 DDLT) at 2 centers between January 2003 and December 2012, in which CKD progression and regression were evaluated within the first 3 years after transplantation. Results: Waiting time from evaluation to transplantation was significantly lower in LDLT patients compared to recipients of DDLT. CKD stage progression from preoperative transplant evaluation to transplantation was significantly greater in DDLT. Deceased-donor liver transplant recipients continued to have higher rates of clinically significant renal disease progression (from stage I­II to stage III­V) across multiple time points over the first 3 years posttransplant. Furthermore, a greater degree of CKD regression was observed in recipients of LDLT. Conclusion: It can be concluded that LDLT provides excellent graft and patient survival, significantly reducing the overall incidence of clinically significant CKD stage progression when compared to DDLT. Moreover, there is a significantly higher incidence of CKD stage regression in LDLT compared to DDLT. These observations were maintained in both high and low model for end-stage liver disease(MELD)populations. This observation likely reflects earlier access to transplantation in LDLT as one of the contributing factors to preventing CKD progression.

Posthepatectomy liver failure

Liver surgery is one of the most complex surgical interventions with high risk and potential for complications. Posthepatectomy liver failure (PHLF) is a serious complication of liver surgery that occurs in about 10% of patients undergoing major liver surgery. It is the main source of morbidity and mortality. Appropriate surgical techniques and intensive care management are important in preventing PHLF. Early start of the liver support systems is very important for the PHLF patient to recover, survive, or be ready for a liver transplant. Nonbiological and biological liver support systems should be used in PHLF to prepare for treatment or organ transplantation. The definition of the state, underlying pathophysiology and treatment strategies will be reviewed here.

Results of pediatric living donor compared to deceased donor liver transplantation in the PELD/MELD era: Experience from two centers on two different continents.

The LDLT option in the pediatric population allows recipients to be transplanted early. A total of 202 consecutive pediatric liver transplants from two different institutions--108 (LDLT) and 94 (DDLT)--were retrospectively compared. Overall, one- and three-yr patient and graft survival were similar between DDLT and LDLT. ACR was greater in recipients of DDLT at one and three yr (50.8% and 61.0%) compared to LDLT (30.8% and 32.2%) (p = 0.002). When the data were stratified according to PELD/MELD score, LDLT with a low score had better one- and three-yr graft survival (96.2% and 96.2%) compared to DDLT (88.2% and 85.2%) (p = 0.02), with comparable patient survival (p = 0.75). Patient and graft survival were similar between DDLT and LDLT in the high PELD/MELD group. Lower incidence of ACR in both low and high PELD/MELD groups was (29.6% and 34.3%) for LDLT compared to DDLT (50.3% and 53.3%, p = 0.002 and p = 0.028, respectively). Regardless of PELD/MELD score, status, age group, and recipient weight, LDLT provides excellent patient and graft survival with a lower incidence of rejection compared to DDLT.

A very original case of a mini accessory liver lobe with its own gallbladder.

PURPOSE: Anatomic variation of the hepatobiliary system is often related to the biliary tract and vascular supply of the liver. We present here one of the smallest accessory hepatobiliary system. METHODS: The case of a 30-year-old male who was a living liver donor is presented. RESULTS: During the dissection of the portal hilum, 1.5 cm of accessory liver (AL) tissue was noted below the left lobe of the liver. This AL tissue had a gallbladder of 1.5 cm and which had a cystic duct opening to the bile duct of the accessory liver. The AL bile duct opened to the left bile duct of the liver. The arterial and portal supply of the AL came from the left artery and left portal vein of the liver. The accessory gallbladder also had a cystic artery coming from the arterial branch of the AL. It was noted that the hepatic vein of the AL opened directly to left lobe tissue. CONCLUSIONS: The hepatobiliary system has many anatomic variations, but this case is rare and original in the literature in that it may be a cause of confusion and even a false diagnosis.

