A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

Pediatric combined living donor liver and kidney transplantation for primary hyperoxaluria type 2.

We report the case of a 12-year-old boy with primary hyperoxaluria type 2 (PH2) presenting with end-stage renal disease and systemic oxalosis who underwent a combined living donor liver and kidney transplant from 3 donors, 1 of whom was a heterozygous carrier of the mutation. Plasma oxalate and creatinine levels normalized immediately following the transplant and remain normal after 18 months. We recommend combined liver and kidney transplantation as the preferred therapeutic option for children with primary hyperoxaluria type 2 with early-onset end-stage renal disease.

Delayed Expulsion of biliary cast after hepaticojejunostomy for post-liver transplantation biliary stricture-better cut than canulate?

BACKGROUND: Biliary strictures after living donor liver transplantation (LDLT) are a significant cause of post-transplant morbidity. Endoscopic therapy is usually the first choice of treatment though surgical treatment may provide better biliary drainage. METHODS: We report a case of LDLT performed in a child for acute liver failure who developed an anastomotic biliary stricture with biliary cast formation. We performed a Roux en Y hepaticojejunostomy to treat the stricture. RESULTS: Allograft function improved after surgery with no further episodes of cholangitis. Two months after the surgery, the child passed a large biliary cast in the stools. This reiterates the advantage of wide biliary drainage provided through surgical therapy. CONCLUSIONS: Surgery for biliary strictures following LDLT may provide superior long term biliary drainage- especially when biliary casts are present.

Scoring Systems that Predict Mortality at Admission in End-stage Liver Disease.

BACKGROUND: Various scoring systems have been developed to assess the severity and survival in end-stage liver disease. AIM OF THE STUDY: Prospective study to compare and analyze the efficacy of scoring systems in predicting mortality in ESLD patients who present with cirrhosis specific complications to the emergency room. MATERIALS AND METHODS: This prospective, single point study was conducted over a two year period from September 2014 to August 2016 among 162 ESLD patients seeking admission to the emergency unit of Gleneagles Global Health City, Chennai. Baseline investigations incorporated hemogram, liver biochemical parameters, coagulation parameters (PT/INR), serum creatinine, serum electrolytes and blood gas analysis, to calculate the CTP score, MELD, MELD-Na, MESO, iMELD, Updated MELD, UKELD, SOFA and APACHE II. Comparison of MELD snd non MELD scores were done between survivors and nonsurvivors. The mortality rate for the same admission was calculated. RESULTS: Of the 162 patients requiring emergency admision, 148 were men (91.4%). The median age of patients was 56 years (range 25-75 years). The cause for liver cirrhosis was alcohol followed by nonalcoholic steatohepatitis and hepatitis B. The indications for emergency admissions were fever, tense ascites, reduced urine output and altered sensorium. Thirty patients (18.5%) expired during the same admission. The predictive accuracy of all scores for predicting mortality by ROC curves was between 0.7 and 0.8 (p < 0.05). CONCLUSION: Although, all scores appear to be equally good, simple scores like CTP and MELD is all that is required to ascertain the prognosis of patients seeking emergency admission. HOW TO CITE THIS ARTICLE: Mangla N, Bokarvadia R, Jain M, Varghese J, Venkataraman J. Scoring Systems that Predict Mortality at Admission in End-stage Liver Disease. Indian J Crit Care Med 2019;23(10):445-448.

Double-blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation.

Perioperative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intraoperative portal pressures and improve renal function. Its role and safety profile have never been evaluated in a double-blind randomized controlled trial (RCT). The aim was to evaluate the hemodynamic effects, clinical benefits, and safety of perioperative Tp infusion in adult LDLT. This was a single-center double-blind RCT. Consenting adults with chronic liver disease and low risk of posttransplant renal dysfunction undergoing their first LDLT were randomized. The study group (terlipressin group [TpG]) received an initial bolus of Tp during surgery followed by a Tp infusion for 72 hours in the postoperative period. The placebo group (PbG) received a saline infusion. The primary endpoint was portal pressure after arterial reperfusion. Multiple intraoperative and postoperative variables served as secondary endpoints. A total of 41 patients were enrolled in the trial (TpG, 21; PbG, 20). There were no significant differences in intraoperative portal pressures, blood loss, fluid requirement, vasopressor requirement, or urine output. Peak intraoperative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in postoperative liver function tests. Incidence of acute kidney injury as assessed by Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria was lower in the Tp group (27% versus 60%; P = 0.04). The TpG had less postoperative ascites, a lower need for percutaneous interventions, and a shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in the TpG. In conclusion, this study has not demonstrated a reduction in postreperfusion portal pressure with Tp. However, Tp infusion reduced postoperative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intraoperative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high-volume ascites, and it needs close monitoring during drug infusion. Liver Transplantation 23 1007-1014 2017 AASLD.

