Total bile acid better reflects the early biochemical biliary drainage response after endoscopic retrograde cholangiopancreatography

Table 1 Baseline characteristics according to early biochemical drainage response after endoscopic retrograde cholangiopancreatography, n (%)/mean ± SD

Variable	No response	Response	P value
n	618	278
Age, years	57.68 ± 14.32	57.50 ± 15.69	0.867
Male sex	411 (66.5)	178 (64.0)	0.518
Initial ERCP	442 (71.5)	238 (85.6)	< 0.001
Main diagnosis			0.001
Stone disease	436 (70.6)	225 (80.9)
Malignant stricture	89 (14.4)	36 (12.9)
Benign stricture	80 (12.9)	12 (4.3)
Other biliary disease	6 (1.0)	0 (0.0)
Clonorchiasis	5 (0.8)	4 (1.4)
Biliary dilation of unknown cause	2 (0.3)	1 (0.4)
Drainage strategy			< 0.001
ENBD only	347 (56.1)	203 (73.0)
ENBD + stent	87 (14.1)	26 (9.4)
No continuous drainage device	9 (1.5)	4 (1.4)
Stent only	175 (28.3)	45 (16.2)
Common bile duct diameter, mm	10.15 ± 6.01	11.53 ± 6.16	0.002
Stone clearance			< 0.001
No/partial clearance	47 (7.6)	14 (5.0)
Complete clearance	405 (65.5)	230 (82.7)
Baseline Tbil	87.75 ± 118.75	111.36 ± 98.09	0.004
Baseline Dbil	68.85 ± 99.26	85.42 ± 75.87	0.013
Baseline ALP	234.44 ± 213.50	269.77 ± 192.43	0.019
Baseline GGT	328.31 ± 349.96	539.38 ± 585.05	< 0.001
Baseline TBA	192.09 ± 270.53	315.57 ± 537.64	< 0.001
Baseline WBC	7.97 ± 4.14	9.37 ± 4.84	< 0.001

Early biochemical drainage response was defined according to the study criteria described in the Methods section. ERCP: Endoscopic retrograde cholangiopancreatography; ENBD: Endoscopic nasobiliary drainage; Tbil: Total bilirubin; Dbil: Direct bilirubin; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TBA: Total bile acid; WBC: White blood cell count.

Table 2 Three-time-point changes in key liver biochemical markers before and after endoscopic retrograde cholangiopancreatography, median (interquartile range)

Marker	Baseline	24 hours after ERCP	5 days after ERCP	P value (baseline vs 24 hours after ERCP)	P value (baseline vs 5 days after ERCP)
Tbil	49.30 (15.95, 126.40)	39.85 (19.48, 103.83)	29.35 (15.70, 83.42)	< 0.001	< 0.001
Dbil	37.10 (7.80, 101.48)	26.20 (9.40, 83.10)	19.80 (8.30, 65.90)	< 0.001	< 0.001
ALP	184.00 (109.50, 294.50)	173.00 (108.00, 282.00)	151.00 (102.00, 243.00)	< 0.001	< 0.001
GGT	284.00 (108.00, 552.00)	255.00 (108.00, 457.00)	198.00 (92.00, 353.50)	< 0.001	< 0.001
TBA	123.70 (22.05, 326.40)	10.40 (2.80, 83.50)	4.80 (1.80, 18.35)	< 0.001	< 0.001

P values were calculated for paired comparisons between baseline and postoperative measurements. Sample sizes differed slightly across markers because of missing laboratory measurements. ERCP: Endoscopic retrograde cholangiopancreatography; Tbil: Total bilirubin; Dbil: Direct bilirubin; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TBA: Total bile acid.

Table 3 Generalized estimating equation analyses of postoperative time effects after endoscopic retrograde cholangiopancreatography

Marker	Variable	β	SE	Wald χ2	P value
Tbil	Time: 24 hours after ERCP vs baseline	-0.025	0.020	1.567	0.211
	Time: 5 days after ERCP vs baseline	-0.229	0.023	98.944	< 0.001
Dbil	Time: 24 hours after ERCP vs baseline	-0.063	0.022	8.362	0.004
	Time: 5 days after ERCP vs baseline	-0.249	0.025	99.213	< 0.001
TBA	Time: 24 hours after ERCP vs baseline	-1.633	0.054	929.271	< 0.001
	Time: 5 days after ERCP vs baseline	-2.322	0.065	1265.955	< 0.001
GGT	Time: 24 hours after ERCP vs baseline	-0.074	0.015	24.117	< 0.001
	Time: 5 days after ERCP vs baseline	-0.269	0.018	217.510	< 0.001
ALP	Time: 24 hours after ERCP vs baseline	-0.044	0.008	27.219	< 0.001
	Time: 5 days after ERCP vs baseline	-0.145	0.011	163.313	< 0.001

Generalized estimating equation models were fitted separately for each marker and adjusted for diagnosis category and drainage strategy. Only the primary time effects comparing 24 hours after endoscopic retrograde cholangiopancreatography and 5 days after endoscopic retrograde cholangiopancreatography with baseline are shown. Negative coefficients indicate lower postoperative values relative to baseline. ERCP: Endoscopic retrograde cholangiopancreatography; Tbil: Total bilirubin; Dbil: Direct bilirubin; TBA: Total bile acid; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase.

