’Letters to the Editor Directions of odds ratios might be inappropriate in the paper by Tafarel et al.

Neutrophil-to-lymphocyte ratio as a predictor of fibrosis in inactive hepatitis B carriers

Han Denga, Xingshun Qia, Yongji Wangb,c and Xiaozhong Guoa, aLiver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, bMedical Department, 309th Hospital of Chinese People’s Liberation Army, Beijing and cDepartment of Health Statistics, Fourth Military Medical University, Xi’an, China

Cemal N. Ercina, Teoman Dogrua and Erdim Sertoglub, aDepartment of Gastroenterology, Gulhane School of Medicine and bBiochemistry Laboratory, Ankara Mevki Military Hospital, Anittepe Dispensary, Ankara, Turkey

Correspondence to Xiaozhong Guo, MD, Department of Gastroenterology, General Hospital of Shenyang Military Area, No. 83 Wenhua Road, Shenyang 110840, China Tel: + 86 24 28897603; fax: + 86 24 28851113; e-mail: [email protected] Received 7 January 2015 Accepted 8 January 2015

Recently, we have read with great interest the paper by Tafarel et al. [1] evaluating the role of noninvasive markers in predicting the presence of esophageal varices in cirrhotic patients. In the multivariate analyses, the variables that were associated significantly with the absence of esophageal varices (without vs. with esophageal varices in Table 2) included the model for the end-stage liver disease (MELD) score [odds ratio (OR) = 0.70; 95% confidence interval (CI) = 0.50–1, P = 0.02], aspartate aminotransferase to platelets index (APRI) (OR = 0.80; 95% CI = 0.70–1, P = 0.01), aspartate aminotransferase (AST) level (OR = 1.40; 95% CI = 1–2, P = 0.01), total bilirubin (TB) level (OR = 3.20; 95% CI = 1.40–7.20, P = 0.04), and platelets count (OR = 0.80; 95% CI = 0.80–0.90, P < 0.01). As we all know, OR is used to observe the relationship between exposed factors and the risk of disease. If OR is greater than 1, the presence of exposed factors increases the risk of disease; otherwise, it decreases the risk of disease. On the basis of the above-mentioned findings, it can be concluded that an increased MELD score, APRI, and platelets count should be associated significantly with a lower proportion of patients without esophageal varices; by contrast, an increased AST and TB level should be associated significantly with a higher proportion of patients without esophageal varices. If so, their conclusions might be misleading. The directions of ORs for the MELD score and APRI were right, but those for AST, TB, and platelets were inconsistent with our clinical practices. Therefore, we enquire about whether the directions of ORs for AST, TB, and platelets count were appropriate in their multivariate analyses. Acknowledgements Conflict of interests

There are no conflicts of interest. Reference 1

Tafarel JR, Tolentino LH, Correa LM, Bonilha DR, Piauilino P, Martins FP, et al. Prediction of esophageal varices in hepatic cirrhosis by noninvasive markers. Eur J Gastroenterol Hepatol 2011; 23:754–758. DOI: 10.1097/MEG.0000000000000301

European Journal of Gastroenterology & Hepatology 2015, 27:475–477

Correspondence to Erdim Sertoglu, MD, Biochemistry Laboratory, Ankara, Mevki Military Hospital, Anittepe Dispensary, Ankara, 06580, Turkey Tel: + 90 507 140 3616; fax: + 90 312 304 3300; e-mail: [email protected] Received 12 January 2015 Accepted 14 January 2015

We read with great interest the article by Yilmaz et al. [1] reporting the neutrophil–lymphocyte ratio (NLR) as a noninvasive tool for the prediction of fibrosis in inactive hepatitis B carriers. We believe that some points should be discussed. First, some patients had hyperglycemia that is consistent with the diagnosis of type 2 diabetes. Although BMI was similar in both groups, there was no information on BMI values, and systolic and diastolic blood pressure levels. Moreover, there were no data on the prevalence of metabolic syndrome in the study population. However, it is well known that NLR can easily be affected by this metabolic abnormality [2–5]. Second, the European Association for the Study of the Liver (EASL) guideline recommends that liver biopsy should be performed in patients with either increased alanine transaminase and hepatitis B virus (HBV) DNA levels more than 2000 IU/ml (or both) to determine the degree of necroinflammation and fibrosis [6]. In this study, although some patients had minimally elevated aspartate aminotransferase and alanine transaminase levels, HBV DNA levels of all patients were lower than 2000 IU/ml. Consequently, the indication of the liver biopsy in the study is not clear and questionable. Third, study participants were divided into two groups according to the fibrosis score: 0–1 as inactive carriers and above 2 as patients with chronic active HBV. However, there are no data on this classification in the literature. Finally, the authors concluded that histologic activity index and NLR were found to be correlated negatively. However, there is no information on inflammatory activity, defined as histology activity indexes, and other histologic findings of the study population. Therefore, we would like to ask the authors whether they can present some data on the issues mentioned above. This may provide the readers with clearer information on the relationship between NLR and liver injury in this clinically relevant condition.

Acknowledgements Conflicts of interest

There are no conflicts of interest.

