Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis

Lin HAN; Qingsheng LIANG; Huan XIE; Ying CHEN; Jun ZHAO; Mingyue ZHANG; Baosen LI; Yanli DONG; Ying SUN

doi:10.3969/j.issn.1001-5256.2022.04.015

Volume 38 Issue 4

Apr. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(4): 815-820

PDF( 2631 KB)

Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2022.04.015

Lin HAN¹,
Qingsheng LIANG¹,
Huan XIE¹,
Ying CHEN¹,
Jun ZHAO¹,
Mingyue ZHANG^{1, 2},
Baosen LI¹,
Yanli DONG^{3
,
,
,},
Ying SUN^{1, 2
,
,
,}

1.
Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
2.
Graduate School, Medical School of Chinese PLA, Beijing 100039, China
3.
Department of Hepatic Oncology, Mudanjiang Kangan Hospital, Mudanjiang, Heilongjiang 157010, China

Research funding:

National Natural Science Foundation of China (General Program) (81873564)

More Information

Corresponding author: DONG Yanli, dyl19751975@126.com(ORCID: 0000-0002-6587-9939); SUN Ying, sunying_302@yahoo.com(ORCID: 0000-0002-2570-9206)
Received Date: 2021-08-15
Accepted Date: 2021-10-08
Published Date: 2022-04-20

Abstract

Abstract

Objective To investigate the association between baseline IgM level and treatment response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods A retrospective analysis was performed for the clinical data of 637 PBC patients who were diagnosed and treated with UDCA for the first time in The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to January 2020. The PBC patients were divided into UDCA complete response group with 436 patients and UDCA poor response group with 201 patients, and baseline clinical data were compared between the two groups. According to the optimal cut-off value of IgM determined by the area under the ROC curve (AUC) of baseline indices in predicting the risk of poor treatment response, the patients were divided into IgM ≥1.5×ULN group and IgM < 1.5×ULN group, and baseline parameters, treatment response, and prognostic model score were compared between groups. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Cochran-Mantel-Haenszel test was used for subgroup analysis, and forest plots were plotted for related risk values. Results Compared with the UDCA complete response group, the UDCA poor response group had significantly higher proportion of patients with liver cirrhosis, levels of total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol (TC), IgA, and IgM, and positive rate of anti-Gp210 antibody at baseline (χ²=4.596, Z=-9.932, -8.931, -8.361, -7.836, -4.694, -3.242, and -2.115, χ²=15.931, all P < 0.05). The UDCA poor response group had significantly higher Mayo Risk Score, Globe score, and UK-PBC risk score than the UDCA complete response group (t=4.092, Z=-10.910 and -11.646, all P < 0.001). Compared with the normal IgM group, the elevated IgM group had significantly higher levels of AST, ALP, TC, IgA, and IgG and a significantly higher positive rate of anti-Gp210 antibody (Z=-3.774, -5.063, -4.344, -2.051, and -6.144, χ²=25.180, all P < 0.05). IgM had an AUC of 0.552 in predicting poor treatment response. Compared with the IgM < 1.5×ULN group, the IgM ≥1.5×ULN group had significantly higher levels of AST, ALP, TC, and IgG, a significantly higher positive rate of anti-Gp210 antibody, and a significantly higher poor UDCA response rate (Z=-4.193, -5.044, -3.250, and -5.465, χ²=25.204 and 8.948, all P < 0.05). IgM ≥1.5×ULN had an odds ratio of 1.416 (95% confidence interval [CI]: 1.129-1.776, P=0.003) in predicting poor response. The subgroup analysis showed that for patients without liver cirrhosis, IgM ≥1.5×ULN had an odds ratio of 1.821 (95%CI: 1.224-2.711, P=0.003) in predicting poor response. Conclusion Baseline IgM level has an important value in predicting UDCA response. IgM level should be closely monitored during treatment in PBC patients with a high baseline IgM level, and second-line drugs should be given in time if the abnormality persists.
- Primary Biliary Cholangitis,
- Cholestasis,
- Immunoglobulin M,
- Therapeutics

FullText(HTML)

References(21)

