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.

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.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS: A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS: It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS: Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

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.

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.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

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.

Role of Combined CT Pulmonary Angiography and Indirect CT Venography in Diagnosing Venous Thromboembolism in COVID-19 Patients - Experience From an Indian Quaternary Centre.

OBJECTIVES: To study the role of combined CTPA and indirect CT venogram to diagnose venous thromboembolism (VTE) in patients with COVID-19 pneumonia and to compare the clinical characteristics, laboratory parameters, CT findings and clinical outcomes between the VTE positive and negative groups. METHODS: In this retrospective study, 131 patients with COVID-19 pneumonia who underwent CTPA and venogram between August 2020 and January 2021 were included. Relevant demographical, clinical and laboratory data and CT images were collected. Two thoracic radiologists independently reviewed the CTPA and venogram images. RESULTS: VTE was identified in 29 patients (22% of the study population). CT venogram identified DVT in 9 patients. No statistical difference was observed between the two groups with respect to age, gender, BMI and presence of comorbidities. There was a significant difference in the hospital stay duration, which is increased in the VTE positive group. The number of patients who were dependent on oxygen and mortality were also high in the positive group. There was statistically significant difference in the mean D-dimer value and the mean Neutrophil/lymphocyte ratio, which were higher in the VTE positive group. CONCLUSION: Combined CTPA and venogram can be used as a one-stop investigation for diagnosing PE and DVT of lower limbs in patients with COVID-19 pneumonia. CTPA with venogram should be performed in patients with D-dimer value in the range of 1000 - 1200 µg/L and above to rule out VTE as the hospital stay duration and final outcomes vary between the positive and negative groups.

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.

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

BACKGROUND: While preoperative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown. OBJECTIVES: We aim to identify predonation physiologic evaluation strategies to improve postoperative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and experts' opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation predonation. The outcomes of interest were length of stay, postoperative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662. RESULTS: Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (< 70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8 vs 21.7 kg/m2 , OR 1.67 (1.14-2.48), P = .01) and absent in another (< 30 vs 30-35 kg/m2 , P = .61). One study demonstrated decreased risk for postdonation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on predonation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations. CONCLUSION: Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific predonation BMI cut-off. Abbreviated predonation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong).

Perioperative screening and management in elective complex hepatobiliary surgery.

PURPOSE OF REVIEW: Preoperative optimization and structured evidence-based perioperative care of a patient undergoing complex hepatobiliary (HPB) surgery are essential components in their management. Apart from advances in surgical technique, these perioperative measures have resulted in substantial reductions in morbidity and mortality. There hence, remains a continued need to have evidence-based updation in their management algorithm to ensure optimal outcomes. RECENT FINDINGS: We present an evidence-based overview of the preoperative screening, optimization and perioperative management of patients undergoing complex HPB surgery. SUMMARY: Perioperative care of these fragile patients is an evidence-based dynamic process. Optimal patient management undergoing HPB surgery requires risk assessment and stratification, and meticulous attention to the correction of underlying conditions. Despite this, postoperative morbidity remains relatively high and requires a cohesive multidisciplinary approach to minimize complications.

Therapeutic Plasma Exchange for Management of Early Allograft Dysfunction After Living Donor Liver Transplant: An Unmatched Cohort Study.

