ArticleThe American journal of gastroenterology2018
Acute Liver Failure of Indeterminate Etiology: A Comprehensive Systematic Approach by An Expert Committee to Establish Causality.
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Article in The American journal of gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48citing papers in PubMed
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48 citing papers in PubMed, 94 citations in OpenAlex.
- Role of viral and host factors in determining the outcome of HBV-associated acute liver failure.Journal of translational medicine · 2026Article
- Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers.The American journal of gastroenterology · 2026Article
- Non hepatotropic virus induced hepatitis - rising importance in a changing world.World journal of virology · 2025Review
- Acute Liver Failure with Determinate rather than Indeterminate Etiology Facilitates Therapy and May Avoid Liver Transplantation: A Critical Analysis.Journal of clinical and translational hepatology · 2025Review
- Does Prior Bariatric Surgery Predispose to Acetaminophen-Related Acute Liver Failure?Clinical and translational gastroenterology · 2025Article
- Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing.Viruses · 2025Article
- Integrated cross-linking by TG2 and FXIII generates hepatoprotective fibrin(ogen) deposits in injured liver.Blood · 2025Article
- Demonstration of Hepatic Vein Abnormalities Using Contrast-Enhanced Sonography in Liver Diseases.Diagnostics (Basel, Switzerland) · 2025Review
- Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure.The American journal of gastroenterology · 2025Observational
- Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN).Hepatology international · 2024Review
- Acute presentation of autoimmune hepatitis -from acute hepatitis to ALF and ACLF.Hepatology international · 2024Review
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- Whole-exome sequencing for genetic diagnosis of idiopathic liver injury in children.Journal of cellular and molecular medicine · 2024Article
- A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2024Article
- [Advancements in the diagnosis and treatment of pediatric acute liver failure].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- Indeterminate etiology of acute liver failure in North America: Less common, still grave prognosis.Clinical transplantation · 2023Article
- Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.Open forum infectious diseases · 2023Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Daniel R GangerDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jody RuleDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jorge RakelaDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nathan BassDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
A ReubenDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
R T StravitzDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Norman SussmanDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Anne M LarsonDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Laura JamesDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Charles ChiuDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
William M LeeDepartment of Medicine, Division of Gastroenterology and Hepatology, Northwestern university Feinberg School of Medicine, Chicago, IL, uSA. Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA. Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA. Department of Medicine, UCSF San Francisco, San Francisco, CA, USA. Medical University of South Carolina, Charleston, SC, USA. Section of Hepatology Virginia Commonwealth University, Richmond, VA, USA. Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA. Hepatology and Liver Transplantation, University of Washington, Seattle, WA, USA. Section of Pediatric Pharmacology and Toxicology, Arkansas Children's Hospital and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Acute Liver Failure Study Group
Northwestern University · USMayo Clinic in Arizona · USMedical University of South Carolina · US
Funding
Adduct Dipstick for Diagnosis of Acetaminophen ToxicityR42DK079387 · NIDDK · ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC · PI JAMES, LAURA PHILLIPS · 2011 to 2018
$4.4MNIDDK NIH HHS R42 DK079387
Abstract
objectivesIn the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases.
methodsSpecific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide liver biopsy and/or explant reports and to update serological findings not reported previously.
resultsNearly half (142, 46.9%) of the 303 IND-ALF cases could be reassigned to a single, defined etiology and rated as highly likely or probable; 11 additional cases, upon review, did not meet ALF criteria. Amongst reassigned etiologies, 45 were previously unrecognized APAP, 34 autoimmune hepatitis (AIH), 24 drug-induced liver injury (DILI), 13 various viral causes, 12 ischemia, and 14 miscellaneous other etiologies. The remaining 150, deemed true IND-ALF, represented just 5.5%.
conclusionsThe indeterminate etiology in ALF includes patients with a diagnosis that is discernible after closer examination. Revision of etiologic diagnoses of indeterminate cases using added testing and expert opinion is useful in understanding all aspects of ALF.
Indexed as
AcetaminophenAdolescentAdultAgedAged, 80 and overAlgorithmsChemical and Drug Induced Liver InjuryDNA, ViralFemaleHepatitis, AutoimmuneHepatitis, Viral, HumanHepatitis VirusesHigh-Throughput Nucleotide SequencingHumansLiver Failure, AcuteMaleAcetaminophenDNA, ViralRNA, Viral
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