Cause Of Fulminant Hepatic Failure Research Articles

Inactivated TZ84 strain hepatitis A vaccine and its impact: A narrative review

Hepatitis A (HepA) represents a significant global public health challenge. At present, there is no definitive treatment available for managing HepA. Before the availability of HepA vaccines, hepatitis A virus (HAV) infection had emerged as a leading cause of fulminant hepatic failure and a significant indication for liver transplantation in children living in Argentina, Brazil, the Republic of Korea, and India. Inactivated HAV vaccines have demonstrated a high level of immunogenicity. In addition, there is evidence supporting the use of inactivated HepA vaccines in immunocompromised individuals and as post-exposure prophylaxis. Recently, the inactivated TZ84 strain hepatitis A vaccine, which has shown superior immunogenicity for up to 30 years and fewer adverse reactions when compared with other inactivated HepA vaccines, has become available in India. Moreover, the TZ84 strain of the inactivated HAV vaccine has the potential to control community-wide outbreaks. This narrative review offers an overview of the existing evidence concerning immunization against HepA in India, with a particular emphasis on the TZ84 strain of the inactivated HAV vaccine.

Inactivated TZ84 strain hepatitis A vaccine and its impact: A narrative review

Hepatitis A (HepA) represents a significant global public health challenge. At present, there is no definitive treatment available for managing HepA. Before the availability of HepA vaccines, hepatitis A virus (HAV) infection had emerged as a leading cause of fulminant hepatic failure and a significant indication for liver transplantation in children living in Argentina, Brazil, the Republic of Korea, and India. Inactivated HAV vaccines have demonstrated a high level of immunogenicity. In addition, there is evidence supporting the use of inactivated HepA vaccines in immunocompromised individuals and as post-exposure prophylaxis. Recently, the inactivated TZ84 strain hepatitis A vaccine, which has shown superior immunogenicity for up to 30 years and fewer adverse reactions when compared with other inactivated HepA vaccines, has become available in India. Moreover, the TZ84 strain of the inactivated HAV vaccine has the potential to control community-wide outbreaks. This narrative review offers an overview of the existing evidence concerning immunization against HepA in India, with a particular emphasis on the TZ84 strain of the inactivated HAV vaccine.

An unusual cause of fulminant hepatic failure: Metastatic infiltration by infiltrating ductal carcinoma of the breast

An unusual cause of fulminant hepatic failure: Metastatic infiltration by infiltrating ductal carcinoma of the breast

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

FATAL CASE OF FULMINANT HEPATIC FAILURE DUE TO HERPES SIMPLEX VIRUS REACTIVATION IN SETTING OF IMMUNOSUPPRESSION FROM CHRONIC STEROID AND METHOTREXATE USE: A RARE PRESENTATION

Scrub typhus, a rare of cause of fulminant hepatic failure: A common disease with uncommon presentation

Scrub typhus (bush typhus) is a potentially lethal mite-borne, acute febrile infectious illness caused by Orientia tsutsugamushi, reported precipitating frequent outbreaks in the Asia-pacific belt. Usual presentation after a median incubation period of 10–14 days, stretches from pathognomonic eschar, high-grade fever, centrifugal skin rash, jaundice, regional lymphadenopathy to frontal headache, nevertheless complicated at times with myocarditis, acute respiratory distress syndrome, acute kidney injury, encephalitis, and shock. Although patients with scrub typhus invariably do display mild liver injury, fulminant hepatic failure (FHF) is rarely reported. We describe herein, a case of FHF in an elderly male that responded well to antibiotics. Early diagnosis and sensitive antibiotic administration aids in mortality prevention of the former.

Presentation of Intrahepatic Cholangiocarcinoma with Fulminant Hepatic Failure: A Case Report

AbstractFulminant hepatic failure as initial presentation due to diffuse parenchymal infiltration by cholangiocarcinoma is a rare entity. We present the case of a 49-year-old female patient who had a fatal outcome with acute liver failure due to diffuse intrahepatic cholangiocarcinoma. No definite mass lesion was identified on cross-sectional imaging. The final diagnosis was made on transjugular liver biopsy. This discussion highlights the possibility of infiltrative cholangiocarcinoma as a rare cause of fulminant hepatic failure.

