Original Article


Association of Helicobacter Pylori Infection with Anemia: A Retrospective Study

Authors: Misbah Vaqar Patoli , Fasiha Sohail , Muhammad Fahad Zakir , Arfeen Azam Khan , Daara Jamali , Arzu Jadoon khan
DOI: https://doi.org/10.37184/lnjpc.2707-3521.4.11
Year: 2022
Volume: 4
Received: Jan 31, 2022
Revised: Mar 11, 2022
Accepted: Mar 18, 2022
Corresponding Auhtor: Misbah Vaqar Patoli (dr.misbahirfan@gmail.com)
All articles are published under the Creative Commons Attribution License



Abstract

Background: Helicobacter pylori (Hpylori) infection affects around half of the worlds’ population. Anemia is considered a complication

of Hpylori infection. The present study aimed to determine the association of Hpylori infection with anemia in the Pakistani population.

Methods: This retrospective observational study was conducted in Ziauddin University Hospital after taking ethical approval from the ethics committee. Medical records were reviewed for all those patients who investigated for helicobacter pylori infection and hematological parameters during 2020. Patients’ age, gender, residence, body mass index, presenting features, comorbidity, Hpylori status and other hematological parameters including hemoglobin (g/dL), packed cell volume (L/L), red blood cells (mcL), mean corpuscular volume (fL), mean corpuscular hemoglobin (pg) and mean corpuscular hemoglobin concentration (g/dL) were retrieved and analyzed.

Results: A total of 370 records were reviewed. The median age of patients was 39 (IQR=27–50.3) years and the majority of them were females (54.6%). Nearly half of the participants had a helicobacter pylori infection (48.1%). Patients’ age (p=0.034), body mass index (p=0.048), gender (p=0.048) and symptom of heartburn (p=0.002) were significantly different among patients with and without Hpylori infection. 194 (52.4%) patients had anemia. The frequency of anemia among Hpylori positive and negative was 53.9% and 51% respectively. The risk of anemia was higher among Hpylori infected patients than non-infected patients but statistically, it was not significant (aOR=1.22, 95% CI: 0.79 - 1.86). The likelihood of microcytic hypochromic anemia was significantly higher in Hpylori infected patients than non-infected (aOR=1.78, 95% CI: 1.14 - 2.76).

Conclusion: The present study did not find the association of Hpylori infection with anemia among the Pakistani population.

Keywords: Helicobacter pylori, anemia, hematological parameters, gastrointestinal diseases.

INTRODUCTION

Helicobacter pylori (Hpylori) is a gram-negative bacteria spiral-shaped which is colonizing on the gastric mucosa to lead to upper gastrointestinal (GI) diseases and affecting around half of the population around the world and is highly prevalent in developing countries [1, 2]. Although Hpylori is a global public health issue its prevalence differs from country to country [3]. The prevalence of Hpylori infection ranges from 20%-40% in European countries while in the Eastern Mediterranean region, the reported prevalence ranges from 22% to 87.6% [4]. A high prevalence of 67.28% was also reported from Pakistan in patients with symptoms of heartburn, nausea, dyspepsia, epigastric pain, belching and vomiting [5].

The following are the states of patient presentation; abdominal pain, occasional fevers, gastric reflux, intestinal bleeding, and weight loss. Owing to these states, gastric ulceration and perforation can happen if not timely treated [6]. Hpylori is the leading basis for chronic or atrophic gastritis, gastric lymphoma, gastric

carcinoma and peptic ulcer [7]. In the preceding three decades, hematological disorders have also been reported as the epigastric manifestation of Hpylori but still, the contribution of this infection on hematological system diseases is not deeply studied and more strong evidence is needed. The most frequent hematological disorder is anemia which increases with increasing age [8, 9].

It was demonstrated in a study that Hpylori was linked with iron deficiency anemia (IDA) even in patients of celiac disease, which was intensely evidence-based, however inadequately noted in practice [10]. There is much evidence from clinical and epidemiological studies that support a link between anemia and Hpylori. To the best of our familiarity, no local investigation has been conducted yet to determine the Hpylori impact on anemia. Therefore, we planned the current study to determine the association of Hpylori infection with anemia in the Pakistani population.