Nocardia liver abscess post liver transplantation-A rare presentation.

Nocardiosis is usually a disseminated disease seen in immunocompromised individuals. We herein present a rare case of isolated Nocardia liver abscess post liver transplantation. The patient responded well to treatment and is on long-term antibiotics for Nocardia infection.

Seroprevalence of cytomegalovirus in donors & opportunistic viral infections in liver transplant recipients.

BACKGROUND & OBJECTIVES: Opportunistic virus infections are common in liver transplant (LT) recipients. There is a risk of developing infection with cytomegalovirus (CMV) and herpes-related viruses such as herpes simplex virus-1 and 2 (HSV-1 & 2), Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV), reactivation of infection and recurrent infection. This study was conducted to determine CMV seropositivity in donors and its influence on LT recipients and seropositivity of CMV, HSV-1 and 2, EB viral capsid antigen (EBVCA) and VZV in LT recipients and their reactivation. METHODS: Pre-transplant data for IgG and IgM for CMV (and donor), HSV-1 and -2, EB viral capsid antigen (VCA) and VZV were available for 153 recipients. All recipients were on ganciclovir or valganciclovir prophylaxis for three months after LT. For reactivation rates, findings of post-transplant CMV quantitative reverse transcription polymerase chain reaction (CMV qRT-PCR) assay were associated with pre-transplant serological profile. RESULTS: Of the 153 LT recipients, 131 were men (85.6%). The median age of LT was 46 yr (range 9 months-71 yr). Overall exposure to CMV was 71.8 per cent followed by EB VCA (61.4%) and VZV (49.6%). Susceptibility to both HSV-1 and -2 was high across all decades (P<0.001). Seropositivity of CMV in donor was 90.9 per cent (100 out of 110). Post-transplant CMV qRT- PCR was positive in 17 (26.6%; 3 in recipient negative) of 64 samples tested. qRT-PCR assay was positive in one out of four (25%) tested for HSV-1 and nine out of 19 (47.4%) tested for EBV. Two recipients tested for HSV-2 and one for VZV were negative. There were three deaths in recipients (D+ R+) who were also positive for CMV qRT PCR. There was one death due to HSV-1 pneumonia. One patient with EBV reactivation developed post-transplant lymphoproliferative disorder two years after transplant. INTERPRETATION & CONCLUSIONS: Transplant recipient were at highest risk of acquiring HSV-1 and -2 more so for HSV-2. CMV exposure in transplant recipients and donors were very high and at greatest risk for recipient reactivation rate. Despite this, death related to CMV reactivation was low.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. MATERIAL AND METHODS: We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. RESULTS: Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. CONCLUSION: TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Safe emergency evacuation of a Tertiary Care Hospital during the "once in a century" floods in Chennai, India.

The coastal city of Chennai, India, was inundated by unprecedented heavy rains during the last week of November 2015, in what was billed as a "once in a century" floods. Over 350 people lost their lives in the floods. Global Hospital, a 250-bedded tertiary care hospital in Chennai, was heavily flooded leaving more than 100 patients and their relatives stranded inside with access totally cutoff from the rest of the world. This article describes how these patients, many in the Intensive Care Unit on ventilators, were safely managed within the hospital for over 48 h on very limited power supply and resources and then safely evacuated by fishing boats to three other city hospitals. Careful planning, anticipating hazards, identifying critical areas, effective communication and team work contributed to the successful management of this situation.

Defining Surgical Difficulty During Open Right Lobe Donor Hepatectomy and its Prediction Using Preoperative Donor Computed Tomography Morphometry.