References

[1]	HIRSCHFIELD GM, MASON A, LUKETIC V, et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J]. Gastroenterology, 2015, 148(4): 751-761. e8. DOI: 10.1053/j.gastro.2014.12.005.
[2]	LINDOR KD, BOWLUS CL, BOYER J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2019, 69(1): 394-419. DOI: 10.1002/hep.30145.
[3]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Socitety of infectious Diseases, Chinese Mdical Association. Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis) (2015)[J]. J Clin Hepatol, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004. 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J]. 临床肝胆病杂志, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004.
[4]	CORPECHOT C, ABENAVOLI L, RABAHI N, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis[J]. Hepatology, 2008, 48(3): 871-877. DOI: 10.1002/hep.22428.
[5]	CORPECHOT C, CHAZOUILLÈRES O, POUPON R. Early primary biliary cirrhosis: Biochemical response to treatment and prediction of long-term outcome[J]. J Hepatol, 2011, 55(6): 1361-1367. DOI: 10.1016/j.jhep.2011.02.031.
[6]	DICKSON ER, GRAMBSCH PM, FLEMING TR, et al. Prognosis in primary biliary cirrhosis: Model for decision making[J]. Hepatology, 1989, 10(1): 1-7. DOI: 10.1002/hep.1840100102.
[7]	LAMMERS WJ, HIRSCHFIELD GM, CORPECHOT C, et al. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy[J]. Gastroenterology, 2015, 149(7): 1804-1812. e4. DOI: 10.1053/j.gastro.2015.07.061.
[8]	CARBONE M, SHARP SJ, FLACK S, et al. The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis[J]. Hepatology, 2016, 63(3): 930-950. DOI: 10.1002/hep.28017.
[9]	HUANG SS, MA X. The immunological and clinical significance of IgM in primary biliary cirrhosis[J]. Chin J Lab Med, 2013, 36(3): 201-205. DOI: 10.3760/cma.j.issn.1009-9158.2013.03.002. 黄珊珊, 马雄. IgM在原发性胆汁性肝硬化中的免疫学意义及其临床应用[J]. 中华检验医学杂志, 2013, 36(3): 201-205. DOI: 10.3760/cma.j.issn.1009-9158.2013.03.002.
[10]	LIAN C, ZHAO Y, SUN J, et al. Role of cell autophagy in the generation of IgM and hepatic fibrosis in primary biliary cholangitis[J]. Clin Rheumatol, 2020, 39(11): 3499-3506. DOI: 10.1007/s10067-020-05111-6.
[11]	HAO J, LYU J, XING F, et al. Advances in drug therapy for primary biliary cholangitis[J]. J Clin Hepatol, 2020, 36(1): 222-226. DOI: 10.3969/j.issn.1001-5256.2020.01.053. 郝娟, 吕靖, 邢枫, 等. 原发性胆汁性胆管炎的药物治疗进展[J]. 临床肝胆病杂志, 2020, 36(1): 222-226. DOI: 10.3969/j.issn.1001-5256.2020.01.053.
[12]	YANG N, TIAN SY, ZHANG M, et al. Effect of ursodeoxycholic acid combined with glucocorticoid in the treatment of primary biliary cholangitis with autoimmune hepatitis[J]. Med & Pharm J Chin PLA, 2021, 33(3): 72-77. DOI: 10.3969/j.issn.2095-140X.2021.03.016. 杨宁, 田思远, 张苗, 等. 熊去氧胆酸联合糖皮质激素治疗伴自身免疫性肝炎特征原发性胆汁性胆管炎的效果分析[J]. 解放军医药杂志, 2021, 33(3): 72-77. DOI: 10.3969/j.issn.2095-140X.2021.03.016.
[13]	SMETS L, VERBEEK J, KORF H, et al. Improved markers of cholestatic liver injury in patients with primary biliary cholangitis treated with obeticholic acid and bezafibrate[J]. Hepatology, 2021, 73(6): 2598-2600. DOI: 10.1002/hep.31613.
[14]	KIKUCHI K, HSU W, HOSOYA N, et al. Ursodeoxycholic acid reduces CpG-induced IgM production in patients with primary biliary cirrhosis[J]. Hepatol Res, 2009, 39(5): 448-454. DOI: 10.1111/j.1872-034X.2008.00474.x.
[15]	TAKANO K, SAEKI C, OIKAWA T, et al. IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate[J]. J Gastroenterol Hepatol, 2020, 35(4): 663-672. DOI: 10.1111/jgh.14900.
[16]	NAKAMURA M, KONDO H, TANAKA A, et al. Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis[J]. Hepatol Res, 2015, 45(8): 846-855. DOI: 10.1111/hepr.12423.
[17]	ABE K, TAKAHASHI A, NOZAWA Y, et al. The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases[J]. Med Mol Morphol, 2014, 47(3): 162-168. DOI: 10.1007/s00795-014-0082-z.
[18]	LUO Y, BRIGHAM D, BEDNAREK J, et al. Unique cholangiocyte-targeted IgM autoantibodies correlate with poor outcome in biliary atresia[J]. Hepatology, 2021, 73(5): 1855-1867. DOI: 10.1002/hep.31504.
[19]	YANG XL, ZHUANG L, HE HY, et al. Correlation between serum indexes and pathological stages in patients with PBC, and Logistic regression analysis on risk factors of patients with advanced PBC[J]. Chin J Gastroenterol Hepatol, 2019, 28(10): 1157-1161. DOI: 10.3969/j.issn.1006-5709.2019.10.014. 杨晓玲, 庄琳, 和海玉, 等. PBC患者血清学指标与肝组织活检病理分期的关系及进展期PBC危险因素的Logistic回归分析[J]. 胃肠病学和肝病学杂志, 2019, 28(10): 1157-1161. DOI: 10.3969/j.issn.1006-5709.2019.10.014.
[20]	JOHN BV, KHAKOO NS, SCHWARTZ KB, et al. Ursodeoxycholic acid response is associated with reduced mortality in primary biliary cholangitis with compensated cirrhosis[J]. Am J Gastroenterol, 2021, 116(9): 1913-1923. DOI: 10.14309/ajg.0000000000001280.
[21]	GOET JC, MURILLO PEREZ CF, HARMS MH, et al. A comparison of prognostic scores (Mayo, UK-PBC, and GLOBE) in primary biliary cholangitis[J]. Am J Gastroenterol, 2021, 116(7): 1514-1522. DOI: 10.14309/ajg.0000000000001285.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(2) / Tables(5)

Get Citation

PDF

XML

Article Metrics

Article views (608) PDF downloads(82)

Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2022.04.015

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2022.04.015

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content