Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study

doi:10.3748/wjg.v31.i45.113060

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World Journal of Gastroenterology

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

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World J Gastroenterol. Dec 7, 2025; 31(45): 113060
Published online Dec 7, 2025. doi: 10.3748/wjg.v31.i45.113060

Table 1 Baseline demographic characteristics of refractory gastroesophageal reflux disease and non-refractory gastroesophageal reflux disease patients, mean ± SD/n (%)

Baseline characteristics	Refractory GERD (n = 256)	Non-refractory GERD (n = 655)	P value
Age (years)	54.79 ± 12.52	52.54 ± 11.94	0.012^a
Gender
Male	94 (36.72)	252 (38.47)	0.624
Female	162 (63.28)	403 (61.53)	0.624
BMI (kg/m²)	23.33 ± 2.71	23.25 ± 2.44	0.684
Disease duration (years)	4.12 ± 3.46	3.05 ± 3.01	< 0.001^c

^aP < 0.05.

^cP < 0.001.

BMI: Body mass index; GERD: Gastroesophageal reflux disease.

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Table 2 Characteristics of clinical manifestations of refractory gastroesophageal reflux disease and non-refractory gastroesophageal reflux disease patients, mean ± SD/n (%)

Symptom	Refractory GERD (n = 256)	Non-refractory GERD (n = 655)	z/χ² value	P value
Typical symptoms
Heartburn, median IQR	2 (2.0, 4.0)	2 (0.0, 4.0)	-1.388	0.165
Regurgitation, median IQR	2 (2.0, 4.0)	2 (2.0, 4.0)	-0.55	0.582
Esophageal chest pain, median IQR	2 (0.0, 2.0)	0 (0.0, 2.0)	-2.543	0.011^a
Atypical symptoms
Nausea	102 (39.84)	226 (34.50)	2.278	0.131
Belching	150 (58.59)	360 (54.96)	0.985	0.321
Sensation of pharyngeal obstruction	101 (39.45)	199 (30.38)	6.858	0.009^b
Dryness or soreness of the throat	105 (41.02)	245 (37.40)	1.014	0.314
Cough	109 (42.58)	243 (37.10)	2.33	0.127
Epigastric pain or burning	109 (42.58)	254 (38.78)	1.109	0.292
Abdominal distension	130 (50.78)	319 (48.70)	0.318	0.573
Poor appetite	124 (48.44)	284 (43.36)	1.92	0.166
Constipation	113 (44.14)	239 (36.49)	4.546	0.033^a
Diarrhea	37 (14.45)	99 (15.11)	0.063	0.801
Number of atypical symptoms	4.22 ± 2.18	3.77 ± 2.08	2.901	0.004^c

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

IQR: Interquartile range; GERD: Gastroesophageal reflux disease.

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Table 3 Comparison of lifestyle and dietary habits between refractory gastroesophageal reflux disease and non-refractory gastroesophageal reflux disease patients, n (%)

Factors	Refractory GERD (n = 256)	Non-refractory GERD (n = 655)	χ² value	P value
Dietary habits
Eating beyond fullness	38 (14.84)	63 (9.62)	5.098	0.024^a
Skipping breakfast	29 (11.33)	75 (11.45)	0.003	0.958
Eating before bedtime	35 (13.67)	100 (15.27)	0.371	0.542
Sweet food	60 (23.44)	149 (22.75)	0.049	0.824
Greasy food	54 (21.09)	134 (20.46)	0.045	0.831
Raw or cold foods	18 (7.03)	63 (9.62)	1.521	0.218
Spicy foods	69 (26.95)	151 (23.05)	1.528	0.216
Sour foods	25 (9.77)	49 (7.48)	1.287	0.257
Hot foods	37 (14.45)	84 (12.82)	0.424	0.515
Strong tea	41 (16.02)	101 (15.42)	0.05	0.824
Chocolate	23 (8.98)	69 (10.53)	0.487	0.485
Coffee	56 (21.88)	141 (21.53)	0.013	0.909
Carbonated beverages	31 (12.11)	75 (11.45)	0.078	0.780
Dairy products	57 (22.27)	165 (25.19)	0.855	0.355
Lifestyle habits
Smoking	23 (8.98)	80 (12.21)	1.914	0.166
Drinking	47 (18.36)	120 (18.32)	0.001	0.989
Staying up late	37 (14.45)	129 (19.69)	3.394	0.065
Early awakening	44 (17.19)	128 (19.54)	0.666	0.414
Frequent dreaming	49 (19.14)	94 (14.35)	3.191	0.074
Exercise	40 (15.63)	173 (26.41)	11.956	0.001^b

^aP < 0.05.

