240
Letters to the Editor
Letters to the Editor European Journal of Gastroenterology & Hepatology 2014, 26:240–248
Mean platelet volume in chronic viral hepatitis Bahadır Ceylana, Muzaffer Fincancıb, Cem Yardımcıb, Gu¨lhan Erenb, ¨ mit To¨zalganb, Cu¨neyt Mu¨derrisog˘luc and Esra Pasaog ˘ lud, aDepartment U ¸ of Infectious Diseases and Clinical Microbiology, Medical Faculty, Bezmialem Vakıf University, bMinistry of Health, Istanbul Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, cMinistry of Health, Istanbul Training and Research Hospital, Department of Internal Diseases and d Ministry of Health, Istanbul Training and Research Hospital, Department of Pathology, Istanbul, Turkey Correspondence to Bahadır Ceylan, MD, Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Bezmialem Vakıf University, Istanbul, Fatih 34096, Turkey Tel: + 90 507 231 0236; fax: + 90 212 621 7585; e-mail: [email protected]
the active role of platelets in liver inflammation. The only parameter used in our study as an indicator for determining inflammation in the liver was the MPV value; other inflammation indicators such as neutrophil– lymphocyte ratio and serum C-reactive protein level were not included in the study because while predicting the severity of inflammation in the liver, all the parameters that indicate inflammation cannot be included in the same logistic regression analysis because of the correlation between them. Besides, the MPV value does not only function as a variable that increases with inflammation but also as a variable that increases when the life of platelets shortens as the liver disease progresses.
Received 10 May 2013 Accepted 18 May 2013
Mean platelet volume (MPV) is a routinely observed parameter in blood count analysis and has been considered as an indicator of inflammation [1]. In cases accompanied by inflammation, it is reported that increasing interleukin-6 levels enhance platelet generation in the bone marrow. Moreover, MPV values also increase because of the increase in the number of young platelets entering into circulation [2]. In another study, it has been suggested that MPV values increase very rapidly in a patient with sepsis, and such a rapid increase is related to the activation and growth of platelets rather than the young platelets entering into circulation [3]. In two studies, it has been shown that MPV levels increase in chronic viral hepatitis [4–6]. As viral hepatitis is also one of the diseases accompanied by inflammation, we consider this as an expected result. However, unlike other diseases accompanied by inflammation, there is another factor in viral hepatitis that may increase MPV values, which is the shortening of life in platelets and, accordingly, the increase in young platelets that enter into circulation from the bone marrow [7,8]. It has been observed that platelet generation in the bone marrow increases for various reasons in chronic viral hepatitis [7,8]. (a) Especially in patients with cirrhosis, splenomegaly-induced platelet sequestration has been considered to be the main reason for the decrease in platelet survival in chronic hepatitis and, accordingly, the increase in platelet generation in the bone marrow [7]. (b) In chronic viral hepatitis, it has been reported that platelets accumulate in the liver and especially in inflamed periportal areas, and this has also been suggested as a factor in the development of thrombocytopenia [8]. In this study, it was observed that the accumulation of platelets was higher in the liver of those with a higher fibrosis score, and this was associated with c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-691X
It has been reported that MPV values vary in individuals with smoking habits, hypertension, diabetes, dyslipidemia, atherosclerotic diseases, venous thromboembolism, rheumatologic diseases, and inflammatory bowel diseases [1]. Thus, patients with the above-mentioned factors were not included in our study. Although individuals with atherosclerotic diseases were not included in our study, the probability of subclinical atherosclerotic disease is always present in our cases. The possibility that this situation may have affected the results of our study cannot be ignored. It has been suggested that an increase in platelet activation is seen in patients with diabetes, which is associated with an increase in the MPV values [1,9]. Many factors have been associated with platelet activation in diabetes [9]. The most significant ones are systemic inflammation, oxidative stress, inconstant calcium metabolism, increased phosphorylation of cellular proteins, and decrease in nitric oxide [9]. It has been reported that MPV values increase as the insulin resistance increases in patients with diabetes [10,11]. Individuals with blood glucose beyond the normal upper limit and individuals known to have diabetes were not included in our study because of their interaction with MPV values. Insulin resistance values and the waistto-hip ratio, which is a good indicator of insulin resistance, were not included in our study because of its retrospective structure. Moreover, it is apparent that BMI, which was evaluated in our study, is less successful as an insulin indicator compared with the waist-to-hip ratio. It may be supposed that increased insulin resistance will affect MPV values even though the blood glucose level is normal. The fact that insulin resistance was not included in our study as a variable, which may affect MPV values, is a limitation of our study. However, fatty liver is also known to be a good indicator of insulin resistance [12]. Fatty liver was not included in our study as a variable that may affect MPV values. We obtained data related to fatty liver from our DOI: 10.1097/MEG.0b013e328363714b
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letters to the Editor 241
Table 1
Findings of multivariable logistic regression analysis that reviews variables determining the severitya of the histological activity
index
Serum g-glutamyl transpeptidase level Serum globulin level Mean platelet volume
Odds ratio
95% confidence interval
P
2.255 1.016 1.513
1.015–5.011 1.005–1.027 1.145–1.977
0.046 0.005 0.004
a
Patients with a histological activity index above 9 are considered as patients with a high index.
