Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions

Table 1 Baseline demographic and clinical characteristics of patients who underwent Helicobacter pylori eradication

Parameters	Patients (n = 85)
Age, mean (SD), yr	56.1 (12.3)
Gender, n (%)
Female	53 (62.4)
BMI, mean (SD), kg/m2	25.1 (2.2)
Alcohol users (12-24 g/dL /die), n (%)	27 (31.8)
Previous smokers, n (%)	12 (14.1)
Drug users, n (%)	23 (27.1)
Family history of gastric cancer, n (%)	4 (4.7)
Family history of other cancer, n (%)	9 (10.6)
Autoimmune comorbidity
Autoimmune atrophic gastritis	12 (14.1)
Autoimmune thyroiditis	6 (7.1)
Type-1/2 diabetes mellitus	3 (3.5)
Skin psoriasis	1 (1.2)
Rheumatoid arthritis	1 (1.2)
Sjögren syndrome	1 (1.2)
A. thyroiditis + vitiligo	1 (1.2)
A. thyroiditis + Crohn’s disease	1 (1.2)
A. thyroiditis + Sjögren syndrome	1 (1.2)
APCA and/or AIF antibody positivity	12 (14.1)
Endoscopy indication, n (%)
Gastroesophageal reflux	17 (20)
Recurrent abdominal pain	12 (14.1)
Dyspepsia	41 (48.2)
Unexplained anemia	15 (17.7)
H. pylori eradication scheme, n (%)
Quadruple1	53 (62.4)
Modified triple2	28 (32.9)
Triple3	3 (3.6)
Sequential4	1 (1.2)
H. pylori eradication cycles, n (%)
One-cycle	71 (83.5)
Two-cycles	14 (16.5)

Data are expressed as number of patients and percentage (in parenthesis).

¹Bismuth + Metronidazole + Tetracycline + Proton pump inhibitor.

²Amoxicillin + Levofloxacin + Proton pump inhibitor.

³Amoxicillin + Clarithromycin + Proton pump inhibitor.

⁴Amoxicillin + Clarithromycin + Proton pump inhibitor Amoxicillin (5 d), then Clarithromycin + Metronidazole (5 d) + Proton pump inhibitor. BMI: Body mass index; SD: Standard deviation; APCA: Anti-parietal cell antibody; AIF: Anti-intrinsic factor; H. pylori: Helicobacter pylori; PPI: Proton pump inhibitor.

Table 2 Endoscopic and histological characteristics of patients before and after Helicobacter pylori eradication

Parameters	Before H. pylori eradication (n = 85)	After H. pylori eradication (n = 85)	P value
Endoscopic atrophy1, n (%)
Absent	5 (5.9)	4 (4.7)	1.0
Antrum	19 (22.4)	19 (22.4)	1.0
Antrum-predominant	18 (21.2)	12 (14.1)	0.23
Corpus-predominant	21 (24.7)	23 (27.1)	0.73
Pan-atrophy	22 (25.9)	27 (31.8)	0.40
OLGA-scale, n (%)
Stage 0	4 (4.7)	4 (4.7)	1.0
Stage 1	22 (25.9)	28 (32.9)	0.31
Stage 2	34 (40)	23 (27.1)	0.07
Stage 3	20 (23.5)	25 (29.4)	0.38
Stage 4	5 (5.9)	5 (5.9)	1.0
EGGIM-scale, n (%)
0-2	47 (55.3)	45 (52.9)	0.76
3-4	21 (24.7)	10 (11.8)	0.03a
5-6	12 (14.1)	21 (24.7)	0.08
7-8	4 (4.7)	4 (4.7)	1.0
9-10	1 (1.2)	5 (5.9)	0.21
OLGIM-scale, n (%)
Stage 0	40 (47.1)	29 (34.1)	0.08
Stage 1	14 (16.5)	17 (20)	0.55
Stage 2	14 (16.5)	14 (16.5)	1.0
Stage 3	13 (15.3)	18 (21.2)	0.32
Stage 4	4 (4.7)	7 (8.2)	0.53
Gastritis at histology2, n (%)
Quiescent	0	81 (95.3)	< 0.0001b
Mild	19 (22.4)	4 (4.7)	0.001b
Moderate	46 (54.1)	0	< 0.0001b
Severe	20 (23.5)	0	< 0.0001b
MALT-hyperplasia, n (%)
Absent	46 (54.1)	82 (96.5)	< 0.0001b
Mild	25 (29.4)	3 (3.5)	< 0.0001b
Moderate	11 (12.9)	0	0.007b
Severe	3 (3.5)	0	0.24
Histological LGD3, n (%)
Absent	70 (82.4)	57 (67.1)	0.02a
On random biopsies	15 (17.6)	9 (10.6)	0.19
On random + on lesions biopsies	0	6 (7)	0.03b
Only on visible lesions	0	13 (15.3)	0.0001b