^bP < 0.01.

GERD: Gastroesophageal reflux disease.

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Table 4 Assessment of somatic symptoms, mental and psychological health status, and quality of life of refractory gastroesophageal reflux disease and non-refractory gastroesophageal reflux disease patients, mean ± SD

Variable	Refractory GERD (n = 256)	Non-refractory GERD (n = 655)	t value	P value
Somatic symptom
SSS-CN score	28.85 ± 7.68	27.00 ± 6.91	3.512	< 0.001^c
Mental and psychological health status
HADS-A score	5.30 ± 3.78	3.76 ± 3.74	5.551	< 0.001^c
HADS-D score	6.62 ± 4.07	5.07 ± 4.16	5.075	< 0.001^c
Quality of life
GERD-HRQL score	11.34 ± 6.76	9.66 ± 6.52	3.467	0.001^b
SF-36 score	114.35 ± 18.70	112.64 ± 18.35	1.255	0.21

^bP < 0.01.

^cP < 0.001.

SSS-CN: Somatic symptom scale-China; HADS-A: Hospital anxiety and depression scale-anxiety; HADS-D: Hospital anxiety and depression scale-depression; GERD-HRQL: Gastroesophageal reflux disease health-related quality of life; SF-36: 36-Item short form survey; GERD: Gastroesophageal reflux disease.

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Table 5 Correlation analysis between exercise and other relevant variables

Variable	Exercise
Variable	r/χ² value	P value
Esophageal chest pain	-0.158	0.011^a
Eating beyond fullness	0.265	0.607
Sensation of pharyngeal obstruction	0.006	0.939
Constipation	0.330	0.566
Disease duration	-0.013	0.831
SSS-CN score	-0.016	0.805
HADS-A score	-0.163	0.009^b
HADS-D score	-0.161	0.010^a
GERD-HRQL score	-0.224	< 0.001^c

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

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Table 6 Correlation analysis between clinical manifestations and somatic symptom scale-China score, hospital anxiety and depression scale-anxiety score, and hospital anxiety and depression scale-depression score

Factors	SSS-CN score		HADS-A score		HADS-D score
Factors	r/ρ value	P value	r/ρ value	P value	r/ρ value	P value
Esophageal chest pain	0.142	0.023^a	0.268	< 0.001^c	0.187	0.003^b
Sensation of pharyngeal obstruction	-0.140	0.025^a	-0.184	0.003^b	-0.106	0.092
Constipation	-0.260	< 0.001^c	-0.223	< 0.001^c	-0.148	0.018^a

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

SSS-CN: Somatic symptom scale-China; HADS-A: Hospital anxiety and depression scale-anxiety; HADS-D: Hospital anxiety and depression scale-depression.

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Table 7 Correlation analysis between lifestyle and dietary habits and somatic symptom scale-China score, hospital anxiety and depression scale-anxiety score, and hospital anxiety and depression scale-depression score

