Deceased Donor Liver Transplantation in India: First Report of 5-Y Outcomes.

BACKGROUND: Paucity of deceased donor livers has resulted in a 10-fold rise in living donor liver transplantations (LDLTs) performed in India over the past decade. Nonetheless, number of deceased donor liver transplantation (DDLT) performed has improved with the establishment of simplified legal framework for certification of brain death and organ donation. In this study, we present our outcomes of DDLT performed at various centers, comparing their outcomes and provide a snapshot of the increasing number of DDLT across the state over the years. METHODS: All consecutive patients who underwent liver transplants from January 2010 till December 2019 by our transplant team in the state of Tamil Nadu, India, were included in the study. The program was established initially at the primary hospital in the year 2010 and with the evolution of the initial experience, transplant programs were expanded to the others hospital from the year 2015. Preoperative clinical data, intraoperative characteristics, and posttransplant outcomes of DDLT were analyzed from our prospective database. RESULTS: A total of 362 DDLTs (331 adults, 31 children) were performed at 11 centers. Median (range) model for end-stage liver disease score was 16 (6-39). Forty-eight split, 11 combined liver kidney, and 4 auxiliary DDLTs were performed. One-, 3-, and 5-y survival was 87.2%, 80.4%, and 76.6% in adults and 80.6%, 80.6%, and 80.6% in children, respectively. CONCLUSIONS: In a country where over 80% of the LTs are performed as LDLT, we provide the first report of a heartening trend of increasing number of DDLT programs being established with excellent 5-y outcomes.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Experience With Establishing a Robotic Donor Hepatectomy Program for Pediatric Liver Transplantation.

BACKGROUND: The benefits of minimal invasive donor hepatectomy, especially for left lateral sectionectomy (LLS) have been unequivocally demonstrated. Moreover, donors in pediatric liver transplantation (LT) are usually parents who need to recover quickly to take care of the child. There are inherent limitations to conventional laparoscopic surgery including surgeon's experience with advanced laparoscopic surgery and steep learning curve which limits the wide application of minimal invasive donor hepatectomy. We share our experience of establishing a program of robotic donor hepatectomy (RDH) and achieving proficiency in performing RDH for pediatric LT. METHODS: Data were prospectively collected of consecutive LLS RDH based on a structured learning algorithm. Donor and recipient outcomes were analyzed. RESULTS: Seventy-five consecutive cases of LLS RDH were performed. The median primary warm ischemia time was 6 min (interquartile range [IQR]: 5-7 min). No major complications (grade ≥IIIb Clavien-Dindo) were noted in the cohort. There were no emergency conversion to open surgery and neither were there postoperative explorations through a laparotomy. Seven grafts were hyper-reduced and 5 required venoplasty. Two recipients died because of severe sepsis and multiorgan failure. Major complications occurred in 15 children (20%), none of which were attributable to RDH. Median hospital stay of the donors and recipients was 5 d (IQR: 5-6) and 12 d (IQR: 10-18) respectively. CONCLUSIONS: We share our experience of starting a RDH program for pediatric LT. We highlight the challenges and our learning algorithm to spur teams on the cusp of starting robotic transplant programs.

Anatomical variations of left hepatic vein and outflow reconstruction techniques in pediatric living donor liver transplantation.

Anatomical variations of left hepatic vein are observed in nearly a third of left lateral segment (LLS) donors in living donor liver transplantation. However, there is a paucity of studies and no structured algorithm for customized outflow reconstruction in LLS grafts with variant anatomy. Analysis of a prospectively collected database of 296 LLS pediatric living donor liver transplantation was done to identify different venous drainage patterns of segments 2 (V2) and 3 (V3). Left hepatic vein anatomy was classified into 3 types: type 1 (n = 270, 91.2%): V2 and V3 joined to form a common trunk which drains into the middle hepatic vein/inferior vena cava (IVC), subtype 1a length of trunk ≥9 mm and subtype 1b length of trunk <9 mm; type 2(n = 6, 2%): V2 and V3 drain independently into IVC; type 3 (n = 20, 6.8%): V2 and V3 drain into IVC and middle hepatic vein respectively. Analysis of postoperative outcomes between LLS grafts with single and reconstructed multiple outflows showed no difference in the occurrence of hepatic vein thrombosis/stenosis, major morbidity (P = .91), and 5-year survival (log-rank P = .562). This classification is a simple yet effective tool for preoperative donor assessment, and we propose a schema for the customized reconstruction of LLS grafts with excellent and consistently reproducible outcomes.

