Evolution of Hepatitis A-Related Acute Liver Failure in North America Over 22 Years.

Hepatitis A virus (HAV) is a rare cause of acute liver failure (ALF) that carries a relatively good prognosis for recovery. In recent years, overall numbers of HAV cases have declined, likely due to increased hepatitis A vaccination rates. We reviewed the Acute Liver Failure Study Group registry for the number HAV-related ALF cases over 24 years.

Assessment of Hemophagocytic Lympho-Histiocytosis (HLH) in the Setting of Adult Acute Liver Failure.

Hemophagocytic lympho-histiocytosis (HLH) is a life-threatening disease, only occasionally presenting as acute liver failure (ALF) in adults. HLH is challenging to diagnose. We reviewed the ALF Study Group (ALFSG) registry for suspected HLH subjects, as well as 184 with other ALF etiologies for cases that might have been missed, assessing standard laboratory tests, as well as interleukin-18 (IL-18) and soluble interleukin-2 receptor (sIL-2r), to determine the diagnostic utility of these biomarkers.

Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers.

Introduction: In acute liver failure due to Wilson disease (ALF-WD), early and correct diagnosis is critical. Readily available biochemical parameters, e.g.

Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing.

Clinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver disease and identified eight contigs that could not be annotated.

Does Prior Bariatric Surgery Predispose to Acetaminophen-Related Acute Liver Failure?

Introduction: Prior small studies have suggested that patients with prior metabolic and bariatric surgery (MBS) may have increased susceptibility to acetaminophen (APAP)-related acute liver failure/acute liver injury (ALF/ALI). The aim of this study was to compare the presentation, etiology, and outcome of adult ALI/ALF patients who were enrolled in a prospective registry study with prior bariatric surgery to those without.

Methods: Among 3,364 ALF/ALI patients in the Acute Liver Failure Study Group registry enrolled between January 1998 and August 2019, 85 (2.

Clinical and pathological spectrum of disease severity among patients with acute liver failure (ALF) undergoing deceased donor liver transplantation.

Listing and transplanting patients with acute liver failure (ALF) is challenging, requiring rapid assessment of the likelihood of recovery. The availability of a large number of ALF liver explants, along with their clinical data, afforded an opportunity to retrospectively evaluate liver transplantation (LT) decision-making. We hypothesized that, with the benefit of hindsight, a small number of patients might have recovered without LT.

Serum proteomics of adults with acute liver failure provides mechanistic insights and attractive prognostic biomarkers.

Background & Aims: Acute liver failure (ALF) is defined as rapid onset coagulopathy and encephalopathy in patients without a prior history of liver disease. We performed untargeted and targeted serum proteomics to delineate processes occurring in adult patients with ALF and to identify potential biomarkers.

Methods: Sera of 319 adult patients with ALF (∼50% acetaminophen [APAP]-related cases) were randomly selected from admission samples of the multicenter USA Acute Liver Failure Study Group consortium and subdivided into discovery/validation cohorts.

The endothelial growth factor Angiopoietin-2 is an accurate prognostic biomarker in patients with acetaminophen-induced acute liver failure.

Background And Aims: Acetaminophen (APAP) overdose is the leading individual cause of acute liver failure (ALF) in the United States, with many patients rapidly progressing to hyperacute liver failure. While hepatocytes are the main target of APAP toxicity, endothelial cells (ECs) are also affected. However, the efficacy of an endothelial-specific biomarker to predict patient outcomes remains unknown.

Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.

Background And Aims: Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.

Ammonia and urea metabolism in acute liver failure: A multicentre cohort study.

Background & Aims: Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied.

Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure.

Introduction: Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. The use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF.

The chemokine CXCL14 is a novel early prognostic biomarker for poor outcome in acetaminophen-induced acute liver failure.

Background And Aims: Patients with acetaminophen-induced acute liver failure are more likely to die while on the liver transplant waiting list than those with other causes of acute liver failure. Therefore, there is an urgent need for prognostic biomarkers that can predict the need for liver transplantation early after an acetaminophen overdose.

