Etiology Of Acute Liver Failure Research Articles

S2420 A Rare Case of Fluconazole-Induced Fulminant Hepatic Failure

INTRODUCTION: There are many well-known etiologies of acute liver failure. In the United States, DILI is the most common cause of fulminant hepatic failure1. Fluconazole is an antifungal medication that is frequently prescribed in the outpatient setting. Common side effects include vomiting, diarrhea, and headache. Here, we present a rare case of fluconazole induced acute liver failure. CASE DESCRIPTION/METHODS: An 80-year-old male with a history of prostate cancer presented to his PCP with complaints of worsening fatigue for several days. He had associated symptoms of fevers, decreased appetite, weight loss, and dark urine. His PCP, who noted his LFTs to be abnormal (Table 1), advised him to seek medical attention. On arrival to the ED, the patient reported having "sensitivity" in his hands and fingers for two months prior to arrival. He was seen by his dermatologist, who prescribed him Fluconazole 200 mg weekly. The medication was stopped after three doses due to development of a rash on bilateral hands and trunk, with the last dose being one-week prior to arrival. A thorough evaluation to exclude other causes was performed. Imaging demonstrated benign hepatic cysts largest measuring 3 cm but no findings of chronic liver disease. Over his hospital course, his condition worsened with the development of hepatic encephalopathy requiring intubation, coagulopathy, and acute renal failure (fulminant liver failure). Figure 1 demonstrates the trend in liver enzymes over the hospital stay. He was not a candidate for liver transplantation due to active cancer. Ultimately, his family withdrew support, and the patient passed away. DISCUSSION: Azole antifungal induced liver injury is largely asymptomatic and associated with mild LFT elevation. Overt liver failure and death occurs in less than 1% of this population2,3. One study found that users of fluconazole with a history of chronic liver disease had higher rates of severe acute liver injury than users of azole drugs without underlying chronic liver disease4. Few cases of fulminant liver failure in patients without underlying liver disease have been reported. Fluconazole is a commonly prescribed medication. It is important to be aware of the risk of liver injury in patients on antifungal azole medications. Further investigation is needed to ascertain the correlation of liver toxicity of fluconazole in patients without underlying liver disease.Figure 1.: Linear depiction of our patient's liver enzymes during hospitalization.Table 1.: Comprehensive metabolic panel on patient's admission.Table 2.: Coagulation studies on admission and nine days following admission.

THU181 - Hasi-iquest: investigating viral etiologies of acute liver failure of unknown cause

THU181 - Hasi-iquest: investigating viral etiologies of acute liver failure of unknown cause

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Aetiology, Clinical Profiles, Laboratory Profile, Outcome and Prognostic Factors of Pediatric Acute Liver Failure: Experience at a Tertiary Hospital of Bangladesh

Introduction: Acute liver failure is one of the common causes of death in pediatric gastroenterology and hepatology department. Outcome is different according to aetiology.
 Objective: To observe the aetiology, outcome and prognostic factors of pediatric acute liver failure.
 Methods: Consecutive 62 children aged 2 to 16 years of age who were diagnosed as acute liver failure from November 2015 to April 2018 were included in this study. All the clinical profiles, laboratory data and outcome were recorded in a preformed data sheet. Data were analysed by SPSS for Windows version 20.
 Results: Mean age was 8.5 years. Thirty-nine (62.9%) patients were between 5-10 years of age. Male were 53%. We made a diagnosis of 39 (63%) patients as Wilson disease alone, Another 3 Wilson disease acute liver failure patients had concomitent with either HAV, HEV or HSV in each one. HAV only was responsible for 17 patients and HEV for 1. One patient was Haemophagocyic lymphohistiocytosis and aetiology could not be identified in 1 patient. The overall death in study population was 48% (30). Twenty-four (57%) of 42 acute liver failure patients due to Wilson disease had died. Five (29%) of 17 patients due to HAV infection and 1 patient with HLH died. Ascites, high total bilirubin, high INR and etiology like Wilson disease were the worse pronostic factors for outcome of acute liver failure in children.
 Conclusion: Wilson disease was the most common aetiology of acute liver failure in children in this study. Early diagnosis is essential as outcome was worse. Majority of viral etiology improved with supportive care.
 Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 56-61

Whole Exome Sequencing Among 26 Patients With Indeterminate Acute Liver Failure: A Pilot Study.