Etiological profile and clinical characteristics in fulminant hepatic failure in North India

Background: Acute liver failure (ALF) is a rare but severe, life-threatening, multisystemic medical emergency. ALF of duration <8 weeks in a patient is considered as fulminant hepatic failure (FHF). Its rapid progression and high mortality demand early diagnosis and expert management. Clinical and etiological profile varies with geographical area and time. The objective of this prospective study was to determine the clinical characteristics and etiological profile of FHF.Methods: A total of eighty consecutive patients with a diagnosis of FHF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), internal normalization ratio (INR) etc.) and etiological profile.Results: Most of the patients were <35 years of age and males. Viral hepatitis 35 (43.8%) was the most common cause of FHF but the majority of the patients 25 (31.2%) had undetermined etiology. Among viral causes, acute hepatitis E was most common followed by hepatitis B and A. Drug or toxic induced liver failure (18.8%) also contributed a significant proportion of cases. The three groups (viral, drug-induced and indeterminate) were comparable for the various baseline characteristics (bilirubin, alanine aminotransferase, INR, creatinine, albumin, grade of encephalopathy, MELD score etc.).Conclusions: Like the rest of India, viral hepatitis was the common cause of FHF but the majority of the patients 25 (31.2%) had undetermined etiology. Our study highlights the differences in the profile of FHF from other earlier studies in India and the west. Each different etiology leads to a similar final common pathway. Trying to determine etiology is essential, however, as outcomes and the use of antidotes depend on the identification of the causative process.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure From Heatstroke

BackgroundExertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. Methods and MaterialsOur prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. ResultsAll patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. ConclusionExtreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Insuficiência hepática fulminante após transplante simultâneo de rim‐pâncreas: um relato de caso

We describe an unusual case of hyperacute hepatic failure following general anesthesia in a patient receiving a simultaneous kidney-pancreas transplant. Despite an aggressive evaluation of structural, immunological, viral, and toxicological causes, a definitive cause could not be elucidated. The patient required a liver transplant and suffered a protracted hospital course. We discuss the potential causes of fulminant hepatic failure and the perioperative anesthesia management of her subsequent liver transplantation.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure from Exertional Heatstroke

Introduction Exertional heatstroke is an extremely rare cause of fulminant hepatic failure, and when complicated by multiorgan failure, is fatal without liver transplantation. The ability to support patients with heat stroke complicated by massive hepatic necrosis with mechanical replacement therapies while awaiting recovery or transplantation has not been reported. We utilized a multidisciplinary approach of critical care and liver transplant specialists to rapidly identify and treat cases of heat stroke-induced liver failure. Methods A retrospective review of three consecutive cases of male patients with fulminant hepaticfailure from exertional heatstroke was performed after IRB approval. Results All patients developed multiorgan failure, and required intubation, renal replacement therapy, and vasopressor support. All patients were listed urgently for liver transplantation, and were supported with the Molecular Adsorbent Recirculating System while awaiting transplantation. All patients underwent liver transplantation alone, and the liver explant showed massive hepatic necrosis in all cases. All patients required multiple operations including fasciotomy, serial washout, and wound closure. Renal replacement therapy was weaned within 30 days.All patients remain alive and well, with normal renal function, normal liver allograft function,and no long term sequelae of their multiorgan failure at 1, 2, and 4 years post-transplant.Conclusion Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that can be successfully treated with liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Study of acute viral hepatitis with special reference to fulminant hepatic failure

Background: Fulminant hepatic failure is a complication of viral hepatitis and is one of the leading causes of death in hospitalized children with viral hepatitis in India.Methods: All the patients suspected to have acute viral hepatitis and/or fulminant hepatic failures with hepatic encephalopathies were included in the study and the diagnosis was made on the basis of history, clinical examination including a detailed neurological examination. Triage scoring, Glasgow coma scale, encephalopathy grading were recorded at the time of admission and necessary investigations were carried out.Results: The occurrence of acute viral hepatitis and fulminant hepatic failure was 200 (2.004%) and 40 (0.401%) respectively during study period. Highest occurrence of 35.50% in the age group of 4-6 years, yellowish discoloration of the eyes or the urine was the most common presenting complaint. Only 45 % of the children who had fulminant hepatic failure survived and mortality was found to be 100% in those children who had grade 4 hepatic encephalopathy. Mortality was higher in those children who had duration of more than 10 days between the onset of jaundice and encephalopathy. Mortality was higher in those with prothrombin time between 41 to 50 seconds and with serum ammonia level more than 200 mmol/l. Hepatitis A virus was the most common cause of fulminant hepatic failure and Hepatitis E virus with hepatic encephalopathy was associated with 100 % mortality.Conclusions: Hepatitis A infection though associated with a good prognosis, younger age group (< 6 years) and co infection with Hepatitis E virus have a poor prognosis. Good hygiene practices and early immunization could be a step towards the prevention of Hepatitis A infection.