OBJECTIVES: Therapeutic plasma exchange has been reported to be useful in the management of acute liver failure and acute-on-chronic liver failure. This retrospective study evaluated therapeutic plasma exchange as an adjunct to standard supportive care for early allograft dysfunction after living donor liver transplant. MATERIALS AND METHODS: All consecutive adult living donor liver transplants performed from January 2015 to February 2019 were included. Patients treated without or with therapeutic plasma exchange for early allograft dysfunction (Olthoff criteria) were compared. RESULTS: There were 465 adult transplant recipients, and 67 (14.4%) had early allograft dysfunction, of which 43 (64%) had therapeutic plasma exchange and 24 (36%) did not. Fourteen patients were excluded, as they had both preoperative and immediate postoperative therapeutic plasma exchange (5 patients with acute liver failure and 9 with acute-on-chronic liver failure). The therapeutic plasma exchange group (n = 29) had more preoperative acute kidney injury (55.2% vs 25.0%; P = .009), lower graft-recipient weight ratio (0.96 vs 1.09; P = .043), and slightly higher final portal pressure (11 vs 10 mg/dL; P = .027). Therapeutic plasma exchange was started at a median of postoperative day 9, with median serum bilirubin of 13.6 mg/dL and a median of 3 sessions per patient. There was no 90-day mortality in the group without therapeutic plasma exchange; however, in the therapeutic plasma exchange group, 13 patients (45%) died (P < .001). Patients who received therapeutic plasma exchange had more septic complications (62.1% vs 12.5%; P < .001) and needed more postoperative renal replacement therapy (51.7% vs 8.3%; P < .001). CONCLUSIONS: This is the first study to compare patients treated with or without therapeutic plasma exchange for early allograft dysfunction in the living donor liver transplant setting. Within the limitations of this retrospective study, we were unable to confirm whether therapeutic plasma exchange could increase early mortality.

Liver Transplantation Society of India Guidelines for the Management of Acute Liver Injury Secondary to Yellow Phosphorus-Containing Rodenticide Poisoning Using the Modified Delphi Technique of Consensus Development.

BACKGROUND: Acute liver failure caused by the ingestion of yellow phosphorus-containing rodenticide has been increasing in incidence over the last decade and is a common indication for emergency liver transplantation in Southern and Western India and other countries. Clear guidelines for its management are necessary, given its unpredictable course, potential for rapid deterioration and variation in clinical practice. METHODS: A modified Delphi approach was used for developing consensus guidelines under the aegis of the Liver Transplantation Society of India. A detailed review of the published literature was performed. Recommendations for three areas of clinical practice, assessment and initial management, intensive care unit (ICU) management and liver transplantation, were developed. RESULTS: The expert panel consisted of 16 clinicians, 3 nonclinical specialists and 5 senior advisory members from 11 centres. Thirty-one recommendations with regard to criteria for hospital admission and discharge, role of medical therapies, ICU management, evidence for extracorporeal therapies such as renal replacement therapy and therapeutic plasma exchange, early predictors of need for liver transplantation and perioperative care were developed based on published evidence and combined clinical experience. CONCLUSION: Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research.

Auto-immune hepatitis following COVID vaccination.

Unprecedented loss of life due to the COVID pandemic has necessitated the development of several vaccines in record time. Most of these vaccines have received approval without being extensively whetted for their adverse effect and efficacy profiles. Most adverse effects have been mild, nonetheless, more serious thromboembolic events have also been reported. Autoimmune hepatitis (AIH) can occur in predisposed individuals where an immune mediated reaction against hepatocytes is triggered by environmental factors. Vaccines are a very rare cause of AIH. We report two such cases of AIH triggered by COVID (Covishield) vaccination. While one patient made an uneventful recovery, another succumbed to the liver disease. Ours is the first report of Covishield vaccination related AIH and second ever after any form of COVID vaccination. We hope that our report does not deter COVID vaccination drives. However, we also hope to raise awareness of its potential side effects and the increased role of pharmacovigilance in guiding treatment.

Renal Dysfunction in Cirrhosis: Critical Care Management.

