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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years. [ABSTRACT FROM AUTHOR]

The modified derivatives of testosterone, termed as androgenic steroids are indicated in the management of hypogonadism, visceral obesity and metabolic disorders. Anabolic androgenic steroids (AASs) however are surreptitiously used by athletes and body builders for cosmetic purpose owing to their anabolic effects on muscle mass and strength. The unsurveilled use of AASs subjects these users to various side effects involving multiple systems such as the endocrine, genitourinary, hepatobiliary, central nervous, musculoskeletal and psychosocial system. The liver is a hormone-sensitive organ owing to abundance of androgen receptors and is vulnerable to a wide array of hepatotoxicity ranging from asymptomatic liver enzyme elevation to life-threatening subacute liver failure. The type of drug-induced liver injury (DILI) due to AASs can be hepatocellular injury, cholestasis, fatty liver disease, chronic vascular injury and neoplastic disease. Herein, we report three cases of AAS-related DILI associated with AAS abuse. [ABSTRACT FROM AUTHOR]

• Patients with coronavirus disease 2019 (COVID-19) had significantly low zinc levels in comparison to healthy controls. • Zinc deficient patients developed more complications (70.4% vs 30.0%, p = 0.009). • Zinc deficient COVID-19 patients had a prolonged hospital stay (7.9 vs 5.7 days, p = 0.048). • In vitro studies have shown that reduced zinc levels favour the interaction of angiotensin-converting enzyme 2 (ACE2) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and likewise that increased zinc levels inhibit ACE2 expression resulting in reduced viral interaction. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rebleeding after initially successful endoscopic variceal ligation (EVL) occurs in 20-60% of patients, most commonly from band ulcers, and is associated with 20-50% mortality. Although band ulcer bleeding has been treated in a number of different ways, no single therapeutic intervention has shown a clear benefit. Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a relatively new non-contact hemostatic modality used in the management of bleeding peptic ulcers. It is a nano-powder that can be sprayed over a larger mucosal area. Here we describe a patient with end stage liver disease who presented with recurrent bleeding from a deep esophageal ulcer following band ligation and sclerotherapy, effectively managed with multiple sessions of Hemospray. [ABSTRACT FROM AUTHOR]

Severe Jaundice in a COVID-19 Patient-Virus or Drug?. [Extracted from the article]

Background Eighty percent (80%) of patients with Autoimmune hepatitis (AIH) respond to a combination of prednisolone and Azathioprine (AZA). Choice of treatment is limited for those who do not respond to this standard therapy. We evaluated the role of Mycophenolate mofetil (MMF) as a second line therapy in AIH. Method A retrospective observational study was carried out on all patients who received MMF for AIH. Results Twenty out of 117 patients with AIH received MMF due to AZA intolerance (18 patients) or refractory disease (2 patients). Median age of the study patients was 56 (18–79) years, Male, n = 3 (15%) and Female, n = 18 (85%). After a median follow-up period of 47 (5–83) months, 14 (73.6%) patients were still on MMF with biochemical remission, including 4 out of 5 patients with cirrhosis. One patient was lost to follow-up. Three patients were intolerant of MMF due to adverse events, and two had disease refractory to MMF. Both these patients with refractory disease to MMF were initially unresponsive to AZA therapy. Conclusion MMF is a safe second line agent in patients with autoimmune hepatitis including those with cirrhosis. [ABSTRACT FROM AUTHOR]

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. 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. 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. Development of these guidelines should help standardise care for patients with yellow phosphorus poisoning and identify areas for collaborative research. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and there are obvious concerns for the immunocompromised patient population including transplant recipients. Creating awareness and understanding patient concerns will play an important role in protecting this vulnerable group in developing timely and appropriate healthcare interventions. A cross-sectional online survey was conducted between 23rd March 2020 and 1st April 2020 among 154 liver transplant recipients, transplanted between October 2018 and February 2020. An 18-point questionnaire explored their knowledge of COVID-19, awareness of recipient's high-risk status, interventions to minimize cross-infections, and concerns of this patient group regarding the pandemic. There were 112 (73%) respondents, with median age of 53 years (81% males). There was no difference in demographics between those who responded (n = 112) and those who did not respond to the survey (n = 42). Most of the recipients were aware of the main symptoms of COVID-19, such as fever (92%), breathlessness (86%), and dry cough (87%), but less than half were aware of diarrhea (39%) as a symptom. Awareness about spread from asymptomatic individuals was limited (26%). Majority (95%) understood their high-risk status, but worryingly, 23% of the respondents felt that there was no risk in visiting the hospital for routine clinic visit and blood tests. Concerns were raised by the recipients mostly regarding the uncertainties of COVID-19 infection and its treatment options, the quality of information on social messaging platforms, and lack of access to routine tests/immunosuppression levels because of lockdown/social distancing. Our liver transplant recipients have a reasonable awareness regarding COVID-19. Problems in accessing the healthcare system during prolonged periods of lockdown was a major concern. It is important for each transplant unit to educate, support, and remain accessible to this vulnerable patient cohort as the pandemic continues to progress worldwide. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug–induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document. [ABSTRACT FROM AUTHOR]