Estimation of vitamin C human protective dose for acetaminophen toxicity, using acute animal toxicity study

Acetaminophen (APAP) is the main cause of fulminant hepatic failure. Vitamin C is a natural antioxidant with protective potentials against APAP toxic damage. In this animal study, and after an LD50 determination and selection of suitable lethal dose, the investigation was done to select a proper protective dose of vitamin C against lethal APAP dose. All 6 animal groups received a lethal dose of APAP (3250 mg/kg), group II, III and IV received 500, 1000 and 1500 mg/kg vitamin C respectively, group V received 1200 mg/kg N-Acetylcysteine (NAC), and group VI receive 1000 mg/kg vitamin C and 1200 mg/kg NAC. Mortality was recorded and liver histopathology was carried out. The results showed, the mortality rate in the group I was 68.75% and 37.5%, 31.25% in group II and III respectively, while group IV Showed a higher mortality rate and in group V and VI it was 25%. There was also a gradual reduction in the grade of histopathological damage in all groups, ranging from 2.4 ± 0.55 in group I to 0.4 ± 0.55 in group V and VI. In conclusion, vitamin C showed an increasing reduction in mortality and more histopathological protection, and it was more significant at 1000 mg/kg. NAC adds no more protection or reduction in mortality. The estimated protective dose of vitamin C was 700 to1127 mg for each gram of APAP. Incorporation of this dose of vitamin C with APAP preparations may be considered as a promising method for reducing mortality or severity of APAP intoxication.

PTU-082 Clinical Outcomes after Transplantation for Paracetamol Overdose: Evaluation of Predictors of Outcome, Adherence and Pre-Transplant Psychiatric History

Introduction Paracetamol hepatoxicity is the most common cause of fulminant hepatic failure in the UK 1 and NHSBT criteria for super-urgent liver transplantation in these patients are well described. 2 While potentially life-saving, transplanted patients must live with the consequences of immunosuppression and life-long follow up. Patients transplanted for paracetamol overdose have an increased risk of post-transplant death compared to patients transplanted for other indications, particularly due to suicide, trauma & non-adherence to treatment. 3 Outcome after transplantation may be adversely affected by persisting physical/psychological/psychiatric/social & addiction circumstances that may make adherence unmanageable, even with full social support. Given the shortage of organ donors, rationing is inevitable and not all patients who fulfil the NHSBT criteria are listed for transplantation, despite a predicted poor/fatal outcome without. There is currently no clear way of pre-operatively predicting the risk of poor outcomes after transplant for paracetamol overdose. Our aim was to identify factors in the presenting history that could suggest that these patients might be unlikely to fully benefit from undergoing liver transplantation. Methods We retrospectively analysed all patients transplanted for fulminant liver failure due to paracetamol overdose at University Hospitals Birmingham from 2000–2014, using standard clinical and transplant databases. Survival and graft related outcomes were assessed using Kaplan-Meier survival curves, with log-rank tests used to make comparisons across factors. Patients with DNAs and non-compliance were then compared to compliant patients using Mann-Whitney tests, for continuous variables, and Fisher’s exact test, for categorical variables. Results 59 patients were transplanted for POD during this period with median follow up of 6 years, mean age of 35 (range 17–57 years). 59% of patients were female. 57% of patients had a pre-existing psychiatric diagnosis however only 36% had a history of previous overdose. 12 patients died before discharge from hospital (main causes of death were multi-organ failure & sepsis) with a further 6 patients dying after initial discharge (all associated with non-compliance and 33% were due to suicide). Overall 5 year survival was 69%, which rose to 87% if the patient survived to discharge from hospital. Having a history of domestic abuse was associated with a higher risk of death (p = 0.001). Of 36 patients under long-term follow up at our centre, 15 have had at least one episode of biopsy proven rejection (41.7%) with a 5 year rejection rate of 46%. To date this has resulted in two patient deaths and two re-grafts. Patients aged 16–35 were significantly more likely to experience rejection than the older cohort (p = 0.04). 73% of patients with rejection had a history of non-compliance with medication compared to 27% in compliant patients (p = 0.031). In the 2007–2015 patient cohort, both staggered and mixed overdosed were found to give significantly increased risk of rejection (p = 0.027 and 0.011 respectively). Conclusion Patients transplanted for paracetamol overdose have poorer long term survival and graft function than other transplant patients. There remains no clear way of predicting post-operative mortality/graft dysfunction from pre-admission factors. However, domestic abuse may be associated with increased patient mortality and patients under 35, staggered and mixed overdoses are at higher risk of graft rejection. These results are unlikely to change the decision to list for transplantation, but could help identify those at higher risk post-discharge and aid in tailoring follow up. References 1 Riordan S, Williams R. Cause and prognosis in acute liver failure. Liver Transpl 2003; 5 (1):86–89. 2 Mitchell I, Bihari D, Chang R, Wendon J, Williams R. Earlier Identification of patients at risk from acetominophen-induced acute liver failure. Cri Care Med 1998; 26 (2):279–284. 3 Germani G, Theocharidou E, Adam R, Karam V, Wendon J, et al . Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol 2012; 57 :288–296. Disclosure of Interest None Declared

