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Hepatitis A is the most prevalent viral hepatitis in India and rarely can lead to life-threatening complications such as acute liver failure (ALF). Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world, and in the setting of acute viral hepatitis, it can cause massive intravascular hemolysis, resulting in acute kidney injury. Here, we report a case of a 12-year-old male child who had hepatitis A–associated ALF, which was complicated by massive hemolysis due to underlying G6PD deficiency, manifesting as acute renal failure requiring renal replacement therapy with other supportive management. He had a prolonged, protracted stormy clinical course, which was further complicated by dialysis disequilibrium syndrome, posterior reversible encephalopathy syndrome, and nosocomial sepsis, which improved over 4 weeks. Our case highlights the importance of having high index of clinical suspicion for G6PD deficiency in a child with acute viral hepatitis with complications. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries. Methods: A systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger's test and Begg's test were performed to assess publication bias. Results: A total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28–0.52), 30.0% (95% CI: 0.18–0.44), and 61.0% (95% CI: 0.49–0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62–0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20–0.37) and 10.0% (95% CI: 0.01–0.28) in India and China, and it was 34.0% (95% CI: 0.27–0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23–0.42) and 64.0% (95% CI: 0.50–0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14–0.34) in Chinese non-pregnant participants. Conclusions: The burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations. Registration: PROSPERO registration ID is CRD42022382101. [ABSTRACT FROM AUTHOR]

Background: Indications for therapeutic plasma exchange (TPE) in the pediatric intensive care unit (PICU) are expanding. We aimed to study the demographics, clinical indications, and outcomes of patients who have undergone TPE in our PICU. Materials and methods: This is a retrospective study performed among children aged from 1 month to 16 years of age. Demographics, indications, therapeutic response, serious adverse events (SAE), PICU length of stay (LOS), and death during hospitalization were studied as outcome variables. Results: Therapeutic plasma exchange was performed in 115 sessions on 24 patients for 12 different indications falling under various American Society for Apheresis (ASFA) categories. Therapeutic plasma exchange was performed on ten, four, and ten children for ASFA category I, II, and III indications, respectively. The most common indications were thrombotic microangiopathy (TMA) (8/24) and acute liver failure (ALF) (6/24). During those 115 sessions, a total of five serious adverse events (SAEs) occurred, accounting for 4.3% of the cases. Minor adverse events occurred in 12 sessions (10.4%). Therapeutic response was good in 17 patients (71%) including 5 patients who underwent standard volume TPE (SV-TPE) for ALF. Median PICU LOS was 9 (range 2-120) days. The mortality rate was 12.5% (3/24). Conclusion: Therapeutic plasma exchange is effective in various clinical conditions involving various organ systems. It is an excellent therapeutic modality in children with ALF, irrespective of the exchange volume and TMA. However, SAEs do occur in the minority. [ABSTRACT FROM AUTHOR]

Background: We evaluated the prevalence, risk factors, and impact of bacterial/fungal infections in acute liver failure (ALF) patients. Methods: We analyzed clinical, biochemical, and microbiological data of ALF patients with and without bacterial/fungal infections admitted at an institute over the last 5 years. Results: We enrolled 143 patients, 50% males, median age 25 years, with acute viral hepatitis (32.2%), drug-induced injury (18.2%), and tropical illness (14%) as aetiologies of ALF. 110 patients (76.9%) developed bacterial/fungal infections [Bacterial infection: MDR: 70%, PDR: 7%, ESBL: 40%, CRE: 30%, CRAB: 26.6%, MDR-EF: 13.3% and fungal infection: 19 (17.3%)]. On univariable analysis, SIRS (33.6% vs.3%), ICU admission (78.2% vs. 45.5%), mechanical ventilation (88.2% vs. 51.5%), inotropes (39.1% vs. 6.1%), invasive catheters (91.8% vs. 39.4%), and prolonged catheterization (6 days vs. 0 days) were significant risk factors for infections (p < 0.05, each). In contrast, SIRS and catheterization independently predicted infection on multivariable regression. Organ failures [3 (2–4) vs. 1 (0–2)], grade-III–IV HE (67.3% vs. 33.3%), circulatory failure (39.1% vs. 6.1%), coagulopathy (INR > 2.5: 58.2% vs. 33.3%), renal injury (28.2% vs. 6.1%) (p < 0.05), MELD (32.9 ± 8.2 vs. 26.7 ± 8.3) and CPIS [3(2–4) vs. 2(0–2)] were higher in infected vs. non-infected patients (p < 0.001). 30-day survival was significantly lower in infected vs. non-infected patients (17.3% vs. 75.8%, p < 0.001), while no patient survived with fungal infections. Refractory septic shock was the commonest cause of mortality in patients. Conclusions: Infections due to MDR organisms are high, fungal infections are fatal, and refractory septic shock is the dominant reason for mortality, implying bacterial and fungal infections as the major killer in ALF patients. [ABSTRACT FROM AUTHOR]

