International multicenter study of ultralow graft-to-recipient weight ratio grafts in adult living donor liver transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P < .05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P = .035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Temporary Portocaval Shunt Provides Superior Intraoperative Hemodynamics and Reduces Blood Loss and Duration of Surgery in Live Donor Liver Transplantation: A Randomized Control Trial.

OBJECTIVE: To compare intraoperative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without temporary portocaval shunt (TPCS) in live donor liver transplantation (LT) recipients. Secondary objectives were postoperative early graft dysfunction, morbidity, mortality, total intensive care unit, and hospital stay. BACKGROUND: Blood loss during recipient hepatectomy for LT remains a major concern. Routine use of TPCS during LT is not yet elucidated. METHODS: This study is a single-center, open-label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS vs no TPCS) were recruited in the trial. RESULTS: The baseline recipient and donor characteristics were comparable between the groups. The median intraoperative blood loss ( P = 0.004) and blood product transfusions ( P < 0.05) were significantly less in the TPCS group. The TPCS group had significantly improved intraoperative hemodynamics in the anhepatic phase as compared with the no TPCS group ( P < 0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in the TPCS group ( P = 0.002). Because of technical simplicity, the TPCS group had significantly fewer inferior vena cava injuries (3.3 vs 26.7%, P = 0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs 606.83 ± 48.13 min, P < 0.0001). The time taken for normalization of lactate in the immediate postoperative period was significantly shorter in the TPCS group (median, 6 vs 13 h; P = 0.04). Although postoperative endotoxemia, major morbidity, 90-day mortality, total intensive care unit, and hospital stay were comparable between both groups, tolerance to enteral feed was earlier in the TPCS group. CONCLUSIONS: In live donor LT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery.

Graft Inflow Modulation by Splenic Artery Ligation for Portal Hyper Perfusion does not Decrease Rates of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation: A Randomized Control Trial.

OBJECTIVE: The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality. BACKGROUND: GIM can prevent EAD in ALDLT patients with portal hyper-perfusion. METHODS: A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15 mm Hg with a gradient (PVP - central venous pressure) of ≥ 7 mm Hg and/or portal venous flow (PVF)>250 mL/min/100 grams of liver were randomized into two groups: GIM and No GIM. RESULTS: 75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes. CONCLUSION: SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT.

Lifestyle Optimization Leads to Superior Liver Regeneration in Live Liver Donors and Decreases Early Allograft Dysfunction in Recipients: A Randomized Control Trial.

INTRODUCTION: The aim of the current randomized control trial was to assess the efficacy of donor lifestyle optimization on liver regeneration and outcome following live donor liver transplantation. METHODS: Live liver donors (LLDs) who were fit with no or minimal steatosis were randomized to receive either a customized low-calorie diet with calorie intake equalling their basal requirement along with exercise for 2 weeks before surgery versus to continue their normal routine lifestyle. Primary objectives were the difference in the day of normalization of serum bilirubin and PT-International normalized ratio and the percentage growth of the liver at postoperative day 7 and 14. Secondary objectives were differences in intraoperative liver biopsy, liver-regeneration markers, blood loss, hospital stay, the complication rate in LLDs, and rates of early graft dysfunction (EGD) in recipients. RESULTS: Sixty-two consecutive LLDs were randomized (28 in intervention vs. 34 in control). Baseline parameters and graft parameters were similar in both groups. LLDs in the intervention arm had significantly decreased calorie intake ( P <0.005), abdominal girth ( P <0.005), BMI ( P =0.05), and weight ( P <0.0005). The mean blood loss ( P =0.038), day of normalization of bilirubin ( P =0.005) and International normalized ratio ( P =0.061), postoperative peak aspartate transaminase ( P =0.003), Alanine transaminase ( P =0.025), and steatosis ( P <0.005) were significantly less in the intervention group. There was significantly higher volume regeneration ( P =0.03) in donors in the intervention arm. The levels of TNF-α, IL-6, and IL-10 levels were significantly higher, while the TGF-ß level was lower in donors in the intervention group. The rate of EGD was significantly higher in recipients in the control group ( P =0.043). CONCLUSION: Lifestyle optimization of LLD is simple to comply with, improves liver regeneration in LLDs, and decreases EGD in recipients, thus can enhance donor safety and outcomes in live donor liver transplantation.

