Long-Term Amino Acid Homeostasis, Neurodevelopmental and Growth Profiles Following Liver Transplantation in Maple Syrup Urine Disease.

INTRODUCTION: Maple syrup urine disease (MSUD) is caused by the deficiency of branched-chain keto acid dehydrogenase (BCKAD) and, it is well described that BCKAD contributed by an allograft following liver transplantation (LT) phenotypically normalizes this inborn error of metabolism (IEM). There is, however, a paucity of data especially with regards to the neurodevelopmental aspects and catch-up growth profiles after LT in a resource-challenged setting. We present our series of children under 6 years of age who underwent LT for MSUD particularly focusing on their amino acid homeostasis, neurodevelopmental and somatic growth profiles. METHODS: Of 580 consecutive pediatric LT (PLT) performed between January 2011 and December 2022, all children who underwent LT for MSUD were included for analysis. Data accrued included peri-LT details, pre- and post-LT metabolic profile, neurodevelopmental assessment, somatic growth evaluation, and long-term outcomes. RESULTS: Six children underwent LT for MSUD with a median age and weight at LT of 20.5 (IQR: 8-60) months and 10.1 (IQR: 6.7-15.8) kg, respectively. One explanted liver was used as a domino graft for Arginase deficiency. Median follow-up period was 52.5 (IQR: 27-94) months. None had vascular or biliary complications. Following LT, all children were started on an unrestricted protein diet and had normalization of BCAA levels. Post-LT height and weight improved by 1 SD but did not achieve the normal profile. None of the children had neuro-deterioration and have achieved new milestones. CONCLUSION: This is the first-report presenting the growth aspects, amino acid and neurodevelopmental profiles of children who underwent LT for MSUD within the socio-economic-cultural idiosyncrasies and constraints prevalent in our part of the world.

Liver Transplantation for Dengue-induced Acute Liver Failure.

Although liver involvement has been observed in over two-third cases of dengue viral infection, less than 1% cases progress to dengue-related acute liver failure (D-ALF). Various aspects of management of this disease remain debated including the need and timing of liver transplantation (LT). Moreover, the outcomes of LT for D-ALF have been suboptimal. We present four contrasting cases of D-ALF, two managed with LT and the other two conservatively to highlight the management dilemmas concerning LT in D-ALF. Based on our 4 cases, we would consider dengue shock syndrome, multisystem involvement and neurological deficit not completely accounted for by the ALF as potential contraindications for LT. These would need to be revisited on a case-to-case basis till larger studies define objective selection criteria for LT in D-ALF.

Treatment and prognostic implications of strong PD-L1 expression in primary hepatic sarcomatoid carcinoma.

Primary hepatic sarcomatoid carcinoma (HSC) is an extremely rare and aggressive subtype of primary liver cancer. HSC has uncertain pathogenesis and dismal prognosis with overall survival of only 8.3 months. The molecular alterations of HSC are also not well understood. In this study, the authors describe a patient who presented with a large liver mass. The patient underwent complete surgical resection and histological examination demonstrated HSC, infiltrating the stomach. PD-L1 was strongly positive in the tumor cells. The patient was started on anti-PD-L1 immunotherapy postsurgery and is doing well 15 months after surgical resection. Tumor whole exome sequencing revealed genetic alterations in TP53, NF2 and MAGEC3 genes, indicating their potential role in tumor development.

Primary sarcomatoid cancer of the liver is a rare type of severe cancer that generally has a very poor prognosis. People diagnosed with primary sarcomatoid of the liver normally survive for only a few months. Surgery is not very effective in treating this type of cancer and recurrence is common even after complete removal. In this paper, the authors report a patient who presented to them with a large liver tumor. The patient underwent operation and the tumor was completely removed from the liver. Pathological testing of the tumor revealed it was severe primary sarcomatoid liver cancer. The patient was started on an immunotherapy treatment. The treatment enhanced the ability of the body's immune system to fight cancer. The patient is doing well 15 months after the operation, which might mean that this type of immunotherapy treatment after surgery helps prolong the life of people diagnosed with primary sarcomatoid cancer of the liver.

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.

Role of Donor-derived Cell-free DNA In Predicting Short-term Allograft Health In Liver Transplant Recipients.

Background/Aims: Predicting allograft dysfunction prior to clinical or biochemical evidence remains one of the challenges in transplantation, and a preclinical detection and early management of its cause allows for improved post-transplant outcomes. Donor-derived cell-free DNA (ddcfDNA) has been proposed as an important biomarker of allograft injury and has shown to predict dysfunction prior to any biochemical derangements. We aimed to investigate the diagnostic performance of ddcfDNA in detecting and differentiating the causes of early pre-biochemical detection of graft injury and in predicting the short-term outcomes of graft health using a patented protocol and proprietary set of single-nucleotide polymorphisms. Methods: Blood samples were collected on defined postoperative days (1, 3, 7, and at 3 months) and were analysed through relatively economical patented protocol (Trunome™). Biopsy, biochemical tests, and clinical criteria were analysed between various subgroups. Results: Of a total 50 patients, percentage ddcfDNA (%ddcfDNA) levels were significantly elevated in the rejection group (n = 8) as compared to that in the non-rejection group (n = 42; median elevation: 12.8% vs 4.3%, respectively), with a significant correlation (r = 0.92, P < 0.0001). Area under the receiver operating characteristic curve (AUC-ROC) analysis revealed that the %ddcfDNA levels can predict graft health more precisely than the conventional liver function tests (AUC for %ddcfDNA: 0.86; P < 0.001; AUC for aspartate transaminase 0.65, P = 0.08; AUC for alanine transaminase: 0.75, P < 0.01). Moreover, %ddcfDNA levels (with a threshold of >10.2%) on post-operative day 7 accurately predicted short-term (3 months) health status of the graft with 93.33% sensitivity, 94.44% specificity, 87.50% positive predictive value, 97.14% negative predictive value, and 94.12% accuracy. Conclusion: A single-timepoint ddcfDNA on postoperative day 7 accurately predicts graft health and improves risk stratification in the short-term.