End-stage liver disease (ESLD) patients undergoing liver transplant (LT) surgery are often multiply alloimmunized and pose significant challenges to the transfusion services in terms of red cell cross-match incompatibility, unpredictable blood requirements, and often lead to significant delays in availing compatible red cell units. We report a case of a 64-year-old female from Bahrain, a known case of hepatitis C-related ESLD referred for LT surgery. She had a history of multiple uneventful transfusions in the preceding year. Her blood group was A-positive, direct antiglobulin test, and cold antibodies were negative. Indirect antiglobulin test was positive, and antibody identification confirmed the presence of anti-C, anti-e, and anti-K. Her red cell phenotype was R2R2and Kell negative (C-c+E+e-K-). The patient was started on erythropoietin. Requests for R2R2and Kell negative units were sent to various blood banks across the country. After >800 A/O group units phenotyping and a waiting period of 6 weeks, two compatible R2R2phenotypes and Kell negative could be arranged in-house and three units were received from Gurgaon, North India. Intraoperative management included blood preservation techniques including cell salvage, antifibrinolytic drug, and monitoring using thromboelastography. The estimated blood loss was 350 ml with pre- and postoperative Hb 10.4 gm% and 9.2 gm%, respectively. She received intraoperatively two units of single-donor platelet and four units of fresh frozen plasma and postoperatively one unit of leukocyte-depleted-packed red cells and doing well at 12-month follow-up. This case highlights the importance of advance immunohematology for timely detection of alloimmunization and providing antigen-negative compatible units, proper communication between the transfusion specialists, and the clinical team for proper patient blood management as well as the need for central rare donor registry program to avoid delays in providing compatible blood in such inevitable cases. [ABSTRACT FROM AUTHOR]

Background Prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs can prevent hepatitis B virus (HBV) recurrence after liver transplant (LT). Aim To determine the efficacy and cost of maintaining immunoprophylaxis with HBIG and hyperimmune plasma (HIP) for 6 months after LT. Material & methods The study included 22 HBV related LT recipients who were on entecavir and either HBIG or HIP for 6 months. Post transplant HBIG or HIP dose and cost incurred towards prophylaxis were noted. The cost of 200 IU of HBIG at the time of study was Rs 8250/- (US Dollars 135) and that of 2000 IU of HIP was Rs 8000/- (USD 130.7). The loading and maintenance costs at end of 6 months were compared between the two groups. Response to HBIG and HIP was assessed by checking for HBsAg reactivity, anti HBs titer response and HBV DNA viral load. Statistical analysis Median and range, Kruskal Wallis (KW) sign rank Sum Test and Correlation Coefficient (r2) was used for analysis. Results Thirteen recipients received HBIG and 9 recipients HIP. The anti HBs response to HIP was significantly high compared to HBIG (KW Sign rank Sum test P < 0.05); titers remained high until the study period. Between 8 and 30 days, the titer achieved by both HBIG and HIP was similar (KW Sign rank Sum test not significant). Despite low anti HBs titer of <100 IU/L, none of the recipients on HBIG had HBsAg reactivity while 3 on HIP had transient HBsAg positivity. The total cost with HBIG was 13.9 times the cost of HIP. Conclusion HIP immunoprophylaxis in combination with entecavir achieves a high anti HBs titer at a significant low cost during anhepatic and loading phase. HBV reactivation rates with HBIG and HIP is low despite low anti HBs titer. [ABSTRACT FROM AUTHOR]