Fulminant Hepatic Failure Secondary to Herpes Hepatitis in a Patient With Myasthenia Crisis: An Elusive Diagnosis

Herpes hepatitis is a rare cause of fulminant hepatic failure contributing to less than 1% of all cases. It is most often seen in persons who are immunosuppressed and in pregnant women. The presentation is usually non-specific and rapidly progressive, thus making antemortem diagnosis of this condition rare. We present a patient who was on chronic immunosuppressive therapy for systemic lupus erythematosus and subsequently developed multi-organ failure with anicteric transaminitis as a result of disseminated herpes infection. The diagnosis was only made post-mortem. A confounding factor in this case was the fact that the patient underwent plasmapheresis, which skewed the interpretation of liver function tests in the setting of acute liver failure.

Ethical dilemmas in psychiatric evaluations in patients with fulminant liver failure

Fulminant hepatic failure (FHF) is one of the more dramatic and challenging syndromes in clinical medicine. Time constraints and the scarcity of organs complicate the evaluation process in the case of patients presenting with FHF, raising ethical questions related to fairness and justice. The challenges are compounded by an absence of standardized guidelines. Acetaminophen overdose, often occurring in patients with histories of psychiatric illness and substance dependence, has emerged as the most common cause of FHF. The weak correlations between psychosocial factors and nonadherence, as per some studies, suggest that adherence may be influenced by systematic factors. Most research suggests that applying rigid ethical parameters in these patients, rather than allowing for case-dependent flexibility, can be problematic. The decision to transplant in patients with FHF has to be made in a very narrow window of time. The time-constrained process is fraught with uncertainties and limitations, given the absence of patient interview, fluctuating medical eligibility, and limited data. Although standardized scales exist, their benefit in such settings appears limited. Predicting compliance with posttransplant medical regimens is difficult to assess and raises the question of prospective studies to monitor compliance.

Changing etiologies and outcomes of acute liver failure: Perspectives from 6 transplant centers in Argentina

There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.

Seroprevalence of hepatitis A virus infection in different age groups of children

