Autoimmune liver diseases in systemic rheumatic diseases

Table 1 Hepatic abnormalities associated with common medications used in systemic rheumatic diseases

Medications	Hepatic abnormalities	2Likelihood score category in DILI
NSAIDs	LEE, cholestasis, acute liver failure, VBDS	A for diclofenac, ibuprofen, sulindac
Glucocorticoids	LEE, NAFLD, acute liver failure, HBV reactivation	A in high dosages
Immunosuppressive agents
Azathioprine	LEE, cholestasis, NRH, peliosis hepatis, VOD	A
Mycophenolate mofetil	LEE	D
Cyclophosphamide	LEE, VOD	B
Cyclosporine	LEE, cholelithiasis	C
Tacrolimus	LEE	C
Conventional SDMARDs
Hydroxychloroquine	LEE	C
Leflunomide	LEE, acute liver failure, HBV reactivation	B
Methotrexate	LEE, NAFLD, HBV reactivation, fibrosis, cirrhosis	A
Penicillamine	LEE, cholestasis	A
Sulfasalazine	LEE, cholestasis, DRESS	A
Biologic/targeted SDMARDs
Abatacept	LEE, HBV reactivation	C
Anakinra	LEE	C
Apremilast	Unlikely liver injury	E
Belimumab	Unlikely liver injury	E
Mepolizumab	Unlikely liver injury	E
Rituximab	LEE, HBV reactivation	A
TNF blockers1	LEE, cholestasis, HBV reactivation, AIH	A for infliximab
Tocilizumab	LEE, HBV reactivation	C
Tofacitinib	Suspected liver injury, potential HBV reactivation	E’
Ustekinumab	Suspected liver injury, possible HBV reactivation	E’

¹TNF blockers including adalimumab, certolizumab, etanercept, golimumab and infliximab.

²Categorization of Likelihood Score in drug-induced liver injury. A: Definite; B: Highly likely; C: Probable, D: Possible, E: Unlikely; E’: Suspected.

NSAIDs: Non-steroidal anti-inflammatory drugs; HBV: Hepatitis virus B; DILI: Drug-induced liver injury; DRESS: Drug rash with eosinophilia and systemic symptoms; LEE: Liver enzyme elevation; NAFLD: Nonalcoholic fatty liver disease; NRH: Nodular regenerative hyperplasia; SDMARDs: Synthetic disease-modifying antirheumatic drugs; SRDs: Systemic rheumatic disease; VBDS: Vanishing bile duct syndrome; VOD: Veno-occlusive disease.