Clinical observation of umbilical cord mesenchymal stem cell therapy on patients with primary biliary cholangitis with poor response to ursodeoxycholic acid

doi:10.3877/cma.j.issn.2095-1221.2022.01.005

Chinese Journal of Cell and Stem Cell(Electronic Edition) ›› 2022, Vol. 12 ›› Issue (01): 26-33. doi: 10.3877/cma.j.issn.2095-1221.2022.01.005

• Original Research • Previous Articles Next Articles

Clinical observation of umbilical cord mesenchymal stem cell therapy on patients with primary biliary cholangitis with poor response to ursodeoxycholic acid

Shida Pan¹, Nan Su², Siyu Wang³, Yingjuan Shen³, Junqing Luan⁴, Lei Shi⁵, Shuangjie Yu⁵, Limin Liu⁵, Fusheng Wang⁶, Fanping Meng⁷^,^†()

^1. Medical School of Chinese PLA, Beijing 100853, China; Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Infectious Diseases Division 4 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^2. The Second School of Clinical Medicine, Southern Medical University, Guangzhou 501515, China; Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Infectious Diseases Division 4 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^3. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Infectious Diseases Division 4 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^4. Department of Infectious Disease, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Infectious Diseases Division 4 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^5. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Biological Injury Treatment Division 1 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^6. Medical School of Chinese PLA, Beijing 100853, China; Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China
^7. Medical School of Chinese PLA, Beijing 100853, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 501515, China; Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China; Infectious Diseases Division 4 Ward, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China

Received:2021-09-08 Online:2022-02-01 Published:2022-03-23
Contact: Fanping Meng

Abstract

Abstract:

Objective

The objective of this study was to evaluate the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSCs) infusion for patients with ursodeoxycholic acid (UDCA) -resistant primary biliary cirrhosis (PBC) , and analyzed related factors influencing the therapeutic effect of UC-MSCs.

Methods

Twenty-nine patients with UDCA-resistant PBC were enrolled in this trial of UC-MSCs from August 2010 to October 2017 in the Fifth Medical Center of Chinese PLA General Hospital. UC-MSCs were intravenously infused 3 times at a density of 1.0×10⁶ cells per kg of body weightat intervals of 4 weeks. The safety of UC-MSCs treatmentwas measured using vital signs, laboratory tests and occurrence of adverse events. The clinical symptoms, liver function indexes, and Child-Pugh scores were used to evaluate the efficacy of UC-MSCs treatment. The "Paris I criteria" was used as the curative effect standard to evaluate the curative effect response of patients after UC-MSCs treatment, to compare the differences in baseline clinical symptoms and liver function between the effective and ineffective patients, and to analyze the related factors affecting the curative effect of UC-MSCs. Student t test was used to analyze age, Mann-Whitney U test was used to compare the time of UDCA treatment, hormone treatment time and laboratory data between the two groups, Wilcoxon rank sum test was used to compare the data between groups, and χ² test was used to compare the gender, clinical symptoms, Child-Pugh grading and other indicators. Multivariate Cox regression analysis on the related factors affecting the efficacy of UC-MSCs.

Results

One patient developed high fever due to severe infection after treatment, and no serious adverse events related to UC-MSCs occurred in all patients. Serum alkaline phosphatase (ALP) [281.00 (182.50, 428.50) vs 201.00 (149.50, 402.00) ], γ-glutamyltransferase (GGT) [156.00 (73.00, 390.00) vs 84.00 (43.50, 312.50) ], and total cholesterol (TC) [5.10 (3.14, 7.69) vs 3.94 (3.00, 6.01) ] decreased after UC-MSCs infusion compared with baseline (P all < 0.05) . Among them, 9 patients (31﹪) had obvious curative effect after treatment and reached the "Paris I standard". Compared with the baseline of 20 patients in the ineffective group, aspartate aminotransferase (AST) [53.00 (46.00, 78.00) vs 93.50 (77.75, 100.75) ], ALP [185.00 (152.50, 295.50) vs 342.00 (237.25, 516.00) ], and total bilirubin (TBIL) [13.10 (11.25, 20.25) vs 58.50 (33.45, 69.33) ] were all lower than those in the ineffective group (P all < 0.05) . Multivariate Cox regression analysis showed that serum TBIL was an important independent factor affecting the efficacy of UC-MSCs [HR:0.817 (95﹪CI: 0.715 ~ 0.935) , P < 0.05].

