European Journal of Gastroenterology & Hepatology:
Original Articles: General Hepatology
Association between Helicobacter pylori and liver-to-spleen ratio: a randomized-controlled single-blind study
Doğan, Zeynal; Filik, Levent; Ergül, Bilal; Sarikaya, Murat; Akbal, Erdem
Ankara Education and Research Hospital, Ankara, Turkey
Correspondence to Zeynal Doğan, MD, Ankara Education and Research Hospital, Sükriye district, 89 Ulucanlar street, 06230 Altindağ, Ankara, Turkey Tel: +90 312 595 4273; fax: +90 312 363 3396; e-mail: firstname.lastname@example.org
Received July 7, 2012
Accepted August 7, 2012
Background and aim: Helicobacter pylori infection is reported to be associated with some extragastrointestinal manifestations, such as hematological diseases (thrombocytopenia, anemia), obesity, and fatty liver disease. The length or the volume ratio of liver to spleen was suggested to be changed in some hematological and hepatobiliary disorders. We hypothesized that the liver-to-spleen ratio may be affected in H. pylori-positive patients. In this respect, we aimed to evaluate the effect of H. pylori infection on the liver-to-spleen ratio and platelet indices.
Method: A total of 174 patients with functional dyspepsia were included in the study. Patients were divided into group 1 (H. pylori-positive gastritis) (n=95) and group 2 (H. pylori negative, control group) (n=79). Liver, spleen length measurement, and liver steatosis scores were performed by ultrasonography by the same physicians who were blinded to the H. pylori results. Blood count values including the platelet count and the mean platelet volume (MPV) were compared between the two groups. BMI was also evaluated as a potential confounding factor for fatty liver.
Results: The liver-to-spleen ratio, platelet-to-spleen ratio, MPV-to-spleen ratio, and the MPV-to-liver ratio were significantly lower in the H. pylori-positive group compared with the H. pylori-negative group (P<0.001, <0.001, <0.001, and 0.038, respectively). Fatty liver was significantly more frequent in H. pylori-positive patients.
Conclusion: Liver-to-spleen ratio and the MPV-to-spleen ratio are important indices in the pathogenesis of H. pylori-linked liver and spleen manifestations, and thrombocytopenia.
Recent publications have advocated a role for Helicobacter pylori infection in a variety of extraintestinal manifestations 1–3. Increasing evidence supports H. pylori infection as a cause of fatty liver disease, but the relationship is still being debated 4. In the Maastricht IV consensus report was stated that H. pylori eradication does not cause or worsen obesity and related disorders. Although further research is needed. Also, in the Maastricht IV consensus report, it was stated that H. pylori should be sought and eradicated in patients with immune thrombocytopenia in statement 13 5. The spleen plays a central role in thombocyte-related disorders 6. The relationship between thrombocytopenia and spleen size is another issue of concern in this respect. We hypothesized that the liver-to-spleen ratio might be affected in H. pylori-positive patients with respect to these hematologic alterations. There are no current data that establish the relationship between the liver-to-spleen ratio and H. pylori. In this study, we aimed to evaluate the effect of H. pylori infection on the liver-to-spleen ratio and platelet count and the mean platelet volume (MPV).
Patients and methods
This study is a randomized-controlled study carried out in our gastroenterology department. Consecutive patients (n: 174) admitted to our outpatient clinic in June 2012 for dyspepsia were recruited. Informed consent was provided by all patients. After approval, patients were randomized into two groups: group 1 (H. pylori positive) and group 2 (H. pylori negative). Esophagogastroduodenoscopy was performed on patients included in the study, and histological analysis was carried out by obtaining two specimens from the antrum, corpus, and incisura angularis. All specimens were evaluated using the rapid urease test (H. pylori fast).