Data are expressed as number of patients and percentage (in parenthesis).

¹By Kimura and Takemoto[32].

²By Sydney System.

³LGD: Low-grade dysplasia according to World Health Organization classification.

^aBy χ² test.

^bby Fisher’s exact test. H. pylori: Helicobacter pylori; EGGIM: Endoscopic grading of gastric intestinal metaplasia; MALT: Mucosa-associated lymphoid tissue; OLGA: Operative Link on Gastritis Assessment; OLGIM: Operative Link on Gastric Intestinal Metaplasia.

Table 3 Demographic and clinical characteristics of patients with low-grade dysplasia detected on visible gastric lesions or randomly and without low-grade dysplasia, before and after Helicobacter pylori eradication

Parameters	With LGD (n = 28)	Without LGD (n = 57)	P value
Age, mean (SD), yr	60.9 (8.2)	53.7 (13.4)	0.01a
Gender, n (%)
Female	15 (53.6)	38 (66.7)	0.24
BMI, mean (SD), kg/m2	25 (2.4)	25 (2.3)	1.0
Alcohol users (12-24 g/dL/die), n (%)	15 (53.6)	12 (21.1)	0.002b
Previous smokers, n (%)	10 (35.7)	2 (3.5)	< 0.0001c
Family history of gastric cancer, n (%)	4 (14.3)	0	0.001c
Family history of other cancer, n (%)	6 (21.4)	3 (5.3)	0.001c
Autoimmune comorbidity
Autoimmune atrophic gastritis	8 (28.6)	4 (7)	0.02c
Autoimmune thyroiditis	3 (10.7)	3 (5.3)	0.39
A. thyroiditis + vitiligo	1 (3.6)	0	0.33
A. thyroiditis + Crohn’s disease	1 (3.6)	0	0.33
A. thyroiditis + Sjögren syndrome	0	1 (1.7)	1.0
Sjögren syndrome	0	1 (1.7)	1.0
Type-1/2 diabetes mellitus	1 (3.6)	2 (3.5)	1.0
Skin psoriasis	1 (3.6)	0	0.33
Rheumatoid arthritis	0	1 (1.7)	1.0
APCA and/or AIF antibody positivity	8 (28.6)	4 (7)	0.02c
H. pylori eradication scheme, n (%)
Quadruple1	17 (60.7)	36 (63.2)	0.82
Modified triple2	9 (32.1)	19 (33.3)	0.91
Triple3	1 (3.6)	2 (3.5)	1.0
Sequential4	1 (3.6)	0	0.33
H. pylori eradication cycles, n (%)
One cycle	22 (78.6)	46 (86)	0.82
Two cycles	6 (21.4)	8 (14)	0.82
OLGA scale before5
Stage 0	0	4 (7)	0.3
Stage 1-2	8 (28.6)	48 (84.2)	< 0.0001b
Stage 3-4	20 (71.4)	5 (8.8)	< 0.0001c
OLGA scale after6
Stage 0	0	4 (7)	0.3
Stage 1-2	7 (25)	44 (77.2)	< 0.0001b
Stage 3-4	21 (75)	9 (15.8)	< 0.0001b
OLGIM scale before
Stage 0	0	40 (70.1)	< 0.0001c
Stage 1-2	12 (42.8)	16 (28.1)	0.17
Stage 3-4	16 (57.1)	1 (1.8)	< 0.0001c
OLGIM scale after
Stage 0	0	29 (50.9)	< 0.0001c
Stage 1-2	7 (25)	24 (42.1)	0.12
Stage 3-4	21 (75)	4 (7)	< 0.0001c
Gastritis at histology before, n (%)
Quiescent	0	0	1.0
Mild	3 (10.7)	16 (28.1)	0.10
Moderate-severe	25 (89.3)	41 (71.9)	0.10
Gastritis at histology after, n (%)
Quiescent	26 (92.9)	55 (96.5)	0.59
Mild	2 (7.1)	2 (3.5)	0.50
Moderate-severe	0	0	1.0
MALT hyperplasia before, n (%)
Absent	10 (35.7)	36 (63.2)	0.02b
Mild	10 (35.7)	15 (26.3)	0.37
Moderate	6 (21.4)	5 (8.8)	0.17
Severe	2 (7.2)	1 (1.8)	0.25
MALT hyperplasia after, n (%)
Absent	10 (35.7)	36 (63.2)	0.02b
Mild	18 (64.3)	21 (36.8)	0.02b
Moderate	0	0	1.0
Severe	0	0	1.0

