Table 1.
Multiparametric diagnosis guide for acute liver failure.
| Aetiologic trigger | Clinical phenotype | Testing | Liver histology |
|---|---|---|---|
| HAV, HBV, HCV, HEV | Epidemiological background Viral prodromes (malaise, fever, diarrhoea) Hyperacute course High AST, ALT, and INR |
Anti-HAV IgM Anti-HB core IgM, HBV surface antigen, and HBV-DNA Anti-HCV Ig and HCV-RNA Anti-HEV IgM and HEV-RNA |
Massive or submassive hepatocellular necrosis Lymphocytic infiltrates Varying degrees of fibrosis in HBV reactivation Immunohistochemical staining |
| HSV, VZV, CMV, EBV, ADV, PB1924 | Immunocompromised (but also in immunocompetent) Hyperacute course High fever with or without skin/mucosal lesions in HSV and VZV Disseminated infection Multiorgan failure |
IgM and blood viral load | Massive or submassive hepatocellular necrosis Viral inclusions Immunohistochemical staining |
| Paracetamol overdose | Intentional (younger) or accidental overdose Hyperacute course Metabolic acidosis and acute kidney injury |
Drug serum concentration | Coagulative confluent hepatocellular necrosis in centrilobular areas |
| DILI | Epidemiological background Acute or subacute clinical course Varying patterns of liver injury |
Exclude other causes of ALF | Necroinflammatory pattern Massive or submassive hepatocellular necrosis Lymphocytic infiltrates |
| Autoimmune hepatitis25 | Young women History of other autoimmune disorders High transaminases and high bilirubin May follow a subacute course (ascites) |
High gamma globulin levels Autoantibodies (not in 50% of cases) |
Centrilobular and confluent necrosis Lymphoplasmacytic infiltration Interface hepatitis Varying degrees of fibrosis |
| Wilson’s disease | Young patients Neurologic or psychiatric background Acute intravascular non-immune haemolysis High bilirubin and low alkaline phosphatase Modest elevations of transaminases with high AST/ALT ratio Progression to AKI |
High 24h-cupruria High relative exchangeable copper Low serum copper and low ceruloplasmin |
Microvesicular steatosis Glycogenated nuclei Varying degrees of fibrosis |
| Hypoxic hepatitis | History of congestive heart failure or refractory shock Very sudden and high increase in transaminases and INR with abrupt recovery Transient elevation of bilirubin after recovery Other signs of end-organ damage |
Perform liver imaging to assess vascular permeability | Predominant centrilobular necrosis |
| Heatstroke | Hyperthermia > 40 °C History of physical exhaustion (exercise, heat wave) Concomitant recreational use of cocaine or MDMA Very high transaminases and INR Other signs of end-organ damage (AKI, rhabdomyolysis, ARDS) |
Exclude other causes of ALF | Predominant centrilobular necrosis |
| Mushroom poisoning | Epidemiologic background Severe gastroenteritis High transaminases |
Amatoxins in urine | Massive hepatocellular coagulative necrosis |
| Malignant infiltration | Lymphoma, leukaemia, breast cancer, colon cancer Toxic syndrome, B symptoms High bilirubin and cholestasis Hepatomegaly and lymphadenopathies |
Liver biopsy | Atypical cell infiltration in sinusoids |
| HELLP syndrome26 | Third trimester of pregnancy (frequent history of preeclampsia/eclampsia) Coombs negative haemolysis High transaminases and low platelets May progress to liver rupture |
Exclude other causes of ALF | Microvascular fibrin deposition, neutrophilic infiltrate, fatty infiltration, lobular necrosis, and periportal haemorrhage |
| Acute fatty liver of pregnancy26 | Third trimester of pregnancy (infrequent history of preeclampsia/eclampsia) Abdominal pain and vomiting Ascites Severe coagulopathy and encephalopathy Low transaminases Progression to AKI |
Swansea criteria | Microvesicular steatosis |
| Acute Budd-Chiari syndrome25 | Myeloproliferative neoplasm or other prothrombotic disease Abdominal pain Painful hepatomegaly and ascites |
Hepatic vein congestion on ultrasound Vein thrombosis identification on imaging |
Centrilobular vein dilation |
ADV, adenovirus; AKI, acute kidney injury; ALF, acute liver failure; ALT, alanine aminotransferase; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; CMV, cytomegalovirus; DILI, drug-induced liver injury; EBV, Epstein-Barr virus; HSV, herpes simplex virus; PB19, parvovirus B19; VZV, herpes zoster virus.