METHODS

This retrospective observational study was conducted at Dr. Ziauddin Univesity Hospital, Keamari campus after taking approval from the hospital ethics committee (ERC# 3370221MVMED). Data were retrieved for the year 2020. Patients of both the gender of age 18 to 60

years who were investigated for Hpylori infection and hematological parameters were included in the study. Patients with peptic ulcers, erosive hemorrhagic gastritis, gastric malignancy, varices, malabsorption features, intestinal worm infestation, concomitant other severe systemic diseases, regular users of non-steroidal anti- inflammatory drugs, diagnosed cases of hematological diseases, pregnant and lactating women were excluded. In a previously conducted study, the frequency of anemia in Hpylori positive and negative was 35.6% and 22.1% respectively [11]. At a 95% confidence interval and power of 80%, a sample of 354 patients is required with a 1:1 ratio of exposed and unexposed groups. Sample size calculation was performed on the online available calculator Open-Epi.

Patients’ records were reviewed to retrieve their age, gender, body mass index, residence, presenting features, comorbidity, Hpylori status and other hematological parameters including hemoglobin (g/ dL), packed cell volume (PCV, %), red blood cells (RBC, mcL), mean corpuscular volume (MCV, fL), mean corpuscular hemoglobin (MCH, pg) and mean corpuscular hemoglobin concentration (MCHC, g/dL).

Body mass index (BMI) was computed by dividing weight (kg) by a square of height (m). According to Asian thresholds, participants were labelled as underweight, normal, overweight and obese with BMI range of <18.5 kg/m2, 18.5 – 22.9 kg/m2, 23-24.9 kg/m2 and ≥25 kg/m2 respectively [12]. Hpylori status was determined either through a stool antigen test or gastric biopsy. Following samples were drawn for gastric biopsy according to hospital protocol; 1 sample from antrum and incisura, and 2 from the body. If there was a lesion, multiple samples were taken from edges also. The presence of comma or curved-shaped organisms on gastric biopsy was considered positive for Hpylori infection. On stool antigen test, if the white line above the C and T marks on the kit turned from white to red, it is labelled as Hpylori infection. World Health Organization (WHO) hemoglobin thresholds were used to define anemia. Males and females were labelled as anemic for hemoglobin levels

<14 g/dL and <12 g/dL respectively. Based on the levels of hemoglobin, severity of anemia was assessed and labelled as normal (12-16.g/dL for women, 14.0 – 18.0 g/dL for men), mild (10g/dL to levels within normal limits), moderate (8.0 – <10.0 g/dL), severe (6.5 - <8g/ dL) and life-threatening (<6g/dL) [13]. Morphological types of anemia were categorized as normocytic anemia (NA, 80 ≤ MCV ≤ 100 fL), macrocytic anemia (MA, MCV > 100 fL), and microcytic hypochromic anemia (MHA, MCV < 80 fL) [14].

Data were entered into SPSS version 21 for statistical analysis. Categorical variables were expressed as frequency and percentage. Continuous variables were presented as median with inter-quartile range (IQR) after assessing the assumption of normality with the Shapiro-Wilk test. Chi-square/Fisher exact test was

applied to compare categorical variables among two groups of patients. Mann-Whitney U test was applied to compare non-normal numerical variables among two study groups. Binary logistic regression was applied to assess the association of Hpylori with anemia. Multinomial logistic regression was applied to determine the association of Hpylori infection with morphological types of anemia. Odds ratios were adjusted for socio- demographic variables such as age, gender, residence and effect of comorbidity was also studied in a regression model. Variables with p>0.25 were not entered to compute adjusted odds ratios. Statistical significance was considered when the two-tailed p-value was less than or equal to a 5% level of significance.

RESULTS

Total 370 records were reviewed in this study with median age of 39 (IQR=27–50.3) years. Majority of the study participants were females (n=202, 54.6%) and belonging to urban areas (n=294, 79.5%). Mostly participants were obese (n=150, 40.5%) whereas 128 (34.6%) had normal weight. Few participants were overweight (n=62, 16.8%) and underweight (n=30, 8.1%). The most prevalent symptom was epigastric pain (n=109, 29.5%) followed by heart burn (n=86, 23.2%), nausea (n=63, 17%), indigestion (n=47, 12.7%), loss of appetite (n=43, 11.6%), bloating (n=38, 10.3%), taste disturbances (n=37, 10%), early satiety (n=30, 8.1%), regurgitation (n=25, 6.8%), belching (n=15, 4.1%), postprandial symptoms (n=7, 1.9%) and diarrhea (n=2, 0.5%).

Nearly half of the study participants were positive forHpylori infection (n=178, 48.1%). Hpylori infected patients were significantly younger thanHpylori negative patients (p=0.034). The median BMI of Hpylori infected patients was significantly lower than patients without Hpylori (p=0.048). Females were significantly more likely to be affected with Hpylori infection than males (p=0.040). The frequency of heartburn was higher in Hpylori infected group than the non-infected group (p=0.002) ( Table 1). None of the hematological parameters was significantly different among patients with and without Hpylori infection (Table 2).