Living donor liver transplantation in an adult patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare congenital anomaly, and liver transplantation (LT) in an adult SIT patient is extremely rare. Liver transplantation in a SIT patient is also technically challenging due to reversed anatomical structures. Here we present the case of an 18-year-old female with SIT in whom left lobe living donor LT was performed. The patient suffered from cirrhosis due to autoimmune hepatitis. The recipient and donor are doing well without complications 20 months after LT. Situs inversus totalis should not be considered a contraindication for LT. If possible, use of a living donor left lobe graft for LT is more feasible than a living donor right lobe graft. It is also technically easier than using deceased donor full-size liver graft in SIT patients who require liver transplantation.

Leiomyosarcoma of the retrohepatic vena cava: Report of a case treated with resection and reconstruction with polytetrafluoroethylene vascular graft.

Leiomyosarcoma of the vena cava is a rare malignant tumor. A 61-year-old woman was admitted with right upper quadrant abdominal pain. Computed tomography revealed a retrohepatic vena cava tumor originating 2 cm below the confluence of the hepaic veins and ending 2 cm above the renal veins. The tumor was resected with 1 cm clear surgical margins, without requiring liver resection. Polytetrafluoroethylene vascular graft was used for reconstruction of the vena cava. Now 32 months postoperatively, there has been no recurrence or metastasis. Radical resection with negative surgical margins is the best curative therapy for leiomyosarcoma. Polytetrafluoroethylene vascular graft can be used in extensive tumors located at the vena cava.

Liver Transplant and Improvements in Cholesterol Biosynthesis Defects: A Case Report of Smith-Lemli-Opitz Syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic disease characterized by mental retardation and multiple congenital anomalies. The main pathology is the lack of the enzyme 3ß-hydroxysterol Δ7-reductase, which is the last enzymatic step in cholesterol synthesis, ending with a low cholesterol level. Cholesterol is vitally important in cell membranes and myelination of the nervous system. The cholesterol level affects many systems of the body, especially the nervous system. The cause of liver involvement in Smith-Lemli-Opitz syndrome is unclear, and many hypotheses have been suggested. Here, we present the early results of a patient with Smith-Lemli-Opitz syndrome who underwent living-donor liver transplant due to cirrhosis. As a result of liver transplant, normal cholesterol levels were shown, as well as improvements in the patient's neurodevelopment and behavior. Early liver transplant may be considered for patients with a defect of cholesterol biosynthesis, even in the absence of cirrhosis, and may be a future treatment option to prevent risks of neurologic deterioration.

Liver transplantation as a treatment option for three siblings with homozygous familial hypercholesterolemia.

FH is a hereditary inherited disorder of cholesterol metabolism. Homozygous form of the disease associates severe form of atherosclerotic disease. Clinicians have been tried to inhibit the progression of the homozygous FH with medical and surgical treatment. We here present three siblings with homozygous FH who were successfully treated with liver transplantation.

The advantage of early liver transplantation for Wilson's disease using living donors.

AIM: The aim of the study was to investigate the surgical timing, results, and advantages of living-donor liver transplantation in patients who underwent liver transplantation due to Wilson's disease. MATERIAL AND METHODS: The study included Wilson's patients who underwent liver transplantation and their live donors. Demographic information, preparations for surgery, liver transplant type, grafts used, results, and complications were examined. RESULTS: Between 2006 and 2020, 29 liver transplants were performed for 27 Wilson's patients in our clinic. The study included 11 female and 16 male patients, with a mean age of 20.8 ±11.1 years and a mean body mass index of 20.5 ±3.2 kg/m2. The mean MELD score of the adult patients was 16.5 ±6.3, and the mean PELD score of the paediatric patients was 19.6 ±17.2. Five patients underwent transplantation due to acute liver failure, and 22 patients with low MELD score had liver transplants due to chronic liver disease. Three patients who were referred with acute liver failure died in the perioperative period; no mortality was observed in the 22 elective patients. The overall survival was calculated as 88.8%. The 1-, 3-, and 5-year survival were 100% among elective early transplanted patients. CONCLUSIONS: Liver transplant is the most effective treatment for liver failure caused by Wilson' s disease. When performed promptly, living-donor liver transplantation results in high survival rates in cases of both acute liver failure and chronic liver failure, and it no deterioration of the patient's condition is evident.

