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.

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.

National Liver Allocation Policy-Consensus Document by the Liver Transplantation Society of India for a Nationally Uniform System of Allocation of Deceased Donor Liver Grafts.

Background: Deceased donor liver transplantation (DDLT) is increasing in India and now constitutes nearly one-third of all liver transplantation procedures performed in the country. There is currently no uniform national system of allocation of deceased donor livers. Methods: A national task force consisting of 19 clinicians involved in liver transplantation from across the country was constituted under the aegis of the Liver Transplantation Society of India to develop a consensus document addressing the above issues using a modified Delphi process of consensus development. Results: The National Liver Allocation Policy consensus document includes 46 statements covering all aspects of DDLT, including minimum listing criteria, listing for acute liver failure, DDLT wait-list management, system of prioritisation based on clinical urgency for adults and children, guidelines for allocation of paediatric organs and allocation priorities for liver grafts recovered from public sector hospitals. Conclusion: This document is the first step in the setting up of a nationally consistent policy of deceased donor liver allocation.

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.

Outcome of Patients Waitlisted for Deceased Donor Liver Transplantation During COVID-19 Pandemic: A Single-Center Experience.

Background and aim: COVID-19 pandemic has strained several healthcare resources across the world. While liver transplantation (LT) is the only curative therapy for patients with end-stage liver disease, we aimed to determine the clinical outcome of patients waitlisted for deceased donor liver transplantation (DDLT) during COVID-19 pandemic. Methods: A retrospective comparative observational study of adult patients waitlisted for DDLT from January 2019 to January 2022 at our liver unit (Dr Rela Institute and Medical Center, Chennai, Tamil Nadu, India) was carried out. Patient demographics, disease etiology, Model for End-Stage Liver Disease - Sodium (MELD-Na) score were calculated for all patients listed during the study period. Clinical event was defined as number of DDLT, death in the absence of transplant, and patients awaiting LT were compared. Statistical analysis was performed with SPSS V24.0. Results: In total, 310 patients were waitlisted for DDLT, of whom 148, 63, and 99 patients listed during 2019, 2020, and 2021 (till January 2022), respectively; 22 (53.6%), 10 (24.3%), and 9 (21.9%) patients underwent DDLT in the year 2019, 2020, and 2021 (P = 0.000); 137 patients (44.19%) died on the DDLT waitlist of whom 41 (29.9%), 67 (48.9%), and 29 (21.1%) in the year 2019, 2020, and 2021 (P = 0.000), respectively. Waitlist mortality was significantly higher during the COVID first wave. Conclusion: COVID-19 pandemic has significantly impacted patients waitlisted for DDLT in India. With limited access to healthcare facilities and decreased organ donation rates during the pandemic, there was a considerable reduction in the patients waitlisted for DDLT, lesser number of patients underwent DDLT, and higher waitlist mortality during the pandemic year. Efforts to improve organ donation in India should be strongly implemented.

COVID-19: Time for a clinical classification?

COVID-19 pandemic caused by SARS-CoV-2 virus has been around for 2 years causing significant health-care catastrophes in most parts of the world. The understanding of COVID-19 continues to expand, with multiple newer developments such as the presence of asymptomatic cases, feco-oral transmission, and endothelial dysfunction. The existing classification was developed before this current understanding. With the availability of recent literature evidences, we have attempted a classification encompassing pathogenesis and clinical features for better understanding of the disease process. The pathogenesis of COVID-19 continues to evolve. The spiked protein of the SARS-CoV-2 virus binds to ACE2 receptors causes direct cytopathic damage and hyperinflammatory injury. In addition to alveolar cells, ACE2 is also distributed in gastrointestinal tract and vascular endothelium. ACE2-SARS-CoV-2 interaction engulfs the receptors leading to depletion. Accumulation of Ang2 via AT1 receptor (AT1R) binding causes upregulation of macrophage activity leading to pro-inflammatory cytokine release. Interleukin-6 (IL-6) has been attributed to cause hyperinflammatory syndrome in COVID-19. In addition, it also causes severe widespread endothelial injury through soluble IL-6 receptors. Thrombotic complications occur following the cleavage and activation of von Willebrand factor. Based on the above understanding, clinical features, organ involvement, risk stratification, and disease severity, we have classified COVID-19 patients into asymptomatic, pulmonary, GI, and systemic COVID-19 (S-COVID-19). Studies show that the infectivity and prognosis are different and distinct amongst these groups. Systemic-COVID-19 patients are more likely to be critically ill with multi-organ dysfunction and thrombo-embolic complications.