Metabolomic analysis shows dysregulation in amino acid and NAD+ metabolism in palmitate treated hepatocytes and plasma of non-alcoholic fatty liver disease spectrum.

There is an alarming increase in incidence of fatty liver disease worldwide. The fatty liver disease spectrum disease ranges from simple steatosis (NAFL) to steatohepatitis (NASH) which culminates in cirrhosis and cancer. Altered metabolism is a hallmark feature associated with fatty liver disease and palmitic acid is the most abundant saturated fatty acid, therefore, the aim of this study was to compare metabolic profiles altered in hepatocytes treated with palmitic acid and also the differentially expressed plasma metabolites in spectrum of nonalcoholic fatty liver. The metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) platform. Hepatocyte cell lines PH5CH8 and HepG2 cells when treated with 400 µM dose of palmitic acid showed typical features of steatosis. Metabolomic analysis of lipid treated hepatocyte cell lines showed differential changes in phenylalanine and tyrosine pathways, fatty acid metabolism and bile acids. The key metabolites tryptophan, kynurenine and carnitine differed significantly between subjects with NAFL, NASH and those with cirrhosis. As the tryptophan-kynurenine axis is also involved in denovo synthesis of NAD+, we found significant alterations in the NAD+ related metabolites in both palmitic acid treated and also fatty liver disease with cirrhosis. The study underscores the importance of amino acid and NAD+supplementation as promising strategies in fatty liver disorder.

Bile multi-omics analysis classifies lipid species and microbial peptides predictive of carcinoma of gallbladder.

BACKGROUND AND AIMS: Histopathological examination is the gold standard for detection of gallstone (GS) or gallbladder carcinoma (CAGB). Bile concentrated in the gallbladder (GB) is expected to recapitulate metagenomics and molecular changes associated with development of CAGB. APPROACH AND RESULTS: Bile samples were screened for lipidomics and metaproteome (metagenomics) signatures capable of early detection of cancer in GB anomalies. Analysis of the training cohort (n = 87) showed that metastability of bile was reduced in CAGB (p < 0.05). CAGB bile showed significant alteration of lipidome and microbiome as indicated by multivariate partial least squares regression analysis and alpha-diversity and beta-diversity indexes (p < 0.05). Significant reduction of lipid species and increase in bacterial taxa were found to be associated with patients with CAGB, CAGB with GS, and GS (p < 0.05, log fold change >1.5). A multimodular correlation network created using weighted lipid/metaproteomic correlation network analysis showed striking associations between lipid and metaproteomic modules and functionality. CAGB-linked metaproteomic modules/functionality directly correlated with lipid modules, species, clinical parameters, and bile acid profile (p < 0.05). Increased bacterial taxa (Leptospira, Salmonella enterica, Mycoplasma gallisepticum) and their functionality showed a direct correlation with lipid classes such as lysophosphatidylinositol, ceramide 1-phosphate, and lysophosphatidylethanolamine and development of CAGB (r2  > 0.85). Lipid/metaproteomic signature-based probability of detection for CAGB was > 90%, whereas that for GS was > 80% (p < 0.05). Validation of eight lipid species using four machine learning algorithms in two separate cohorts (n = 38; bile [test cohort 1] and paired plasma [test cohort 2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. CONCLUSIONS: Bile samples of patients with CAGB showed significant reduction in lipid species and increase in bacterial taxa. Our study identifies a core set of bile lipidome and metaproteome signatures which may offer universal utility for early diagnosis of CAGB.