More than half of the participants had anemia (n=194, 52.4%). Out of 194 anemic patients, 164 (84.5%),

29(14.9%) and 1 (0.5%) had mild, moderate and severe anemia respectively. Only gender distribution was significantly different among patients with and without anemia (p<0.001) (Table 1). The frequency of anemia amongHpylori infected and non-infected is depicted in Fig. (1).

Table 3 displays the association of anemia with Hpylori infection. The model was adjusted with age, gender body mass index, residence, presence of diabetes, hypertension, and coronary artery diseases. The risk of anemia was higher amongHpylori positive patients than patients who were negative for Hpylori but statistically, it was not significant (aOR=1.22, 95% CI: 0.79 - 1.86).

Table 1: Comparison of participants’ characteristics among patients with and without Helicobacter pylori infection and anemia.

Study Variables

Hpylori Infection

Anemia

Positive n(%)

Negative n(%)

p-value

Yes n(%)

No n(%)

p-value

Age (in years)#

36(25 - 49)

41(29 - 52)

*0.034

36.5(28 - 50.25)

39.5(26 - 50.75)

0.431

Body mass index

Underweight

18(60)

12(40)

0.205

13(43.3)

17(56.7)

0.781

Normal

67(52.3)

61(47.7)

68(53.1)

60(46.9)

Overweight

25(40.3)

37(59.7)

29(46.8)

33(53.2)

Obese

68(45.3)

82(54.7)

80(53.3)

70(46.7)

Gender

Male

71(42.3)

97(57.7)

*0.040

105(62.5)

63(37.5)

**<0.001

Female

107(53)

95(47)

89(44.1)

113(55.9)

Residence

Rural

30(39.5)

46(60.5)

0.091

53(56.6)

33(43.4)

0.417

Urban

148(50.3)

146(49.7)

151(51.4)

143(48.6)

Comorbid

Diabetes

9(37.5)

15(62.5)

0.282

11(45.8)

13(54.2)

0.503

Hypertension

12(38.7)

19(61.3)

0.274

17(54.8)

14(45.2)

0.779

Coronary artery disease

5(35.7)

9(64.3)

0.344

7(50)

7(50)

0.853

Presenting symptoms

Epigastric pain

50(45.9)

59(54.1)

0.578

53(48.6)

56(51.4)

0.343

Heartburn

54(62.8)

32(37.2)

**0.002

46(53.5)

40(46.5)

0.823

Nausea

34(54)

29(46)

0.307

37(58.7)

26(41.3)

0.272

Bloating

17(44.7)

21(55.3)

0.661

21(55.3)

17(44.7)

0.712

Belching

5(33.3)

10(66.7)

0.242

8(53.3)

7(46.7)

0.943

Loss of appetite

23(53.5)

20(46.5)

0.453

21(48.8)

22(51.2)

0.616

Taste disturbances

17(45.9)

20(54.1)

0.781

18(48.6)

19(51.4)

0.627

Early satiety

15(50)

15(50)

0.829

20(66.7)

10(33.3)

0.103

Indigestion

25(53.2)

22(46.8)

0.455

28(59.6)

19(40.4)

0.294

Regurgitation

16(64)

9(36)

0.100

11(44)

14(56)

0.382

Diarrhea

1(50)

1(50)

1.00

1(50)

1(50)

ǂ1.00

Postprandial symptoms

2(28.6)

5(71.4)

0.451

2(28.6)

5(71.4)

ǂ0.264

Dry mouth

8(47.1)

9(52.9)

0.929

12(70.6)

5(29.4)

0.125

#: Age is presented as median (quartile 1 - quartile 3), ǂ: Fisher-exact test was reported *Significant at p<0.05, **Significant at p<0.01 IQR= interquartile range (first quartile – third quartile), PCV= Packed cell volume, RBC= Red blood cell, MCV= Mean corpuscular volume, MCH= Mean corpuscular hemoglobin, MCHC= Mean corpuscular hemoglobin concentration

Table 2: Comparison of hematological parameters among patients with and without Helicobacter pylori infection.

Hematological Parameters

With Helicobacter pylori Infection Median (IQR)

Without Helicobacter pylori Infection Median (IQR)

p-value

Hemoglobin

12 (10.6 - 13.5)

12.3 (10.53 - 13.7)

0.174

PCV

37 (33 - 40)

38 (34 - 41)

0.059

RBC

4.69 (4.36 - 5.09)

4.73 (4.36 - 5.20)

0.525

MCV

80 (74 - 85)

82 (74.3 - 86)

0.219

MCH

26 (23 - 28)

27 (24 - 29)

0.117

MCHC

32 (31 - 33)

32 (31 - 33)

0.073

Table 4 presents the association of Hpylori with morphological types of anemia. Multinomial logistic regression was built adjusting the effects for age, gender, body mass index, residence and comorbidities. The likelihood of MHA was nearly twice than NA in Hpylori infected patients than non-infected (aOR=1.78, 95% CI: 1.14 - 2.76).

