Living donor liver transplant in acute on chronic liver failure grade 3: Who not to transplant.

BACKGROUND AND AIM: Liver transplantation(LT)offers definitive treatment for acute on chronic liver failure(ACLF) patients. This study was done to analyze and compare the outcomes of living donor LT(LDLT) in patients with ACLF versus Chronic liver disease(CLD) and within the grades of ACLF. Factors affecting mortality in patients with ACLF and ACLF grade3 (ACLF3) following LDLT were also derived. METHODS: Records of adult LDLT between 1/2/2017 and 30/9/2021 were analyzed. ACLF was classified based on EASL-CLIF definition. Post-transplant outcomes of ACLF were compared with CLD and within ACLF grades. Post LDLT mortality predictors were identified in ACLF and ACLF3 patients. RESULTS: Out of 853 patients who had LT in that period; 704 patients with CLD and 103 with ACLF [of which 54 (52.42%) had ACLF3] underwent LDLT. The one month and one-year post LDLT mortality was 8.81% and 9.80% in CLD; 19.42% and 31.06% in ACLF; and 25.92% and 38.89% in ACLF3 respectively. On log regression analysis, use of grafts from older donors and pre-operative respiratory failure in recipients was associated with poor survival in ACLF, while respiratory failure was a predictor of poor survival in ACLF3 following LDLT. CONCLUSION: Outcomes following LDLT are poorer in ACLF as compared to after CLD. Higher donor age and preoperative respiratory failure with PF Ratio<200 were associated with poor survival post LDLT in ACLF and ACLF3.

Domino liver transplantation for maple syrup urine disease in children: A single-center case series.

BACKGROUND: Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. METHODS: It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. RESULTS: Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. CONCLUSION: DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.

LTSI Consensus Guidelines: Preoperative Pulmonary Evaluation in Adult Liver Transplant Recipients.

The relationship between chronic liver disease and respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease (CLD) have been characterized: hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. Apart from that coexisting pulmonary disease like chronic obstructive lung disease and interstitial lung disease also complicate the outcomes after liver transplantation (LT). Assessment for evaluation of underlying pulmonary disorders is essential to improve outcomes in patients with CLD, posted for LT. This consensus guideline of the Liver Transplant Society of India (LTSI) provides a comprehensive review of pulmonary issues in CLD, related and unrelated to underlying liver disease and gives recommendations for pulmonary screening in specific clinical scenarios in adults with chronic liver disease planned for LT. This document also aims to standardize the strategies for preoperative evaluation of these pulmonary issues in this subset of patients. Proposed recommendations were based on selected single case reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Additionally, this review will highlight the lacunae in our current evaluation strategy, challenges faced, and will provide direction to potentially useful futuristic preoperative evaluation strategies.

Safety and feasibility of immediate tracheal extubation of small pediatric patients after living donor liver transplantation.

BACKGROUND: Immediate extubation is integral constituent of enhance recovery protocols. Purpose of this study was to examine success rates and safety of protocolized immediate extubation in pediatric living donor liver transplant recipients and to find out factors associated with non-immediate extubation in operation room. METHODS: We performed retrospective analysis for data of small (≤20 kg) pediatric patients transplanted between 2017 and 2019 (protocolized duration) and compared with data of transplants done between 2014 and 2016 (non-protocolized duration). Further, we compared data during each time duration between immediate extubation and non-immediate extubation group to find risk factors in that particular duration. RESULTS: Immediate extubation rates were significantly higher during protocolized duration compared with non-protocolized duration (85.52% vs. 48.29%, p < .001). Reintubation rates decreased during protocolized duration (10.9% vs. 4.6%). Hospital stays (20.47 ± 7.06 vs. 27.8 ± 6.2 days, p < .001) and mortality (13.2% vs. 28%, p = .04) were significantly decreased in protocolized duration. Higher age (OR: 2.85, 95% CI 1.22-6.67, p = .02), weight > 10 (OR: 4.37, 95% CI 1.16-16.46, p = .029) and high vasopressor support (OR: 32, 95% CI 6.4-160.13, p < .001) found as significant predictors of non-immediate extubation however only high vasopressor support found to be independent predictor during protocolized duration. CONCLUSIONS: Outcomes in pediatric transplants can be optimized by immediate extubation in majority of cases when protocolized as part of policy.

