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

Table 1 Biologics for the treatment of autoimmune hepatitis

Ref.	Country	Age	Patient-comorbidity	Type of AIH	Previous intervention	Intervention	Comparison	Study design	Outcomes measured	Result
Kolev et al[22]	Switzerland	37-65 (6 pt)	There were 3 patients with AIH and 3 with PBC. Pt 1: AIH, Sjögren’s disease; Pt 2: AIH, PBC, Coeliac, Asthma; Pt 3: AIH, Autoimmune thyroiditis	3 patients with type 1 AIH	Pt 1: Prednisolone, AZA, rituximab, MMF, UDCA; Pt 2: Prednisolone, AZA, UDCA, MMF, CyA; Pt 3: Prednisolone, AZA, MMF, budesonide, CyA	Belimumab 200 mg SC weekly	No comparison	Case series	Improvement of Fibroscan and normalization of AST and ALT	3/3 patients respond positively to Belimumab
Arvaniti et al[23]	Greece	27 and 58	Pt 1: AIH, SLE, Hypergammaglobulinemia; Pt 2: Acute severe hepatitis	Refractory AIH	Pt 1: Prednisolone, AZA; Pt 2: prednisolone, AZA and MMF	Belimumab: 10 mg/kg initially every 28 days	No comparison	Case series	Improvement of Fibroscan, Histology and normalization of AST and ALT	Both patients (2/2) achieved and maintained complete response to Belimumab
Burak et al[24]	Canada	36-68 (6 pt)	Pt 1: T2DM, HTN; Pt 2: Osteoporosis; Pt 3: Asthma; Pt 4: None reported; Pt 5: CAD Pt 6: CKD	Refractory AIH	Pt 1: Prednisone; Pt 2: prednisone; Pt 3: prednisone; Pt 4: AZA + MMF Pt5: Prednisone; Pt6: prednisone + AZA + MMF	Rituximab 1000 mg given each two weeks day 1 and 15 over 72 weeks	No comparison	Case series	Improvement of liver histology and of AST and ALT levels and reduction of steroids dose	All 6 patients had significant improvement histology: 4/6 improved inflammation grades in all and 2/6 patients improved fibrosis stages
Carey et al[25]	Arizona- United States	44	Several autoimmune disorders including Evan syndrome	Refractory AIH	Prednisolone and AZA	Rituximab for 375 mg/m2 once a week /four weeks	No comparison	Case report	Normalization of haemoglobin, platelets, AST and ALT	Complete response
Al-Busafi et al[26]	Canada	68	Hypertension, osteoporosis and a Waldenström macroglobulinemia	Refractory AIH	Prednisone	Rituximab given as high-dose-rituximab four weekly 375 mg/m2 rituximab	No comparison	Case report	Histological, AST and ALT improvement	Partial responde, demanding the use of prednisone and AZA
Barth et al[27]	United States	27	B cell lymphoma	AIH intolerance to steroid	Prednisone	Rituximab 375 mg/m² weekly for 8 weeks and extra four weeks upon relapse	No comparison	Case report	Improvement in AST and ALT	Complete remission, with a relapse which responded to an increase of rituximab frequency
Riveiro-Barciela et al[28]	Barcelona	19-73 (32 pts)	10 patients with cirrhosis, 4 patients with overlap with PBC or PSC	Refractory AIH	Corticosteroids and immunosuppressive medications	Rituximab 1 g/2 weeks in (9%) patients, periodical doses in 32 (91%), fixed/6 months in 16 (46%) and 16 (46%) in periods	No comparison	Case series	Improvement in AST and ALT	Biochemical response in 31 89% patients, discontinuation of ≥ 1 immunosuppressive drugs in 47%, significant reduction in corticosteroid dose in most patients; safe even in cirrhotic patients
Santos et al[29]	United States	52	Asthma, DM, ITP	Refractory AIH	Methylprednisolone, prednisone, IV immune globulin (IVIG), anti-D immune globulin, danazol	Rituximab administration: 375 mg/m2 IV weekly for 4 weeks	No comparison	case report	Normalization of AST and ALT	Complete laboratorial remission
Zarrabi et al[30]	United States	22	PBC overlap, recurrent metastatic osteosarcoma	Refractory AIH	Steroids, tacrolimus and MMF	Basiliximab six doses of 20 milligrams/dose, then weekly for four weeks	No comparison	Case report	Normalization of AST and ALT	Complete and sustained response

AIH: Autoimmune hepatitis; Pt: Patient; PBC: Primary biliary cholangitis; AZA: Azathioprine; MMF: Mycophenolate mofetil; UDCA: Ursodeoxycholic acid; CyA: Cyclosporine A; SLE: Systemic lupus erythematosus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HTN: Hypertension; T2DM: Type 2 Diabetes mellitus; IV: Intravenous; SC: Subcutaneous; ITP: Immune thrombocytopenia; CKD: Chronic kidney disease.