Details of the Drug Combination

General Information of Drug Combination (ID: DCDDCQB)

• Drug Combination Name: Methylprednisolone + Prednisone
• Indication: IgA Nephropathy; Status: Phase 1 [1]
• Component Drugs:
  Methylprednisolone (DM4BDON): Small molecular drug
  Prednisone (DM2HG4X): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Methylprednisolone

Disease Entry	ICD 11	Status	REF
Acute adrenal insufficiency	N.A.	Approved	[2]
Acute asthma	CA23	Approved	[2]
Addison disease	5A74.0	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Angioedema	4A00.15	Approved	[2]
Aspiration pneumonitis	N.A.	Approved	[2]
Autoimmune haemolytic anaemia	3A20	Approved	[2]
Bursitis	N.A.	Approved	[2]
Cerebral edema	8D60.1	Approved	[2]
Chronic graft versus host disease	N.A.	Approved	[2]
Congenital adrenal hyperplasia	5A71.01	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Epicondylitis	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Fever	MG26	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Ischemia-reperfusion injury	DB98.B	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
Microscopic polyangiitis	N.A.	Approved	[2]
Miliary tuberculosis	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Psoriasis	EA90	Approved	[2]
Psoriatic arthritis	FA21	Approved	[2]
Rheumatic heart disease	N.A.	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Sarcoidosis	4B20.5	Approved	[2]
Seasonal allergic rhinitis	CA08.01	Approved	[2]
Serum sickness	N.A.	Approved	[2]
Severe asthma	CA23	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]
Perennial allergic rhinitis	CA08.03	Investigative	[2]
Spinal cord injury	ND51.2	Investigative	[5]
Synovitis	N.A.	Investigative	[2]
Trichinellosis	N.A.	Investigative	[2]

Methylprednisolone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Modulator	[12]

Methylprednisolone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]

Methylprednisolone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]