Factors	SSS-CN score		HADS-A score		HADS-D score
Factors	r value	P value	r value	P value	r value	P value
Dietary habits
Eating beyond fullness	-0.077	0.22	-0.007	0.905	-0.018	0.778
Skipping breakfast	-0.068	0.278	-0.037	0.557	-0.052	0.408
Eating before bedtime	-0.089	0.154	-0.104	0.097	-0.11	0.078
Sweet food	0.033	0.604	0.098	0.118	-0.007	0.915
Greasy food	0.082	0.189	0.087	0.165	0.029	0.643
Raw or cold foods	-0.063	0.315	0.050	0.423	0.012	0.852
Spicy foods	-0.035	0.580	-0.015	0.816	0.008	0.901
Sour foods	-0.015	0.812	0.065	0.303	0.099	0.115
Hot foods	-0.088	0.162	0.006	0.920	0.0350	0.576
Strong tea	-0.035	0.579	0.046	0.462	-0.004	0.944
Chocolate	-0.033	0.601	0.076	0.227	0.122	0.052
Coffee	-0.035	0.578	0.047	0.452	0.053	0.403
Carbonated beverages	0.115	0.067	0.185	0.003^b	0.207	0.001^b
Dairy products	-0.053	0.396	0.107	0.086	0.102	0.103
Lifestyle habits
Smoking	0.015	0.808	-0.033	0.600	-0.026	0.676
Drinking	0.199	0.001^b	0.027	0.666	0.032	0.607
Staying up late	-0.057	0.362	0.001	0.995	-0.020	0.755
Early awakening	-0.057	0.360	-0.115	0.067	-0.089	0.156
Frequent dreaming	-0.088	0.158	-0.048	0.443	-0.117	0.062

^bP < 0.01.

SSS-CN: Somatic symptom scale-China; HADS-A: Hospital anxiety and depression scale-anxiety; HADS-D: Hospital anxiety and depression scale-depression.

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Table 8 Multivariate binary logistic regression analysis of factors associated with refractory gastroesophageal reflux disease

Factors	β	SE	Wald	P value	OR	OR (95%CI)
Age	-0.009	0.006	1.784	0.182	0.991	0.979-1.004
Disease duration	-0.089	0.023	14.943	< 0.001^c	0.915	0.874-0.957
Eating beyond fullness	0.362	0.231	2.453	0.117	1.436	0.913-2.260
Exercise	0.588	0.207	8.091	0.004^b	1.800	1.201-2.698
Esophageal chest pain	-0.008	0.061	0.018	0.892	0.992	0.879-1.118
Sensation of pharyngeal obstruction	0.232	0.171	1.833	0.176	1.261	0.901-1.763
Constipation	0.135	0.163	0.685	0.408	1.145	0.831-1.576
SSS-CN score	-0.014	0.013	1.239	0.266	0.986	0.961-1.011
HADS-A score	-0.085	0.024	13.122	< 0.001^c	0.918	0.877-0.962
GERD-HRQL score	0.006	0.014	0.161	0.689	1.006	0.978-1.034

^bP < 0.01.

^cP < 0.001.

OR: Odds ratio; CI: Confidence interval; SSS-CN: Somatic symptom scale-China; HADS-A: Hospital anxiety and depression scale-anxiety; GERD-HRQL: Gastroesophageal reflux disease health-related quality of life.

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Citation: Zhang N, Wang Y, Fang SS, Han M, Zheng QW, Zhu YY, Zhang MY, Li JJ, Cui LX, Tian JL, Deng YH, Zhu SL, Ni HM, Zhou L, Zuo GL, Huang TS, Liao Q, Li XQ, Shang YY, Wang YJ, Tian Y, Ge LY, Han HQ, Hu WM, Jiang Y, Li YJ, Mao X, Yang LH, Yao JM, Zheng X, Wang HW, Fang SQ. Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study. World J Gastroenterol 2025; 31(45): 113060
URL: https://www.wjgnet.com/1007-9327/full/v31/i45/113060.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i45.113060

Zhang N, Wang Y, Fang SS, Han M, Zheng QW, Zhu YY, Zhang MY, Li JJ, Cui LX, Tian JL, Deng YH, Zhu SL, Ni HM, Zhou L, Zuo GL, Huang TS, Liao Q, Li XQ, Shang YY, Wang YJ, Tian Y, Ge LY, Han HQ, Hu WM, Jiang Y, Li YJ, Mao X, Yang LH, Yao JM, Zheng X, Wang HW, Fang SQ. Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study. World J Gastroenterol 2025; 31(45): 113060 [DOI: 10.3748/wjg.v31.i45.113060]

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