Cirrhotic patients with manifestations of the end-stage liver disease have a high risk for developing renal dysfunction even with minor insults. The development of renal dysfunction increases the morbidity and mortality of these patients. Causes of renal dysfunction in cirrhotics can be due to hepatorenal syndrome (HRS) or acute kidney injury (AKI) resulting from prerenal, renal, and postrenal causes. Development of pretransplant renal dysfunction has been shown to affect post-liver transplantation outcomes. Early detection and aggressive strategies for the prevention of further progression of renal dysfunction seem to decrease the morbidity and improve survival in this group of patients. This article aims to outline the pathogenesis of renal dysfunction in cirrhosis, etiological factors, and evaluation of renal dysfunction, strategies for aggressive therapy for renal dysfunction, the indications of renal replacement therapy (RRT) in this group of patients, and the various modalities of RRT with their merits and demerits. A thorough understanding of the pathogenesis, early detection, and aggressive corrective measures for AKI can prevent further progression. In conclusion, a good knowledge of treatment modalities available for renal dysfunction in cirrhosis and institution of timely interventions can significantly improve survival in this group of patients. KEY MESSAGES: Development of renal dysfunction in cirrhotics increases the morbidity and mortality of these patients and results in poor outcomes after liver transplantation. Early detection and aggressive strategies for the prevention of further progression of renal dysfunction seem to decrease the morbidity and improve survival in this group of patients. HOW TO CITE THIS ARTICLE: Rajakumar A, Appuswamy E, Kaliamoorthy I, Rela M. Renal Dysfunction in Cirrhosis: Critical Care Management. Indian J Crit Care Med 2021;25(2):207-214.

Thrombotic Thrombocytopenic Purpura After Live Liver Donation: Villain or Scapegoat?

Living donor liver transplantation is a complex surgery, where the donor's safety is of paramount importance. Despite all precautions, donor morbidity may be inevitable, and long-term follow-up data attest to this fact. However, being a "past donor" all ailments are intuitively attributed to the donation process, which may not always be the case. We present the case of a 47-year-old lady, who developed thrombotic thrombocytopenic purpura secondary to systemic lupus erythematosus 18 months following her liver donation, when she detected to be anti-nuclear antibody (ANA) positive. She developed neurological signs and was managed successfully with therapeutic plasma exchange and steroids. She was discharged home on immunosuppression and remains well on follow-up. We present the medical and social issues that were addressed in the case and highlight the need for a more stringent follow-up protocol in those who are ANA positive. This would also help detect morbidities that may be unrelated to the donation process.

Propensity Score-Matched Analysis of Posttransplant Outcomes in Living Donor Liver Transplantation for Older Adult Recipients.

The impact of increasing recipient age on morbidity and mortality following living donor liver transplantation (LDLT) remains controversial. The study aims to analyze the impact of recipient age on outcomes following LDLT. Data on adult LDLTs performed between November 2009 and February 2020 were retrieved from a prospectively maintained database. Patients were stratified into 2 groups based on recipient age: 18 to 65 years (younger adults) and >65 years (older adults). Propensity score matching (PSM) using nearest-neighbor matching was used to match each older recipient with up to 2 younger adult recipients using multiple preoperative parameters. Outcomes evaluated were duration of ventilation, need for reintubation, tracheostomy, intensive care unit (ICU) readmission, length of ICU and hospital stays, postoperative complications, reoperation within 90 days, and patient survival. A total of 801 adult LDLT recipients were included in the study; 751 (93.7%) were younger adults, and 50 (6.3%) were older adults. Older recipients were more likely to be diabetic (60.0% versus 39.7%) and hypertensive (44.0% versus 20.4%) with preexisting cardiac disease (28.0% versus 11.2%). However, their pretransplant Model for End-Stage Liver Disease score was significantly lower (14.5 versus 17.7), and they were more likely to receive a transplant because of hepatocellular carcinoma (38.0% versus 17.7%). Older recipients had longer durations of ventilation after LT both before (3.7 versus 1.9 days) and after PSM (4.0 versus 1.5 days). After PSM, the 30-day (13.0% versus 2.4%), 90-day (15.2% and 2.4%), and overall mortality rates (21.7% versus 7.1%) were significantly higher for older recipients when compared with younger recipients. There was no difference between the younger and older recipients with respect to other postoperative outcomes. This propensity score-matched study shows that the older LDLT recipients have higher 30-day, 90-day, 1-year, and 5-year mortality rates when compared with matched younger counterparts.