Role of cytomegalovirus specific cell-mediated immunity in the monitoring of cytomegalovirus infection among living donor liver transplantation adult recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) is one of the most common post-transplant viral infections causing significant morbidity and occasional mortality. Limited literature on the potential role of pre-transplant CMV-specific cell-mediated immunity (CMV-CMI) is available. This study aimed to evaluate the clinical utility of pre-transplant CMV-CMI monitoring in the occurrence of post-transplant CMV infection. METHODS: This was a prospective, observational study where all adult CMV seropositive patients undergoing living donor liver transplantation at a tertiary care institute were enrolled. CMV-CMI was measured using QuantiFERON-CMV (Qiagen GmbH, Hilden, Germany) and interpreted as positive if the value was ≥0.2 IU/ml, 1-2 days prior to the transplant. Based on pre-transplant CMV-CMI, cases were classified into Group 1 (n = 13, 43.3%) (positive) and Group 2 (n = 17, 56.7%) (negative). CMV infection was defined as the detection of CMV-DNA > 2.7 log10 IU/ml in plasma specimens. RESULTS: The mean age was 43 years with male (n = 29, 96.9%) predominance. Overall 40% of recipients developed post-transplant CMV infection, two (15.4%) in group 1 and 10 (58.8%) in group 2 (p-value = 0.016). Recipients in group 2 had 87% higher odds (odds ratio 0.13, confidence interval [CI] 95) of developing post-transplant CMV infection compared to group 1. The overall median duration of occurrence of post-transplant CMV infection was 26 days with the median viral load being 2.8 log10 IU/ml. The treatment duration was 13 days in group 1 and 28 days in group 2 (p = 0.003). Group 1 recipients showed rapid clearance of CMV-DNA within 7 days compared to group 2 in which it was 21 days (p = 0.004, CI 95). CONCLUSION: Pre-transplant CMV-CMI may play a protective role against post-transplant CMV infection and can serve as an adjunct for pre-transplant risk stratification.

Early drain removal after live liver donor hepatectomy is safe - a randomized controlled pilot study.

INTRODUCTION: The current study aimed to assess the safety of early drain removal after live donor hepatectomy (LDH). METHODS: One hundred eight consecutive donors who met the inclusion criteria were randomized to early drain removal (EDR - postoperative day (POD) 3 - if serous and the drain bilirubin level was less than 3 mg/dl - "3 × 3" rule) and routine drain removal (RDR - drain output serous and less than 100 ml). The primary outcome was to compare the safety. The secondary outcome was to compare the postoperative morbidity. RESULTS: Preoperative, intraoperative, and postoperative parameters except for the timing of drain removal were comparable. EDR was feasible in 46 out of 54 donors (85.14%) and none required re-intervention after EDR. There was significantly better pain relief with EDR (p = 0.00). Overall complications, pulmonary complications, and hospital stay were comparable on intention-to-treat analysis. However, pulmonary complications (EDR - 1.9% vs RDR - 16.3% P = 0.030), overall complications (18.8% vs 36.3%, P = 0.043), and hospital stay (8 vs 9, P = 0.014) were more in the RDR group on per treatment analysis. Bile leaks were seen in three donors (3.7% in the EDR group vs 1.9% in RDR, P = 0.558), and none of them required endo-biliary interventions. Re-exploration for intestinal obstruction was required for 3 donors in RDR (0% vs 5.7%; p = 0.079). CONCLUSION: EDR by the "3 × 3" rule after LDH is safe and associated with better pain relief. On per treatment analysis, EDR was associated with significantly less hospital stay and lower pulmonary and overall complications. CLINICAL TRIAL REGISTRY: Clinical Trials.gov - NCT04504487.

Utility and diagnostic accuracy of intraoperative frozen sections in hepato-pancreato-biliary surgical pathology.

BACKGROUND AND PURPOSE: Hepato-pancreato-biliary (HPB) surgeries are one of the most challenging and complex procedures. Intraoperative frozen section (IFS) diagnosis plays a pivotal role in management decisions. Comprehensive large cohort studies evaluating utility of IFS in HPB malignancies are lacking. This study aimed to evaluate the accuracy of frozen section analysis and to analyse discrepancies and impact of IFS on the surgical decisions. PATIENTS AND METHODS: This was a retrospective study of IFS received for the HPB specimens between years 2009 and 2021. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity. Indications, disagreements and impact on the surgical management were analysed. RESULTS: A total of 1008 specimens were evaluated: bile duct margin (279; 27.7%), gallbladder (203; 20.1%), liver lesions (125 cases; 12.4%), lymph nodes (147; 14.6%), pancreatic margin (120; 11.9%) and deposits (134; 13.3%). IFS were diagnosed as negative for malignancy (805; 79.9%), positive for dysplasia (8; 0.8%), suspicious for malignancy (6; 0.6%) and positive for malignancy (189; 18.8%). The overall diagnostic accuracy was 98.4%, and the discordant rate was 1.6%. The sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 99.4%, 97.5% and 98.6% respectively. The most important reason of discordant results was technical, followed by interpretational and sampling errors. CONCLUSION: The study demonstrates high diagnostic accuracy (98.4%) of IFS in a large dataset of HPB specimens. This comprehensive analysis apprises of the indications, errors and the impact of IFS diagnosis on subsequent HPB surgical management.

