Evaluation of biological therapies in autoimmune hepatitis: A case-based systematic review

Table 2 Anti-TNFα induced autoimmune hepatitis

Ref.	Country	Age	Comorbidities	AIH type	Previous intervention	Intervention	Comparison	Type of the study	Outcome	Result
Jenkins et al[31]	United States	31	UC	AIH induced by infliximab	Mesalamine, prednisone, adalimumab, Clostridioides difficile colitis	Suspension of Infliximab and use of Vedolizumab	None	Case report	AST and ALT improvement -AIH; Clinical and endoscopic improvement - UC	UC was controlled with the use of Vedolizumab AST and ALT normalized after infliximab was withdrawn
Wong et al[32]	Canada	69	AIH, HTN, diverticular disease	AIH induced by infliximab	Prednisolone	Infliximab	No comparison	Case report	Elevated AST and ALT, with elevated INR and positive ASMA and ANA. Liver biopsy showed multiacinar hepatocyte necrosis and interface hepatitis	Infliximab led to deterioration in liver markers compared to baseline instead of improvement
Mancini, et al[33]	Italy	33	Psoriasis	AIH induced by infliximab	Methotrexate	Infliximab and prednisone	No comparison	Case report	Elevated AST and ALT levels, positive ANA and anti-dsDNA	Infliximab induced AIH
Adar et al[34]	Israel	36	Psoriasis and psoriatic arthritis, hypothyroidism, Crohn’s disease	AIH induced by adalimumab	AZA, methotrexate and prednisolone	Adalimumab	No comparison	Case report	Elevated AST and ALT and IgG levels, positive ANA and anti-DNA. Liver biopsy showed fibrosis, inflammatory cell infiltrate, interface hepatitis, and hepatic rosettes	Adalimumab induced AIH, which was discontinued due to adverse effects
Karanfilian et al[35]	United States	37	Crohn’s disease, psoriasis	AIH induced by infliximab	Prednisone	Infliximab	No comparison	Case report	Elevated AST and ALT, positive ANA and weakly positive smooth muscle antibody Liver biopsy showed active hepatitis with moderate interface activity, cholestasis, and infiltrate of eosinophils and plasma cells	Severe drug-induced autoimmune hepatitis secondary to infliximab and discontinuation of infliximab led to improvement in liver function tests
Rodrigues et al[36]	Portugal	22-69 year (8 pts)	Ulcerative colitis, Ankylosing spondylitis, Psoriatic arthritis, Rheumatoid arthritis; Crohn’s disease, Palmoplantar pustular psoriasis	AIH induced by infliximab	Prednisone administered all AIH patients	Infliximab administered in 7 cases. Adalimumab administered in 1 case	No comparison	Case series	Infliximab: Six patients developed AIH and one patient developed DILI and cirrhosis	Normalisation of the liver function testes after discontinuation of anti-TNF
Yilmaz et al[37]	United States	39	Ankylosing spondylitis	AIH induced by infliximab	Methotrexate, sulfasalazine, hydroxychloroquine	Infliximab	No comparison	Case report	ALT and AST elevated with positive ANA. Liver biopsy showed an acute autoimmune hepatitis with a lymph plasmatic infiltration	Normal liver function tests two months after discontinuation of the anti-TNF drug
Dang et al[38]	Australia	47	Chronic plaque psoriasis	AIH induced by infliximab	Methotrexate	Infliximab	No comparison	Case report	Elevated AST, ALT and IgG levels. Liver biopsy indicated acute AIH	Infliximab discontinued and liver condition improved
van Casteren-Messidoro et al[39]	Netherlands	46 and 30	Case 1: Crohn's disease, erythema nodosum Case 2: UC	AIH induced by infliximab	Prednisone and AZA	Case 1: Infliximab; Case 2: Pregnant, infliximab and azathioprine	No comparison	Case series	Case 1 After the fourth infliximab dose, positive ANA and IgG; liver biopsy indicated acute AIH Case 2: Elevated AST and ALT; liver biopsy showed hepatitis	In both cases liver enzymes improved after infliximab was withdrawn
Cravo et al[40]	Portugal	38	Crohn’s disease	AIH induced by infliximab	Azathioprine and prednisolone	Infliximab and Adalimumab	Infliximab vs Adalimumab	Case report	AIH induced by Infliximab and switched to adalimumab. Elevated AST and ALT and IgG with positive ANA, anti-dsDNA, and antihistone antibodies. Liver Biopsy showed chronic hepatitis and mild periportal fibrosis	Infliximab discontinued and with adalimumab liver function normalized
Grasland et al[41]	France	35	Hypertension, obesity	AIH induced by adalimumab	Methotrexate, prednisone, NSAIDs, paracetamol and etanercept	Adalimumab	Adalimumab vs Abatacept	case report	AIH induced by Adalimumab - AST and ALT elevated	Adalimumab was discontinued and liver function improved Abatacept was restarted and liver enzymes normalized
Petríková et al[42]	Slovakia	33	Sjögren syndrome, rheumatoid arthritis	AIH induced by adalimumab	Etanercept, certolizumab and anakinra	Adalimumab	No comparison	Case report	Increased AST, ALT, IgG and positive ASMA and AMA. Liver biopsy showed chronic hepatitis suggestive of AIH	Adalimumab induced autoimmune hepatitis and liver enzymes improved with withdrawal of adalimumab

AIH: Autoimmune hepatitis; Pt: Patient; UC: Ulcerative colitis; HTN: Hypertension; DILI: Drug-induced liver injury; AZA: Azathioprine; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ANA: Antinuclear antibodies; ASMAs: Anti-smooth muscle antibodies; INR: International normalised ratio; IgG: Immunoglobulin G; NSAID: Non-steroidal anti-inflammatory drug; AMA: Anti-mitochondrial antibodies; TNF: Tumor necrosis factor.