INTRODUCTION:The etiology of acute liver failure (ALF) remains an important prognostic factor. The Acute Liver Failure Study Group recently reported that 150 of 2,718 adult patients with ALF (5.5%) had an indeterminate etiology. Our aim was to use whole exome sequencing to identify genetic variants associated with phenotypic, biochemical, and histologic features among patients with indeterminate ALF.METHODS:This effort has defined a cohort of well-pedigreed patients with indeterminate ALF; DNA samples extracted from whole blood samples were obtained from 26 respective patients with indeterminate ALF. These samples were kept at the Acute Liver Failure Study Group repository at the NIDDK, Bethesda. Whole exome sequencing and bioinformatics analysis were performed at the Mayo Clinic Center of Individualized Medicine in Rochester, MN.RESULTS:Of the 26 patients, 8 survived spontaneously, 6 died, and 12 underwent a liver transplantation; all those transplanted were alive at 21 days after enrollment in the study. Twenty-two of the 26 patients presented as ALF. We found 12 variants associated with 11 genes. The most common variant was rs4940595 in the SERPINB11 gene which was found in 23 of the 26 patients. This variant had a stop codon; no reports of disorders have been associated with this variant. The next most commonly found variant was rs1135840 in the CYP2D6 gene; this mutation is a missense_variant and has been reported to be associated with hepatotoxicity of antituberculous therapy. None of our patients were receiving this therapy. We also found a significant asymmetric distribution of rs1800754 of the CYP2D7 gene and rs1135840 of the CYP2D6 gene between patients who survived spontaneously (75%) and those who died or underwent liver transplantation (30.5% and 25%, respectively).DISCUSSION:We found 12 variants of 11 genes significantly associated with ALF among adults with indeterminate etiology. We also found a significant asymmetric distribution of 2 variants belonging to the CYP2D7 and CYP2D6 genes, respectively, between those who survived spontaneously and those who died or underwent liver transplantation. The 2 most common variants, rs4940595 and rs1135840, of the SERPINB11 and CYP2D6 genes, respectively, found in our patients with ALF have been described as potentially important in the adaptive response combating the emergence of infectious diseases and associated with hepatotoxicity of antituberculous therapy, respectively. Our findings need to be expanded to include more patients with indeterminate ALF as well as viral, drug toxicity, and autoimmune etiologies to determine whether our findings are associated with the specific etiology, indeterminate, or with the overall ALF syndrome itself.

2359 Acute Liver Failure in the Setting of HSV-Induced Hemophagocytic Lymphohistiocytosis

INTRODUCTION: Acute liver failure (ALF) is characterized by acute (< 26 weeks) liver injury, encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without a preexisting liver disease carries a poor prognosis1. Common etiologies of ALF include acetaminophen toxicity, sepsis, and toxin exposure2. Here, we present a rare case of ALF secondary to HSV-induced Hemophagocytic lymphohistiocytosis (HLH). CASE DESCRIPTION/METHODS: A 57-year old male with a history of hypertension presented with a week history of cough and fever. Review of systems also included fatigue, decreased appetite, and decreased interactiveness. Labs were remarkable for anemia, thrombocytopenia (plt 15,000), tranaminitis (AST/ALT 6943/1551), ferritinemia (>105,000 ng/mL) and hypofibrinogenemia (134 mg/dL). Workup for causes of ALF was unrevealing, including acetaminophen, viral hepatitis, Wilson Disease, and autoimmune hepatitis. Blood and urine cultures, respiratory viral PCR, Adenovirus PCR, HIV Ab/Ag, Lyme IgM/IgG, ANA and RF were negative. HSV and EBV antibodies were collected early in admission. A CT Chest was unremarkable and a CT abdomen showed diffuse hepatic hypo-attenuation. His course was complicated by hypothermia, hypotension, and unresponsiveness prompting intubation and admission into the ICU. He was started on broad spectrum antibiotics as well as high dose steroids. His clinical status continued to deteriorate after-which his family requested comfort care measures. Postmortem autopsy demonstrated hepatomegaly with HSV hemorrhagic and necrotic hepatitis resulting in confluent non-zonal hepatic necrosis, as well as splenomegaly. Postmortem his HSV IgM (type 1 and 2) was not detected. His serum EBV IgM and IgG elevated with PCR showing 2246 copies/mL. DISCUSSION: This was a case of ALF due to suspected HSV-induced HLH. In review of the literature, only one other case study has reported ALF in the setting of HSV-induced HLH3. The diagnosis of HLH clinically requires 5/8 criteria [Table 1]4. Our patient met five of eight criteria for HLH. Notably, both EBV and HSV have been strongly implicated as potential triggers for HLH5. Although primary liver disease and HLH can present in a similar fashion, HLH tends to incorporate more extensive organ involvement, cytopenias, extremely high ferritin, and neurologic findings. Our case a rare precipitating cause of ALF, highlighting the importance of considering HSV-induced HLH early in the course of newly diagnosed ALF given their rapid deterioration.

