PREDICTIVE FACTORS OF RESPONSE TO URSODEOXYCHOLIC ACID TREATMENT IN MEXICAN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS

Introduction and Objectives

Non-responders (NR) to ursodeoxycholic acid (UDCA) are at risk of disease progression. The aim was to identify risk factors associated with treatment response (improvement or failure) to UDCA in primary biliary cholangitis (PBC).

Materials and Methods

A case-control study nested within a cohort. Treatment response with UDCA was evaluated with the Barcelona criteria. We compared variables between responders (R) and NR. To evaluate risk factors we performed uni and multivariate logistic regression analyses. A P-value < 0.01 was considered significant.

Results

329 patients with PBC from 5 tertiary-care centers in Mexico, 95.4% women, mean age 52.5±10.9 years. All received UDCA (13-15 mg/kg/day) and reported treatment adherence; 159 (48.3%) NR. In a sample of 119 patients with complete data for analysis, 98.3% women, mean age 49.9±11.4 years, 49 (41.2%) NR. Univariate analysis: albumin 3.5 range=2.0-4.8 vs. 4.0 range=2.6-4.8 mg/dL; and platelet count 118 range=52-518 vs. 200 78-436 cell/10⁹/L were lower in NR (P<0.0001). Bilirubin 1.9 range=1.0-6.4 vs. 1.6 range=1.0-3.0 mg/dL (P<0.0001), and alkaline phosphatase 666 range=143-1445 vs. 480 range=170-1556 IU/L (P=0.01) were higher in NR. NR had a higher proportion of advanced fibrosis/cirrhosis 83.7% vs. 25.7%; P<0.0001; OR=14.8, 95%CI=5.8-37.4; obesity 81.6% vs.31.4%; P<0.0001; OR=9.7, 95%CI=4.0-23.4; autoimmune hepatitis overlap (AIHo) 42.9% vs. 7.1%; P<0.0001; OR=9.8, 95%CI=3.3-28.5; and longer disease course: 5-10 years 44.9% vs. 38.6%; P=0.004; OR=4.3, 95%CI=1.6-11.5; and >10 years 40.8% vs. 8.6%; P<0.0001; OR=17.6, 95%CI=5.2-59.6. The statins add-on enhanced the response to UDCA 60% vs. 16.3%; P<0.0001; OR=0.1, 95%CI=0.05-0.3. Fibrates use, age, AST, ALT, GGT, cholesterol, and INR were not different between groups. The results obtained in the multivariate analysis are shown in Table 1.

Conclusions

Statins improved response to UDCA. AIHo, advanced fibrosis/cirrhosis, bilirubin >2.0 mg/dL, and obesity were factors related to NR.

Conflict of interest: None

Comparison of Clinical and Biochemical Characteristics Between Responders and Non-Responders to UDCA Treatment in Patients with PBC According to Barcelona Criteria: Univariate Analysis

Clinical and Biochemical Characteristics	Responders (n = 70)	Non-Responders (n = 49)	P-value	OR (95% CI)
Age, years	50.5 ± 11.8	48.9 ± 10.9	0.46	NA
Alkaline phosphatase, U/L	480 (170–1556)	666 (143–1445)	0.01	NA
Platelets, x 10?/L	200 (78–436)	118 (52–518)	< 0.0001	NA
Total bilirubin, mg/dL	1.6 (1.0–3.0)	1.9 (1.0–6.4)	< 0.0001	NA
ALT, U/L	75 (21–185)	102 (19–456)	0.07	NA
AST, U/L	77 (23–204)	98 (18–333)	0.12	NA
GGT, U/L	354 (86–1349)	444 (99–1238)	0.05	NA
Cholesterol, mg/dL	215 (85–779)	198 (85–409)	0.29	NA
Albumin, g/dL	4.0 (2.6–4.8)	3.5 (2.0–4.8)	< 0.0001	NA
INR	1.0 (0.7–1.5)	1.0 (0.8–1.5)	0.50	NA
Fibrosis F3 or F4, n (%)	18 (25.7%)	41 (83.7%)	< 0.0001	14.8 (5.8–37.4)
Obesity, n (%)	22 (31.4%)	40 (81.6%)	< 0.0001	9.7 (4.0–23.4)
AIH overlap, n (%)	5 (7.1%)	21 (42.9%)	< 0.0001	9.8 (3.3–28.5)
Dyslipidemia, n (%)	44 (62.9%)	11 (22.4%)	< 0.0001	0.2 (0.08–0.4)
Statin use, n (%)	42 (60%)	8 (16.3%)	< 0.0001	0.1 (0.05–0.3)
Fibrate use, n (%)	33 (47.1%)	23 (46.9%)	0.98	1.0 (0.5–2.1)
PBC duration < 5 years	37 (52.8%)	7 (14.3%)	Ref	Ref
PBC duration 5 to 10 years	27 (38.6%)	22 (44.9%)	0.004	4.3 (1.6–11.5)
PBC duration > 10 years	6 (8.6%)	20 (40.8%)	< 0.0001	17.6 (5.2–59.6)
Total bilirubin > 2.0 mg/dL, n (%)	13 (18.6%)	24 (48.9%)	< 0.0001	4.2 (1.8–9.6)

Multivariate Analysis of Factors Associated with Response or Failure to UDCA Treatment in PBC Patients (Barcelona Criteria)

Variable	OR (95% CI)	P-value
Total bilirubin > 2.0 mg/dL	4.4 (1.1 – 17.0)	0.03
Fibrosis F3 or F4	7.1 (1.9 – 26.6)	0.004
Obesity	4.9 (1.4 – 17.9)	0.015
AIH overlap	20.8 (3.1 – 137.6)	0.002
Statin use *	0.08 (0.02 – 0.4)	0.002
PBC duration 5 to 10 years	1.2 (0.3 – 5.4)	0.78
PBC duration > 10 years	6.1 (1.0 – 38.3)	0.05

Abbreviations: AIH = Autoimmune Hepatitis; CI = Confidence Interval; F3 = Advanced Fibrosis; F4 = Cirrhosis; OR = Odds Ratio; PBC = Primary Biliary Cholangitis; UDCA = Ursodeoxycholic Acid.

* = Protective factor.

Multivariate analysis: Binary logistic regression.