Methylprednisolone Interacts with 87 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[16]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[10]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Increases Expression	[10]
Phospholipid phosphatase 3 (PLPP3)	OTSSF7BK	PLPP3_HUMAN	Decreases Expression	[10]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Decreases Expression	[10]
Calmegin (CLGN)	OTEWVFQV	CLGN_HUMAN	Decreases Expression	[10]
D-3-phosphoglycerate dehydrogenase (PHGDH)	OT1LMRTG	SERA_HUMAN	Decreases Expression	[10]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Decreases Expression	[10]
Gasdermin-E (GSDME)	OT1ZWY32	GSDME_HUMAN	Decreases Expression	[10]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Decreases Expression	[10]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Increases Expression	[10]
Antiviral innate immune response receptor RIG-I (RIGI)	OTFIIC43	RIGI_HUMAN	Decreases Expression	[10]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Decreases Expression	[10]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[10]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[10]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Decreases Expression	[10]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[10]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Decreases Expression	[10]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[10]
Steryl-sulfatase (STS)	OTXTJQPC	STS_HUMAN	Increases Expression	[10]
Neuromedin-B (NMB)	OT4NLN6H	NMB_HUMAN	Decreases Expression	[10]
Stromelysin-2 (MMP10)	OTJDWW8Q	MMP10_HUMAN	Decreases Expression	[10]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[10]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[10]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[10]
Interleukin-1 receptor antagonist protein (IL1RN)	OT308CBE	IL1RA_HUMAN	Decreases Expression	[10]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Decreases Expression	[10]
C-X-C motif chemokine 3 (CXCL3)	OTSL94KH	CXCL3_HUMAN	Decreases Expression	[10]
Interferon-induced GTP-binding protein Mx1 (MX1)	OT6X8G5T	MX1_HUMAN	Decreases Expression	[10]
Fibulin-1 (FBLN1)	OT5MHHOP	FBLN1_HUMAN	Increases Expression	[10]
Atypical chemokine receptor 3 (ACKR3)	OTA6GA4F	ACKR3_HUMAN	Decreases Expression	[10]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Decreases Expression	[10]
Adenosine receptor A2a (ADORA2A)	OTVRBZ0I	AA2AR_HUMAN	Decreases Expression	[10]
CCN family member 2 (CCN2)	OTC39NSU	CCN2_HUMAN	Increases Expression	[10]
Myristoylated alanine-rich C-kinase substrate (MARCKS)	OT7N056G	MARCS_HUMAN	Decreases Expression	[10]
Guanylate-binding protein 1 (GBP1)	OTUM7RPJ	GBP1_HUMAN	Decreases Expression	[10]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[10]
Macrophage metalloelastase (MMP12)	OT9Z7LHM	MMP12_HUMAN	Decreases Expression	[10]
Interferon alpha-inducible protein 27, mitochondrial (IFI27)	OTI2XGIT	IFI27_HUMAN	Decreases Expression	[10]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Decreases Expression	[10]
Regulator of G-protein signaling 4 (RGS4)	OTG94HHL	RGS4_HUMAN	Decreases Expression	[10]
Prolargin (PRELP)	OT9EEBUJ	PRELP_HUMAN	Increases Expression	[10]
Spermine synthase (SMS)	OT8JYKNH	SPSY_HUMAN	Decreases Expression	[10]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Decreases Expression	[10]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[10]
Interferon-induced 35 kDa protein (IFI35)	OTV9RZ53	IN35_HUMAN	Decreases Expression	[10]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Increases Expression	[10]
Tumor necrosis factor alpha-induced protein 2 (TNFAIP2)	OTRZH80H	TNAP2_HUMAN	Decreases Expression	[10]
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Increases Expression	[10]
Bone marrow stromal antigen 2 (BST2)	OTU4LCJV	BST2_HUMAN	Decreases Expression	[10]
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)	OTZVUOOB	FBLN3_HUMAN	Increases Expression	[10]
Neuronal membrane glycoprotein M6-b (GPM6B)	OT8Q1582	GPM6B_HUMAN	Increases Expression	[10]
Laminin subunit beta-3 (LAMB3)	OTFPU6W8	LAMB3_HUMAN	Decreases Expression	[10]
Nidogen-2 (NID2)	OTHC33FF	NID2_HUMAN	Increases Expression	[10]
Signal transducer and activator of transcription 4 (STAT4)	OTAK3VFR	STAT4_HUMAN	Decreases Expression	[10]
2'-5'-oligoadenylate synthase-like protein (OASL)	OTZ05YRP	OASL_HUMAN	Decreases Expression	[10]
Bcl-2-related protein A1 (BCL2A1)	OTWRYSNA	B2LA1_HUMAN	Decreases Expression	[10]
Lymphocyte antigen 6E (LY6E)	OTMG16BZ	LY6E_HUMAN	Decreases Expression	[10]
Interferon-induced protein 44-like (IFI44L)	OTXKORJP	IF44L_HUMAN	Decreases Expression	[10]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[10]
Amphoterin-induced protein 2 (AMIGO2)	OTPAIT1O	AMGO2_HUMAN	Decreases Expression	[10]
Probable E3 ubiquitin-protein ligase HERC6 (HERC6)	OT7G9PQE	HERC6_HUMAN	Decreases Expression	[10]
Equilibrative nucleobase transporter 1 (SLC43A3)	OTR60ZLA	S43A3_HUMAN	Decreases Expression	[10]
Interferon-induced protein 44 (IFI44)	OTOKSZVA	IFI44_HUMAN	Decreases Expression	[10]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Decreases Expression	[10]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Decreases Expression	[10]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Increases Expression	[10]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Decreases Expression	[10]
Interferon-stimulated gene 20 kDa protein (ISG20)	OTCWRJJW	ISG20_HUMAN	Decreases Expression	[10]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Decreases Expression	[10]
Anthrax toxin receptor 1 (ANTXR1)	OT5W1GPC	ANTR1_HUMAN	Increases Expression	[10]
Interleukin-23 subunit alpha (IL23A)	OTYO99HC	IL23A_HUMAN	Decreases Expression	[10]
NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2)	OTK0PG7R	NUA4L_HUMAN	Decreases Expression	[10]
E3 ISG15--protein ligase HERC5 (HERC5)	OTZ5PR39	HERC5_HUMAN	Decreases Expression	[10]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[10]
Hypoxia-inducible lipid droplet-associated protein (HILPDA)	OTEID3ZM	HLPDA_HUMAN	Decreases Expression	[10]
2'-5'-oligoadenylate synthase 3 (OAS3)	OT6E5FYS	OAS3_HUMAN	Decreases Expression	[10]
Coagulation factor VIII (F8)	OTH6XHDU	FA8_HUMAN	Increases Expression	[11]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Decreases Expression	[17]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Decreases Expression	[17]
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Decreases Activity	[18]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Increases ADR	[19]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases ADR	[19]
Thrombopoietin (THPO)	OTO73DZ2	TPO_HUMAN	Increases ADR	[19]
P-selectin (SELP)	OTWR90PK	LYAM3_HUMAN	Increases ADR	[19]