The liver-to-spleen ratio, platelet count, MPV, platelet count-to-spleen ratio MPV-to-spleen ratio, MPV-to-liver ratio, and BMI were analyzed with reference to H. pylori infection. Liver and spleen length measurements were carried out and liver steatosis was assessed by ultrasonography (Hitachi USG 5500; Hitachi Medical Systems America Inc., Twinsburg, Ohio, USA) by the same physicians who were blinded to the presence of H. pylori. Fatty liver was defined on the basis of ultrasonographic findings. Hepatorenal echo contrast, liver brightness, deep attenuation, and vascular blurring are the four known criteria for the diagnosis of fatty liver. Liver steatosis scores were determined by ultrasonography between grade 0 and 3 using the Hamaguchi method in all patients 7.
MPV is a machine-calculated measurement of the average size of platelets found in blood and is typically included in blood tests as part of the blood count. As the average platelet size is larger when the body is producing increased numbers of platelets, the results of the MPV test can be used to make inferences about platelet production in the bone marrow or problems linked to platelet destruction. The normal MPV range in our laboratory is 7.5–11.5 fl.
Patients with known acute and chronic infectious disease, hematologic abnormality, liver disease, and diabetes mellitus were excluded. Patients with a history of previous H. pylori eradication treatment were also excluded from the study. Age younger than 16 years, pregnancy, lactation, drug (such as proton pump inhibitors, antibiotics, antiaggregants, and anticoagulants) use, alcohol consumption, and smoking were among the other exclusion criteria.
This study was approved by the local ethics committee.
Numerical values were presented as mean, SD, minimum, and maximum values. The Student's t-test was used to compare the means of the control and the patient groups for the studied variables. The χ2 test was used for the clinical variables between the groups. Multivariable regression analysis was carried out to examine the effect of H. pylori and fatty liver on the liver-to-spleen, MPV-to-spleen, MPV-to-liver, and platelet-to-spleen ratios. Statistical significance was set at 5% (P<0.05). The SPSS (ver. 16; SPSS, Chicago, Illinois, USA) statistical program was used for all statistical computations.
In total, 174 patients (female: 112, male: 62) were included in the study. The mean age of the patients was 41.4±13.3 years. Patients were randomized into two groups: group 1 (H. pylori positive, n=95, 54.5%) and group 2 (H. pylori negative, n=79, 45.5%). The demographic findings, clinical variables, and blood count parameters are shown in Table 1. No significant differences were found for age, sex, and BMI between groups. The platelet count was significantly lower in the H. pylori-positive group than the control group (P<0.05).
The liver and spleen were measured to be 130.5±10.8 and 101.8±12.3 mm in length in the H. pylori-positive group. These values were 120.3±13.7 and 87.2±8.1 mm in the control group, respectively. Although the lengths of the spleen and liver were within the normal range for all patients (70–100 and 80–120 mm, respectively), the difference between groups was significant (P<0.001 for the liver and P<0.001 for the spleen) (Table 2).
The liver-to-spleen ratio, platelet count-to-spleen ratio, MPV-to-spleen ratio, and MPV-to-liver ratio were significantly lower in the H. pylori-positive group compared with the control group (P<0.001, <0.001, <0.001, and 0.038, respectively) (Table 2).
Fatty liver was found significantly more frequently in the H. pylori-positive group (P=0.02). A relationship between H. pylori and fatty liver was observed with univariate analysis (P=0.006, F=7.6). Liver and spleen lengths were significantly higher and the MPV-to-spleen ratios were significantly lower in patients with fatty liver when all patients were evaluated for the presence of fatty liver (P<0.001, 0.001, and 0.009, respectively) (Table 3).
Multivariable regression analysis showed that H. pylori, as an independent factor, had an effect on all variables (for all variables P<0.001 and for MPV-to-liver ratio P=0.04). The presence of fatty liver had an effect on the liver as indicated by a covariate analysis. However, fatty liver had an effect on the liver and spleen lengths, but not on the liver-to-spleen ratio, MPV-to-spleen ratio, MPV-to-liver ratio, and platelet-to-spleen ratio (P=0.789, 0.094, 0.916, and 0.876, respectively).