Conclusions

UC-MSCs infusion was safe, feasible and well-tolerated in PBC patients who resistant to UDCA, and some patients have improved liver function. Serum TBIL was an independent important factor affecting the therapeutic efficacy of UC-MSCs, suggesting that UC-MSCs treatment in the early stage of disease progression with low TBIL may effectively improve and slow down the disease process of patients.

Key words: Primary biliary cholangitis, Mesenchymal stem cells, Ursodeoxycholic acid

Shida Pan, Nan Su, Siyu Wang, Yingjuan Shen, Junqing Luan, Lei Shi, Shuangjie Yu, Limin Liu, Fusheng Wang, Fanping Meng. Clinical observation of umbilical cord mesenchymal stem cell therapy on patients with primary biliary cholangitis with poor response to ursodeoxycholic acid[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(01): 26-33.

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Figures/Tables 4

References 29

1	Gulamhusein AF, Hirschfield GM. Hirschfield GM Primary biliary cholangitis: pathogenesis and therapeutic opportunities[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(2):93-110.
2	Shah RA, Kowdley KV. Current and potential treatments for primary biliary cholangitis[J]. Lancet Gastroenterol Hepatol, 2020, 5(3):306-315.
3	European Association for the Study of the Liver. EASL Clinical Practice Guidelines:management of cholestatic liver diseases[J]. J Hepatol, 2009, 51(2):237-267.
4	Harrell CR, Sadikot R, Pascual J, et al. Mesenchymal stem cell-based therapy of inflammatory lung diseases:current understanding and future perspectives[J]. Stem Cells Int, 2019, 2019:4236973.doi: 10.1155/2019/4236973.
5	Watanabe Y, Tsuchiya A, Terai S. The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future[J]. Clin Mol Hepatol, 2021, 27(1):70-80.
6	Sun L, Wang D, Liang J, et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus[J]. Arthritis Rheum, 2010, 62(8):2467-2475.
7	Liu Y, Mu R, Wang S, et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis[J]. Arthritis Res Ther, 2010, 12(6):R210.doi: 10.1186/ar3187.
8	Ono-Uruga Y, Ikeda Y, Matsubara Y. Platelet production using adipose-derived mesenchymal stem cells:Mechanistic studies and clinical application[J]. J Thromb Haemost, 2021, 19(2):342-350.
9	Yun CW, Lee SH. Potential and therapeutic efficacy of cell-based therapy using mesenchymal stem cells for acute/chronic kidney disease[J]. Int J Mol Sci, 2019, 20(7):1619. doi: 10.3390/ijms20071619.
10	Meng F, Xu R, Wang S, et al. Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19:a phase 1 clinical trial[J]. Signal Transduct Target Ther, 2020, 5(1):172.
11	Yang X, Meng Y, Han Z, et al. Mesenchymal stem cell therapy for liver disease:full of chances and challenges[J]. Cell Biosci, 2020, 10:123.
12	Peng L, Xie DY, Lin BL, et al. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B:short-term and long-term outcomes[J]. Hepatology, 2011, 54(3):820-828.
13	Amer ME, El-Sayed SZ, El-Kheir WA, et al. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells[J]. Eur J Gastroenterol Hepatol, 2011, 23(10):936-941.
14	Suk KT, Yoon JH, Kim MY, et al. Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis:phase 2 trial[J]. Hepatology, 2016, 64(6):2185-2197.
15	Shi M, Liu Z, Wang Y, et al. A pilot study of mesenchymal stem cell therapy for acute liver allograft rejection[J]. Stem Cells Transl Med, 2017, 6(12):2053-2061.
16	Liang J, Zhang H, Zhao C, et al. Effects of allogeneic mesenchymal stem cell transplantation in the treatment of liver cirrhosis caused by autoimmune diseases[J]. Int J Rheum Dis, 2017, 20(9):1219-1226.
17	Wang L, Li J, Liu H, et al. Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in patients with primary biliary cirrhosis[J]. J Gastroenterol Hepatol, 2013, Suppl 1:85-92.
18	Wang L, Han Q, Chen H, et al. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis[J]. Stem Cells Dev, 2014, 23(20):2482-2489.
19	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.
20	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.
21	徐小元，丁惠国，李文刚等.肝硬化诊治指南[J].临床肝胆病杂志，2019，35(11):2408-2425.
22	Li S, Bi Y, Duan Z, et al. Stem cell transplantation for treating liver diseases:progress and remaining challenges[J]. Am J Transl Res, 2021, 13(5):3954-3966.
23	Liu WH, Song FQ, Ren LN, et al. The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases[J]. J Cell Mol Med, 2015, 19(3):511-520.
24	Wang D, Zhang H, Liang J, et al. Effect of allogeneic bone marrow-derived mesenchymal stem cells transplantation in a polyI:C-induced primary biliary cirrhosis mouse model[J]. Clin Exp Med, 2011, 11(1):25-32.
25	Fisk JD, Ritvo PG, Ross L, et al. Measuring the functional impact of fatigue:initial validation of the fatigue impact scale[J]. Clin Infect Dis, 1994, Suppl 1:S79-83.
26	Elman S, Hynan LS, Gabriel V, et al. The 5-D itch scale:a new measure of pruritus[J]. Br J Dermatol, 2010, 162(3):587-593.
27	Brückner S, Zipprich A, Hempel M, et al. Improvement of portal venous pressure in cirrhotic rat livers by systemic treatment with adipose tissue-derived mesenchymal stromal cells[J]. Cytotherapy, 2017, 19(12):1462-1473.
28	Pietrosi G, Fernández-Iglesias A, Pampalone M, et al. Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats[J]. Liver Int, 2020, 40(10):2500-2514.
29	Wan YM, Li ZQ, Liu C, et al. Mesenchymal stem cells reduce alcoholic hepatitis in mice via suppression of hepatic neutrophil and macrophage infiltration, and of oxidative stress[J]. PloS one, 2020, 15(2):e0228889.doi: 10.1371/journal.pone.0228889.

