Table 1.

Characteristics of included studies

Study	Study design	Aim	Country	Income level	Start of data collection	End of data collection	ALF case definition
Alam et al, 200916	Prospective cohort	To evaluate the aetiology, complications and outcome of FHF	Bangladesh	Lower middle	3 Nov	8 May	Occurrence of hepatic encephalopathy within 8 weeks of onset of jaundice in patients with no previous liver disease and the presence of coagulopathy as proved by a PT>15 s or INR>1.5
Asim et al, 200917	Cross sectional	To analyse serum samples from patients with ALF for hepatitis A-G viral markers	India	Lower middle	1 Jun	4 May	Patient become deeply jaundiced and went into hepatic encephalopathy within 8 weeks of onset of the disease, with no history of chronic hepatitis
Bechmann et al, 201418	Retrospective cohort	To identify currently predominant aetiologies of ALF at a transplant centre	Germany	High	1 Jan	12 Feb	Acute Liver Failure Study Group Germany case definition: INR>1.5 and encephalopathy of any grade. Pre-existing liver disease and systemic cause of liver failure were excluded
Bhatia et al, 201319	Prospective cohort	To analyse clinical features, liver function tests, hepatitis viral markers and clinical outcomes in patients with ALF	India	Lower middle	Jun 99	1 Jan	Development of hepatic encephalopathy within 26 weeks of the first symptoms of acute hepatitis-like illness without any history of underlying liver disease
Borkakoti et al, 201320	Prospective cohort	To determine the viral load of HEV and its association with the disease severity in patients with ALF in comparison with patients with ALF due to other hepatides	India	Lower middle	6 Jan	11 Dec	Development of encephalopathy within 8 weeks of the onset of jaundice without any history of chronic liver disease; diagnosed as a self-limiting disease and a serum aspartate aminotransferase elevation of at least fivefold or clinical jaundice or both
Bravo et al, 201221	Prospective and retrospective cohort	To investigate the aetiology, outcomes and incidence of AHF among children 0–18 years old	Philippines	Lower middle	Jan 00	6 Dec	Onset of coagulopathy and/or encephalopathy ≤4 weeks after the onset of symptoms, a prothrombin time >2, an increased bilirubin and evidence for liver failure complicated by encephalopathy
Cervio et al, 20113	Retrospective cohort	To investigate the impact of HAV UI on the trends in the occurrence of FHF in children	Argentina	High	Mar 93	5 Jul	Mieli-Vergani case definition: a multisystem disorder in which severe impairment of liver function, with or without encephalopathy, occurs in association with hepatocellular necrosis in a patient with or without recognised underlying chronic liver disease22
Das et al, 201623	Prospective cohort	To determine the profile of ALF etiologies	India	Lower middle	7 Jan	15 Dec	History of development of encephalopathy within 8 weeks of disease onset
Gupta et al, 201524	Retrospective cohort	To determine the profile of hepatitis A, B, C and E as a cause of AHF in children in a tertiary care hospital	India	Lower middle	11 Jan	14 Dec	Elevated ALT levels or AST of at least fivefold with clinical jaundice and without evidence of chronic liver disease. Patients who had INR>1.5 with encephalopathy or INR>2 without encephalopathy
Ho et al, 201425	Prospective cohort	To investigate the incidence, aetiology, outcomes and prognostic factors of ALF	Taiwan	High income	05 Jan	07 Sep	International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 570.0
Latif et al, 201026	Prospective cohort	To identify the risk factors for FHF and their relationship with the outcome in children	Pakistan	Lower middle	6 Sep	7 Feb	Development of encephalopathy within 8 weeks of the onset of jaundice having evidence of coagulopathy, that is, PT deranges >4 s of control and deranged liver function that is, TSB>1.5 mg/dL, AT>40 IU/L
Mamun et al, 200927	Retrospective cohort	To assess the burden of HEV as a cause of ALF	Bangladesh	Lower middle	4 Jun	6 Dec	Previously healthy patients who presented with severe impairment of hepatocellular function, that is, encephalopathy, coagulopathy and jaundice, within 6 months of onset of symptoms
Manka et al, 201528	Retrospective cohort	To investigate the causes of previously diagnosed indeterminate cases ALF	Germany	High	6 Nov	13 Dec	Significant liver dysfunction with pathologically increased laboratory parameters (AST, ALT, AP), an existing coagulopathy in terms of an INR>1.5, and with the concomitant presence of any degree of encephalopathy