Efficacy of rectal indomethacin in prevention of post-operative hyperamylasemia following pancreatoduodenectomy: a randomized controlled trial.

BACKGROUND: Post-operative hyperamylasemia (POH) following pancreatoduodenectomy (PD) may play a key role in pathogenesis of post-operative pancreatic fistula (POPF). Aim of the current study was to evaluate efficacy of perioperative administration of indomethacin in preventing POH. METHODS: Single-center, double-blind, randomized controlled trial (RCT) conducted on consecutive patients undergoing PD. Patients received either 100 mg of indomethacin per-rectally at induction of anesthesia or standard care. Primary endpoint was incidence of POH in the two arms. POH was defined as postoperative day (POD) 1 serum amylase (S. amylase) levels greater than the upper limit of normal. RESULTS: After exclusion 44 patients were randomized. The two arms were comparable for preoperative and intraoperative parameters. POH was noted in 20/44 (45.5%) with significantly lower incidence of POH (60.9% vs. 28.6%, p = 0.032) in intervention arm (IA). Median S. amylase, POD 1, 3, and 5 drain amylase, and incidence of clinically relevant POPF (CR-POPF) were lower in IA but failed to reach statistical significance (30.4% vs. 14.3%, p = 0.18). The severity of delayed gastric emptying (DGE) was significantly lower in the IA (grade B/C DGE 23.8% vs. 47.8%, p = 0.023). Evaluation of risk factors for POH showed IA to confer an independent protective effect and increased risk with soft pancreas. CONCLUSION: Perioperative per-rectal indomethacin administration is effective in decreasing the incidence of POH following pancreatoduodenectomy.

Hepatic artery-related complications after live donor liver transplantation.

BACKGROUND: Hepatic artery-related complications (HARC) after live donor liver transplantation (LDLT) is associated with high morbidity and mortality rate. METHODS: Prospectively maintained data from July 2011 to September 2020 was analyzed for etiology, detection, management, and outcome of HARC. RESULTS: Six hundred fifty-seven LDLT (adult 572/pediatrics 85) were performed during the study period. Twenty-one (3.2%) patient developed HARC; 16 (2.4%) hepatic artery thrombosis (HAT) and 5 (0.76%) non-thrombotic hepatic artery complication (NTHAC). Ninety percent (19/21) HARC were asymptomatic and detected on protocol Doppler. Median time to detection was day 4 (range - 1 to 35), which included 18 early (within 7 days) vs 3 late incidents. Only one pediatric patient had HAT. Seven patients underwent surgical revascularization, 11 had endovascular intervention and 3 with attenuated flow required only systemic anticoagulation. All NTHAC survived without any sequelae. Revascularization was successful in 81% (13/16) with HAT. Biliary complications were seen in 5 (23.8%); four were managed successfully. Overall mortality was 14.8% (3/21). The 1-year and 5-year survival were similar to those who did not develop HARC (80.9% vs 84.2%, p = 0.27 and 71.4% vs 75.19%, p = 0.36 respectively) but biliary complications were significantly higher (23.8% vs 14.2%, p = 0.03). On multivariate analysis, clockwise technique of arterial reconstruction was associated with decreased risk of HAT (1.7% vs 4.1% (p value - 0.003)). CONCLUSION: Technical refinement, early detection, and revascularization can achieve good outcome in patients with HARC after LDLT.

Cystic artery pseudoaneurysm-a rare complication of acute cholecystitis: review of literature.