Nonalcoholic Steatohepatitis: A Rapidly Increasing Indication for Liver Transplantation in India.

Background and aims: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. Methods: The study population was stratified into Period 1 (2009-2014) and Period 2 (2015-2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. Results: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19-3.22). Conclusion: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.

Renal Implications of Left Renal Vein Ligation for Portal Flow Augmentation in Liver Transplantation.

BACKGROUND: Spontaneous lienorenal shunts (SLS) siphon blood away from the portal circulation and may compromise portal inflow in liver transplantation (LT). Performing a left renal vein ligation (LRVL) is a relatively easy and efficacious method of overcoming this portal 'steal'. However, given the delicate state of renal function in these patients, its short and long term effects remain undefined. The aim of this study was to evaluate the efficacy of LRVL in augmenting portal flow and safety with regards to renal function. METHODS: A prospectively collected database of 1638 consecutive LT recipients between January 2010 and August 2020 was reviewed. Twenty-eight patients who underwent LRVL were identified. There were six paediatric recipients, who were analysed separately. Data with regards to imaging, renal function, intraoperative portal hemodynamics, and renal morbidity were analysed. RESULTS: Of the 22 adults, 21 underwent live donor LT. 22.5% had a pre-transplant history of acute kidney injury (AKI). Pre-operative CT demonstrated portal vein thrombosis and SLS in 63.6% and 92.9% of patients respectively. LRVL resulted in a significant augmentation of portal hemodynamics in both the adult and paediatric recipients. Postoperatively, 14.3% and 35.7% of patients developed chylous drain output and AKI respectively. Of 13 patients who underwent CT at various timeframes, 5 patients had a partial re-canalisation of LRV at 6 months. CONCLUSION: From renal and portal standpoints, LRVL is a safe and effective technique of augmenting portal inflow. Further large-scale multicentre studies and consensus will help define an objective algorithmic approach to LT recipients with SLS.

Anatomical Basis for Selective Multiple Arterial Reconstructions in Living Donor Liver Transplantation.

BACKGROUND: Need for routine reconstruction of all arteries in grafts with multiple arterial inflows remains an unsettled debate. The aim of following article is to review an anatomical basis of a decision-making strategy to deal with multiple arteries in living donor liver transplantation (LDLT). METHODS: LDLT performed between August 2009-2019 were included. Grafts were classified into grafts with single artery (group 1); multiple arteries, all reconstructed (group 2); and multiple arteries, one reconstructed (group 3). Frequency of double arteries in relation to graft type, type of reconstruction, incidence of arterial and biliary complications and survival was compared. RESULTS: 1086 LDLT were analysed (adults: 750, paediatric: 336). 1007 grafts (92.2%) had single artery (group 1), and 79 (7.8%) grafts had multiple arteries. All arteries were reconstructed in 19 (24%) patients (group 2), while 60 grafts (75.9%) had only one artery reconstructed (group 3). Left lobe (18.8%) and left lateral segments (10.7%) grafts were more likely to have multiple arteries (p = 0.001). The likelihood of reconstructing multiple arteries was similar in all graft types, 27.3% in right and 25% and 21.4% in left lobe and left lateral segments, respectively (p > 0.05). There was no difference in biliary complications (p = 0.85), hepatic artery thrombosis (p = 0.82), and post-surgical hospital stay (p = 0.38) between the three groups. The presence of multiple arteries or their selective reconstruction did not affect survival (p = 0.73). CONCLUSIONS: Multiple arterial inflows are not an uncommon entity and demonstration of good hilar collateralization helps in avoiding unnecessary arterial reconstruction without adverse outcomes.