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. 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. 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. This document is the first step in the setting up of a nationally consistent policy of deceased donor liver allocation. [ABSTRACT FROM AUTHOR]

Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: Hepatitis A Virus (HAV) is the most common cause of Acute Viral Hepatitis (AVH) in children. It causes self-limiting illness and rarely acute liver failure. The shifting pattern in HAV endemicity is rendering adolescents and adults vulnerable to infection., Methods: In this retrospective study, samples received from 14,807 patients with acute onset icteric illness from January 2014-December 2022 were analyzed. HAV infection was detected by anti-HAV IgM positivity. The cases were divided into 3 age groups, pediatric, adolescents and adults, and clinical presentations were compared., Results: Overall, 7.72%(1144) were positive for anti-HAV IgM. Of these, 60%(690) were finally included in the study. The positive cases were divided into adults, ≥18 years (44%, 304); pediatric, <12 years (31%, 212) and adolescents (25%,174) age groups. Overall males were predominant [72.4%(500)], with a median age of 16 (IQR:9-21) years. Cases were characterised into AVH (68.1%, 470/690), Acute Liver Failure (ALF) (31.4%, 217/690) and Acute-on-Chronic Liver Failure (0.43%, 3/690). AVH in the pediatric age group was 69%(146/212), adolescents was 67%(117/174), and adults was 68%(207/304). ALF cases among the 3 groups were 30%(65/212), 33%(57/174), and 31%(95/304) respectively. Overall mortality was seen in 6.52%(45/690), maximum in adolescents with ALF presentation [10.3%(18/174)]. On molecular characterization of infection, viremia was seen in 28.9%(200/690) and all the isolates were Genotype IIIA., Conclusions: The number of adults experiencing symptomatic HAV infection was seen to increase over the years in the present study. Infection in adolescents was associated with higher mortality and ALF as the clinical presentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

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]

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined., (© 2024. Indian Society of Gastroenterology.)

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity., (© 2024. Indian Society of Gastroenterology.)

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]

Cyproterone acetate (CPA), a hydroxyprogesterone derivative, is used to treat advanced prostate cancer and infrequently in women for acne, breast cancer and hirsutism. Transient mild elevation in levels of liver enzymes is reported in 10–30% of patients, and acute liver failure (ALF) is uncommon. Here, we discuss the first case of CPA-induced ALF from India and the available literature. [ABSTRACT FROM AUTHOR]

Objective: To describe our experience of pediatric living donor liver transplantation from India over a period of 12 years. Materials and Methods: A retrospective analysis of 200 living donor liver transplantation in children (18 years or younger) was done for demographic features, indications, donor and graft profile and outcome. Results: Between September 2004 and July 2016, 200 liver transplants were performed on 197 children. Fifty transplants were done in initial 6 years and 150 in next 6 years. All donors (51% mothers) were discharged with a mean stay of 7 days. The leading indications of liver transplants were cholestatic liver disease (46%) followed by metabolic liver disease (33%) and acute liver failure/acute on chronic liver failure (28.5%). Biliary leakage (8.5%), biliary stricture (9%), hepatic artery thrombosis (4.5%) and portal vein thrombosis (4%) were the most common surgical complications; all could be managed by surgical or interventional radiological measures, except in one child who died. Sepsis, acute rejection and CMV hepatitis in first 6 months were seen in 14.5%, 25% and 17% cases, respectively. Post-transplant lymphoproliferative disease was seen in only 1.5%. Re-transplant rate was 1.5%. The overall 1 year survival rate was 94% and 5 year actuarial survival was 87% with no statistically significant difference between children weight <10 kg vs. >10 kg. Outcome in acute liver failure did not differ significantly between those with acute on chronic liver failure vs. those with chronic liver disease. Conclusions: Advances in medical and surgical techniques associated with multidisciplinary teams including skilled pediatric liver transplant surgeons, anesthetists, dedicated pediatric hepatologists, pediatric intensivists, interventional radiologists and pathologists resulted in an excellent outcome of living related liver transplants in children. Low age and weight of the baby does not seem to be a contraindication for liver transplantation as outcome were comparable in our experience. [ABSTRACT FROM AUTHOR]

Acute viral hepatitis as well as typhoid fever is still a significant problem in tropical countries like India. Both have a common route of infection and may cause co-infection. In a patient with symptoms of acute liver failure and/or post icterus persistent high-grade fever with acute abdomen, always suspect co-infection of hepatitis E and typhoid fever in tropical countries and appropriate management can avoid life-threatening complications. [ABSTRACT FROM AUTHOR]