Living donor liver transplant outcomes during the COVID-19 pandemic: does a decrease in case volume impact the overall outcomes?

Background: High-volume centers (HVCs) are classically associated with better outcomes. During the coronavirus disease 2019 (COVID-19) pandemic, there has been a decrease in the regular liver transplantation (LT) activity at our center. This study analyzed the effect of the decline in LT on posttransplant patient outcomes at our HVC. Methods: We compared the surgical outcomes of patients who underwent LT during the COVID-19 pandemic lockdown (April 1, 2020 to September 30, 2020) with outcomes in the pre-pandemic calendar year (April 1, 2019 to March 31, 2020). Results: During the 6 months of pandemic lockdown, 60 patients underwent LT (43 adults and 17 children) while 228 patients underwent LT (178 adults and 50 children) during the pre-pandemic calendar year. Patients in the pandemic group had significantly higher model for end-stage liver disease (MELD) scores (24.39±9.55 vs. 21.14±9.17, P=0.034), Child-Turcotte-Pugh scores (11.46±2.32 vs. 10.25±2.24, P=0.03), and incidence of acute-on-chronic liver failure (30.2% vs. 10.2%, P=0.002). Despite performing LT in sicker patients with COVID-19-related challenges, the 30-day (14% vs. 18.5%, P=0.479), 3-month (16.3% vs. 20.2%, P=0.557), and 6-month mortality rates (23.3% vs. 28.7%, P=0.477) were lower, but not statistically significant when compared to the pre-pandemic cohort. Conclusions: During the COVID-19 pandemic lockdown the number of LT procedures performed at our HVC declined by half because prevailing conditions allowed LT in very sick patients only. Despite these changes, outcomes were not inferior during the pandemic period compared to the pre-pandemic calendar year. Greater individualization of patient care contributed to non-inferior outcomes in these sick recipients.

Paired Exchange Living Donor Liver Transplantation: A Nine-year Experience From North India.

BACKGROUND: Paired exchange liver transplantation is an evolving strategy to overcome ABO blood group incompatibility and other barriers such as inadequate graft-to-recipient weight ratio and low remnant liver volume in donors. However, for the transplant team to carry 4 major operations simultaneously is a Herculean effort. We analyzed our experience with liver paired exchange (LPE) program over the past 9 y. METHODS: This prospective study included 34 of 2340 (1.45%) living donor liver transplantations performed between May 2012 and April 2021. The reason for LPE was ABO incompatibility in all (n = 34) patients included in the study. After donor reassignment through 2-by-2 paired exchange with directed donors, the ABO matching status changed from A to A (n = 17) and B to B (n = 17), which made all matches ABO-identical. Recipients (R) and donors (D) of each swap pair were prospectively divided into R1/D1 and R2/D2 groups for comparative and survival analyses. RESULTS: The recipients (n = 34) had a median age of 45.5 y (11-59 y), and 31 were men. LPEs were performed in 4 operating rooms running simultaneously by 2 independent surgical teams. Donor survival was 100%. Baseline clinical and perioperative parameters, postoperative complications, median intensive care unit/hospital stay, and early deaths were comparable ( P > 0.1) between the R1 and R2 groups. The median follow-up period was 27 mo (1-108 mo). The 30-d and 1-y survivals were 88.2% (n = 30) and 85.3% (n = 29), respectively. CONCLUSIONS: Our experience suggests that with careful attention to ethical and logistical issues, the LPE program can expand the living donor liver pool and facilitate a greater number of living donor liver transplantations.

Normative cutoffs of muscle mass, muscle strength, and frailty for healthy Indian population.