Background: There is no accepted way to define difficult donor hepatectomy (DiffDH) during open right live donor hepatectomy (ORLDH). There are also no studies exploring association between DiffDH and early donor outcomes or reliable pre-operative predictors of DiffDH. Methods: Consecutive ORLDH performed over 18 months at a single center were included. Intraoperative parameters were used to develop an objective definition of DiffDH. The impact of DiffDH on early postoperative outcomes and achievement of textbook outcome (TO) was evaluated. Donor morphometry data on axial and coronal sections of donor computed tomography (CT) at the level of portal bifurcation were collected. Donor and graft factors predictive of DiffDH were evaluated using univariate and multivariate logistic regression. Results: One-hundred-eleven donors (male: 40.5%, age: 34 ± 9.5 years) underwent ORLDH during the study period. The difficulty score was constructed using five intraoperative parameters, i.e., operating time, transection time, estimated blood loss, need for intraoperative vasopressors, and need for Pringle maneuver. Donors were classified as DiffDH (score ≥ 2) or standard donor hepatectomy (StDH) (score <2). Twenty-nine donors (26%) were classified as DiffDH. DiffDH donors suffered greater all-cause morbidity (P = 0.004) but not major morbidity (Clavien-Dindo score >2; P = 0.651), more perioperative transfusion (P = 0.013), increased postoperative systemic inflammatory response syndrome (P = 0.034), delay in achieving full oral diet (P = 0.047), and a 70% reduced chance of achieving TO as compared to StDH (P = 0.007). On logistic regression analysis, increasing right lobe anteroposterior depth (RLdepth) was identified as an independent predictor of DiffDH (Odds ratio: 2.0 (95% confidence interval = 1.2, 3.3), P < 0.006). Receiver operating characteristic curve analysis identified an RLdepth of >14 cm as the best predictor of DiffDH (sensitivity:79%, specificity: 66%, area under curve = 0.803, P < 0.001). Conclusion: We report a novel definition of DiffDH and show that it is associated with worse postoperative outcomes, including a lesser chance of achieving TO. We also report that DiffDH can be predicted from readily available donor CT parameters.

Auxiliary Partial Orthotopic Liver Transplantation Is a Safe and Effective Option for Yellow Phosphorus Toxin-induced Acute Liver Failure.

BACKGROUND: Ingestion of yellow phosphorus-containing rodenticides (YPR) or firecrackers is an important cause of acute liver failure (ALF) in young adults and children, particularly in South and South-East Asia and South America. Emergency liver transplantation is indicated in cases refractory to intensive supportive therapy, including low-volume plasma exchange. There are no published reports on the feasibility of auxiliary partial orthotopic liver transplantation (APOLT) for YPR-induced ALF. METHODS: Clinical details of patients undergoing APOLT for YPR-induced ALF in 1 unit are reported. Details of postoperative follow-up, native remnant regeneration, and immunosuppression withdrawal are also reported. RESULTS: Between January 2021 and December 2023, 3 patients (4 y, 1.5 y, and 26 y) underwent emergency living donor liver transplantation for YPR-induced ALF. All patients were refractory to supportive therapies, including therapeutic plasma exchange, and demonstrated progression of liver injury in the form of severe encephalopathy needing intubation, ventilation, and organ support. APOLT was considered because of their young age and minimal intraoperative inotropic requirement. All explants showed confluent parenchymal necrosis with microvesicular and macrovesicular steatosis. Patients were initially maintained on standard immunosuppression. Good remnant regeneration was noted on follow-up imaging in all cases, enabling gradual withdrawal of immunosuppression. Currently, 1 child has been off immunosuppression for 15 mo and 2 others are on reduced doses of immunosuppression. All patients demonstrated good liver function. CONCLUSIONS: APOLT procedure can be an appropriate transplant option in YPR-related ALF for children and young adults without severe hemodynamic instability.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Overview of hepatocellular carcinoma: from molecular aspects to future therapeutic options.

Hepatocellular carcinoma (HCC) is the seventh most highly prevalent malignant tumor globally and the second most common cause of mortality. HCC develops with complex pathways that occur through multistage biological processes. Non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, alcoholic liver disease, autoimmune hepatitis, hepatitis B, and hepatitis C are the causative etiologies of HCC. HCC develops as a result of epigenetic changes, protein-coding gene mutations, and altered signaling pathways. Biomarkers and potential therapeutic targets for HCC open up new possibilities for treating the disease. Immune checkpoint inhibitors are included in the treatment options in combination with molecular targeted therapy.

Novel radiological technique to recognize acute liver failure caused by yellow phosphorous containing rodenticides.