Extreme living donation: A single center simultaneous and sequential living liver-kidney donor experience with long-term outcomes under literature review.

OBJECTIVES: Living liver and kidney donor surgeries are major surgical procedures applied to healthy people with mortality and morbidity risks not providing any direct therapeutic advantage to the donor. In this study, we aimed to share our simultaneous and sequential living liver-kidney donor experience under literature review in this worldwide rare practice. MATERIAL AND METHODS: Between January 2007 and February 2018, a total of 1109 living donor nephrectomies and 867 living liver donor hepatectomies were performed with no mortality to living-related donors. Eight donors who were simultaneous or sequential living liver-kidney donors in this time period were retrospectively reviewed and presented with their minimum 2- year follow-up. RESULTS: Of the 8 donors, 3 of them were simultaneous and 5 of them were sequential liver-kidney donation. All of them were close relatives. Mean age was 39 (26-61) years and mean BMI was 25.7 (17.7-40). In 3 donors, right lobe, in 4 donors, left lateral sector, and in 1 donor, left lobe hepatectomy were performed. Median hospital stay was 9 (7-13) days. Two donors experienced early and late postoperative complications (Grade 3b and Grade 1). No mortality and no other long-term complication occurred. CONCLUSION: Expansion of the donor pool by utilizing grafts from living donors is a globally-accepted proposition since it provides safety and successful outcomes. Simultaneous or sequential liver and kidney donation from the same donor seems to be a reasonable option for combined liver-kidney transplant recipients in special circumstances with acceptable outcomes.

Complications and outcomes of 890 living liver donor hepatectomies at a single center: risks of saving loved one's life.

OBJECTIVES: Living liver donor surgery is a major surgical procedure applied to healthy people with mortality and morbidity risks and does not provide any direct therapeutic advantage to the donor. We retrospectively analyzed the postoperative complication of our living liver donors to figure out the risks of donation. MATERIAL AND METHODS: Between November, 2006 and December, 2018, a total of 939 living liver donor hepatectomies were performed with no mortality to the living-related donors. Eight hundred and ninety donors with a minimum 1-year follow-up were analyzed retrospectively. RESULTS: Of the 890 donors, 519 (58.3%) were males and 371 (41.7%) were females. Mean age was 35 years (18-64) and mean body mass index was 25.7 kg/m2 (17.7-40). Right donor hepatectomy was performed to 601 (67.5%), left donor hepatectomy to 28 (3.2%) and left lateral sector hepatectomy to 261 (29.3%) of the donors. Of the 890 donors, 174 (19.5%) donors experienced a total of 204 early and late complications including life- threatening and nearly life- threatening complications in 26 (2.9%) of them. Intraoperative complication occurred in 4 (0.5%) donors. Right donors hepatectomy complication rate (23.3%) was higher than left donor (14.3%) and left lateral sector donor hepatectomy (11.5%). CONCLUSION: All donor candidates should be well-informed not only on the details of early and late complications of living liver donation, also possible outcomes of the recipient. In addition to detailed physical evaluation, preoperative psychosocial evaluation is also mandatory. Comprehensive donor evaluation, surgical experience, surgical technique, close postoperative follow-up and establishing a good dialog with the donor allows better outcomes.

Successful treatment of pediatric post-liver transplant Kaposi`s sarcoma with paclitaxel.

BACKGROUND: Kaposi`s sarcoma (KS) is a complication of immunosuppressive therapy for transplant recipients. Unlike adult recipients, KS in pediatric organ transplantation is quite rare. Treatment is usually withdrawal of immunosuppression; non-responders often receive chemotherapy. CASE: We have reported a child with post-liver transplant visceral KS which has progressed despite withdrawal of immunosuppressive therapy, who has been treated with Paclitaxel for three weeks. KS has regressed completely after four cycles of Paclitaxel. CONCLUSION: Paclitaxel should be considered as an effective first line treatment option for patients with posttransplant KS.