cases and re-evaluated our study with these data. We found that in 217 of the participants included in our study, fatty liver evaluation was carried out in histological liver biopsy. Fatty liver was found in 57 (31.5%) of 181 participants, with a histological activity index (HAI) of 9 or below and in 11 (30.6%) of 36 participants with an HAI score above 9, and we concluded that the fatty liver variable is uniform among groups with high and low HAI levels (P = 0.912). No difference could be found in terms of the MPV values among the groups of individuals with and without fatty liver [MPV values were 8.8 (minimum–maximum 6.8–15.7) and 8.8 (minimum–maximum 6.5–13.1), respectively; P = 0.478]. Although fatty liver is not a variable that affects HAI, when it was included in logistic regression analysis that evaluates independent variables affecting the HAI score, it was found that MPV significantly determined the severity of the HAI score independent of fatty liver, which is an indicator of insulin resistance (Table 1).
to thrombocytopenia and liver fibrosis in chronic hepatitis C. J Gastroenterol 2013; 48:526–534. 9 El Haouari M, Rosado JA. Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review. Blood Cells Mol Dis 2008; 41:119–123. 10 Inui Y, Suehiro T, Kumon Y, Hashimoto K. Platelet volume and urinary prostanoid metabolites in non-insulin-dependent diabetes mellitus. J Atheroscler Thromb 1994; 1:108–112. 11 Zuberi BF, Akhtar N, Afsar S. Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects. Singapore Med J 2008; 49:114–116. 12 Caballerı´a L, Arteaga I, Pera G, Rodrı´guez L, Aluma` A, Auladell MA, et al. Risk factors associated with non-alcoholic fatty liver disease: a case–control study. Med Clin (Barc) 2013 . doi: 10.1016/j.medcli.2012.11.034. [Epub ahead of print].
As a consequence, we believe that MPV is a dynamic variable that may be affected by many factors including inflammation; thus, all these factors and period of disease should be taken into consideration when interpreting MPV values.
Bilal Ergu¨l, Murat Sarikaya, Zeynal Dog˘an and Levent Filik, Department of Gastroenterology, Ankara Education and Research Hospital, Ankara, Turkey
Letters to the Editor
Is liver biopsy a problem for patients on chronic hemodialysis?