Yellow phosphorous rodenticide (YPR) poisoning is the commonest cause for acute liver failure (ALF) in southern and western India. Due to medicolegal issues, history of YPR ingestion may not be available. As early recognition of YPR poisoning is important and there are no specific biochemical assays, other early predictors to identify this entity is necessary. We evaluated the diagnostic role of plain computed tomography (CT) in identifying YPR-induced ALF. All patients admitted to the liver unit with a diagnosis of ALF underwent a plain CT scan abdomen. Demographic details, clinical history, laboratory parameters, liver attenuation index (LAI) calculated on CT scan, treatment details, need for liver transplantation and clinical outcome were analyzed. Parameters for YPR-induced ALF (ALF-YPR) and other causes (ALF-OTH) were compared. Ability of LAI to distinguish ALF-YPR and ALF-OTH was analyzed using receiver operating characteristic (ROC) curve analysis. Twenty-four patients (15 female [62.5%]) were included in the study. Thirteen patients (54%) had YPR poisoning, while the rest formed the ALF-OTH group (11,46%). ALF-YPR patients had higher transaminase levels, lower peak serum bilirubin levels. ALF-YPR livers had significantly lower LAI as compared to ALF-OTH (- 30 vs. - 8, p = 0.001). On ROC curve analysis, an LAI greater than - 18 ruled out YPR as the cause for ALF with 91% sensitivity and 85% specificity. On regression analysis, LAI was the only independent factor predicting ALF-YPR (odds ratio - 0.86, [0.76, 0.96] p = 0.008). Our data shows that LAI on plain abdominal CT scan can be used to quickly recognize ALF-YPR in unclear cases so that necessary treatment protocol can be activated, or patient transfer arranged. Our analysis shows that an LAI greater than - 18 can reliably rule out YPR ingestion as the cause for ALF.

Living-Donor Liver Transplantation for Late-Onset Lysosomal Acid Lipase Deficiency.

Late-onset liposomal acid lipase deficiency (LAL deficiency), previously known as Cholesteryl ester storage disease (CESD) is a rare genetic lysosomal storage disorder caused by deficiency of lysosomal acid lipase (LAL) due to mutations in the LIPA gene. LAL deficiency is a systemic disease that leads to the accumulation of fat and inflammation in the liver, premature atherosclerosis and gastrointestinal disease. Most of the patients require liver transplantation due to decompensated cirrhosis. Enzyme replacement therapy has been approved and is available in many countries. Here we describe a 16-year-old patient who was diagnosed to have late-onset LAL deficiency when he presented to us with ESLD. Subsequently, he underwent a living-donor liver transplant (LDLT) successfully. We discuss the ethical dilemmas in considering LDLT for LAL deficiency.

Right Lobe Living Donor Hepatectomy in the Setting of Agenesis of Gall Bladder - A Case Report.

Agenesis of Gall Bladder (AGB) is a rare congenital anomaly with only around 500 cases reported so far. The condition may be associated with other biliary anomalies and present diagnostic and technical challenges during hemi hepatectomy which can be surmounted with careful planning. Live donor hepatectomy in the setting of AGB has not been reported before. We report a case of AGB in a potential living donor and highlight the technical modifications used to perform a safe right hepatectomy in this donor.

First Report of a Paediatric Collision Tumour in the Liver Recognised After Liver Transplantation: Blissful Ignorance Has Benefits!

Liver tumours are uncommon in the paediatric population, constituting 1-2 % of all paediatric tumours and 4% of all paediatric liver tumours. Hepatoblastoma followed by hepatocellular carcinoma is the most common tumours in this age group. Simultaneous development of two discrete liver tumours of distinct histologies (collision tumour) has been occasionally reported in adults but never in children. We hereby present the first reported case of hepatic collision tumours (hepatocellular carcinoma and cholangiocarcinoma) in the explant liver of a child who underwent living donor liver transplantation for end-stage liver disease and severe hepatopulmonary syndrome. The manuscript describes the clinical, radiological and histopathological findings of this case and also highlights the dilemma associated with management of this case had the diagnosis been made in the preoperative setting and also about the proposed management plan for this case in the postoperative period.

When Push Comes to Shove! Emergency ABO-Incompatible Pediatric Living Donor Liver Transplant for Acute Wilson's Disease.

ABO-incompatible living donor liver transplantation (ABOi-LDLT) is on the rise as a viable option in countries with limited access to deceased donor grafts. While reported outcomes of ABOi-LT in children are similar to ABO- Compatible liver transplant (ABOc-LT), most children beyond 1-2 years of age will need desensitization to overcome the immunological barrier of incompatible blood groups. The current standard protocol for desensitization is Rituximab that targets B lymphocytes and is given 2-3 weeks prior to LT. However, this timeline may not be feasible in children requiring emergency LT for acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). In this emergency situation of ABOi-LT, a safe multipronged approach may be an acceptable alternative solution. We report a child with acute Wilson's disease with rapidly deteriorating liver function who underwent a successful ABOi-LDLT using a rapid desensitization protocol.