Use of oral vancomycin in children with autoimmune liver disease: A single centre experience

doi:10.4254/wjh.v13.i12.2113

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World Journal of Hepatology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Hepatol. Dec 27, 2021; 13(12): 2113-2127
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2113

Table 1 Laboratory and histological features at diagnosis of 75 children with autoimmune liver disease

	All patients, n = 75	AIH, n = 54	ASC, n = 21	P value
Biochemical profile
AST U/L (NV ≤ 45)	438 (129-982)	678 (204-1200)	150 (94-333)	< 0.001
GGT U/L (NV ≤ 50)	116 (60-296)	107 (54-196)	360 (68-607)	< 0.001
Total bilirubin (NV ≤ 1 mg/dL)	1.7 (0.6-4.5)	2.7 (0.6-5.3)	1.2 (0.7-2.5)	0.05
ALP (NV ≤ 350 U/L)	296 (204-469)	283 (199-462)	301 (242-494)	0.328
ALP/AST ratio	0.7 (0.3-2.2)	0.4 (0.2-1.6)	2.3 (0.7-3.5)	0.002
Albumin (NV: 30-50 g/dL)	42 (38-44)	42 (37-44)	42 (40-46)	0.082
INR (NV: 0.9-1.2)	1.2 (1.1-1.5)	1.2 (1.1-1.6)	1.1 (1.0-1.2)	< 0.05
Platelet (10⁹/L)	252 (180-350)	234 (167-314)	319 (251-393)	< 0.05
Autoimmune profile
ANA (≥ 1:20): n (%)	55 (73)	38 (70)	17 (81)	0.777
SMA (≥ 1:20): n (%)	53 (71)	38 (70)	15 (71)	1
Anti-LKM-1 (≥ 1:10): n (%)	12 (16)	12 (22)	0 (0)	< 0.05
Anti-LC1: n (%)	9 (12)	9 (17)	0 (0)	< 0.05
ANCA: n (%)	37 (49)	22 (41)	15 (71)	< 0.05
IgG g/dL (NV: 0.5-1.8 g/dL)	2.0 (1.4-3.2)	2.3 (1.4-3.3)	1.7 (1.5-2.2)	0.325
IgG > ULN: n (%)	51 (68)	37 (69)	14 (67)	1
Histology, n (%)
Interface hepatitis	51 (68)	42 (78)	12 (57)	0.09
Fibrosis	61 (81)	42 (78)	19 (90)	0.324
Cirrhosis	17 (23)	15 (28)	2 (10)	0.127
Features of biliopathy¹	62 (83)	37 (68)	17 (81)	0.764

¹It includes at least one of the following: inflammatory injury of the bile duct, ductular reaction, periductular fibrosis, biliary metaplasia, granulomatous cholangitis[16]. Values are expressed as median and interquartile ranges.

AIH: Autoimmune hepatitis; ASC: Autoimmune sclerosing cholangitis; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; INR: International normalized ratio; ANA: Antinuclear antibody; SMA: Smooth muscle antibody; LKM-1: Liver-kidney microsome antibody type 1; LC1: Liver cytosol antibody type 1; SLA: Liver soluble antigen; ANCA: Anti-neutrophil cytoplasmic LT antibodies; ULN: Upper limit of normal; NV: Normal value.

Table 2 Response to medical treatment and outcome of 75 patients with autoimmune liver diseases

Variables	All patients, n = 75	AIH, n = 54	ASC, n = 21	P value
Treatment, n
Prednisone alone	26 (35%)	19 (35%)	7 (33%)	1
Prednisone + Azathioprine	30 (40%)	28 (52%)	2 (10%)	< 0.001
Prednisone + MMF	5 (7%)	3 (5%)	2 (10%)	0.615
Prednisone + Vancomycin	4 (5%)	1 (2%)	3 (14%)	0.064
Prednisone + Azathioprine + Vancomycin	2 (3%)	0 (0%)	2 (10%)	0.075
Prednisone + MMF + Vancomycin	6 (8%)	1 (2%)	5 (23%)	0.005
Prednisone + Tacrolimus	1 (1%)	1 (2%)	0	NA
Cyclosporine	1 (1%)	1 (2%)	0	NA
Response to treatment
Normal AST (NV ≤ 45 U/L): n	69 (92%)	52 (96%)	17 (81%)	0.048
Time to normalize AST (yr)	0.1 (0.1-0.5)	0.2 (0.1-0.6)	0.1 (0.1-0.2)	0.19
GGT (< 50 UI/L), n	68 (91%)	51 (94%)	17 (81%)	0.811
Time to normalize GGT (yr)	0.3 (0.2-0.6)	0.3 (0.2-0.5)	0.3 (0.2-1.1)	0.062
Immunological remission¹: n	25 (33%)	22 (40%)	3 (14%)	0.032
Time to immunological remission	3.1 (2.2-4.2)	3.8 (2.9-4.3)	3.4 (3.2-3.7)	0.86
Relapse of AILD during treatment, n
At least one relapse	36 (48%)	22 (41%)	14 (67%)	< 0.070
1 relapse alone	26 (35%)	17 (31%)	9 (43%)	0.421
≥ 2 relapses	10 (13%)	5 (9%)	5 (24%)	0.131
Outcome at last follow up
Median follow up, yr (range)	4.4 (0.6-13.8)	4.1 (1.2-11.7)	4.5 (0.6-13.8)	0.079
Alive	75 (100%)	54 (100%)	21 (100%)	NA
OFF-IS therapy	6 (8%)	5 (9%)	1 (5%)	0.666
Medical treatment	68 (91%)	49 (91%)	19 (90%)	1
Liver transplant	1 (1%)	0 (0%)	1 (5%)	0.28