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.

Hereditary Persistence of Alpha-Fetoprotein in Chronic Liver Disease-Confusing Genes!

Alpha-fetoprotein (AFP) is a glycoprotein secreted by the embryonic liver and is expressed in tumours with high mitotic index such as hepatocellular carcinoma (HCC) and germ cell tumours. Detection of elevated AFP is strongly associated with underlying HCC or occasionally germ cell tumour. Modest elevation of AFP can be observed in patients with chronic viral hepatitis particularly with active replication. Very rarely, incidental detection of raised AFP in a genetically susceptible individuals has been reported in the absence of the underlying malignant process. This condition is termed as hereditary persistence of AFP (HPAFP), a rare disorder with an autosomal dominant pattern of inheritance. HPAFP should be suspected in patients with high AFP in the absence of radiological evidence of HCC or germ cell tumour. The diagnosis is confirmed by the identification of AFP gene mutation. AFP gene is located in the long arm of chromosome 4. The most common single-nucleotide polymorphism in HPAFP is 119 G > A, rs587776861, interestingly reported only in six family clusters worldwide. Despite being described as a benign disorder, its implication in patients with underlying chronic liver disease needs further clarification. Here, we describe 3 patients in their forties with chronic liver disease and persistently elevated levels of AFP, where genetic studies confirmed HPAFP. None of our patients had HCC despite extensive investigations.

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.

COVID-19: Poor outcomes in patients with zinc deficiency.

BACKGROUND: Zinc is a trace element with potent immunoregulatory and antiviral properties, and is utilized in the treatment of coronavirus disease 2019 (COVID-19). However, we do not know the clinical significance of serum Zinc levels in COVID-19 patients. The aim of this study was to determine the clinical significance of serum zinc in COVID-19 patients and to establish a correlation with disease severity. METHODS: This was a prospective study of fasting zinc levels in COVID-19 patients at the time of hospitalization. An initial comparative analysis was conducted between COVID-19 patients and healthy controls. COVID-19 patients with zinc deficiency were compared to those with normal zinc levels. RESULTS: COVID-19 patients (n = 47) showed significantly lower zinc levels when compared to healthy controls (n = 45): median 74.5 (interquartile range 53.4-94.6) µg/dl vs 105.8 (interquartile range 95.65-120.90) µg/dl (p < 0.001). Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications (p = 0.009), acute respiratory distress syndrome (18.5% vs 0%, p = 0.06), corticosteroid therapy (p = 0.02), prolonged hospital stay (p = 0.05), and increased mortality (18.5% vs 0%, p = 0.06). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients. CONCLUSIONS: The study data clearly show that a significant number of COVID-19 patients were zinc deficient. These zinc deficient patients developed more complications, and the deficiency was associated with a prolonged hospital stay and increased mortality.

Live Liver Donors: Is Right Still Right?

BACKGROUND: Conventional wisdom dictates that a larger hepatectomy is more prone to complications. Consequently, with the donor safety as paramount, the transplant community has intuitively been proponents of left lobe donation in live donor liver transplantation (LDLT), thereby satisfying the tenet of double equipoise. More recently some data suggest that this may not always be the case, especially in established centres. Our aim was to compare right and left lobe donor outcomes in LDLT from a centre with cumulative experience. METHODS: Review of a prospectively collected database of right and left lobe liver donors operated between August 2009 and July 2017 was performed. Their preoperative demographics, operative and post-operative outcomes were compared. RESULTS: Of 904 liver transplantations, 458 were right lobe donors [379 without middle hepatic vein (MHV), 79 with MHV] and 58 left lobe donors. There was a significant difference in GRWR and functional liver remnant between the right and left lobe donors (1.27 ± 0.45 vs. 1.03 ± 0.28 p = 0.004, and 63.2 ± 7.9 vs. 37.7 ± 16.3, respectively, p value). The end portal pressure (7 vs. 8 mmHg p = <0.001), peak bilirubin (1.6 ± 0.8 vs. 2.9 ± 1.5 p = <0.001) and day 5 bilirubin (0.8 ± 0.3 vs. 1.4 ± 0.9 p = <0.001) were significantly higher in right lobe donors. There was no difference in blood loss, duration of surgery or peak lactate between the groups. Complications (20.7% vs. 25.9% p = 0.48), including serious complications (Clavien-Dindo > III) (6.9% vs. 8.1% p = 0.95), duration of ICU and hospital stay, were comparable between the groups. Subgroup analysis between left lobe and right lobe with and without MHV donor was also comparable. CONCLUSION: Though biochemical differences exist between the groups, no difference in outcomes was noted. Despite larger liver mass loss in right lobe donors, a strict protocol-based approach to donor selection leads to comparable outcomes between left lobe and right lobe donations.

