Differences between NAFLD/MAFLD, iDILI, DIS, and alcohol associated hepatitis [7, 15, 20, 34, 38, 58–61]
| Differential diagnosis | DILI [15, 59] | DIS/DISH [20, 58] | NAFLD/MAFLD [15, 34, 38] | Alcohol-associated hepatitis [61] |
|---|---|---|---|---|
| Clinical presentation | Acute or chronic Multiple phenotypes | Acute or chronic | Chronic | Acute or chronic |
| Associated signs and symptoms | Fatigue, weakness, right upper quadrant pain, nausea, jaundice, dark urine, pruritus, fever, and rash | Fatigue, weakness, right upper quadrant pain, nausea, jaundice, dark urine, pruritus, fever, and rash AAS | Asymptomatic Asthenia, malaise, and right upper quadrant pain | Jaundice Ascites, edema, malaise, fever, hepatomegaly, confusion |
| Drugs, HDS, and alcohol | More than 1,000 drugs and HDS More frequent antibiotics (amoxicillin-clavulanic acid) Check-in LiverTox (https://livertox.nih.gov/) [60] | Acute fatty liver: amiodarone, didanosine, stavudine, valproate, and zalcitabine Drug-associated fatty liver disease: methotrexate, 5-fluorouracil, irinotecan, tamoxifen, corticosteroids, lomitapide, and mipomerson | No suspected drugs Alcohol intake: NAFLD: < 20 g/d (F), < 30 g/d (M) MASLD: < 140 g/w (F), < 210 g/w (M) | Alcohol consumption of more than 40 g/d in women and 50–60 g/d for men, with less than 60 days of abstinence before the onset |
| Biochemical parameters | ALT > 5 × ULN ALT > 3 × ULN + TB > 2 × ULN ALP > 2 × ULN | Not established | AST and ALT < 5 × ULN AST/ALT < 1 Normal ALP and TB | TB > 3 mg/dL (> 50 μmol/L) AST/ALT > 1.5 AST, and ALT > 400 UUI/L GGT > 100 U/L |
| Radiological findings | No specific findings | Liver steatosis | Liver steatosis | Liver steatosis Hepatomegaly |
| Liver biopsy | Acute hepatocellular liver injury: lobular inflammation, portal inflammation, interface hepatitis, apoptosis, granulomas, coagulative necrosis, and confluent or bridging necrosis Cholestatic DILI: acute cholestasis, chronic cholestasis, and acute cholestatic hepatitis | Steatosis, steatohepatitis Microvesicular (mitochondrial injury) Macrovesciular Mixed | Steatosis > 5% of hepatocytes, ballooned hepatocytes, lobular inflammation, apoptotic bodies, portal inflammation, perisinusoidal collagen, portal fibrosis, Mallory-Denk, megamitochondria, glycogenated nuclei in periportal hepatocytes, lobular lipogranulomas, PAS-diastase-resistant Kupffer cells, and hepatic siderosis | Ballooned hepatocytes, Mallory-Denk bodies, neutrophil infiltration, ductular reaction, bilirubinostasis, and pericellular, and sinusoidal fibrosis |
d: day; F: female; GGT: gamma-glutamyl transpeptidase; M: male; TB: total bilirubin; w: week; PAS: periodic acid-schiff; ×: times