Fig. (1) : Frequency of anemia among Helicobacter pylori positive and negative cases.

DISCUSSION

The current study enrolled 48% Hpylori infected patients

out of which Hpylori was significantly highly prevalent

Table 3: Association of Helicobacter pylori infection with anemia. aOR: Adjusted Odd ratio, CI: Confidence interval, Ref: Reference category, **Significant at p<0.01 in females (53%) than males (42.3%). Muhammad et al. also reported a higher frequency of Hpylori among females than males (54.1% versus 45.9%) [15]. Another Pakistani study did not report a gender-based prevalence of Hpylori [16]. The study conducted in China reported significantly higherHpylori prevalence among males than females (39.8% versus 457%) [17]. The higher Hpylori prevalence among males in China could be due to differences in geographical regions.

Study Variables

aOR (95% CI)

p-value

Age (in years)

1 (0.98 - 1.01)

0.683

Gender

Male

2.27 (1.47 - 3.49)

**<0.001

Female

Ref

Body mass index

Underweight

Ref

Normal

0.89 (0.38 - 2.07)

0.790

Overweight

0.66 (0.26 - 1.71)

0.390

Obese

0.97 (0.40 - 2.34)

0.940

Residence

Rural

1.27 (0.75 - 2.14)

0.378

Urban

Ref

Comorbid

Diabetes

0.70 (0.27 - 1.83)

0.468

Hypertension

1.46 (0.55 – 3.90)

0.452

Coronary artery disease

0.72 (0.18 - 2.86)

0.641

Helicobacter pylori Infection

Positive

1.22 (0.79 - 1.86)

0.370

Negative

Ref

In the present study, the overall prevalence of anemia was 52.4% whereas anemia prevalence was surprisingly higher in males (62.5%) than females (44.1%). A similar finding was also noted in another Pakistani study that reported 71% anemia prevalence in hospitalized patients with higher anemia prevalence in males (67%) than females (62.5%) [18]. This is also noticeable that anemia frequency in the current study is lower than previously Pakistani study and the most likely reason for this difference is obvious that the previous study was conducted on hospitalized patients while the current study also included samples of outpatients. In contrast to the gender-based prevalence of anemia in the present study, a higher prevalence of anemia among females and lower among males is documented by WHO. According to WHO estimates, globally anemia prevalence is lowest in adult males (12.7%) while highest in pregnant (41.8%) and non-pregnant women (30.2%) [19].

On the other hand, anemia prevalence was 53.9% and 51% among Hpylori infected and non-infected cases respectively in the present study. A similar study conducted in China exhibited a difference of about 3% in the prevalence of anemia among Hplyori positive (5.3%) and negative cases (2.2%). However, statistically, this difference was significant but clinically not a meaningful difference [20]. Another similar study from China also reported significantly higher anemia prevalence in Hpylori infected cohort (5.5%) than the non-infected group (5.2%) but the difference between the two prevalence estimates was not meaningful [17].

Furthermore, it is noticeable that anemia prevalence in both Chinese studies is quite low as compared to our study. The most likely explanation for this difference is that China is economically more stable than our country. Thereby anemia prevalence was low in their study as compared to our study as anemia is linked to socioeconomic status [21]. Hou and coworkers also aOR: Adjusted Odd ratio, CI: Confidence interval, Ref: Reference category, *Significant at p<0.05 did stratification and observed that patients who had a higher comorbidity index, had a higher prevalence of anemia in Hpylori positive cases than Hpylori negative cases (10.3% versus 1.4%) [20]. However, none of the comorbidity in the present study was found to be associated with anemia. In contrast to our findings, a significantly higher prevalence of anemia amongHpylori infected patients (30.9%) as compared to Hpylori negative cases (22.5%) was reported in a study conducted in Ethiopia [22].

Table 4: Association of helicobacter pylori infection with morphological types of anemia.