OBJECTIVE: To acquaint with the presentation and management of the cystic artery aneurysm by enriching the reviewed literature with our own experience. BACKGROUND: Cystic artery pseudoaneurysm is an uncommon entity with varied clinical presentation. Inflammation and trauma are associated with most of the cases. Limited experience with the condition challenges the management of individual cases. MATERIALS AND METHODS: We retrieved all the reported cases of cystic artery pseudoaneurysm, published up to December 2019, from the PubMed database and excluded those arising as postoperative complications. A total of 59 cases were analyzed, and we also included our experience of managing a case of cystic artery pseudoaneurysm. RESULTS: Abdominal pain (77.9%) was the most common presentation followed by upper GI bleed (64.4%), while 19 patients (32.2%) had presented with classic Quincke's Triad. Most of the cases were diagnosed following the rupture of the pseudoaneurysm (n = 49, 83.05%). Fifteen patients presented with shock. Hyperbilirubinemia (59.3%) and anemia (55.9%) were the commonest laboratory findings. Although CT angiogram remains the investigation of choice, a conventional angiogram is the gold standard and sufficed as the definitive management in 20 cases. Cholecystectomy formed the definitive management in the rest of the cases. We successfully managed a middle-aged female patient of cystic artery aneurysm with xanthogranulomatous cholecystitis by open cholecystectomy. CONCLUSION: Cystic artery pseudoaneurysms are amenable to successful management with careful evaluation and timely cholecystectomy or angioembolization or a combination of both.

Expanding donor pool for live donor liver transplantation: utilization of donors with non-alcoholic steatohepatitis after optimization.

INTRODUCTION: Potential live liver donors with non-alcoholic steatohepatitis (NASH) are rejected upfront for donation in live donor liver transplantation (LDLT). Herein, we share our experience of the feasibility of live liver donation in donors with NASH after successful donor optimization. MATERIALS AND METHODS: Prospectively collected data of 410 consecutive donor hepatectomies from June 2011 to January 2018 were analyzed. RESULTS: During the study period, NASH was diagnosed histopathologically in 17 donors. Four donors were rejected in view of grade 2 fibrosis on histology. Out of remaining 13 donors, six became eligible for donation following lifestyle changes, dietary modifications, and target weight reduction of ≥5%. Reversal of NASH was confirmed on repeat liver biopsy in all the 6 donors. Five out of 6 underwent right lobe (without MHV) donor hepatectomies, while one had left lobe donation. These donors had significantly higher peak bilirubin levels in the immediate post-operative period as compared to other non-NASH donors (4.00 ± 0.32 vs. 2.57 ± 1.77 mg/dL, p = 0.043). In addition, post-hepatectomy normalization of hyperbilirubinemia, if any, was slower in donors with NASH (7 ± 1.3 vs. 5 ± 1.7 days, p = 0.016). However, none of these donors had post-hepatectomy liver failure. All these donors were discharged after an average hospital stay of 8 ± 1.7 days. Their respective recipients had uneventful post-operative courses without complications. Both the recipients and donors are having satisfactory liver functions after 46.7 ± 10.2 months of follow-up. CONCLUSION: Scrupulous selection of live liver donors with NASH can open a door for expanding the organ pool in LDLT after a successful donor optimization program.

Biliary Reconstruction in Adult Living Donor Liver Transplantation: The All-Knots-Outside Technique.

Biliary complications (BCs) following living donor liver transplantation (LDLT) can lead to significant morbidity and occasional mortality. The present study describes our experience of the all-knots-outside technique (AKOT) of biliary reconstruction (BR) and its impact on BCs. A retrospective analysis was performed using prospectively collected data of 330 consecutive adult patients undergoing LDLT from July 2011 to February 2018 with a minimal follow-up of 24 months. Only 2.8% required hepaticojejunostomy and were excluded. In an initial 122 patients, BR was performed with the standard technique (ST), and AKOT was performed in the subsequent 208 patients. In the AKOT group, a single anastomosis was attempted even for multiple ducts whenever feasible. A major BC was defined as requiring endoscopic, percutaneous, or surgical interventions. In the AKOT group, significantly more patients received a left lobe graft (5.7% versus 18.3%; P = 0.001), had shorter warm ischemia time (44.6 versus 27 minutes; P < 0.001), and had a left hepatic artery (LHA) in the right lobe that was used for arterial reconstruction (48 [39.3%] versus 122 [58.6%]; P = 0.003). The incidence of BCs in the entire cohort was 47 (14.2%). For the ST versus AKOT groups, the overall BCs (27/122 [22.1%] versus 20/208 [9.6%]; P = 0.003) and major BCs (20.5% versus 6.7%; P < 0.001) decreased significantly. In the multivariate analysis, the number of bile ducts (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.62-10.78; P = 0.003), number of anastomoses (HR, 2.03; 95% CI, 1.03-4.02; P = 0.04), and technique of anastomosis (HR, 0.36; 95% CI, 0.19-0.68; P = 0.002) predicted BCs. In conclusion, in adult LDLT, with standardization of the donor and recipient surgery, preferential use of LHA for right lobe arterial reconstruction, reduction in the number of anastomoses, and AKOT for BR significantly decreased the incidence of BCs.