Indication(s) of Prednisone

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[6]
Addison disease	5A74.0	Approved	[6]
Allergic rhinitis	CA08.0	Approved	[6]
Angioedema	4A00.15	Approved	[6]
Autoimmune haemolytic anaemia	3A20	Approved	[6]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[6]
Congenital adrenal hyperplasia	5A71.01	Approved	[6]
Crohn disease	DD70	Approved	[6]
Dermatitis herpetiformis	EB44	Approved	[6]
Diamond-Blackfan anemia	N.A.	Approved	[6]
Epicondylitis	N.A.	Approved	[6]
Erythema multiforme	N.A.	Approved	[6]
Inflammation	1A00-CA43.1	Approved	[7]
Inflammatory bowel disease	DD72	Approved	[6]
Multiple sclerosis	8A40	Approved	[6]
Mycosis fungoides	2B01	Approved	[6]
Plasma cell myeloma	2A83.1	Approved	[6]
Polymyalgia rheumatica	N.A.	Approved	[6]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[6]
Prostate adenocarcinoma	N.A.	Approved	[6]
Psoriasis	EA90	Approved	[6]
Psoriatic arthritis	FA21	Approved	[6]
Rheumatic heart disease	N.A.	Approved	[6]
Sarcoidosis	4B20.5	Approved	[6]
Serum sickness	N.A.	Approved	[6]
Skin disease	EA00-EM0Z	Approved	[6]
Small lymphocytic lymphoma	2A82.0	Approved	[6]
Systemic lupus erythematosus	4A40.0	Approved	[6]
Atopic dermatitis	EA80	Phase 1	[8]
Eczema	EA80-EA89	Phase 1	[8]
Acquired thrombocytopenia	N.A.	Investigative	[6]
Asthma	CA23	Investigative	[6]
Beta-thalassemia major	N.A.	Investigative	[6]
Classic Hodgkin lymphoma	N.A.	Investigative	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[9]
Follicular lymphoma	2A80	Investigative	[6]
Rheumatoid arthritis	FA20	Investigative	[6]
Trichinellosis	N.A.	Investigative	[6]

Prednisone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Agonist	[22]

Prednisone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[23]

Prednisone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]

Prednisone Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Secretion	[24]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[25]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Activity	[26]
Tissue-type plasminogen activator (PLAT)	OTQPDNAB	TPA_HUMAN	Increases Expression	[27]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Increases Expression	[28]
Alpha-2-macroglobulin (A2M)	OTFTX90K	A2MG_HUMAN	Decreases Expression	[28]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[29]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Decreases Expression	[30]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[31]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[31]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[29]
Glycogen phosphorylase, muscle form (PYGM)	OTWLVWTV	PYGM_HUMAN	Decreases Expression	[32]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Decreases Expression	[33]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[34]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Expression	[34]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[34]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[34]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Expression	[33]
C-C motif chemokine 13 (CCL13)	OTNX0JD0	CCL13_HUMAN	Decreases Expression	[33]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[21]

References

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• [2] Methylprednisolone FDA Label
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• [4] ClinicalTrials.gov (NCT04341038) Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7088).
• [6] Prednisone FDA Label
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7096).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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• [20] Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells. J Steroid Biochem Mol Biol. 1995 Aug;54(3-4):147-53. doi: 10.1016/0960-0760(95)00128-m.
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• [22] Cytochromes P450 (CYP) in the Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1): dose- and time-dependent glucocorticoid potentiation of CYP1A induction without induction of CYP3A. ArchBiochem Biophys. 1996 May 1;329(1):113-22.
• [23] Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803.
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• [25] Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
• [26] Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids. J Steroid Biochem Mol Biol. 2005 Aug;96(3-4):229-34. doi: 10.1016/j.jsbmb.2005.03.004.
• [27] Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation. J Heart Lung Transplant. 1999 Jul;18(7):693-700. doi: 10.1016/s1053-2498(99)00021-2.
• [28] Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report. Am J Ther. 2001 Mar-Apr;8(2):97-107. doi: 10.1097/00045391-200103000-00004.
• [29] Cytokine abnormalities in a patient with eosinophilic fasciitis. Ann Allergy Asthma Immunol. 2003 Apr;90(4):452-5. doi: 10.1016/S1081-1206(10)61832-7.
• [30] Prednisone effects on neurochemistry and behavior. Preliminary findings. Arch Gen Psychiatry. 1990 Oct;47(10):963-8. doi: 10.1001/archpsyc.1990.01810220079010.
• [31] Immune responses in autoimmune hepatitis: effect of prednisone and azathioprine treatment: case report. Int J Med Sci. 2009 Jun 30;6(4):177-83. doi: 10.7150/ijms.6.177.
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