Transient complete atrioventricular block during liver transplantation.

Intraoperative dysrhythmias commonly occur in the surgical management of congenital heart diseases. It may also be seen in other surgical procedures. The initiating factors for an arrhythmia during surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, electrolyte abnormality and acidosis. CAVB is a life-threatening dysrhythmia in all ages. We herein report a case of transient CAVB in a 30-month-old boy during living-related liver transplantation for bile duct paucity-associated liver cirrhosis. Moreover, we discuss the probable etiology and treatment of CAVB in liver transplantation.

Liver Transplant in Children with Hepatoblastoma.

OBJECTIVES: In this paper, the results of liver transplant due to hepatoblastoma in 10 pediatric patients at Istanbul Sisli Memorial Hospital Transplantation Center are presented. MATERIALS AND METHODS: We retrospectively evaluated medical records of pediatric patients diagnosed with hepatoblastoma and who underwent liver transplant at our clinic between January 2009 and March 2014. We examined age, weight, chemotherapy regimen, graft type for liver transplant, duration of hospital stay, complications, follow-up duration, and survival information. RESULTS: The median age of the 10 patients included in our study was 13.5 months (range, 8-120 mo), and the median weight was 10 kg (range, 6.5-30 kg). Two of the patients were twins. Five patients had pretreatment extent of disease III (centrally placed cases), and five had pretreatment extent of disease IV hepatoblastoma. Preoperative chemotherapy was given to 7 patients as cisplatin plus doxorubicin and to 3 patients per the International Childhood Liver Tumors Strategy Group 3 High-Risk Protocol at external centers. These protocols were administered according to treatment center preference. Nine patients received transplants from living donors. Two grafts were right lobes, and 7 were left lateral segments. In the remaining patient, a whole liver was received from a deceased donor. The histopathologic subgroups were epithelial in 5 patients, with others being of mixed type. Postoperative complications occurred in 3 patients as infection, intra-abdominal fluid collection, and acute rejection. The median follow-up was 32 months. One patient died because of lung metastasis within 9 months after transplant. CONCLUSIONS: Centers should offer liver transplant to patients with centrally located tumors. For centers that have an insufficient number of deceased donors, living-donor liver transplant with optimal planning and early treatment can be performed.

Diaphragmatic Hernia After Liver Transplant in Children: Report of 2 Cases.

OBJECTIVES: Diaphragmatic hernia is a rare complication after pediatric liver transplant. This report presents occurrences of diaphragmatic hernia after living-donor liver transplants in 2 children. MATERIALS AND METHODS: In 1 of the 2 patients, a right-sided diaphragmatic hernia developed after a living-donor liver transplant due to progressive familial intrahepatic cholestasis where a left lateral segment graft was used. In the other patient, a left-sided diaphragmatic hernia developed after a living-donor liver transplant due to biliary atresia following Kasai portoenterostomy where a left lateral segment graft was used. RESULTS: After diaphragm repair, the postoperative course was uneventful and there were no recurrences. CONCLUSIONS: A literature review identified nearly 30 cases of diaphragmatic hernia following liver transplants; diaphragmatic hernia should be considered a potential surgical complication after liver transplant.

Argininosuccinic Aciduria-A Rare Indication for Liver Transplant: Report of Two Cases.

Argininosuccinic aciduria is a urea cycle disorder caused by an argininosuccinate lyase enzyme deficiency that ends with nitrogen accumulation as ammonia. Argininosuccinic aciduria patients are at risk for long-term complications including poor neurocognitive outcome, hepatic disease, and systemic hypertension despite strict pharmacologic and dietary therapy. As the liver is the principle site of activity of the urea cycle, it is logical that a liver transplant should be an option, with careful patient selection, even in the absence of cirrhosis. We present 2 pediatric argininosuccinic aciduria patients who underwent a living-donor liver transplant from their mothers. After the liver transplant, the general well-being of the patients and their quality of life improved significantly. Liver transplant should be an option for argininosuccinic aciduria patients to prevent further neurologic deterioration and improve the patient's quality of life.