Recent studies have shown that eradication of H. pylori from the gastric mucosa was associated with an improvement in idiopathic thrombocytopenia 8–10. Several theories, including direct antigen mimicry between H. pylori cagA and platelet glycoprotein antigens and H. pylori binding to von Willebrand factor, have been suggested to explain the platelet response to anti-H. pylori therapy 11,12. It has also been hypothesized that platelet autoantibodies may be produced by autoreactive clonal B cells that are induced by chronic immunological stimulus by H. pylori 13,14. In our study, the platelet count of H. pylori-positive patients was significantly lower compared with the H. pylori-negative group, although the platelet counts were within normal limits. We can speculate that H. pylori could lower the platelet count in patients without idiopathic thrombocytopenia in a similar pathogenesis.
MPV has been used as a simple inflammatory indicator in some diseases 15,16. No statistically significant difference was found in blood MPV levels between H. pylori-positive and H. pylori-negative groups in our study, similar to previous studies 17. However, it is interesting that the mean MPV-to-spleen ratio was found to be significantly lower in the H. pylori-positive group compared with the control group in our study. New studies are required to clarify the association between the spleen size and MPV in patients without thrombocytopenia. However, we propose that the MPV-to-spleen ratio can be used as a marker to reflect the presence of H. pylori.
Splenomegaly is more common in H. pylori-positive patients in our study similar to a previous study 18. It was proposed that H. pylori-related injury in the gastric mucosal cells led to gastric inflammation by neutrophils and other inflammatory cells 19. Therefore, H. pylori and its derived proteins and other bacterial products might alter the immune system, causing gastric and extragastric manifestations of H. pylori infection 20. It can be speculated that although H. pylori caused a local inflammation in gastric mucosa, it could affect the spleen by this inflammatory process.
The relationship between H. pylori and liver diseases is still obscure. The role of H. pylori infection in cholestatic liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis is uncertain 21. Similarly, the question of whether H. pylori could play a role in the development of hepatoma remains debatable 22. In a recent study, H. pylori was shown to be among the independent risk factors for nonalcoholic fatty liver disease 23. Fatty liver was found to be significantly more frequent in the H. pylori-positive group in our study. Similarly, the severity of fatty appearance with USG was also higher in the H. pylori-positive group. Interestingly, H. pylori, as an independent factor, had an effect on all variables (platelet count, liver-to-spleen ratio, platelet count-to-spleen ratio, MPV-to-spleen ratio, MPV-to-liver ratio) in the study. However, fatty liver had an effect on the liver and spleen lengths, but not on the liver-to-spleen ratio, MPV-to-spleen ratio, MPV-to-liver ratio, and platelet-to-spleen ratio. Further investigation is warranted to establish this association.
Data on the liver-to-spleen ratio have been reported in very few studies. The liver-to-spleen ratio should be evaluated by carrying out validation studies to determine the role of H. pylori in extragastrointestinal disorders. In our study, the liver-to-spleen ratio was significantly lower, although fatty liver was more frequent in H. pylori-positive patients. Both the MPV-to-spleen ratio and the liver-to-spleen ratio were significantly lower in the H. pylori-positive group in our study. We can speculate that the increase in spleen size is one of the earliest manifestations in the pathogenesis in H. pylori-linked hepatic and hematologic alterations.
The limitation of our study is the measurement of length instead of liver and spleen volume. Herein, we aimed to provide an easy-to-use approach for new studies.
Liver-to-spleen ratio and MPV-to-spleen ratio are important indices in the pathogenesis of H. pylori-linked liver and spleen manifestations. New prospective validation studies are necessary to elucidate this relationship. Hence, guidelines should be adjusted in accordance with advancing knowledge in this field.
Conflicts of interest
There are no conflicts of interest.
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Helicobacter pylori; liver-to-spleen ratio; platelet indices
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