Multiplex qPCR facilitates identification of betaherpesviruses in patients with acute liver failure of unknown etiology

BackgroundThe etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily.MethodsLiver explant and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated.ResultsBetaherpesviruses infection was effectively detected using multiplex qPCR. Six (22%) HHV-6, one (3%) HCMV and two (7%) dual infections (one with HHV-7/HHV-6, and the other with HHV-7/ HCMV). Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values> 1.5 were determined in all betaherpesvirus-positive patients.ConclusionsMultiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver explant and serum samples were positive for some betaherpesviruses, and coinfection of HHV-7 with HHV-6 and HCMV was additionally detected. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.

The global epidemiology of viral-induced acute liver failure: a systematic review protocol

IntroductionThe burden of viral-induced acute liver failure (ALF) around the world still remains unclear, with little to no data collected regarding the disease incidence in general and synthesised data on...

Epidemiology and outcomes of acute liver failure in Australia.

BACKGROUNDAcute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain.AIMTo describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia.METHODSThe database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001.RESULTSParacetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively.CONCLUSIONParacetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.

Liver transplantation in adults with acute liver failure: Outcomes from the Argentinean Transplant Registry

Introduction and aimLiver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. Material and methodsData were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998–2005 and 2006–2016). We used survival analysis to evaluate risk of death. ResultsA total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02–1.36] and serum creatinine (HR 1.31 [1.01–1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06–2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36–1.05]). ConclusionsSurvival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.

N-Acetylcysteine (NAC) for the Prevention of Liver Failure in Heat Injury-Mediated Ischemic Hepatitis.

Exertional Heat Illness with associated ischemic hepatitis (IH) is a common occurrence among military trainees; however, few specific therapies exist if unresponsive to appropriate supportive measures. A 27-year-old basic combat trainee presented with altered mental status, renal insufficiency, rhabdomyolysis, and a core temp of 107.9 °F after collapsing during a run, leading to the diagnosis of heat stroke. While the patient's azotemia and creatinine kinase levels rapidly improved with aggressive intravenous hydration, transaminases continued to increase to nearly 155 times the upper limit of normal. Further laboratory evaluation revealed coagulopathy and thrombocytopenia suggestive of acute liver failure (ALF). On hospital day three, the patient was started on N-acetylcysteine (NAC). Evaluation for infectious and autoimmune etiologies of ALF was unremarkable; thus, the patient's symptomatology was attributed to IH resulting from heat stroke. Liver function normalized on NAC. Heat Injury is common among US Army recruits and results in thousands of hospitalizations in recent years. IH is characterized by diffuse hepatocyte necrosis following an episode of hemodynamic instability, and is an established sequela of Heat Injury. The mortality of IH among critically ill patients has been estimated to be as high as 60%, with those demonstrating coagulopathy especially at risk. NAC is shown to improve the transplant-free survival rate in non-acetaminophen related ALF, consistent with its proposed mechanisms of improving hepatic blood flow and conjugating toxic metabolites. NAC therapy should be considered early in the course of heat injury-mediated IH to reduce reperfusion injury, improving transplant free outcomes.

Role of formalin fixed paraffin embedded liver tissues in the diagnosis of viral hepatitis E in patients with undiagnosed acute liver failure.