指标		有效组（n = 9）	无效组（n = 20）	t/Z值	P值
年龄（岁， ± s）		52.44±9.18	52.30±8.22	0.042	0.967
性别					0.532
	男（例）	0	3
	女（例）	9	17
临床症状
	乏力（例）	9	20		1.000
	瘙痒（例）	2	5		0.874
	腹胀（例）	3	3		0.444
	水肿（例）	0	4		0.417
	腹水（例）	2	3		1.000
	脾大（例）	4	13		0.422
生化指标
	ALT[U/L，M （Q_L，Q_U）]	50.00（21.00，82.00）	41.50（29.75，66.75）	0.377	0.720
	AST[U/L，M （Q_L，Q_U）]	53.00（46.00，78.00）	93.00（77.75，100.75）	2.475	0.012
	ALP[U/L，M （Q_L，Q_U）]	185.00（152.50，295.50）	342.00（237.25，516.00）	2.192	0.027
	GGT[U/L，M （Q_L，Q_U）]	111.00（71.50，286.50）	173.50（74.00，442.00）	0.660	0.524
	TBIL[μmol/L，M （Q_L，Q_U）]	13.10（11.25，20.25）	58.50（33.45，69.33）	4.243	< 0.001
Child-Pugh分级					0.412
	A（例）	7	11
	B（例）	2	9
	Child-Pugh评分[分，M （Q_L，Q_U）]	5.00（5.00，6.50）	6.00（6.00，7.00）	1.821	0.069
治疗
	UDCA治疗时间[月，M （Q_L，Q_U）]	33.00（12.00，40.00）	39.00（14.50，60.75）	0.477	0.648
	合并激素治疗人数（例）	2	4		1.000
	激素治疗时间[月，M （Q_L，Q_U）]	18.00（9.00，27.00）	10.00（7.00，27.00）	0.926	0.533

指标		有效组（n = 9）	无效组（n = 20）	t/Z值	P值
年龄（岁， ± s）		52.44±9.18	52.30±8.22	0.042	0.967
性别					0.532
	男（例）	0	3
	女（例）	9	17
临床症状
	乏力（例）	9	20		1.000
	瘙痒（例）	2	5		0.874
	腹胀（例）	3	3		0.444
	水肿（例）	0	4		0.417
	腹水（例）	2	3		1.000
	脾大（例）	4	13		0.422
生化指标
	ALT[U/L，M （Q_L，Q_U）]	50.00（21.00，82.00）	41.50（29.75，66.75）	0.377	0.720
	AST[U/L，M （Q_L，Q_U）]	53.00（46.00，78.00）	93.00（77.75，100.75）	2.475	0.012
	ALP[U/L，M （Q_L，Q_U）]	185.00（152.50，295.50）	342.00（237.25，516.00）	2.192	0.027
	GGT[U/L，M （Q_L，Q_U）]	111.00（71.50，286.50）	173.50（74.00，442.00）	0.660	0.524
	TBIL[μmol/L，M （Q_L，Q_U）]	13.10（11.25，20.25）	58.50（33.45，69.33）	4.243	< 0.001
Child-Pugh分级					0.412
	A（例）	7	11
	B（例）	2	9
	Child-Pugh评分[分，M （Q_L，Q_U）]	5.00（5.00，6.50）	6.00（6.00，7.00）	1.821	0.069
治疗
	UDCA治疗时间[月，M （Q_L，Q_U）]	33.00（12.00，40.00）	39.00（14.50，60.75）	0.477	0.648
	合并激素治疗人数（例）	2	4		1.000
	激素治疗时间[月，M （Q_L，Q_U）]	18.00（9.00，27.00）	10.00（7.00，27.00）	0.926	0.533