Approach And Results: We evaluated the prognostic potential of plasma chemokine C-X-C motif ligand 14 (CXCL14) concentrations in patients with acetaminophen (APAP) overdose (n=50) and found that CXCL14 is significantly higher in nonsurviving patients compared to survivors with acute liver failure ( p < 0.

Indeterminate etiology of acute liver failure in North America: Less common, still grave prognosis.

Background: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND-ALF). In this study, we summarize findings from patients with IND-ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND-ALF.

Future directions in acute liver failure.

Acute liver failure (ALF) describes a clinical syndrome of rapid hepatocyte injury leading to liver failure manifested by coagulopathy and encephalopathy in the absence of pre-existing cirrhosis. The hallmark diagnostic features are a prolonged prothrombin time (ie, an international normalized ratio of prothrombin time of ≥1.5) and any degree of mental status alteration (HE).

Declining rates of opioid/acetaminophen combination product overdose: 2011-2020.

Background: During the opioid epidemic, misuse of acetaminophen-opioid products resulted in supratherapeutic acetaminophen ingestions and cases of hepatotoxicity. In 2014, the US Food and Drug Administration (FDA) limited the amount of acetaminophen in combination products to 325 mg, and the US Drug Enforcement Administration (DEA) changed hydrocodone/acetaminophen from schedule III to schedule II. This study assessed whether these federal mandates were associated with changes in acetaminophen-opioid supratherapeutic ingestions.

Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival.

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

Background And Aims: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America.

Changes in Epidemiology of Acetaminophen Overdoses in an Urban County Hospital After 20 Years.

Introduction: Acetaminophen (APAP) toxicity is the main cause of acute liver failure in the United States. A prior series (1992-1995) identified 71 hospitalized adults with APAP toxicity through the International Statistical Classification of Disease and Related Health Problems, 9th revision (ICD-9) code at Parkland Hospital, Dallas, TX.

Methods: We used a laboratory database search of serum APAP levels from 2011 to 2015 to identify patients with APAP toxicity in the same hospital.

Whole Exome Sequencing Reveals Genetic Variants in HLA Class II Genes Associated With Transplant-free Survival of Indeterminate Acute Liver Failure.

Introduction: Indeterminate acute liver failure (IND-ALF) is a rare clinical syndrome with a high mortality rate. Lacking a known etiology makes rapid evaluation and treatment difficult, with liver transplantation often considered as the only therapeutic option. Our aim was to identify genetic variants from whole exome sequencing data that might be associated with IND-ALF clinical outcomes.

Role of Hepatitis C Infection in Acute Liver Injury/Acute Liver Failure in North America.

Background: While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF.

Methods: From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.

Hepatic recruitment of eosinophils and their protective function during acute liver injury.

Background & Aims: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

Methods: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining.

Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry.

Introduction: Idiosyncratic drug-induced liver injury (DILI) is the second leading cause of acute liver failure (ALF) in the United States. Our study aims were to characterize secular trends in the implicated agents, clinical features, and outcomes of adults with DILI ALF over a 20-year period.

Methods: Among 2,332 patients with ALF enrolled in the ALF Study Group registry, 277 (11.

Hypophosphatemia in acute liver failure of a broad range of etiologies is associated with phosphaturia without kidney damage or phosphatonin elevation.

Hypophosphatemia is a common and dangerous complication of acute liver failure (ALF) of various etiologies. While various mechanisms for ALF-associated hypophosphatemia have been proposed including high phosphate uptake into regenerating hepatocytes, acetaminophen (APAP)-associated hypophosphatemia was linked to renal phosphate wasting, and APAP-induced renal tubular injury was proposed as underlying mechanism. We studied 30 normophosphatemic and 46 hypophosphatemic (serum phosphate < 2.

Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure.

Background And Aims: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival.

Approach And Results: A total of 200 patients were recruited from sites of the ALF Study Group.