Correspondence to Bilal Ergu¨l, MD, Ostim mah.1288.sok. Nevbahar konutları No A4/6, Yenimahalle 06100, Ankara, Turkey Tel: + 90 530 692 2302; fax: + 90 312 363 3396; e-mail: [email protected] Received 20 May 2013 Accepted 21 May 2013
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
2
3
4
5
6
7 8
Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des 2011; 17:47–58. Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001; 98:2720–2755. Douglas JT, Lowe GD, Forbes CD, Prentice CR. Beta-thromboglobulin and platelet counts – effect of malignancy, infection, age and obesity. Thromb Res 1982; 25:459–464. Ekiz F, Yuksel O, Kocak E, Yılmaz B, Altınbas A, Coban S, et al. Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B. J Clin Lab Anal 2011; 25:162–165. Purnak T, Olmez S, Torun S, Efe C, Sayilir A, Ozaslan E, et al. Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis. Clin Res Hepatol Gastroenterol 2013; 37:41–46. Ceylan B, Fincanci M, Yardimci C, Eren G, To¨zalgan U, Mu¨derrisog˘lu C, et al. Can mean platelet volume determine the severity of liver fibrosis or inflammation in patients with chronic hepatitis B? Eur J Gastroenterol Hepatol 2013; 25:606–612. Aster R. Pooling of platelets in the spleen: role in the pathogenesis ‘hypersplenic’ thrombocytopenia. J Clin Invest 1996; 45:645–657. Kondo R, Yano H, Nakashima O, Tanikawa K, Nomura Y, Kage M. Accumulation of platelets in the liver may be an important contributory factor
Percutaneous liver biopsy is the standard procedure for obtaining hepatic tissue for histopathological examination and at present plays a major role in diagnosis, assessment of the prognosis, and evaluation of therapeutic management [1]. The most important complication of liver biopsy is bleeding, which when severe occurs intraperitoneally [2]. Herein, we report a patient on chronic hemodialysis who developed severe intraperitoneal bleeding 3 days after liver biopsy. A 47-year-old male patient was referred to our department because of HbeAg-positive chronic hepatitis B. He was on regular hemodialysis for 2 years. Laboratory examination revealed the following: ALT, 82 (< 40) U/l; AST, 76 (< 40) U/l; Hb, 13.4 g/l; and HBV-DNA, 28 525 681 IU/ml. He was hospitalized, and blind aspiration biopsy using the Menghini technique was performed after initial ultrasonographic monitoring and marking of the optimal biopsy site. The biopsy was performed using a Hepafix Lok G 17 1.4-mm needle (B. Braun Melsungen AG, Melsungen, Germany). The Hb levels did not decrease significantly on follow-up and he was discharged.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
Letters to the Editor European Journal of Gastroenterology & Hepatology 2014, 26:240–248
Mean platelet volume in chronic viral hepatitis Bahadır Ceylana, Muzaffer Fincancıb, Cem Yardımcıb, Gu¨lhan Erenb, ¨ mit To¨zalganb, Cu¨neyt Mu¨derrisog˘luc and Esra Pasaog ˘ lud, aDepartment U ¸ of Infectious Diseases and Clinical Microbiology, Medical Faculty, Bezmialem Vakıf University, bMinistry of Health, Istanbul Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, cMinistry of Health, Istanbul Training and Research Hospital, Department of Internal Diseases and d Ministry of Health, Istanbul Training and Research Hospital, Department of Pathology, Istanbul, Turkey Correspondence to Bahadır Ceylan, MD, Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Bezmialem Vakıf University, Istanbul, Fatih 34096, Turkey Tel: + 90 507 231 0236; fax: + 90 212 621 7585; e-mail: [email protected]
the active role of platelets in liver inflammation. The only parameter used in our study as an indicator for determining inflammation in the liver was the MPV value; other inflammation indicators such as neutrophil– lymphocyte ratio and serum C-reactive protein level were not included in the study because while predicting the severity of inflammation in the liver, all the parameters that indicate inflammation cannot be included in the same logistic regression analysis because of the correlation between them. Besides, the MPV value does not only function as a variable that increases with inflammation but also as a variable that increases when the life of platelets shortens as the liver disease progresses.