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References 1 Yilmaz B, Aydin H, Can G, Sentürk Z, Üstüner B, Yilmaz H, et al. The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers. Eur J Gastroenterol Hepatol 2014; 26:1325–1328. 2 Yayla C, Canpolat U, Akyel A, Gayretl Yayla K, Akboğa MK, Eyiol A, et al. Association of neutrophil–lymphocyte ratio with impaired aortic elasticity in newly diagnosed and never-treated hypertensive patients. Blood Press Monit 2015. [Epub ahead of print]. 3 Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M, Sen N. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 2014; 20:159–163. 4 Tsai JC, Sheu SH, Chiu HC, Chung FM, Chang DM, Chen MP, et al. Association of peripheral total and differential leukocyte counts with metabolic syndrome and risk of ischemic cardiovascular diseases in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2007; 23:111–118. 5 Shim WS, Kim HJ, Kang ES, Ahn CW, Lim SK, Lee HC, Cha BS. The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients. Diabetes Res Clin Pract 2006; 73:284–291. 6 European Association for the study of the liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009; 50:227–242. DOI: 10.1097/MEG.0000000000000311

On status of serum iron parameters in chronic hepatitis and cirrhosis: comments on the article by Mao et al. Naciye S. Buyukasika and Yahya Buyukasikb, aDepartment of Gastroenterology, Ankara Atatürk Education and Research Hospital and bDepartment of Internal Medicine, Section of Haematology, Hacettepe University Faculty of Medicine, Ankara, Turkey Correspondence to Yahya Buyukasik, MD, Department of Internal Medicine, Section of Haematology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey Tel: + 90 312 305 3050; fax: + 90 312 305 1614; e-mail: [email protected] Received 18 January 2015 Accepted 20 January 2015

We read the recent paper entitled ‘Abnormal serum iron markers in chronic hepatitis B virus infection may be because of liver injury’ by Mao et al. [1]. They showed that serum iron test abnormalities during hepatitis B-related chronic liver disease were not because of the chronic infection, but they were correlated with virus-related hepatic injury (ferritin and iron) and cirrhosis-related hepatic insufficiency (transferrin). We are pleased with these results, which largely confirm our previous findings and suggestions [2]. Both groups found that aberrant serum iron test results were suggestive for the cirrhotic stage of chronic liver disease. Please note that our finding of decreasing total iron-binding capacity as liver disease progresses from chronic hepatitis toward Child C cirrhosis is the same as their finding of decreasing transferrin values with the progression of chronic hepatitis B toward cirrhosis. The main difference between our results and their results was that we observed lower serum iron levels in cirrhotics compared with patients with hepatitis and the control group. However, they found higher levels in their cirrhotic group. It is difficult to explain this difference. The reason could be that their cirrhotic cohort was largely composed of men (68/12) compared with the healthy controls (32/26). They suggested that serum iron levels were similar in their male and female

participants, especially healthy controls. This is surprising because it is a universal fact that serum iron level in healthy adult women is somewhat lower than that in men. Also, the values they presented when suggesting equal serum iron values in both sexes (second paragraph of the Results section) were quite different from the values in Table 2. We found that simultaneously increased serum iron, ferritin, and transferrin saturation is a finding suggestive for haemochromatosis instead of cirrhosis-related serum iron test abnormalities [2]. Transferrin saturation levels were not presented in the Mao and colleagues study. However, in the presence of increased iron and decreased transferrin, it is reasonable to assume that it was increased in the majority of cirrhotics. We have concluded previously that the acquired hypotransferrinemia of chronic liver disease and related increased transferrin saturation might play pivotal roles in the liver siderosis observed during chronic liver disease just like systemic iron overload states. Decreased hepcidin production of cirrhotic liver could contribute in this process. In accordance with this suggestion, a recent large autopsy study showed that heavy hepatocyte iron deposition secondary to cirrhosis was commonly associated with pancreatic and cardiac iron, a pattern of iron deposition similar to haemochromatosis [3]. We believe that the literature of iron studies in chronic liver disease should be reveiwed again keeping the abovementioned hypothesis in mind. Acknowledgements Conflicts of interest

There are no conflicts of interest. References 1

2

3

Mao W, Hu Y, Lou Y, Chen Y, Zhang J. Abnormal serum iron markers in chronic hepatitis B virus infection may be because of liver injury. Eur J Gastroenterol Hepatol 2015; 27:130–136. Buyukasik NS, Nadir I, Akin FE, Cakal B, Kav T, Ersoy O, Buyukasik Y. Serum iron parameters in cirrhosis and chronic hepatitis: detailed description. Turk J Gastroenterol 2011; 22:606–611. Abu Rajab M, Guerin L, Lee P, Brown KE. Iron overload secondary to cirrhosis: a mimic of hereditary haemochromatosis? Histopathology 2014; 65:561–569. DOI: 10.1097/MEG.0000000000000318

Diabetes is associated with an increased risk of in-hospital mortality in liver cirrhosis with acute upper gastrointestinal bleeding Xingshun Qi*, Ying Peng*, Hongyu Li, Junna Dai and Xiaozhong Guo, Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China Correspondence to Xiaozhong Guo, MD, PhD, Department of Gastroenterology, General Hospital of Shenyang Military Area, No. 83 Wenhua Road, Shenyang 110840, China Tel: + 86 24 28897603; fax: + 86 24 28851113; e-mail: [email protected] * Xingshun Qi and Ying Peng contributed equally to the writing of this article. Received 27 January 2015 Accepted 28 January 2015

Accumulated evidence suggests that the presence of diabetes should be associated with worse outcomes of various liver diseases [1–5].

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