Impact of human leukocyte antigen compatibility on outcomes of living donor liver transplantation: Experience from a tertiary care center.

INTRODUCTION: The role of HLA compatibility in kidney, heart, and stem cell transplantation is well known, but with regard to living donor liver transplantation (LDLT), there is a different scenario. In the present study, we aim to examine the effects of donor-recipient HLA mismatches at A, B, and DR loci on various outcomes of LDLT-like graft survival, early allograft dysfunction (EAD), acute rejection, length of hospital (LOH) stay, sepsis, and cytomegalovirus (CMV) reactivation. METHODS: This is a retrospective single center study of a cohort of adult patients who underwent first time ABO-compatible (ABOc) LDLT between January 2010 and December 2018. Transplants with incomplete records or without HLA typing data were excluded. Donor-recipient HLA-A, B, and DR mismatches were assessed in the host versus graft (HVG) direction and were correlated with various post-transplant outcomes. RESULTS: Among 140 transplants being evaluated, approximately two third had total HLA mismatches between 2 and 3. HLA mismatches at each locus as well as cumulative HLA mismatches did not show any association with overall graft survival, EAD, acute rejection episodes, and LOH stay. However, the presence of minimum one mismatch at HLA-A and DR loci was associated with the development of CMV reactivation (P = .03) and sepsis (P = .02) post-LDLT respectively. CONCLUSION: HLA mismatch is not associated with acute rejection, early graft dysfunction, and overall survival in LDLT. Its impact on CMV reactivation and sepsis needs further evaluation.

Diaphragmatic Hernia after Pediatric Living Donor Liver Transplantation: An Indian Experience with Review of Literature.

AIM: Although intestinal obstruction following living donor liver transplantation (LDLT) is relatively common, diaphragmatic hernia (DH) as the attributing cause is rarely reported. The study aimed to find out the incidence, clinical presentation, and management of DH after liver transplant in pediatric patients. MATERIALS AND METHODS: A retrospective review of all cases of pediatric liver transplants was performed. Case sheets, operation records, and investigations including radiology were studied. RESULTS: Out of 79 cases of pediatric liver transplants, two cases of posttransplant DH were identified. The first case is a 2-year-old male child who was transplanted for progressive familial intrahepatic cholestasis, and the second one is a 4-year-old boy who underwent LDLT for hepatitis A-induced acute liver failure. The first child presented abdominal symptoms and the second one with pulmonary symptoms. The DHs were diagnosed at 132 and 70 days, respectively, posttransplant by chest radiographs and computed tomography scan. The defects were located at the posteromedial aspect of the diaphragm in both the cases and were closed by primary closure with mesh reinforcement. Both the children are doing well with no recurrence. CONCLUSION: High index of clinical suspicion is mandated in pediatric patients after liver transplant and once the diagnosis is confirmed, urgent surgical exploration is mandatory.

Living Donor Liver Transplantation for Acute Liver Failure: Donor Safety and Recipient Outcome.