Objective: To study the etiological spectrum of acute liver failure in infants and young children and to identify clinical and biochemical markers for metabolic liver disease (MLD).Methods: This study was conducted at Department of Pediatric Hepatology, in a tertiary care specialized centre for liver diseases. All children less than 3 y of age, with liver dysfunction and INR ≥2 were included in the study. They were managed as per the departmental protocol. Included children were divided based on the etiology into 2 groups: MLD and non MLD group. Comparison analysis (MLD vs. non MLD) of the clinical and biochemical parameters was done.Results: There were 30 children under 3 y of age with acute liver failure (ALF) with median age of 12.5 mo. Fifteen children were less than 12 mo. MLD (33 %) and hemophagocytic lymphohistiocytosis (HLH) (17 %) together accounted for half of the cases of ALF in children below 3 y of age. The other common etiologies were drug induced liver injury and acute viral hepatitis A. Etiology remained indeterminate in 3 cases (10 %). Comparative analysis of the clinical and biochemical parameters between MLD and non MLD group showed significant difference between the two groups in the median values of age (p = 0.014), bilirubin (p = 0.017), jaundice to encephalopathy (JE) interval (p = 0.039) and blood sugar (p = 0.001). Suggestive family history (OR 3.73, 95 %CI 1.67-8.30), developmental delay (OR 4.4 95 %CI 2.03-9.51), presence of diarrhea/vomiting (OR 3.28, 95 %CI 1.32-8.13) in the history and presence of urinary non glucose reducing substance (NGRS) (OR 15.5, 95 %CI 2.26-106.87) were also significantly associated with MLD group. Only 40 % children survived with native liver.Conclusions: MLD and HLH account for majority of ALF in infants. About 10 % of cases remain indeterminate. Viral hepatitis is more common in young children. Apart from clinical indicators, young age, high bilirubin, synthetic dysfunction, low sugar and NGRS in urine indicate MLD as a cause. Survival with native liver is low. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) is marked by a sudden loss of hepatic function and is associated with a high mortality rate in children. The etiology of ALF is shown to vary geographically. This study assessed the frequency of hepatotropic viruses as etiological agents of ALF in Indian children. Methods: This retrospective study enrolled children aged 0-18 years with confirmed ALF admitted to Christian Medical College, Vellore and King Edward Memorial Hospital and Research Center, Pune between January 2003 and December 2005. The frequency of hepatotropic viruses as etiological agents in children with ALF aged ≤18 years was calculated with 95 % confidence interval (CI). Descriptive analyses of demographic characteristics, clinical signs and symptoms of ALF, choice of treatment and outcomes were performed. Results: Of 76 children enrolled, 54 were included in the per-protocol analyses. Mean age of children with ALF was 5.43 years (standard deviation = 3.62); 51.9 % (28/54) were female. The percentage of children positive for anti-hepatitis A virus (HAV) IgM and hepatitis B surface antigen was 65.9 % (27/41; 95 % CI 49.4-79.9) and 15.9 % (7/44; 95 % CI 6.6-30.1), respectively. The final cause of ALF was HAV (36.3 %) followed by hepatitis B virus (HBV; 8.8 %). Before and during admission, encephalopathy was observed in 77.8 % (42/54) and 63.0 % (34/54) of children, respectively. A high number of children (46/54; 85.2 %) required intensive care and ALF was fatal in 24.1 % (13/54). The proportion of deaths due to HAV and HBV was 18.5 % (5/27) and 57.1 % (4/7), respectively. Conclusions: HAV and HBV were the most common etiological agents of ALF in Indian children. Primary prevention by vaccination against HAV and HBV in young children may be useful in the prevention of ALF due to viral hepatitis in India. [ABSTRACT FROM AUTHOR]

Background/Aims: Acute liver failure (ALF) in pregnancy is often associated with a poor prognosis. In this single‑center observational study we aim to study the incidence, causes, and factors affecting mortality in pregnant women with ALF. Patients and Methods: Sixty‑eight pregnant women reporting with clinical features of liver dysfunction were enrolled as “cases.” Their clinical course was followed and laboratory studies were performed. The presence of ALF was defined as the appearance of encephalopathy. The results were compared with a “control” group of 16 nonpregnant women presenting with similar complaints. The cases were further subdivided into two groups of “survivors” and “nonsurvivors” and were compared to find out the factors that contribute to mortality. Results: ALF was seen in significantly more number of pregnant women than the controls (P = 0.0019). The mortality rate was also significantly higher (P = 0.0287). Hepatitis E virus (HEV) caused jaundice in a higher number of pregnant women (P < 0.001). It also caused ALF in majority (70.3%) of pregnant women, but HEV infection was comparable between the survivors and nonsurvivors (P = 0.0668), hence could not be correlated with mortality. Conclusions: Pregnant women appear to be more susceptible for HEV infection and development of ALF. The mortality of jaundiced pregnant women increased significantly with appearance of ALF, higher bilirubin, lower platelet count, higher international normalized ratio, and spontaneous delivery. [ABSTRACT FROM AUTHOR]