Viral hepatitis E is gaining importance as an emerging worldwide disease. Though viral hepatitis E (HEV) has been attributed as an etiology of acute liver failure (ALF), however its actual incidence and the immunopathogenesis are being under explored. The present study is aimed at detecting HEV in post mortem liver tissues of patients with undiagnosed ALF. Twenty six liver tissues of ALF patients died of unknown etiology are subjected to nested reverse transcriptase PCR with HEV ORF1 gene targeted primers and HEV RNA is detected in 30.4% (7/23) of ALF cases. Out of seven HEV RNA positive cases, three (42.8%) had HEV antigen positivity by immunohistochemistry on liver tissues using HEV ORF2 antibody. Histopathological examination by H&E staining shows multiacinar confluent hepatic necrosis, bile ductular proliferation, bridging hepatic and periportal necrosis in 4, 4, 2 and 1 cases respectively. The isolates were sequenced using RdRp gene specific primers and found to HEV genotype-1. Quantitative TaqMan real time PCR estimated the viral load ranged between 7.77 × 103 and 1.44 × 107 viral copies/µl. HEV has been associated with 30.4% (7/23) of undiagnosed ALF cases. Immuno-histochemistry along with molecular testing in FFPE biopsies might be useful for the detection of HEV in undiagnosed cases.

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.

Treatment of acute liver failure in children

Acute liver failure (ALF) is a syndrome defined by the ra­pid decline of hepatic function, jaundice, coagulopathy (INR>1.5) and hepatic encephalopathy in patients with no evi­dence of previous liver disease. In children, the etiology of ALF is different, depending on age, and is associated with a high mortality, despite optimal medical therapy. The treat­ment for children with ALF will be directed to maintain vital functions, to prevent and treat the complications or against the etiologic agent when it is known. The the­ra­peu­tic measures consist in stabilizing the child by the administration or adjustment of liquids, vasoactive me­di­ca­tion or respiratory support if necessary, the treatment of encephalopathy through measures to reduce the am­monia in the blood, correction of hypoglycemia or hydroelectrolytic imbalances, the treatment of hemorrhage and coagulopathy. Specific treatment can be life-saving if the etiology is known, and includes administering anti­dots in toxic ALF, antivirals or antibacterial medication in infectious causes, immunosuppressive therapy in au­to­im­mune hepatitis, cooper chelators in Wilson disease, or specific diets in metabolic disorders. In severe ALF in chil­dren, extracorporeal methods (hemodiafiltration, plas­ma exchange or hepatic dialysis) may be used, but the only therapeutic option remains emergency liver trans­plan­ta­tion. The management of these cases requires a multi­dis­ci­pli­na­ry team, involving pediatric hepatologist, critical care spe­cia­list, nephrologist, or liver transplant surgeon.

Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group.

Changes in levels of cytokines and chemokines have been proposed as possible biomarkers of tissue injury, including liver injury due to drugs. Recently, in acute drug-induced liver injury (DILI), we showed that 19 of 27 immune analytes were differentially expressed and that disparate patterns of immune responses were evident. Lower values of serum albumin (< 2.8 g/dL) and lower levels of only four analytes, namely, IL-9, IL-17, PDGF-bb, and RANTES, were highly predictive of early death [accuracy = 96%]. The goals of this study were to assess levels of the same 27 immune analytes in larger numbers of subjects to learn whether the earlier findings would be confirmed in new and larger cohorts of subjects, compared with a new cohort of healthy controls. We studied 127 subjects with acute DILI enrolled into the US DILIN. We also studied 118 subjects with severe acute liver injury of diverse etiologies, enrolled into the ALF SG registry of subjects. Controls comprised 63 de-identified subjects with no history of liver disease and normal liver tests. Analytes associated with poor outcomes [death before 6 months, n = 32 of the total of 232 non-acetaminophen (Apap) subjects], were lower serum albumin [2.6 vs 3.0 g/dL] and RANTES [6,458 vs 8,999 pg/mL] but higher levels of IL-6 [41 vs 18], IL-8 [78 vs 48], and MELD scores [30 vs 24]. Similar patterns were observed for outcome of death/liver transplant within 6 months. A model that included only serum albumin < 2.8 g/dL and RANTES below its median value of 11,349 had 83% (or 81%) accuracy for predicting early death (or early death/liver transplant) in 127 subjects from DILIN. No patterns of serum immune analytes were reflective of the etiologies of acute liver failure, but there were cytokine patterns that predicted prognosis in both acute DILI and ALF.