BACKGROUND: Population-derived cutoffs for low skeletal muscle mass, skeletal muscle strength, and frailty among Indians are lacking. Studies describing sarcopenia and frailty among patients with chronic liver diseases have used cutoffs derived from Caucasian populations giving erroneous results. AIMS: We aimed to derive gender-specific cutoffs for low skeletal muscle mass and skeletal muscle strength from healthy Indians. METHODS: Healthy Indian population consisted of two groups. Group 1 (Gp I) included 242 healthy liver donors and group 2 (Gp II) 272 healthy health care workers. Skeletal muscle index (SMI) was calculated from computed tomography (CT) abdomen performed prior to donor hepatectomy only in Gp I. Liver frailty index (LFI) was computed using the online calculator, after recording hand grip strength (HGS), chair stand-up test (CSUT), and balance test in both groups. HGS was measured using the Smedley handgrip dynamometer. CSUT was noted as time to complete 5 chair stand-ups with subjects' arms folded across the chest. Gender-specific cutoffs of SMI and HGS were derived as <5th percentile of the distribution values and as >95th percentile for CSUT and LFI values. RESULTS: The SMI was measured from Gp I subjects (n=242; 120 males [mean age 31.13] and 122 females [mean age 36.60]). The HGS, CSUT, and LFI were measured in Gp I and Gp II subjects (n=514; 272 males [mean age 34.30] and 242 females [mean age 37.52]). The cutoffs for SMI, HGS, CSUT, and LFI were <27.72 cm2/m2, <25.63 kg, >10 s, and >3.49, respectively for healthy males. The corresponding cutoffs for healthy females were <24.4 cm2/m2, <16.7 kg, > 10 s, and >3.68, respectively. CONCLUSIONS: We derived gender-specific cutoffs for SMI, HGS, CSUT, and LFI from healthy adult Indian population, which can be used to detect sarcopenia and frailty among patients with liver diseases, as well as other conditions.

"SARS-CoV-2 Infection in Liver Transplant Recipients - Immunosuppression is the Silver Lining?"

BACKGROUND: COVID-19 is associated with higher mortality among patients who have comorbidities. However, evidences related to COVID-19 among post liver transplant recipients are scarce and evolving. METHODS: Adult Indian patients who had undergone liver transplantation at our centre since 2006 and were under regular follow-up, were contacted either telephonically or on email. Data were recorded related to symptoms and diagnosis of COVID-19, need for hospitalization, and need for ICU stay and mortality. RESULTS: Eighty one (3.71%) of the 2182 adult Liver transplant (LT) recipients on regular follow-up reported SARS-CoV-2 infection between 1st April 2020 and 31st May 2021. Mean age was 51.3(±9.8) years, and 74(91.4%) were males. Thirty five (43.2%) patients had one or more comorbidities. Twenty one (25.9%) patients were transplanted less than 1 year ago. Forty four (54.3% ) patients had mild disease only while 23(28.4%) patients had severe COVID-19 disease. Of the 81 patients 14 patients died and overall mortality was 17.3. CONCLUSION: Uncomplicated liver transplant recipients without comorbidities who acquire SARS-CoV-2 do not have poor outcome.

Patient blood management in India - Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group.

In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.

Living Donor Liver Transplant in patients with Hepatorenal Syndrome without the use of Intraoperative Renal Replacement Therapy, a single-center experience.

BACKGROUND: Continuous Renal Replacement Therapy (CRRT) is often used to support the intraoperative course during liver transplantation (LT) for patients with HRS. However, the use of intraoperative CRRT (IOCRRT) is not without its problems. Living donor liver transplantation (LDLT) is a planned operation and is possible without IOCRRT as the recipient can be optimized. AIM: To study the peritransplant outcomes of patients with CLD and HRS undergoing LT without IOCRRT. METHODS: Analysis of LT program database for perioperative outcomes in patients with HRS from Feb 2017 to Dec 2018. RESULTS: 87/363 (23.9%) adult LDLT patients had HRS, of whom 31 (35.6%) did not respond (NR) to standard medical therapy (SMT) prior to LT. Modified perioperative protocol enabled the NR patients (who were sicker and in persistent renal failure) to undergo LT without IOCRRT. Postoperative renal dysfunction was similar (2 in NR and 2 in R) at 1 year. Post-LT survival was also not different at one month (83.87% in NR and 87.5% in R [p = .640]) and at 1 year (77% in NR vs 80.4% in non-responders [p = .709]). CONCLUSION: IOCRRT can be avoided in HRS patients undergoing LDLT without compromising their outcomes (post-LT survival and RD), even in patients who have not responded to SMT, preoperatively.