指标	基线	12周	24周	基线比12周		基线比24周
指标	基线	12周	24周	Z值	P值	Z值	P值
ALT （U/L）	45.00 （27.50，71.50）	47.00 （19.50，70.00）	27.00 （18.00，50.50）	0.805	0.430	1.934	0.053
AST （U/L）	83.00 （57.50，98.50）	86.00 （58.00，131.50）	67.00 （50.50，104.50）	1.845	0.065	0.930	0.361
ALP （U/L）	281.00 （182.50，428.50）	287 （187.50，379.00）	201.00 （149.50，402.00）	0.487	0.635	2.238	0.024
GGT （U/L）	156.00 （73.00，390.00）	134.00 （56.00，352.00）	84.00 （43.50，312.50）	1.449	0.151	3.071	0.001
TBIL （umol/L）	36.90 （20.25，61.35）	30.00 （18.05，83.50）	37.1 （18.05，89.90）	0.108	0.919	2.000	0.046
TC （mmol/L）	5.10 （3.14，7.69）	4.36 （3.05，6.03）	3.94 （3.00，6.01）	2.292	0.021	2.768	0.005
ALB （g/L）	34.00 （32.00，37.50）	35.00 （33.00，37.5）	34.00 （28.50，38.00）	1.469	0.146	1.242	0.220
AchE （U/L）	4341.00 （2319.00，5528.00）	4223.00 （2687.00，6022.00）	4124.00 （2695.50，5594.50）	0.865	0.396	0.703	0.495
IgG （g/L）	14.38 （13.03，21.03）	15.83 （12.71，21.47）	15.36 （12.86，23.35）	0.615	0.552	1.070	0.295
IgA （g/L）	3.30 （1.93，3.82）	3.04 （1.81，3.52）	2.94 （1.97，4.07）	0.877	0.390	0.250	0.809
IgM （g/L）	2.84 （1.53，3.89）	2.87 （1.63，5.23）	2.57 （1.75，5.30）	0.159	0.880	0.348	0.736
AFP （ng/mL）	3.80 （2.38，8.00）	3.65 （2.31，10.10）	6.91 （3.17，10.50）	1.197	0.238	1.815	0.070
WBC （10⁹/L）	4.33 （3.02，5.09）	3.89 （3.17，4.75）	4.52 （3.24，5.59）	0.281	0.786	1.254	0.215
Hb （g/L）	110.00 （96.50，122.00）	113.00 （103.50，116.50）	109.00 （102.50，115.50）	0.876	0.389	0.536	0.602
PLT （10⁹/L）	103.00 （67.00，182.50）	104.00 （67.00，179.00）	102.00 （60.70，168.00）	1.142	0.261	1.644	0.102
PT （s）	11.90 （10.05，12.95）	11.50 （10.40，12.70）	11.80 （10.45，13.65）	0.814	0.426	2.416	0.014
PA （﹪）	83.80 （72.70，103.95）	84.00 （72.75，103.90）	83.00 （68.75，103.80）	0.685	0.503	1.892	0.058
INR	1.05 （0.86，1.14）	1.08 （0.90，1.11）	1.04 （0.91，1.20）	1.302	0.198	2.910	0.001
UREA （mmol/L）	4.30 （3.00，5.40）	4.10 （2.95，5.55）	4.60 （2.95，5.55）	0.216	0.836	0.373	0.718
CRE （μmol/L）	60.00 （53.00，69.50）	62.00 （56.00，71.00）	62.00 （50.50，71.50）	1.180	0.245	0.217	0.835
UA （μmol/L）	189.00 （158.50，281.00）	199.00 （159.00，303.00）	189.00 （152.00，288.50）	0.227	0.827	0.681	0.508
Child-Pugh评分（分）	6.00 （5.00，7.00）	6.00 （5.00，7.00）	6.00 （5.50，7.50）	0.258	1.000	1.827	0.078