Received 10 May 2013 Accepted 18 May 2013
Mean platelet volume (MPV) is a routinely observed parameter in blood count analysis and has been considered as an indicator of inflammation [1]. In cases accompanied by inflammation, it is reported that increasing interleukin-6 levels enhance platelet generation in the bone marrow. Moreover, MPV values also increase because of the increase in the number of young platelets entering into circulation [2]. In another study, it has been suggested that MPV values increase very rapidly in a patient with sepsis, and such a rapid increase is related to the activation and growth of platelets rather than the young platelets entering into circulation [3]. In two studies, it has been shown that MPV levels increase in chronic viral hepatitis [4–6]. As viral hepatitis is also one of the diseases accompanied by inflammation, we consider this as an expected result. However, unlike other diseases accompanied by inflammation, there is another factor in viral hepatitis that may increase MPV values, which is the shortening of life in platelets and, accordingly, the increase in young platelets that enter into circulation from the bone marrow [7,8]. It has been observed that platelet generation in the bone marrow increases for various reasons in chronic viral hepatitis [7,8]. (a) Especially in patients with cirrhosis, splenomegaly-induced platelet sequestration has been considered to be the main reason for the decrease in platelet survival in chronic hepatitis and, accordingly, the increase in platelet generation in the bone marrow [7]. (b) In chronic viral hepatitis, it has been reported that platelets accumulate in the liver and especially in inflamed periportal areas, and this has also been suggested as a factor in the development of thrombocytopenia [8]. In this study, it was observed that the accumulation of platelets was higher in the liver of those with a higher fibrosis score, and this was associated with c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-691X
It has been reported that MPV values vary in individuals with smoking habits, hypertension, diabetes, dyslipidemia, atherosclerotic diseases, venous thromboembolism, rheumatologic diseases, and inflammatory bowel diseases [1]. Thus, patients with the above-mentioned factors were not included in our study. Although individuals with atherosclerotic diseases were not included in our study, the probability of subclinical atherosclerotic disease is always present in our cases. The possibility that this situation may have affected the results of our study cannot be ignored. It has been suggested that an increase in platelet activation is seen in patients with diabetes, which is associated with an increase in the MPV values [1,9]. Many factors have been associated with platelet activation in diabetes [9]. The most significant ones are systemic inflammation, oxidative stress, inconstant calcium metabolism, increased phosphorylation of cellular proteins, and decrease in nitric oxide [9]. It has been reported that MPV values increase as the insulin resistance increases in patients with diabetes [10,11]. Individuals with blood glucose beyond the normal upper limit and individuals known to have diabetes were not included in our study because of their interaction with MPV values. Insulin resistance values and the waistto-hip ratio, which is a good indicator of insulin resistance, were not included in our study because of its retrospective structure. Moreover, it is apparent that BMI, which was evaluated in our study, is less successful as an insulin indicator compared with the waist-to-hip ratio. It may be supposed that increased insulin resistance will affect MPV values even though the blood glucose level is normal. The fact that insulin resistance was not included in our study as a variable, which may affect MPV values, is a limitation of our study. However, fatty liver is also known to be a good indicator of insulin resistance [12]. Fatty liver was not included in our study as a variable that may affect MPV values. We obtained data related to fatty liver from our DOI: 10.1097/MEG.0b013e328363714b
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letters to the Editor 241
Table 1
Findings of multivariable logistic regression analysis that reviews variables determining the severitya of the histological activity
index
Serum g-glutamyl transpeptidase level Serum globulin level Mean platelet volume
Odds ratio
95% confidence interval
P
2.255 1.016 1.513
1.015–5.011 1.005–1.027 1.145–1.977
0.046 0.005 0.004
a
Patients with a histological activity index above 9 are considered as patients with a high index.
cases and re-evaluated our study with these data. We found that in 217 of the participants included in our study, fatty liver evaluation was carried out in histological liver biopsy. Fatty liver was found in 57 (31.5%) of 181 participants, with a histological activity index (HAI) of 9 or below and in 11 (30.6%) of 36 participants with an HAI score above 9, and we concluded that the fatty liver variable is uniform among groups with high and low HAI levels (P = 0.912). No difference could be found in terms of the MPV values among the groups of individuals with and without fatty liver [MPV values were 8.8 (minimum–maximum 6.8–15.7) and 8.8 (minimum–maximum 6.5–13.1), respectively; P = 0.478]. Although fatty liver is not a variable that affects HAI, when it was included in logistic regression analysis that evaluates independent variables affecting the HAI score, it was found that MPV significantly determined the severity of the HAI score independent of fatty liver, which is an indicator of insulin resistance (Table 1).
