Drug-induced liver injury in inflammatory bowel disease: Challenges in diagnosis and monitoring

Table 1 Hepatotoxic profile of inflammatory bowel disease therapies

Drug class	Agents	Reported hepatotoxicity	Risk profile/mechanism	Risk gradient
5-aminosalicylates	Mesalazine, Sulfasalazine	Rare hepatitis, cholestatic disease, granulomatous hepatitis, mild hepatocellular/cholestatic injury (mesalazine)	Sulfapyridine moiety associated with immune hypersensitivity	Low
Thiopurines	Azathioprine, 6-MP, 6-TG	Transient rise in transaminases, hypersensitivity hepatitis, cholestatic liver injury, vanishing bile duct syndrome; endothelial injury (sinusoidal obstruction syndrome, nodular regenerative hyperplasia, peliosis hepatis)	TPMT activity, 6-MMP accumulation; risk increases with concomitant MASLD	High
Methotrexate		Rise in transaminases, steatosis, steatohepatitis	Risk increases with concomitant obesity, diabetes mellitus, alcohol, metabolic syndrome	Moderate
Anti-TNF agents	Infliximab, adalimumab, golimumab, Certolizumab	Rise in transaminases, alkaline phosphatase, autoimmune hepatitis-like syndrome, cholestatic hepatitis, HBV reactivation	Immune-mediated, genetic (HLA-B39:01)	Moderate
Anti-integrins	Vedolizumab, Natalizumab	Rare; mild rise in transaminases, autoimmune-like hepatitis, cholestatic injury	Minimal risk	Very low
Anti-interleukins	Ustekinumab (anti-IL12/23), Risankizumab, Guselkumab, Mirikizumab (anti-IL23)	Rare; mild rise in transaminases, autoimmune-like hepatitis	Favourable hepatic safety profile, long term data needed	Verly low
JAK inhibitors	Tofacitinib, Upadacitinib, Filgotinib	Mild transient increase in transaminases, usually with other risk factors, autoimmune-like hepatitis, HBV reactivation, no serious DILI reported	CYP3A4 metabolism; caution with CYP3A4 modulators, long term data needed	Low
S1P modulators	Ozanimod, Etrasimod	Gamma-glutamyl transferase elevations	Unclear mechanism; clinical significance uncertain, long term data needed	Low
Corticosteroids	Prednisone, Budesonide, Methylprednisolone	Rare idiosyncratic reactions, HBV reactivation, long-term use associated with steatosis, MASLD	Indirect metabolic injury	Low
Antibiotics	Ciprofloxacin (fluoroquinolones)	Rare cholestatic jaundice, fulminant failure, delayed ductopenic cholestasis	Idiosyncratic hypersensitivity	Moderate
Anti-tubercular therapy	Isoniazid, Rifampicin, Pyrazinamide, Ethambutol	Rise in transaminases, acute hepatitis, fulminant failure (isoniazid and pyrazinamide)	High risk with pre-existing liver disease, polypharmacy	High

6-MMP: 6-methyl mercaptopurine; 6-MP: 6-mercaptopurine; 6-TG: 6-thioguanine; ALP: Alkaline phosphatase; HBV: Hepatitis B virus; IBD: Inflammatory bowel disease; MASLD: Metabolic dysfunction associated steatotic liver disease; TNF: Tumour necrosis factor; TPMT: Thiopurine-S-methyl transferase.