Mendizabal et al, 201429	Retrospective cohort	To determine the causes and short-term outcomes of ALF	Argentina	High	5 Jun	11 Dec	Presence of coagulopathy (INR> 1.5 or prothrombin index <50%)and any grade of HE within 26 weeks of the first symptoms without a known underlying liver disease
Mishra et al, 201630	Retrospective cohort	To assess the relative efficacy of HEV antigen detection by ELISA in patients with ALF	India	Lower middle	13 Nov	15 Jan	Any evidence of coagulation abnormality, generally INR>1.5 and any degree of mental alteration (encephalopathy) without pre-existing cirrhosis and with an illness of <4 weeks duration
Mumtaz et al, 200931	Prospective cohort compared with historical control	To assess the aetiology, prothrombin time (PT), alanine aminotransferase, creatinine, albumin for non-acetaminophen-induced ALF	Pakistan	Lower middle	Jan 00	7 Mar	Rapid development of acute liver injury with impaired synthetic function and encephalopathy in a person who previously had a normal liver
Pandit et al, 201532	Retrospective cohort	To assess the frequency of hepatotropic viruses as aetiological agents of ALF	India	Lower middle	3 Jan	5 Dec	Onset of encephalopathy ≤28 days after the onset of symptoms with INR>2 and increased bilirubin complicated by encephalopathy in patients without a previous history of liver disease
Poovorawan et al, 201333	Prospective cohort	To determine the causes and outcomes of Thai children with AHF	Thailand	Upper middle	2 Jan	5 Sep	International Association for the Study of the Liver case definition: (Tandon et al, 1999)9
Schwarz et al, 201434	Retrospective cohort—Patient registry	To analyse results of viral testing among non-acetaminophen ALF study participants	USA/Canada/UK	High	Dec 99	12 Dec	No known evidence of chronic liver disease, with evidence of acute liver injury, and hepatic-based coagulopathy not corrected by vitamin K with the follow parameters: PT≥15 s or INR≥1.5 in the presence of clinical HE or a PT≥20 s or INR≥2.0 regardless of the presence or absence of clinical HE
Shalimar et al, 201735	Retrospective cohort	To assess the differences in the course of HEV-ALF as compared with other aetiologies of ALF	India	Lower middle	Jan 86	15 Dec	International Association for the Study of Liver (IASL) case definition: Occurrence of encephalopathy within 4 weeks from the onset of symptoms in the absence of pre-existing liver disease
Silverio et al, 201536	Retrospective cohort	To describe the clinical features of children treated for ALF	Cuba	Upper middle	5 Jan	11 Dec	Evidence of liver damage in the absence of prior known chronic liver disease; altered coagulation, expressed as PT>15 s with encephalopathy; or PT>20 s with or without encephalopathy—all this within 8 weeks of onset of clinical symptoms
Somasekar et al, 201737	Retrospective cohort	To investigate the causes of previously diagnosed indeterminate cases ALF	USA	High	Jan 98	10 Dec	US Acute Liver Failure Study Group case definition
Uddin Jamro et al, 201338	Retrospective cohort	To study the aetiology, outcome and risk factors for FHF in children at a tertiary care hospital	Pakistan	Lower middle	7 Jul	12 Jun	Presence of acute liver failure (coagulopathy PT>20 s or INR>2), HE without pre-existing liver disease, within 8 weeks of the onset of clinical liver disease
Tsunoda et al, 201739	Prospective cohort	To identify the roles of CMV, EBV and HHV in immunocompetent children with ALF not resulting from hepatitis virus	Japan	High	7 Jan	13 Dec	Liver dysfunction with elevated AST and ALT>30 IU/L
Zhao et al, 201440	Retrospective cohort	To investigate aetiologies and outcomes of children with ALF	China	Middle	7 Jan	12 Dec	Coagulopathy (PTA≤40% or INR≥1.5 excluding haematologic diseases) and jaundice (Tbil ≥ 171 μmol/L) within 4 weeks in a child without pre-existing liver diseases

AHF, acute hepatic failure; ALF, acute liver failure; ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; CMV, cytomegalovirus; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; FHF, fulminant hepatic failure; HE, hepatic encephalopathy; HEV, hepatitis E virus; HHV, human herpesvirus; INR, international normalised ratio; PT, prothrombin time; PTA, plasma thromboplastin antecedent; s, second; TSB, total serum bilirubin.