Auxiliary Partial Orthotopic Liver Transplantation for Selected Noncirrhotic Metabolic Liver Disease.

Auxiliary partial orthotopic liver transplantation (APOLT) in selected noncirrhotic metabolic liver diseases (NCMLDs) is a viable alternative to orthotopic liver transplantation (OLT) as it supplements the function of the native liver with the missing functional protein. APOLT for NCMLD is not universally accepted due to concerns of increased technical complications and longterm graft atrophy. Review of a prospectively collected database of all pediatric patients (age ≤16 years) who underwent liver transplantation for NCMLD from August 2009 up to June 2017 was performed. Patients were divided into 2 groups: group 1 underwent APOLT and group 2 underwent OLT. In total, 18 OLTs and 12 APOLTs were performed for NCMLDs during the study period. There was no significant difference in the age and weight of the recipients in both groups. All APOLT patients needed intraoperative portal flow modulation. Intraoperative peak and end of surgery lactate were significantly higher in the OLT group, and cold ischemia time was longer in the APOLT group. There were no differences in postoperative liver function tests apart from higher peak international normalized ratio in the OLT group. The incidence of postoperative complications, duration of hospital stay, and 1- and 5-year survivals were similar in both groups. In conclusion, we present the largest series of APOLT for NCMLD. APOLT is a safe and effective alternative to OLT and may even be better than OLT due to lesser physiological stress and the smoother postoperative period for selected patients with NCMLD.

Feasibility and Safety of Split-Liver Transplantation in a Nascent Framework of Deceased Donation.

Split-liver transplantation (SLT) is a valuable option for optimizing the use of good-quality deceased donor grafts. It is not routinely reported outside the West because of limited deceased donor numbers, technical and organizational constraints, lack of experience, and a predominant living donor liver transplantation (LDLT) practice. At our center, 20% of the liver transplantations (LTs) are from deceased donors. We report our experience of SLT and compare outcomes with pediatric and adult LDLT recipients. A prospectively maintained database of all LT recipients between September 2009 and March 2017 was analyzed. Each pediatric SLT recipient was matched to 2 pediatric LDLT recipients for age, weight, urgency, and year of transplant. Each adult SLT recipient was similarly matched to 2 adult LDLT recipients for age, Model for End-Stage Liver Disease score, and year of transplant. Intraoperative and postoperative parameters, including recovery time, morbidity (biliary and vascular complications, Clavien grade >IIIA complications), and mortality were compared. In total, 40 SLTs were performed after splitting 20 deceased donor livers (in situ, n = 11; hybrid split, n = 3; and ex vivo, n = 6). Recipients included 22 children and 18 adults. There were 18 livers that were split conventionally (extended right lobe and left lateral segment [LLS]), and 2 were right lobe-left lobe SLTs. Also, 3 LLS grafts were used as auxiliary grafts for metabolic liver disease. Perioperative mortality in SLT recipients occurred in 3 patients (2 children and 1 adult). Incidence of vascular, biliary, and Clavien grade >IIIA complications were similar between matched adult and pediatric SLT and LDLT groups. In conclusion, SLT is an effective technique with outcomes comparable to living donor grafts for adult and pediatric recipients. Using SLT techniques at centers with limited deceased donors optimizes the use of good-quality whole grafts and reduces the gap between organ demand and availability.

Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.

BACKGROUND: Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. METHODS: All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. RESULTS: Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. CONCLUSION: Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation.