Criteria For Acute Liver Failure Research Articles

Clinical Profile and Outcomes of Children with Acute Liver Failure in a Tertiary Care Center in South India: A Retrospective Study.

In this study, we investigated the clinical profile, survival at discharge, and proportion of children with acute liver failure (ALF) meeting the criteria for, yet surviving without, liver transplantation (LT). Medical case records of children aged >28 days to ≤15 years over a period of 7 years, identified from pediatric admission and discharge registers, were screened. Children satisfying the criteria for ALF were included in this study. A total of 71 records meeting the pediatric ALF (PALF) criteria were included. The survival rate at discharge was 61% (n=44). A considerable proportion of children satisfied the King's College Criteria (KCC) (56.3%) and the European Association for the Study of the Liver (EASL) criteria (7%) for LT at admission. Nonetheless, the survival rate in the absence of LT was 42.5% in children who satisfied the KCC and 20% in those who met the EASL criteria. Infection (29.5%) and paracetamol overdose (19.7%) were the major identifiable causes of PALF. Hepatitis A was the most common infection identified. No significant predictors of poor outcomes were identified in multivariable analysis. Our study highlights the changing survival rates and the clinical and etiological profiles of patients with PALF. In areas with poor access to LT services, survival in these children could be improved through early referral to centers with adequate intensive care facilities. Preventing ALF and referring patients to LT services are paramount to reducing mortality.

Etiological and Clinical Spectrum of Acute Liver Failure of Infancy in Pakistan


 Objective: To describe the aetiology and clinical spectrum of acute liver failure of infancy at a tertiary care hospital
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Paediatric Gastroenterology, Hepatology & Nutrition, Children Hospital and Institute of Child Health, Lahore, from Nov 2020 to May 2021.
 Methodology: Infants under 12 months of age were enrolled having liver-based coagulopathy (not corrected after two doses of parenteral vitamin K, 10 mg) with INR > 2, whether encephalopathy was present or not. Encephalo-pathy is difficult to identify in infants, so it was not essential for the diagnosis of ALFI in our study. Infants diagnosed with chronic liver disease at presentation or those without final etiological diagnosis were excluded.
 Results: A total of 31 infants were enrolled fulfilling the criteria of acute liver failure of infancy and were studied about aetiology and clinical presentation. The mean age of presentation was 4.64±3.16 months, and males predominated in the study group (64.5%). Common clinical features were in descending order ascites in 29 (93.5%), jaundice in 28 (90.3%), pallor in 24 (77.4%) and peripheral oedema in 21 (67.7%). Metabolic liver diseases were the common cause of ALFI, constituting around(18, 58%) followed by sepsis (9, 29%).Galactosemia (11, 35.5%) stands out among the metabolic causes.
 Conclusion: Metabolic disorders followed by sepsis are the most common cause of ALFI.

Severe Hepatitis in Pediatric Coronavirus Disease 2019.

ABSTRACTHepatic involvement in coronavirus disease 2019 (COVID-19) is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of four previously healthy children who presented with significant hepatitis as the primary manifestation of COVID-19 infection. Two of these patients met criteria for acute liver failure. None of the patients had respiratory symptoms. One patient was found to have complement dysfunction resulting in microangiopathic features and was treated successfully with eculizumab. This case is in line with adult post-mortem data showing that more severe cases of hepatic dysfunction secondary to COVID-19 infection may be associated with complement activation and microangiopathic features. Liver function should be evaluated in cases of severe COVID-19, and severe acute respiratory syndrome coronavirus 2 infection should be considered as a cause of acute severe hepatitis even in patients without significant respiratory or other systemic symptoms.

S2841 Autoimmune Hepatitis: Possible Relation to the Pfizer-BioNTech COVID-19 Vaccine?

Introduction: Autoimmune Hepatitis (AIH) is a rare liver injury known to cause approximately 13% of acute liver failure cases in the United States. Drug-induced AIH has similar clinical, serological and histological features of AIH but is less likely to require long term immunosuppression or to relapse after discontinuation of immunosuppressants. It is mostly associated with nitrofurantoin, minocycline, hydralazine, and methyldopa, however other medications may be culprits. Herein, we present a patient with drug-induced AIH with possible relation to Pfizer-BioNTech COVID-19 vaccine. Case Description/Methods: A 38-year-old female with a history of Helicobacter pylori treated with amoxicillin and pantoprazole three months ago and recent COVID-19 vaccination presented with two weeks of right upper quadrant pain and diarrhea. Patient received second dose of vaccination two weeks prior to symptom onset. Five days post-symptom onset, she developed a pruritic rash with vomiting and yellowing of her skin. Physical examination was notable for normal mentation, scleral icterus, jaundice, and a maculopapular rash. Initial blood workup showed international normalized ratio 2.4, alkaline phosphatase 212 U/L, ALT 3769 U/L, AST 1572 U/L and total bilirubin of 23.8 mg/dL. Viral hepatitis serologies, chronic liver disease workup and autoimmune serologies were normal. Imaging demonstrated no intra- or extra-hepatic biliary ductal dilation. Liver biopsy showed portal inflammation with interface activity, diffuse lobular inflammation, and perivenulitis with abundant lymphocytes and plasma cells consistent with seronegative AIH or drug induced AIH. The patient developed altered mental status meeting the criteria of acute liver failure, she was started on corticosteroids as well as supportive care with resolution of encephalopathy and was discharged home on prednisone. Discussion: Several etiologies of drug-induced AIH are well-established, however cases secondary to COVID-19 vaccination have been minimally reported. Common adverse events for COVID-19 vaccination have been noted such as fever, chills, fatigue, headache, and muscle pain. Several rare side effects have occurred including immune thrombocytopenia and one other suspected case of Pfizer-BioNTech COVID-19 vaccination-induced AIH reported in the literature. In that case the patient developed symptoms within one week of the first dose. This case serves to report a potential association and not necessarily causation between the Pfizer-BioNTech COVID-19 vaccination and AIH.Figure 1.: Severely active lymphoplasmacytic hepatitis with frequent apoptotic hepatocytes with confluent necrosis.

S2568 DDD: Diagnostic Dilemma in Drug Induced Liver Injury: Adverse Reaction of Abiraterone in Treatment of Metastatic Prostate Cancer

INTRODUCTION: Drug-induced liver injury (DILI) is a benign and reversible form of liver injury that occurs as an adverse reaction to medication use. It is a leading cause of acute liver failure and requires prompt recognition and discontinuation of the offending agent to avoid development of chronic disease. We present a case of severe DILI secondary to Abiraterone use in a patient with prostate cancer. CASE DESCRIPTION/METHODS: A 67 year-old-male without known liver disease was seen for severely elevated liver enzymes, jaundice and abdominal pain. Pertinent history includes stage IV prostate cancer with metastasis to the bone and lymph nodes with initiation of Abiraterone four months prior. He denies excessive alcohol, acetaminophen or herbal supplement use. Initial liver panel results: AST 1668 (peak 2379), ALT 3093 (peak 3330), alk phos 185 (peak 361) and TB 14.3 (peak 29). INR was 1.40 (peak 1.65). While transplant center transfer was considered, given patient's stability and not meeting King's College Criteria for acute liver failure, this decision was deferred and he was placed on NAC for 48 hours. Extensive workup for other causes of elevated liver enzymes were negative including: Wilson’s disease, autoimmune hepatitis, HAV, HBV, HCV, EBV, HSV, CMV, alpha 1 antitrypsin deficiency, portal vasculature thrombosis and acetaminophen toxicity. Core needle biopsies revealed acute hepatitis with confluent and bridging necrosis as well as mild Kupffer cell siderosis with iron accumulation. Serum ferritin level was 28,441 and IgG4 was mildly elevated, which prompted concern for hemophagocytic lymphohistiocytosis(HLH), hemochromatosis and autoimmune cholangiopathy. Patient did not meet criteria for HLH, hemochromatosis types I-IV in the absence of HFE, HFE2, TFR2, HAMP and SLC40A1 gene mutations, nor did MRI or pathology staining reveal IgG4 cholangiopathy. LFTs normalized within four months and ferritin within six months. Abiraterone was not restarted. DISCUSSION: Abiraterone is an antiandrogen that inhibits CYP17. Although the mechanism of hepatic injury is unknown, Abiraterone has been shown to cause elevations in serum aminotransferase levels in up to 13% of patients and ALT elevations above 5x the ULN in 6% of patients, however only few documented cases are known in which patients displayed associated symptoms such as jaundice and no documentation of severe elevations in serum ferritin as seen in our patient. This case also highlights the diagnostic challenge in DILI.Figure 1.: A. Mild to moderate predominantly lymphocytic inflammation. B. Intact bile ducts.Figure 2.: Confluent necrosis with areas of bridging necrosis.Figure 3.: Iron stain with Kupffer cell siderosis.

NBAS disease: 14 new patients, a recurrent mutation, and genotype-phenotype correlation among 24 Chinese patients.

Neuroblastoma amplified sequence (NBAS)-associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome (OMIM #614800), and a combined phenotype overlapping ILFS2 and SOPH syndrome. The mutation spectra of NBAS and its genotype-phenotype correlation among Chinese were not clear. Clinical and genetic data were retrospectively collected from the medical charts of patients with biallelic NBAS mutations, as well as from Chinese patients in previously published reports. Fourteen new patients were identified, including 10 novel mutations: c.648-1G>A, c.2563_c.2577+5del/p.His855_Gln859del, c.3115C>T/p.Gln1039Ter, c.3284G>A/p.Trp1095Ter, c.2570C>T/p.Ala857Val, c.6859G>T/p.Asp2287Tyr, c.1028G>A/p.Ser343Asn, c.1177_1182delinsAGATAGA/p.Val393ArgfsTer2, c.3432_3435dupCAGT/p.Ala1146GlnfsTer14, and c.680_690dupACTGTTTCAGC/p.Phe231ThrfsTer35. All 14 patients presented as fever-triggered liver injury, including nine patients that satisfied the criteria of acute liver failure (ALF) in whom c.3596G>A/p.Cys1199Tyr occurred five times. Nine patients had extrahepatic manifestations including short stature, skeletal abnormalities, intellectual disability, ophthalmic abnormalities, low levels of serum immunoglobulins, facial dysmorphism, and cardiac abnormalities. Ten other Chinese patients were collected through a review of published works. Genotype-phenotype analysis in 24 Chinese patients revealed that the percentage of ALF patients with variants in the Sec39 domain was significantly higher than that in the C-terminal (100% vs. 12.5%, P = 0.000), and the percentage of multi-organ/system involvement in patients with variants in the Sec39 domain was significantly lower than that in the C-terminal (40% vs. 100%, P = 0.0128). We reported 14 new patients, 10 novel mutations, and a unique recurrent mutation. Correlation analysis indicated that the domain of missense and non-frameshift insertion/deletion mutations in NBAS protein is related to phenotype among Chinese patients.

Mild versus Severe Liver Injury in SARS-CoV-2 Infection

Background: Abnormal liver function has been reported in patients with COVID-19 infection. The aim of our study was to report on the prevalence of liver injury in our cohort, to evaluate the association of mild versus severe liver injury with mortality in COVID-19 patients and to scrutinize the temporal pattern of viral detection and liver injury. Methods: We present data from a German cohort of 147 SARS-CoV-2 infected patients. The patients were divided into 3 groups according to their liver status during treatment. The first group included patients without elevated alanine aminotransferase or bilirubin, the third group patients meeting the biochemical criteria of acute liver failure (ALF), and the second group all other patients. Results: Liver injury was detected in 75 (50.7%) and 93 (63%) patients by admission and during treatment, respectively. ALF was associated with the male sex, younger age, and higher BMI. Mortality was associated with the presence of ALF (OR = 9.423, 95% CI: 2.410–36.858) in contrast to milder liver injury (OR 1.101, 95% CI: 0.435–2.791). In 30% of patients with mild liver injury and in 50% of ALF patients, peak liver injury was observed at a time point when the virus was no longer detectable in the respiratory tract. Conclusion: Mild liver injury was not associated with worse outcome in our cohort, and the pattern of liver injury did not fit well to the theory of SARS-CoV-2 directly causing liver impairment. Instead, severe liver injury in our cohort was associated multiple-organ failure and acute vascular events.

Early Exchange Transfusion to Treat Neonates With Gestational Alloimmune Liver Disease

Exchange transfusion (ET) and intravenous immunoglobulin are potentially life-saving treatment options in newborns with gestational alloimmune liver disease (GALD). Since 2008, early ET has been the standard of care for symptomatic neonates with suspected GALD in our unit. The present study's aim was to investigate the outcomes of this approach. From 2008 to 2018, all neonates who received ET for suspected GALD were identified, and their clinical course and outcomes were analyzed in a descriptive cohort study. In survivors, liver function parameters before ET and maximum values after ET and at discharge were compared. During the 11-year period, 12 infants received ET for suspected GALD at a median (range) chronological age of 11 (1-23) days and gestational age of 38 (32-40) weeks. Signs of impaired liver function, most frequently postnatal hypoglycemia, hyperferritinemia, direct hyperbilirubinemia, and coagulopathy, were present in all infants. Survival without a liver transplant in the overall cohort was 10 of 12 (83.3%) and 7 of 9 (78%) in those fulfilling the criteria of acute liver failure. Two patients died, one of them after liver transplantation. Direct bilirubin typically increased after ET, even in survivors. All survivors recovered and were discharged from the pediatric hepatology outpatient clinic after 8 (3-11) months of follow-up. In newborns with suspected GALD, a limited diagnostic work-up followed by early ET may lead to favorable outcomes. More data are required to develop an evidence-based clinical approach to GALD.

2347 Acute Liver Failure: Drug-Induced Liver Injury and a Perfect Thyroid Storm

INTRODUCTION: Acute liver failure (ALF) is a rare but serious condition defined by severe acute liver injury with coagulopathy (INR ≥ 1.5) and encephalopathy without preexisting cirrhosis. ALF carries a high morbidity and mortality. Liver transplantation (LT) is the only definitive treatment for patients that fail other supportive therapies. CASE DESCRIPTION/METHODS: A 28 year-old female with hyperthyroidism due to Grave disease was transferred to our institution for acute liver failure (ALF) and transplant evaluation. One month prior, she developed jaundice and pruritus. She had been treated with propylthiouracil (PTU) for 1 year but that was stopped 1 week prior to transfer due to elevated liver enzymes. On evaluation she was found to have elevated AST/ALT (2800/1900), hyperbilirubinemia (28.6) and an elevated INR (2.85). The patient progressively worsened and developed encephalopathy thus fulfilling the criteria for ALF. On admission, her MELD-Na was 33 and she had grade III hepatic encephalopathy. Her thyroid studies were found to be TSH <0.010, free T3 17.9 and free T4 >5.6. Her Burch-Wartofsky Point Scale was >45, which is highly suggestive of thyroid storm. She was subsequently started on plasmapheresis, methimazole, hydrocortisone and cholestyramine for thyroid dysfunction. Patient continued to clinically decompensate requiring an emergent thyroidectomy followed by LT. Post-operatively patient had an acute change in her neurological status with loss of reflexes. CT head showed diffuse global cerebral edema with brainstem compression and herniation. Medical care was withdrawn and patient expired. DISCUSSION: This is a case of ALF from PTU drug induced liver injury complicated by thyroid storm. PTU is the second most common non-acetaminophen related cause of DILI that requires liver transplantation. PTU-related ALF can occur at any point of treatment and the onset is usually sudden with rapid progression. While extremely rare, thyroid storm is also a reported cause of ALF. Excess thyroid hormone may cause hepatocyte dysfunction. This case poses a diagnostic dilemma given the coexistence of thyroid storm and PTU therapy. It is possible that the initial hepatic injury due to PTU-related DILI made the liver more susceptible to fulminant hepatic failure from thyroid storm. Despite the rapid listing and transplantation within 48 hours of arrival, the patient did not survive. This case extends the spectrum of the presentation of ALF in the setting of thyroid dysfunction.

Acute onset of autoimmune hepatitis in children and adolescents

BackgroundAutoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). MethodsForty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). ResultsAcute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. ConclusionRapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

31-Year-Old Woman With Jaundice and Abdominal Pain

31-Year-Old Woman With Jaundice and Abdominal Pain

Clinical characteristics of liver failure from a systemic cause: A report from an advanced critical care center

Background/Purpose. In Japan, acute liver failure (ALF) has generally been described using the diagnostic term, “fulminant hepatitis”, because of the fact that most cases of ALF has been thought to occur in association with hepatitis mainly due to a hepatitis virus infection. New diagnostic criteria for ALF, including ALF other than fulminant hepatitis, were established in 2011. We therefore examined the prognostic factors of patients with liver failure from a systemic cause, including warfarin users. Material and methods. Sixty-six patients with ALF that were diagnosed according to the Japanese diagnostic criteria for ALF between 2009 and 2013 were divided into a survivor group and a non-survivor group. The data regarding demography, liver tests, coagulation tests, Sequential Organ Failure Assessment (SOFA) scores, and the use of oral warfarin or aspirin were compared between the two groups. Results. The SOFA score was significantly higher in the non-survivor group (p = 0.025). The proportion of oral warfarin users was significantly higher in the survivor group (p = 0.013) (58.1% vs. 26.1%). A multivariate logistic regression analysis showed the SOFA score (odds ratio: 0.851, 95% confidence interval (CI): 0.728-0.995, p = 0.043) and warfarin use (odds ratio: 3.261, 95% CI: 1.028-10.347, p = 0.045) to be significant factors that were negatively and positively associated with the prognosis, respectively. Conclusion. In this study, among the patients with ALF other than fulminant hepatitis, those with a high SOFA score on admission exhibited a poor prognosis. In addition, oral warfarin use prior to disease onset was found to be a factor which indicated a good prognosis.

Factors Influencing Mortality Following Liver Transplant in Acute Liver Failure: A Single Center Experience.

In irreversible acute liver failure, liver transplant is the only viable treatment option. In this study, our aim was to evaluate and determine the factors related to mortality in patients who received liver transplants in accordance with King's College criteria for acute liver failure in order to prevent futile operations. Our study included 65 adult patients with acute liver failure who received liver transplant according to King's College criteria. Factors related to mortality, including demographic and operative data, causes of acute liver failure, severity of encephalopathy, and laboratory data, were retrospectively analyzed. Patients who received living-donor liver grafts had donations from first-degree to fourth-degree relatives. Of 65 patients analyzed, 55.3% were women. Ninety-day mortality rate was 36.9%. Preoperative bilirubin levels in survivor and nonsurvivor groups were 16.3 ± 9.6 and 21.3 ± 10.7 mg/dL, respectively (P = .03). Mortality rates of patients with bilirubin above and below 9 mg/dL were 31.8% and 8.3%, respectively (P = .03). Of patients who died, 75% were women (significantly more women than men, P = .015). Patients who had deceased-donor liver transplants had a significantly higher mortality rate than those who had living-donor liver transplants (52% vs 27.5% ; P = .046). At 3 days posttransplant, bilirubin, creatinine, aspartate aminotransferase, phosphorus, sodium, and ammonia levels were significantly different between survivor and nonsurvivor groups (P < .05). We found living-donor liver transplant to be superior versus deceased-donor liver transplant with regard to development of acute liver failure. Reasons could include the long wait period for deceased donors and liver grafts coming from marginal donors. Bilirubin level and presence of grade 4 encephalopathy had predictive values for poor prognosis of patients.

Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose

Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity. We performed a retrospective analysis of data from 434 subjects in the Acute Liver Failure Study Group who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) or ALI (severe liver injury with coagulopathy but no encephalopathy) due to acetaminophen toxicity from January 1, 2010 through December 31, 2014. We collected data on patient demographics, biochemical features, reported acetaminophen use, N-acetylcysteine therapy, liver transplant, and outcomes. Descriptive statistics were used to assess patient demographics, clinical characteristics, and outcomes whereas differences in continuous variables between patients with vs without acetaminophen detection on admission were analyzed using the Wilcoxon rank-sum test. The primary aim was to determine the proportion of patients with detectable plasma levels of acetaminophen. Acetaminophen was undetectable in serum samples from 227 patients (52%). There were no significant differences between groups of patients with detectable vs undetectable levels in demographic features, alcohol use, median levels of alanine aspartate, or use of N-acetylcysteine (given to 94.7% of patients with detectable acetaminophen vs 95.9% of those with undetectable acetaminophen; P=.63). We observed a significant difference in median dose taken between patients with detectable (29,500 mg; interquartile range, 15,000 mg-50,007 mg) vs no detectable parent compound (14,950 mg; interquartile range, 3960 mg-25,000) (P=.003). A lower proportion of patients with detectable plasma levels of acetaminophen (72.3%) survived without a liver transplant than of patients with undetectable levels (86.3%) in univariate analysis (P=.0006), although this was not significant in multivariable analysis (P=.12). Although most patients had unintentional overdoses, a higher proportion of patients with suicidal overdoses (43%) had detectable levels of acetaminophen than patients with accidental overdoses (29.3%; P=.01). More than half of patients who present at the hospital with acetaminophen-induced ALI or ALF have undetectable levels of acetaminophen. Clinicians should not exclude acetaminophen toxicity because of undetectable levels or withhold N-acetylcysteine for patients with ALI or ALF when acetaminophen toxicity is suspected.

A study of Acute Liver Failure in adults in a tertiary care hospital

Acute liver failure (ALF) is a condition with rapid deterioration of liver function resulting in hepatic encephalopathy and/or coagulopathy in patients with previously normal liver. Acute liver failure (ALF) is an uncommon condition associated with high morbidity and mortality. The prognosis is poor for untreated cases of Acute liver failure, so early recognition and management of patients with acute liver failure is crucial. A cause for acute liver failure can be identified in 60 to 80 percent of patients. Identifying the underlying cause of the liver failure is important because it influences the approach to management and provides prognostic information. Aims and Objectives: The aim of our study is to identify the clinical features, etiology and outcome of acute liver failure in a tertiary care hospital. Materials and Methods: This study is an observational study where patients with Acute Liver Failure admitted in ICU in our institution after meeting the diagnostic criteria for Acute liver failure were included in the study. Details of history, relevant symptoms and baseline investigations included, complete blood count, blood glucose, renal function test, serum electrolytes, liver function test (LFT), prothrombin time, international normalized ratio (INR), lactate dehydrogenase (LDH), creatine kinase (CK)], arterial blood gas analysis, arterial lactate, arterial ammonia, amylase and lipase level and pregnancy test (if female) and ultrasonography (USG) abdomen were recorded, MRI brain and other investigations relevant to the admission diagnosis, co morbidities and aetiology if needed were recorded. All the patients received standard supportive treatment for ALF. Results: In this study of 57 patients, majority of the patients were from the age group 41 to 50 years (17 patients) and 31 to 40 years (13 patients). 36 patients were male and 21 patients were females. Jaundice and encephalopathy was observed in all 57 (100%) patients, 24 (42%) patients had INR &gt;2.5, 27 (47%) patients had serum creatinine &gt;1.2 mg/dl and 18 (31.5%) patients had serum ammonia levels &gt;100 micromol/L. The lowest value for serum aminotranferase was observed in infections (other than viral hepatitis) and maximum value was observed in drugs leading to ALF.In 20 (35%) patients viral hepatitis was the cause for ALD, followed by drugs and toxins which was the cause of ALD in 18 (31.5%) patients. Infections other viral hepatitis as the aetiology for ALF was observed in 16 (28%) of patients. Ischemic hepatitis was observed in 1 and Wilson’s disease was noted in 2 patients. Total 6 (10.5%) patients out of 57 patients had died, 4 patients with hepatitis B infection, 1 patient with paracetamol over dosage and 1 patient with dengue fever had died. Conclusion: Viral hepatitis and drugs are the commonest cause for acute liver failure. The aetiology of ALF varies significantly worldwide. Determining the etiology of acute liver failure requires a combination of detailed history taking and investigations. A broad evaluation is required to identify a cause of the acute liver failure, as the prognosis is poor in untreated cases of acute liver failure, so early recognition and management of patients with acute liver failure is crucial.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients.

AIMTo investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH).METHODSA total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defined by the “American Association for the Study of the Liver (AASLD)”. According to this definition, patients with “acute-on-chronic” or “acute-on-cirrhosis” liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients’ demographics, causation of liver failure, laboratory data (liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTSThe majority of patients with ALF were female (84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for anti-liver kidney microsomal antibody (LKM). We could identify potential triggering factors in 26/52 (50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF (57.7%), virus-induced ALF (30.8%), and preceding surgery in general anesthesia (11.5%), respectively. Unfortunately, 6 out of 52 patients (11.5%) did not survive ALF and 3 patients (5.7%) underwent liver transplantation (LT). Comparing data of survivors and patients with non-recovery following treatment, MELD-score (P < 0.001), age (P < 0.05), creatinine (P < 0.01), and finally, ALT-values (P < 0.05) reached statistical significance.CONCLUSIONDrugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

Acute liver failure related to inherited metabolic diseases in young children

Abstract Introduction Pediatric acute liver failure (ALF) due to inherited metabolic diseases (IMD) is a rare life-threatening condition with a poor prognosis. Early intervention may be lifesaving. Objective To describe clinical presentation, investigation and outcomes of ALF related to IMD in young children. Material and methods Retrospective review of the medical records of children aged up to 24 months, admitted to a tertiary pediatric and neonatal Intensive Care Unit during a 27-year period, fulfilling the ALF criteria, with documented metabolic etiology. Results From 34 ALF cases, 18 were related to IMD: galactosemia (4), mitochondrial DNA depletion syndrome (MDS) (3), ornithine transcarbamilase deficiency (3), congenital defects of glycosylation (2), tyrosinemia type 1 (2), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1), hereditary fructose intolerance (1), classic methylmalonic aciduria (1) and citrulinemia type 1 (1). The median age was 1.3 months. At least one previous suggestive sign/symptom of IMD (vomiting, failure to thrive, hypotonia or developmental delay) was observed in 67% of the cases. The most common physical signs at admission included: hepatomegaly (72%), jaundice (67%) and encephalopathy (44%). The peak laboratorial findings were: mean international normalizad ratio 4.5, median lactate 5 mmol/L, mean bilirubin 201 μmol/L, median alanine aminotransferase (ALT) 137 UI/L and median ammonia 177 μmol/L. One patient was submitted to liver transplant in ALF context (MSD). The mortality rate was 44%. Discussion The identification of IMD as a frequent cause of ALF allowed specific therapeutic measures and adequate family counseling. Particular clinical features and moderated ALT and bilirubin levels can lead to its suspicion.

Acute liver failure related to inherited metabolic diseases in young children

Pediatric acute liver failure (ALF) due to inherited metabolic diseases (IMD) is a rare life-threatening condition with a poor prognosis. Early intervention may be lifesaving. To describe clinical presentation, investigation and outcomes of ALF related to IMD in young children. Retrospective review of the medical records of children aged up to 24 months, admitted to a tertiary pediatric and neonatal Intensive Care Unit during a 27-year period, fulfilling the ALF criteria, with documented metabolic etiology. From 34 ALF cases, 18 were related to IMD: galactosemia (4), mitochondrial DNA depletion syndrome (MDS) (3), ornithine transcarbamilase deficiency (3), congenital defects of glycosylation (2), tyrosinemia type 1 (2), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1), hereditary fructose intolerance (1), classic methylmalonic aciduria (1) and citrulinemia type 1 (1). The median age was 1.3 months. At least one previous suggestive sign/symptom of IMD (vomiting, failure to thrive, hypotonia or developmental delay) was observed in 67% of the cases. The most common physical signs at admission included: hepatomegaly (72%), jaundice (67%) and encephalopathy (44%). The peak laboratorial findings were: mean international normalizad ratio 4.5, median lactate 5mmol/L, mean bilirubin 201μmol/L, median alanine aminotransferase (ALT) 137 UI/L and median ammonia 177μmol/L. One patient was submitted to liver transplant in ALF context (MSD). The mortality rate was 44%. The identification of IMD as a frequent cause of ALF allowed specific therapeutic measures and adequate family counselling. Particular clinical features and moderated ALT and bilirubin levels can lead to its suspicion.

Predictive formula of coma onset and prothrombin time to distinguish patients who recover from acute liver injury.

Acute liver failure (ALF) is defined as acute liver injury (ALI) associated with coagulopathy. A follow-up strategy for ALI and characterization of ALI patients with a risk of progressing to ALF have never been established. To establish predictive markers for progression from ALI to ALF, this study compared the clinical characteristics and laboratory data on the day of registration to data from a regional referral system of patients with ALI. This prospective, observational study enrolled 365 consecutive patients with ALI/ALF between 2007 and 2016. We evaluated 109 ALI patients, 27 of whom satisfied the ALF criteria during observation and another 82 patients who recovered without progression to ALF. Four patients died; all were in the ALF group. The variables of age, incidence of autoimmune hepatitis, model of end-stage liver disease score, values for total bilirubin and prothrombin time (PT)-international ratio, and Japan Hepatic Encephalopathy Prediction Model (JHEPM) probability at registration were significantly higher in ALF patients than in ALI patients. In multivariate analysis, PT and JHEPM were identified as risk factors for progression to ALF. The cut-off values of 13%, 4.9%, 65%, and 1.32% for the model of end-stage liver disease score, JHEPM probability, PT, and PT-international ratio values, respectively, had high negative predictive values. Furthermore, among patients whose JHEPM was underestimated, none died due to ALF. The JHEPM probability is a predictive parameter that can be used to decide a follow-up treatment strategy for ALI patients.

Drug-induced acute liver failure in children and adults: Results of a single-centre study of 128 patients.

Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analysed the predictors of mortality and their relationship with MELD, King's College criteria (KCC) and ALFSG prognostic index. We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017). RUCAM was used for case adjudication. Patients who fulfilled criteria for acute liver failure and drug-induced liver injury were included. Primary outcome measure was spontaneous survival or death. There were 128 cases of DIALF (14%) among 905 patients with DILI. Mean age was 38years, 68 (53%) female and 21(16.4%) children <18years. Combination anti-TB drugs (ATD) (n=92, 72.4%) accounted for a majority of DIALF. Others were anti-epileptic drugs (AED, n=11, 10%), dapsone (n=7, 5.5%), hormones (n=2), ferrous sulphate overdose (n=2), acetaminophen (APAP) (n=2), antiretroviral (n=2), CAM (N=2), chemotherapy agents (N=3), amoxicillin-clavulanic acid (n=2) and others (n=3). Forty-four patients (34%) recovered spontaneously and 84(66%) including 13 children (62%) died. Females, ascites, albumin, bilirubin, INR and MELD were significantly associated with mortality. Mortality was 79% for ATD and 100% for APAP and iron overdose. Area under ROC was 0.76 for MELD and ALFSG index and 0.51 for KCC. Fourteen percent of DILI resulted in DIALF. ATD, AED, dapsone and antiretroviral drugs are most common agents. Spontaneous survival was only 34% with an even higher mortality with ATD. Non-ATD and non-APAP drugs had a better survival (51%).INR and MELD predicted mortality.