Data are expressed as number of patients and percentage (in parenthesis).

¹Bismuth + Metronidazole + Tetracycline + Proton pump inhibitor.

²Amoxicillin + Levofloxacin + Proton pump inhibitor.

³Amoxicillin + Clarithromycin + Proton pump inhibitor.

⁴Amoxicillin + Clarithromycin + Proton pump inhibitor Amoxicillin (5 d), then Clarithromycin + Metronidazole (5 d) + Proton pump inhibitor.

⁵Before Helicobacter pylori eradication (by Sydney System).

⁶After Helicobacter pylori eradication.

^aBy t-test.

^bBy χ² test.

^cBy Fisher’s exact test. BMI: Body mass index; SD: Standard deviation; APCA: Anti-parietal cell antibody; AIF: Anti-intrinsic factor; H. pylori: Helicobacter pylori; PPI: Proton pump inhibitor; OLGA: Operative Link on Gastritis Assessment; OLGIM: Operative Link on Gastric Intestinal Metaplasia; MALT: Mucosa-associated lymphoid tissue.

Table 4 Probability of detecting low-grade dysplasia randomly or on visible lesions after Helicobacter pylori eradication

	Univariate		Multivariate
Variable	OR (95% CI)	P value	OR1 (95%CI)	P value
Age, yr	1.05 (1.01-1.11)	< 0.02	1.05 (1.00-1.10)	0.07
Gender
Female	1.002		-
Male	1.73 (0.69-4.37)	0.24	-	-
BMI, kg/m2	0.93 (0.75-1.15)	0.49	-	-
Alcohol use
No	1.002		1.002
Yes	4.33 (1.63-11.51)	< 0.01	3.88 (1.31-11.49)	0.01
Drug use
No	1.002		-
Yes	1.45 (0.54-3.94)	0.46	-	-
MALT hyperplasia regression/reduction
No	1.002		-
Yes	3.90 (1.20-7.91)	< 0.02	3.10 (1.05-9.12)	0.04
APCA and/or AIF antibody positivity
No	1.002
Yes	5.30 (1.44-19.56)	0.01	5.47 (1.33-22.39)	< 0.02

¹Ajusted for age, alcohol use, Mucosa-associated lymphoid tissue hyperplasia reduction/regression and anti-parietal cell antibody and/or anti-intrinsic factor antibody positivity.

²Reference group. LGD: Low-grade dysplasia; H. pylori: Helicobacter pylori; OR: Odds ratio; BMI: Body mass index; MALT: Mucosa-associated lymphoid tissue; APCA: Anti-parietal cell antibody; AIF: Anti-intrinsic factor.