¹Normal aspartate aminotransferase, normal IgG, and negative or low titer autoantibodies.

AIH: Autoimmune hepatitis; ASC: Autoimmune sclerosing cholangitis; AST: Aspartate aminotransferase; MMF: Mycophenolate mofetil; GGT: Gamma-glutamyl transferase; IS: Immunosuppressive; NA: Not applicable; ALID: Autoimmune liver disease; NV: Normal value.

Table 3 Demographic, biochemical and histological features of 12 patients with autoimmune liver disease treated with oral vancomycin

Patients/ diagnosis	Gender	Age at diagnosis (yr)	Type of presentation	IBD	Splenomegaly¹	IgG > ULN	Auto-antibodies	Histology				Medications
Patients/ diagnosis	Gender	Age at diagnosis (yr)	Type of presentation	IBD	Splenomegaly¹	IgG > ULN	Auto-antibodies	Interface hepatitis	Fibrosis	Cirrhosis	Biliopathy³	Medications
AIH	F	4.2	Asymptomatic	IC	Not	Yes	SMA 1:40; p-ANCA	No	Yes	No	Yes	Pred/MMF/UDCA/Mesa
AIH	F	10.9	Asymptomatic	UC	Not	Yes	ANA 1:320; SMA 1:160; p-ANCA positive	Yes	Yes	No	Yes	Pred/UDCA/Mesa
ASC	F	16	Insidious	None	Yes	Not	ANA 1:160; p-ANCA positive	Yes	Yes	Yes	No	Pred/MMF/UDCA
ASC	M	4.3	Asymptomatic	CD	Not	Yes	ANA 1:160; SMA 1:160; p-ANCA +++	Yes	Yes	No	Yes	Pred/UDCA/Mesa
ASC	F	8.6	Insidious	UC	Not	Not	SMA 1:40; p-ANCA positive	No	No	No	Yes	Pred/AZA/UDCA/Mesa
ASC	F	12.1	Insidious	UC²	Not	Not	SMA 1:40; p-ANCA positive	No	No	No	Yes	Pred/AZA/UDCA
ASC	M	14.1	Insidious	None	Not	Not	SMA 1:40; p-ANCA positive	Yes	Yes	No	Yes	Pred/AZA/UDCA
ASC	M	14.3	Acute	UC	Not	Yes	ANA 1:320; SMA 1:320	Yes	No	No	Yes	Pred/UDCA/Mesa
ASC	F	13.8	Asymptomatic	UC	Yes	Yes	ANA 1:640; p-ANCA positive	No	Yes	Yes	Yes	Pred/MMF/UDCA/Mesa
ASC	F	5.1	Acute	IC	Not	Not	ANA 1:160; p-ANCA positive	No	Yes	No	Yes	Pred/MMF/UDCA/Mesa
ASC	F	13.1	Acute	CD	Yes	Yes	ANA 1:80; p-ANCA positive	No	Yes	No	Yes	Pred/MMF/UDCA/Mesa
ASC	F	3.6	Asymptomatic	UC	Yes	Not	ANA 1:160; SMA 1:80; p-ANCA positive	Yes	Yes	No	Yes	Pred/MMF/UDCA/Mesa

¹Spleen size detected on liver scan o magnetic resonance cholangiopancreatography.

²Patient underwent colectomy at age of 14 years.

³It includes at least one of the following: Inflammatory injury of the bile duct, ductular reaction, periductular fibrosis, biliary metaplasia, granulomatous cholangitis[16].