Propensity Score-Matched Analysis of Posttransplant Outcomes in Living Donor Liver Transplantation for Older Adult Recipients.

The impact of increasing recipient age on morbidity and mortality following living donor liver transplantation (LDLT) remains controversial. The study aims to analyze the impact of recipient age on outcomes following LDLT. Data on adult LDLTs performed between November 2009 and February 2020 were retrieved from a prospectively maintained database. Patients were stratified into 2 groups based on recipient age: 18 to 65 years (younger adults) and >65 years (older adults). Propensity score matching (PSM) using nearest-neighbor matching was used to match each older recipient with up to 2 younger adult recipients using multiple preoperative parameters. Outcomes evaluated were duration of ventilation, need for reintubation, tracheostomy, intensive care unit (ICU) readmission, length of ICU and hospital stays, postoperative complications, reoperation within 90 days, and patient survival. A total of 801 adult LDLT recipients were included in the study; 751 (93.7%) were younger adults, and 50 (6.3%) were older adults. Older recipients were more likely to be diabetic (60.0% versus 39.7%) and hypertensive (44.0% versus 20.4%) with preexisting cardiac disease (28.0% versus 11.2%). However, their pretransplant Model for End-Stage Liver Disease score was significantly lower (14.5 versus 17.7), and they were more likely to receive a transplant because of hepatocellular carcinoma (38.0% versus 17.7%). Older recipients had longer durations of ventilation after LT both before (3.7 versus 1.9 days) and after PSM (4.0 versus 1.5 days). After PSM, the 30-day (13.0% versus 2.4%), 90-day (15.2% and 2.4%), and overall mortality rates (21.7% versus 7.1%) were significantly higher for older recipients when compared with younger recipients. There was no difference between the younger and older recipients with respect to other postoperative outcomes. This propensity score-matched study shows that the older LDLT recipients have higher 30-day, 90-day, 1-year, and 5-year mortality rates when compared with matched younger counterparts.

Recurrent Intestinal Perforation After Cessation of Immunosuppression in Posttransplant Lymphoproliferative Disease in Pediatric Liver Transplant Recipient.

Posttransplant lymphoproliferative disease (PTLD) is the most common malignant complication after solid organ transplantation. Gastrointestinal involvement as the presentation in early PTLD can occur in 25-30% of pediatric liver transplant recipients and can be the only system involved in 20%. Recurrent gastrointestinal perforation due to resolution of PTLD is an extremely rare complication. We report a 13-month-old male child diagnosed with PTLD, treatment of which lead to recurrent intestinal perforations. The child presented with gastrointestinal bleed 5 months after living donor liver transplantation for biliary atresia. Evaluation was suggestive of PTLD and biopsy confirmed diffuse large B-cell lymphoma. Positron emission tomography scan showed diffuse involvement of small intestine and ileum. Tacrolimus was withdrawn abruptly following diagnosis of PTLD as there was associated renal impairment. Child developed six episodes of small intestinal perforations over 3 weeks which required multiple laparotomies with closure of perforation and/or small bowel resection. Complete remission was achieved six months after diagnosis with cessation of immunosuppression alone and child is alive at 48 months follow-up without any recurrence. To avoid bowel perforation and complications related to tumor necrosis, immunosuppression reduction in PTLD should be gradual while carefully monitoring Epstein-Barr virus levels, tumor response, graft function, and general health status of the patient.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

Portal flow modulation in auxiliary partial orthotopic liver transplantation.

APOLT is a suitable technique of liver transplantation in patients with ALF and some types of MLD. Portal venous steal is a problem with this procedure that leads to graft dysfunction and failure. Modulation of the portal flow to the graft and native liver can help in preventing this problem. We discuss the pathophysiology of this complication, review available literature regarding its management, and describe our results using the technique of graded hemiportal banding to achieve adequate perfusion for the graft and native liver.