Summary. The early prognostic indicators for acute liver failure in endemic zones for hepatitis E virus have not been determined. All consecutive patients with acute liver failure from a geographically defined region endemic for hepatitis E virus were studied over the period April 1989–April 1996. Demographic, clinical and biochemical parameters were recorded at presentation and serum samples were analysed for known viral hepatitis (A–E) markers. Multiple parameters were compared in survivors and non-survivors in a univariate analysis. All significant factors on univariate analysis were entered into a stepwise logistic regression analysis to identify independent variables of prognosis. The sensitivity and specificity of significant prognostic factors was then assessed. A total of 180 [69 males and 111 females: age (mean ± SD) 31.1 ± 14.7 years] with acute liver failure were studied. Of these, 131 (72.8%) patients died. Hepatitis E virus was the aetiological cause in 79 (43.9%) patients, while hepatitis A virus, hepatitis B virus, hepatitis C virus and non-A, non-E agent/'s could be incriminated in four (2.1%), 25 (13.9%), 13 (7.2%) and 56 (31.1%) patients respectively. Of 83 women in childbearing age, 49 (59.0%) were pregnant, 33 (67.3%) of these were in the third trimester. Forty-seven (95.8%) pregnant women had HEV infection. Nine variables differed significantly between survivors and non-survivors on univariate analysis. Of these, four variables which predicted the adverse outcome on multivariate analysis were non-hepatitis-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years in that order of significance. Pregnancy per se or duration of gestation did not adversely affect the prognosis. In endemic areas, hepatitis E virus is the commonest cause of acute liver failure. Acute liver failure occurs in a high proportion of pregnant women, mostly in third trimester. Early predictors of a poor outcome are non-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years. [ABSTRACT FROM AUTHOR]

Background and Aim: Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India., Methods: We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases., Results: Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15-34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265-6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%., Conclusion: Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this., (© 2021. Indian Society of Gastroenterology.)

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Background: Hepatitis A virus (HAV) is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Our objective was to develop and validate a HAV-etiology specific prognostic model in PALF., Methods: All children with HAV induced PALF (IgM HAV reactive) were included. Outcome was defined at day 28. Only those with death or native liver survival were included. The model (Peds-HAV) was derived using the independent predictors of outcome and validated in a prospective independent cohort., Results: Hepatitis A accounted for 131 (45.9%) of total 285 PALF. After excluding 11 children who underwent liver transplant, 120 children (74 survivors and 46 death) were included. The first 75 patients formed the derivation cohort and the next 45 patients formed the prospective validation cohort. In the derivation cohort, INR: OR 2.208, (95% CI 1.321-3.690), p = 0.003, grade of hepatic encephalopathy (HE): OR 3.078, (95% CI 1.017-9.312), p = 0.047 and jaundice-to-HE interval: OR 1.171, (95% CI 1.044-1.314), p = 0.007 were independent predictors of death. The final model comprised three criteria: (1) presence of grade 3-4 HE, (2) INR greater than 3.1, and (3) jaundice to HE interval more than 10 days. Presence of 2 or more of these criteria predicted death with 90% sensitivity, 81.4% specificity and 84.9% accuracy. Peds-HAV model was superior to existing prognostic models. In the validation cohort, Peds-HAV model predicted death with 83.3% sensitivity and 92.6% specificity., Conclusion: Peds-HAV model is a simple, bedside, dynamic, etiology (HAV) specific prognostic model based on 3 objective parameters with optimum sensitivity and specificity, hence should be used as liver transplant listing criteria in HAV induced PALF.

A virus belonging to the Flaviviridae group causes dengue haemorrhagic fever. Dengue presenting as acute liver failure is rare. Dengue is endemic in India. The last epidemic of dengue occurred in Delhi in 2003. During this epidemic, 2185 confirmed cases of dengue were reported. Dengue virus serotypes 2 and 3 were responsible for this epidemic. A 19-yr-old male presented to our hospital with the complaints of fever for 12 days, during this epidemic. He was diagnosed as having dengue shock syndrome, stage IV with acute liver failure. He had primary dengue infection. He made complete recovery with supportive management. [ABSTRACT FROM AUTHOR]

A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture. [ABSTRACT FROM AUTHOR]

Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity., (Copyright © 2016 Elsevier B.V. All rights reserved.)