Variables

Microcytic Hypochromic Anemia Versus Normocytic Anemia

Macrocytic Anemia Versus Normocytic Anemia

aOR (95% CI)

p-value

aOR (95% CI)

p-value

Age (in years)

0.99 (0.97 - 1)

0.278

0.97 (0.93 - 1.01)

0.096

Gender

Male

0.69 (0.45 - 1.08)

0.104

1 (0.41 - 2.45)

1.000

Female

Ref

Ref

Body mass index

Underweight

0.73 (0.30 - 1.83)

0.511

0.65 (0.11 – 3.97)

0.643

Normal

0.75 (0.44 - 1.27)

0.282

0.99 (0.34 – 2.89)

0.978

Overweight

0.92 (0.49 - 1.74)

0.805

0.66 (0.16 - 2.72)

0.569

Obese

Ref

Ref

Residence

Rural

1.21 (0.71 - 2.07)

0.478

0.15 (0.02 - 1.16)

0.069

Urban

Ref

Ref

Comorbid

Diabetes

0.59 (0.20 - 1.72)

0.335

1.30 (0.20 - 8.41)

0.782

Hypertension

0.90 (0.34 - 2.36)

0.832

2.29 (0.43 – 12.26)

0.332

Helicobacter pylori

Infection

Positive

1.78 (1.14 - 2.76)

*0.011

0.48 (0.18 - 1.24)

0.129

Negative

Ref

Ref

In 1991, Blecker et al. presented a case of hemorrhagic gastritis of Hpylori infection and a relationship of iron deficiency anemia and Hpylori infection was shown [23]. We have found no significant association between Hpylori and anemia in our study. Our findings are contradictory to other studies that reported a significant association of Hpylori and anemia [11, 22]. The most likely reason for this conflicting finding may be participants’ characteristics as these studies recruited dyspeptic patients only whereas in our study, regardless of any specific conditions, all patients who underwent Hpylori testing were included. Antacids are usually used to treat dyspepsia and may inhibit iron absorption which may lead to anemia [24, 25]. Moreover, Hpylori infection is also responsible for impaired iron absorption due to gastritis hypochlorhydria which further leads to impaired reduction of the dietary iron from the ferric to ferrous form due to which anemia and iron deficiency anemia has been found to be associated with Hpylori in studies recruited only dyspeptic patients. The finding of our study was consistent with a Brazilian study that was a community-based study and concluded that there was no association between Hpylori and anemia among adults who attended primary healthcare units [26]. Another similar study conducted in Bangladesh recruited all patients who underwent Hypylori irrespective of whether they had dyspepsia or not and no association was observed between Hpylori and anemia [27].

In the present study, the association of Hpylori was observed with morphological types of anemia with a significantly higher risk of MHA as compared to NA anemia among Hpylori infected patients than patients found to be negative for Hpylori. The association of Hpylori and morphological anemia types was also concluded by Xu et al. However, Xu et al. fitted the regression model by treating morphological types as a predictor of Hpylori and we did oppositely [17]. A study conducted in India also reported that Hpylori is related to a moderate degree of anemia, mainly NA type. We believe the evidence of association of Hpylori with anemia and its types is weak in this Indian study as the author only enrolled participants having Hpylori infection and a conclusion was drawn based on the frequency of anemia and its type [28].

The current study is retrospective in nature with a limited sample size. We were not able to collect complete records for serum iron and ferrous and hence did not

analyze iron deficiency anemia. Secondly, to the best of our knowledge, the association of Hpylori with a morphological type of anemia has not been widely studied. Therefore, a future study can be conducted in our region while addressing these limitations.

CONCLUSION

The present study did not find the association of Hpylori

infection with anemia among the Pakistani population.

LIST OF ABBREVIATIONS

aOR : Adjusted odd ratio BMI : Body mass index CI : Confidence interval Hpylori : Helicobacter pylori

IDA : Iron deficiency anemia IQR : Inter-quartile range MA : Macrocytic anemia

MCHC : Mean corpuscular hemoglobin concentration MHA : Microcytic hypochromic anemia

NA : normocytic anemia

OR : Odd ratio

WHO : World Health Organization

ETHICS APPROVAL

The present study was conducted after taking ethical approval from Ziauddin Hospital Ethics Committee (IRB# 3370221MVMED).

CONSENT FOR PUBLICATION

The study is retrospective in nature and data was retrieved from medical records. Thus patient consent was not taken.

AVAILABILITY OF DATA

The data is confidential and is only available for reviewers and journal’s editorial panel upon their request.

FUNDING

None

CONFLICT OF INTEREST

Authors declare none of the conflict of interest

ACKNOWLEDGEMENTS

Declared none.

AUTHORS’ CONTRIBUTION

MVP conceptualized the study. FS and MVP prepared the protocol for data collection. DJ and AAK were involved in data collection. FB entered and analyzed the data. MVP and FB wrote the results. AJK and FS wrote the initial draft of the manuscript. MVP and DJ critically revised the study initial draft and finalized the manuscript. All authors read and approved the manuscript.

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