AIH: Autoimmune hepatitis; ASC: Autoimmune sclerosing cholangitis; IBD: Inflammatory bowel disease; UC: Ulcerative colitis, CD: Crohn disease; IC: Indeterminate colitis; ULN: Upper limit of normal; F: Female; M: Male; ANA: Anti-nuclear antibody; SMA: Smooth muscle antibody; ANCA: Anti-neutrophil cytoplasmic antibodies; Pred: Prednisone; UDCA: Ursodeoxycholic acid; MMF: Mycophenolate mofetil; Mesa: Mesalazyne.

Table 4 Biochemical response to oral vancomycin and Sclerosing Cholangitis Outcomes in Pediatrics index score of 12 patients with autoimmune liver disease treated with oral vancomycin

Patients/diagnosis	Age at OVT (yr)	AST (NV ≤ 45 U/L)				ALT (NV ≤ 45 U/L)				GGT (NV ≤ 50 U/L)				Response to OVT ¹	SCOPE index score²		Time on OVT (mo)	OVT side-effect	Overall FU³ (mo)
Patients/diagnosis	Age at OVT (yr)	Before OVT	After OVT	TTN	Result	Before OVT	After OVT	TTN	Result	Before OVT	After OVT	TTN	Result	Response to OVT ¹	Before OVT	After OVT	Time on OVT (mo)	OVT side-effect	Overall FU³ (mo)
AIH	5.4	212	39	4 mo	NV	147	17	6 mo	NV	73	22	6 mo	NV	Complete	3 low risk	0 low risk	99	None	113
AIH	11.8	251	31	2 mo	NV	359	39	9 mo	NV	26	34	8 mo	NV	Complete	3 low risk	0 low risk	72	None	73
ASC	16.8	98	47	3 mo	< 1.5 NV	140	70	4	< 1.5 NV	39	83	4	< 1.5 NV	Partial	8 high risk	8 high risk	16	None	26
ASC	4.8	86	28	7 d	NV	156	38	14 d	NV	84	44	14 d	NV	Complete	4 medium risk	1 low risk	37	None	39
ASC	13.1	60	14	1 mo	NV	365	38	3 mo	NV	68	27	4 mo	NV	Complete	5 medium risk	2 low risk	31	None	84
ASC	15.2	71	40	14 mo	NV	140	56	14 mo	< 1.5 NV	52	164	12 mo	-	None	6 high risk	6 high risk	6	None	68
ASC	17.4	113	65	1 mo	< 1.5 NV	205	141	1 mo	-	49	226	1 mo	-	None	6 high risk	4 medium risk	3	None	52
ASC	15	407	30	6 mo	NV	856	35	6 mo	NV	61	28	1 mo	NV	Complete	5 medium risk	2 low risk	40	None	49
ASC	17.3	102	37	2 mo	NV	111	36	2 mo	NV	135	82	5 mo	< 1.5 NV	Partial	6 high risk	4 medium risk	18	None	61
ASC	12.5	76	31	2 mo	NV	124	40	7 mo	NV	86; TX	42	6 mo	NV	Complete	5 medium risk	4 medium risk	47	None	135
ASC	13.9	123	155	-	-	165	154	-	-	165	1800	-	-	None	8 high risk	8 high risk	6	None	86; TX
ASC	13.2	141	135	-	-	156	180	-	-	71 mo (range 26-165)	136	-	-	None	7 high risk	7 high risk	4	None	165
Response to OVT					10/12 (83%)				9/12 (75%)				8/12 (67%)				Median: 34 (range 1-99)		71 (range 26-165)

¹Complete response is defined as “normalization of all three liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT)]”, partial response as “AST, ALT or GGT levels decreasing to < 1.5 × ULN without reaching normal value”, and no response as “no significant changes in liver enzymes”.

²Sclerosing Cholangitis Outcomes in Pediatrics: Points 0-3: Low risk; Points 4-5: Medium risk; Points 6-11: High risk.

³Time from diagnosis to last follow up visit.

AIH: Autoimmune hepatitis; ASC: Autoimmune sclerosing cholangitis; OVT: Oral vancomycin treatment; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; TTN: Time to normalize or to achieve the lowest value; NV: Normal value; FU: Follow up; SCOPE: Sclerosing Cholangitis Outcomes in Pediatrics.

Citation: Di Giorgio A, Tulone A, Nicastro E, Norsa L, Sonzogni A, D'Antiga L. Use of oral vancomycin in children with autoimmune liver disease: A single centre experience. World J Hepatol 2021; 13(12): 2113-2127
URL: https://www.wjgnet.com/1948-5182/full/v13/i12/2113.htm
DOI: https://dx.doi.org/10.4254/wjh.v13.i12.2113