In countries where deceased organ donation is sparse, emergency living donor liver transplantation (LDLT) is the only lifesaving option in select patients with acute liver failure (ALF). The aim of the current study is living liver donor safety and recipient outcomes following LDLT for ALF. A total of 410 patients underwent LDLT between March 2011 and February 2018, out of which 61 (14.9%) were for ALF. All satisfied the King's College criteria (KCC). Median admission to transplant time was 48 hours (range, 24-80.5 hours), and median living donor evaluation time was 18 hours (14-20 hours). Median Model for End-Stage Liver Disease score was 37 (32-40) with more than two-thirds having grade 3 or 4 encephalopathy and 70% being on mechanical ventilation. The most common etiology was viral (37%). Median jaundice-to-encephalopathy time was 15 (9-29) days. Preoperative culture was positive in 47.5%. There was no difference in the complication rate among emergency and elective living liver donors (13.1% versus 21.2%; P = 0.19). There was no donor mortality. For patients who met the KCC but did not undergo LT, survival was 22.8% (29/127). The 5-year post-LT actuarial survival was 65.57% with a median follow-up of 35 months. On multivariate analysis, postoperative worsening of cerebral edema (CE; hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.01-6.31), systemic inflammatory response syndrome (SIRS; HR, 16.7; 95% CI, 2.05-136.7), preoperative culture positivity (HR, 6.54; 95% CI, 2.24-19.07), and a longer anhepatic phase duration (HR, 1.01; 95% CI, 1.00-1.02) predicted poor outcomes. In conclusion, emergency LDLT is lifesaving in selected patients with ALF. Outcomes of emergency living liver donation were comparable to that of elective donors. Postoperative worsening of CE, preoperative SIRS, and sepsis predicted outcome after LDLT for ALF.

Cascade plasmapheresis as a desensitization strategy for patients undergoing ABO incompatible living donor liver transplantation (ABOi LDLT): A single center experience.

BACKGROUND AND AIM: The reduction of antibody titres (AT's) to a safe level is essential pre-requisite for patients awaiting ABO-incompatible liver transplantation (ABOi LT). We report our experience of performing cascade plasmapheresis (CP) on 2 different apheresis platforms (COBE Spectra and Spectra Optia) as a desensitization strategy for patients undergoing ABOi LT in our centre. METHODS: This retrospective observational study was conducted on patients who underwent CP included in the desensitization protocol for ABOi LDLT. CP/conventional TPE was performed (daily/alternate day with daily estimation of AT) until a target titre of ≤ 8 was achieved. RESULTS: During the study period, 4 patients (mean age 46.7 years; 100% males) underwent desensitization for ABOi LDLT with baseline AT (combined IgM and IgG) ranging from 64 to 512. A total of 15 CP sessions (range 2 - 6) were performed with a median of 3.5 sessions/patient. Desensitization rate was 100%. Only 1 patient underwent conventional TPE in the post-transplant due to rise in AT level to 64 (post-operative day 8). Average post-operative length of stay was 49 days (range 30 - 105). None of the patients experienced any episode of rejection (repeat liver biopsy). On follow up (1 year), 2 patients were alive and doing well, while other 2 patients succumbed during their hospital stay due to sepsis. CONCLUSION: In our limited experience, the use of CP was safe and effective desensitization strategy for patients undergoing ABOi LDLT.

Donor CD163 and nestin-positive cells predict graft function in living donor liver transplant.

AIMS: To evaluate the effect of donor liver resident mesenchymal cells, M2 macrophages on liver graft outcome after living donor liver transplantation. MATERIALS AND METHODS: Seventy donor biopsies were included in the study. Outcomes at day 3, 7, 30, and 180 postliver transplantation were assessed. Mesenchymal stem cells and M2 macrophages in donor liver biopsies were evaluated. RESULTS: Mean age of recipients was 40.9 ± 13.6 years. Sex mismatched transplants were 44 (M→F = 9; F→M = 35). On area under receiver operative curve analysis, donor biopsy (DB) nestin ≥3 and CD 163 ≥ 32/200x at day 3; CD163 ≥ 32 at day 7; CD 163 > 32, pRBC of <6.5 units at day 30, and DB nestin ≥3, CD 163 ≥ 32 and pRBC<6.5 units at day 180 predicted adequate graft functions. On multivariate analysis, higher DB nestin (P = .009) and lower cryoprecipitate (P = .009) usage at day 3, higher DB CD163 (P = .006) at day 7, higher DB CD163 (P = .018) and reduced transfusion of packed cell (pRBC) (P = .014) at day 30 and higher DB nestin (P = .011), higher CD163 (P = .009), and reduced pRBC (P = .045) at day 180 were the predictors of better outcome. CONCLUSIONS: Donor liver biopsy nestin+ and CD163+ can predict early graft outcome in living donor liver transplantation.