to thrombocytopenia and liver fibrosis in chronic hepatitis C. J Gastroenterol 2013; 48:526–534. 9 El Haouari M, Rosado JA. Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review. Blood Cells Mol Dis 2008; 41:119–123. 10 Inui Y, Suehiro T, Kumon Y, Hashimoto K. Platelet volume and urinary prostanoid metabolites in non-insulin-dependent diabetes mellitus. J Atheroscler Thromb 1994; 1:108–112. 11 Zuberi BF, Akhtar N, Afsar S. Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects. Singapore Med J 2008; 49:114–116. 12 Caballerı´a L, Arteaga I, Pera G, Rodrı´guez L, Aluma` A, Auladell MA, et al. Risk factors associated with non-alcoholic fatty liver disease: a case–control study. Med Clin (Barc) 2013 . doi: 10.1016/j.medcli.2012.11.034. [Epub ahead of print].
As a consequence, we believe that MPV is a dynamic variable that may be affected by many factors including inflammation; thus, all these factors and period of disease should be taken into consideration when interpreting MPV values.
Bilal Ergu¨l, Murat Sarikaya, Zeynal Dog˘an and Levent Filik, Department of Gastroenterology, Ankara Education and Research Hospital, Ankara, Turkey
Letters to the Editor
Is liver biopsy a problem for patients on chronic hemodialysis?
Correspondence to Bilal Ergu¨l, MD, Ostim mah.1288.sok. Nevbahar konutları No A4/6, Yenimahalle 06100, Ankara, Turkey Tel: + 90 530 692 2302; fax: + 90 312 363 3396; e-mail: [email protected] Received 20 May 2013 Accepted 21 May 2013
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
2
3
4
5
6
7 8
Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des 2011; 17:47–58. Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001; 98:2720–2755. Douglas JT, Lowe GD, Forbes CD, Prentice CR. Beta-thromboglobulin and platelet counts – effect of malignancy, infection, age and obesity. Thromb Res 1982; 25:459–464. Ekiz F, Yuksel O, Kocak E, Yılmaz B, Altınbas A, Coban S, et al. Mean platelet volume as a fibrosis marker in patients with chronic hepatitis B. J Clin Lab Anal 2011; 25:162–165. Purnak T, Olmez S, Torun S, Efe C, Sayilir A, Ozaslan E, et al. Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis. Clin Res Hepatol Gastroenterol 2013; 37:41–46. Ceylan B, Fincanci M, Yardimci C, Eren G, To¨zalgan U, Mu¨derrisog˘lu C, et al. Can mean platelet volume determine the severity of liver fibrosis or inflammation in patients with chronic hepatitis B? Eur J Gastroenterol Hepatol 2013; 25:606–612. Aster R. Pooling of platelets in the spleen: role in the pathogenesis ‘hypersplenic’ thrombocytopenia. J Clin Invest 1996; 45:645–657. Kondo R, Yano H, Nakashima O, Tanikawa K, Nomura Y, Kage M. Accumulation of platelets in the liver may be an important contributory factor
Percutaneous liver biopsy is the standard procedure for obtaining hepatic tissue for histopathological examination and at present plays a major role in diagnosis, assessment of the prognosis, and evaluation of therapeutic management [1]. The most important complication of liver biopsy is bleeding, which when severe occurs intraperitoneally [2]. Herein, we report a patient on chronic hemodialysis who developed severe intraperitoneal bleeding 3 days after liver biopsy. A 47-year-old male patient was referred to our department because of HbeAg-positive chronic hepatitis B. He was on regular hemodialysis for 2 years. Laboratory examination revealed the following: ALT, 82 (< 40) U/l; AST, 76 (< 40) U/l; Hb, 13.4 g/l; and HBV-DNA, 28 525 681 IU/ml. He was hospitalized, and blind aspiration biopsy using the Menghini technique was performed after initial ultrasonographic monitoring and marking of the optimal biopsy site. The biopsy was performed using a Hepafix Lok G 17 1.4-mm needle (B. Braun Melsungen AG, Melsungen, Germany). The Hb levels did not decrease significantly on follow-up and he was discharged.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
