Table Info

Table 1.

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

Declarations

Author contributions

MGC: Conceptualization, Writing—original draft, Writing—review & editing. JPTO and AGG: Conceptualization, Writing—original draft.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was supported by grants from Instituto de Salud Carlos III, cofounded by the Fondo Europeo de Desarrollo Regional—FEDER contract numbers: [FIS 21-01248; PI18/00901; UMA18-FEDERJA-193]. Cofunded by European Union. CIBERehd is funded by the Instituto de Salud Carlos III (ISCIII). MGC is a member of the COST ACTION “CA-17112”, Prospective European DILI Network, supported by European Cooperation in Science and Technology (COST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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