指标	基线	12周	24周	基线比12周		基线比24周
指标	基线	12周	24周	Z值	P值	Z值	P值
ALT （U/L）	45.00 （27.50，71.50）	47.00 （19.50，70.00）	27.00 （18.00，50.50）	0.805	0.430	1.934	0.053
AST （U/L）	83.00 （57.50，98.50）	86.00 （58.00，131.50）	67.00 （50.50，104.50）	1.845	0.065	0.930	0.361
ALP （U/L）	281.00 （182.50，428.50）	287 （187.50，379.00）	201.00 （149.50，402.00）	0.487	0.635	2.238	0.024
GGT （U/L）	156.00 （73.00，390.00）	134.00 （56.00，352.00）	84.00 （43.50，312.50）	1.449	0.151	3.071	0.001
TBIL （umol/L）	36.90 （20.25，61.35）	30.00 （18.05，83.50）	37.1 （18.05，89.90）	0.108	0.919	2.000	0.046
TC （mmol/L）	5.10 （3.14，7.69）	4.36 （3.05，6.03）	3.94 （3.00，6.01）	2.292	0.021	2.768	0.005
ALB （g/L）	34.00 （32.00，37.50）	35.00 （33.00，37.5）	34.00 （28.50，38.00）	1.469	0.146	1.242	0.220
AchE （U/L）	4341.00 （2319.00，5528.00）	4223.00 （2687.00，6022.00）	4124.00 （2695.50，5594.50）	0.865	0.396	0.703	0.495
IgG （g/L）	14.38 （13.03，21.03）	15.83 （12.71，21.47）	15.36 （12.86，23.35）	0.615	0.552	1.070	0.295
IgA （g/L）	3.30 （1.93，3.82）	3.04 （1.81，3.52）	2.94 （1.97，4.07）	0.877	0.390	0.250	0.809
IgM （g/L）	2.84 （1.53，3.89）	2.87 （1.63，5.23）	2.57 （1.75，5.30）	0.159	0.880	0.348	0.736
AFP （ng/mL）	3.80 （2.38，8.00）	3.65 （2.31，10.10）	6.91 （3.17，10.50）	1.197	0.238	1.815	0.070
WBC （10⁹/L）	4.33 （3.02，5.09）	3.89 （3.17，4.75）	4.52 （3.24，5.59）	0.281	0.786	1.254	0.215
Hb （g/L）	110.00 （96.50，122.00）	113.00 （103.50，116.50）	109.00 （102.50，115.50）	0.876	0.389	0.536	0.602
PLT （10⁹/L）	103.00 （67.00，182.50）	104.00 （67.00，179.00）	102.00 （60.70，168.00）	1.142	0.261	1.644	0.102
PT （s）	11.90 （10.05，12.95）	11.50 （10.40，12.70）	11.80 （10.45，13.65）	0.814	0.426	2.416	0.014
PA （﹪）	83.80 （72.70，103.95）	84.00 （72.75，103.90）	83.00 （68.75，103.80）	0.685	0.503	1.892	0.058
INR	1.05 （0.86，1.14）	1.08 （0.90，1.11）	1.04 （0.91，1.20）	1.302	0.198	2.910	0.001
UREA （mmol/L）	4.30 （3.00，5.40）	4.10 （2.95，5.55）	4.60 （2.95，5.55）	0.216	0.836	0.373	0.718
CRE （μmol/L）	60.00 （53.00，69.50）	62.00 （56.00，71.00）	62.00 （50.50，71.50）	1.180	0.245	0.217	0.835
UA （μmol/L）	189.00 （158.50，281.00）	199.00 （159.00，303.00）	189.00 （152.00，288.50）	0.227	0.827	0.681	0.508
Child-Pugh评分（分）	6.00 （5.00，7.00）	6.00 （5.00，7.00）	6.00 （5.50，7.50）	0.258	1.000	1.827	0.078

指标	单因素分析		多因素分析
指标	HR （95﹪CI）	P值	HR（95﹪CI）	P值
AST	0.974 （0.950 ~ 0.998）	0.036	1.016 （0.980 ~ 1.054）	0.384
ALP	0.995 （0.998 ~ 1.001）	0.084
GGT	0.999 （0.996 ~ 1.002）	0.463
TBIL	0.835 （0.740 ~ 0.941）	0.003	0.817 （0.715 ~ 0.935）	0.003
UDCA治疗时间	0.989 （0.960 ~ 1.019）	0.476
Child-Pugh评分	0.461 （0.200 ~ 1.066）	0.070

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Clinical observation of umbilical cord mesenchymal stem cell therapy on patients with primary biliary cholangitis with poor response to ursodeoxycholic acid

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