Table 4 Cross-marker comparisons of total bile acid, direct bilirubin, and total bilirubin after endoscopic retrograde cholangiopancreatography (descriptive relative declines)

Marker	Time point	n	Median (interquartile range)
TBA	24 hours after ERCP	836	79.69 (42.81, 95.37)
TBA	5 days after ERCP	836	92.00 (56.23, 98.52)
Dbil	24 hours after ERCP	836	5.70 (-31.98, 34.92)
Dbil	5 days after ERCP	836	18.58 (-22.85, 52.99)
Tbil	24 hours after ERCP	836	3.98 (-35.82, 32.32)
Tbil	5 days after ERCP	836	17.91 (-24.21, 52.57)

Table 4 presents descriptive relative declines from baseline. TBA: Total bile acid; Dbil: Direct bilirubin; Tbil: Total bilirubin; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 5 Cross-marker comparisons of total bile acid, direct bilirubin, and total bilirubin after endoscopic retrograde cholangiopancreatography (paired comparisons)

Time point	Comparison	n	Median decline of first marker (%)	Median decline of second marker (%)	P value	Adjusted P value
24 hours after ERCP	TBA vs Dbil	836	79.69	5.70	< 0.001	< 0.001
	TBA vs Tbil	836	79.69	3.98	< 0.001	< 0.001
5 days after ERCP	TBA vs Dbil	836	92.00	18.58	< 0.001	< 0.001
	TBA vs Tbil	836	92.00	17.91	< 0.001	< 0.001

Table 5 presents paired within-patient comparisons of relative decline between markers. Higher relative decline indicates greater postoperative reduction from baseline. ERCP: Endoscopic retrograde cholangiopancreatography; TBA: Total bile acid; Dbil: Direct bilirubin; Tbil: Total bilirubin.

Table 6 Unified generalized estimating equation model comparing total bile acid, gamma-glutamyl transferase, and alkaline phosphatase after endoscopic retrograde cholangiopancreatography

Variable	Estimate	SE	Wald χ2	P value
Marker: GGT (vs TBA at 24 hours after ERCP)	1.537	0.057	725.857	< 0.001
Marker: ALP (vs TBA at 24 hours after ERCP)	1.566	0.056	793.137	< 0.001
Time: 5 days after ERCP vs 24 hours after ERCP (for TBA)	-0.719	0.086	70.145	< 0.001
Interaction: GGT × 5 days after ERCP	0.523	0.089	34.226	< 0.001
Interaction: ALP × 5 days after ERCP	0.616	0.087	49.795	< 0.001

The unified model was based on the log-transformed postoperative-to-baseline ratio and was adjusted for diagnosis category and drainage strategy. Positive coefficients for marker terms indicate smaller relative declines than total bile acid at 24 hours after endoscopic retrograde cholangiopancreatography. Significant interaction terms indicate temporal patterns that differ from that of total bile acid between 24 hours and 5 days after endoscopic retrograde cholangiopancreatography. ERCP: Endoscopic retrograde cholangiopancreatography; TBA: Total bile acid; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase.

Table 7 Multivariable logistic regression analysis of factors associated with early biochemical drainage response after endoscopic retrograde cholangiopancreatography

Variable	OR (95%CI)	P value
Initial ERCP	1.772 (1.163-2.748)	0.009
Drainage strategy: ENBD + stent	0.496 (0.284-0.838)	0.011
Drainage strategy: Stent only	0.564 (0.354-0.887)	0.015
Common bile duct diameter, mm	1.026 (0.997-1.056)	0.083
Baseline Tbil	1.003 (1.001-1.005)	< 0.001
Baseline ALP	0.999 (0.998-1.000)	0.105
Baseline GGT	1.002 (1.001-1.002)	< 0.001
Baseline WBC	1.042 (1.006-1.080)	0.021

Only variables retained in the final multivariable model are shown. Odds ratios were estimated for early biochemical drainage response after endoscopic retrograde cholangiopancreatography. Continuous variables were modeled per unit increase. ERCP: Endoscopic retrograde cholangiopancreatography; OR: Odds ratio; CI: Confidence interval; ENBD: Endoscopic nasobiliary drainage; Tbil: Total bilirubin; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; WBC: White blood cell count.