Acute Liver Failure.

Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. This article focuses on the diagnosis and management of ALF. We provide a detailed review of the common etiologies of ALF, including acetaminophen overdose, viral hepatitis, drug-induced liver injury, Wilson's disease, and autoimmune hepatitis. The article then addresses how to recognize ALF and reviews the role of common laboratory and imaging tests in establishing this diagnosis. The remainder of the article details the management of hepatic and extrahepatic organ dysfunctions in ALF. The article concludes with a discussion regarding the prognostication of patients with ALF and the criteria for considering liver transplantation.

Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases.

The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.

Drug idiosyncrasy due to pirfenidone presenting as acute liver failure: Case report and mini-review of the literature.

Idiosyncratic drug‐induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant‐free survival. Pirfenidone is an anti‐inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini‐review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF. A 77‐year‐old man with known Parkinson's disease and IPF presented with jaundice for 7 days and altered mental status for 4 days. His long‐term medications included a levodopa/carbidopa combination with a recent addition of pirfenidone over the previous 1 month; there was no monitoring of liver function tests. The evaluation suggested features of acute liver failure with grade III hepatic encephalopathy, acute kidney injury, and metabolic acidosis. The diagnostic workup ruled out viral, toxic, ischemic, and other etiologies for acute liver failure. Based on a Roussel Uclaf Causality Assessment Method score of 7 and possible DILI‐ALF, pirfenidone was withdrawn. He was evaluated for liver transplantation but was declined. Despite all supportive measures in intensive care, organ failure progressed and he succumbed to the illness on day 4. Postmortem liver biopsy revealed findings consistent with DILI (final Roussel Uclaf Causality Assessment score, 10). Conclusion: DILI‐ALF carries poor prognosis, and liver transplantation should be considered early in the course. Characterization, reporting, monitoring, and labeling of pirfenidone‐related hepatotoxicity is vital given its common use in IPF. (Hepatology Communications 2018;2:142–147)

Pericardial Tamponade: A Rare Etiology of Acute Liver Failure

Acute liver failure is defined as severe hepatic injury within 26 weeks of an insult without prior cirrhosis or liver disease. Criteria for diagnosis include both synthetic liver dysfunction (INR>1.5) and hepatic encephalopathy. Acute liver failure has an annual incidence of 2000 cases in the United States and a mortality approaching 50%. Here we report acute liver failure as the presenting syndrome for pericardial tamponade. A 57-year-old man with refractory paroxysmal atrial fibrillation and no history of hepatic disease presented to an outside hospital with progressive non-bloody, non-bilious emesis. The patient underwent an unsuccessful left atrial hybrid maze procedure 3 weeks prior. Over his 5-day hospitalization, he was treated with anti-emetics for presumed gastroenteritis. However, routine exam and labwork revealed progressive mental status changes, increases in AST/ALT to 938/1000 mg/dL, and an INR of 4.1 - all of which were normal on admission. Given these findings and concern for acute liver failure, the patient was transferred to our hospital for further evaluation. Upon arrival, the patient was afebrile, pulse 87 bpm, and blood pressure of 96/69 mmHg. Physical exam was notable for somnolence, asterixis, scleral icterus, elevated jugular venous distention, and a distended abdomen. Laboratory studies confirmed elevated AST/ALT and INR. Viral and autoimmune hepatitis serologies were unremarkable. Abdominal ultrasound with doppler demonstrated normal hepatic contour with no venous thrombosis. Chest radiograph revealed a globular cardiac silhouette and a trans-thoracic echocardiogram revealed a pericardial effusion with evidence of hemodynamic compromise. A pericardial drain was placed, removing 700 mL of hemorrhagic fluid from the pericardial sac. Within 3 days, the patient's mental status, synthetic function, and hepatic indices improved, remaining stable on outpatient follow-up. This case highlights a rare etiology of acute liver failure. The patient developed pericardial tamponade, an infrequent but known complication of a hybrid maze procedure. The pericardial tamponade led to the development of poor forward flow, right-sided venous congestion, an ultimately hepatic ischemia. Ischemic etiologies of acute liver failure can occur in >50% of cases without a documented hypotensive event, which likely occurred in our patient. This case highlights how clinicians must remain vigilant for rare manifestations of highly mortal diseases.

Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.