Context: Hepatitis A is one of the most common causes of hepatitis in the pediatric age group and the most common cause of fulminant hepatic failure (FHF) among children in India. Hepatitis A is a waterborne disease. High endemicity obviates the need for vaccine in the community. Aims: We studied 116 children in the outpatient department (OPD) to know the seroprevalence of hepatitis A virus (HAV), total antibodies, and the effect of various demographic and water sanitation variables on it. Settings and Design: Children attending the pediatric OPD with minor problems in a medical college hospital were chosen for this study. It is a descriptive, cross-sectional, and seroepidemiologic investigative study. Materials and Methods: Blood samples of randomly selected children were collected and competitive enzyme-linked immunosorbent assay (ELISA) test was done for the detection of total anti-HAV antibodies, [both immunoglobulin M (IgM) and immunoglobulin G (IgG)], using a commercially available ELISA kit. Dia.Pro (Diagnostic Bioprobes srl via Columella n° 31 20128 Millano, Italy). Statistical Analysis Used: Statistical analysis was performed by the chi-square test using Epi Info software 3.5.4 version (2012) [Center for disease control and prevention (CDC), Atlanta, Georgia (USA)]. Results: Seroprevalence in children from the upper social class was 54.5% versus 87.2% in the lower social class ( P = 0.00075). 90.9% of the children with rural background were seropositive compared to 77.1% of children with urban background. The mother's education above and below secondary level had a seropositivity for HAV in children up to 69.23% and 87.1%, respectively. The method of water treatment using boiled water, mechanical filtration, filtration plus ultraviolet (UV) light treatment, and no treatment had a seropositivity of 50.0%, 83.33%, 37.5%, and 84%, respectively, ( P = 0.0036). Seropositivity was the highest when the water source was municipal bore well pipeline (88.88%), followed by municipal dam water through pipeline (79.16%), and personal bore well (68.16%) ( P = 0.026). Conclusion: Children of this geographical area have high seroprevalence for HAV antibodies at a younger age with a significant difference between their social classes, water sources, and water treatment methods.

Accidental Acetaminophen Overdose Results in Liver Transplant During Second Trimester of Pregnancy: A Case Report

Acetaminophen overdose is the most rapidly growing cause of fulminant hepatic failure in Western countries. Pregnant women are counseled that acetaminophen is safe during pregnancy and an alternative to nonsteroidal anti-inflammatory medications. This report describes a case of acetaminophen overdose during the second trimester of pregnancy with resultant fulminant hepatic failure requiring liver transplantation. The fetus was previable at the time of liver transplantation, and methods to preserve viability during and after transplantation are discussed. Despite the best attempts of the team, the fetus expired. The challenges and outcomes of fulminant hepatic failure in pregnancy are discussed in detail.

Successful extracorporeal liver dialysis for the treatment of trimethoprim-sulfamethoxazole-induced fulminant hepatic failure

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a commonly used antibiotic that has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and one or more major organ involvement. Although rare, TMP-SMZ is a recognised cause of fulminant hepatic failure. We report a 17-year-old Chinese male adolescent who presented with fever, myalgia, generalised maculopapular rash and lymphadenopathy after taking TMP-SMZ for acne vulgaris. He subsequently developed hepatic encephalopathy and was worked up for urgent liver transplantation. He responded well to extracorporeal liver dialysis (originally intended as a bridging therapy) and subsequently recovered without the need for liver transplantation. This case report highlights the importance of early recognition of TMP-SMZ-induced DRESS syndrome and the need for early discontinuation of the drug in the affected patient. Extracorporeal liver dialysis and transplantation should be considered in the management of TMP-SMZ-induced fulminant hepatic failure.

The different etiology of fulminant hepatic failure (FHF) in Korea and prognostic factors in patients undergoing liver transplantation for FHF

The prognosis of fulminant hepatic failure (FHF) depends on the etiology and reversibility. In this study, we identified the etiological difference of FHF in Korea and analyzed the prognostic factors after liver transplantation (LT) for FHF. We retrospectively reviewed 42 patients with FHF who underwent LT from April 1999 to April 2011 at Samsung Medical Center, Seoul, Korea. The patients were categorized into two groups according to the short-term result of LT, and perioperative profiles were compared to identify the short-term poor prognostic factors. Unlike Western countries, there was no paracetamol-related FHF but herbal/folk medicines were the most frequent causes of FHF (26.2%). HAV-related FHF increased significantly and comprised the main portion of FHF with Herbal/folk medicines after 2005. Encephalopathy grade, onset time, pre-transplantation need of renal replacement, and ventilator treatment were significantly different between groups in univariate analysis. In multivariate analysis, pre-transplantation renal replacement treatment and hepatic encephalopathy grade IV were the independent prognostic factors after LT. The etiologies of FHF in Korea were different compared with Western reports. The requirement of renal replacement treatment and hepatic encephalopathy grade IV were identified as independent poor prognostic factors after LT for FHF in this study.