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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 47  |  Issue : 3  |  Page : 102-106

Red blood cell distribution width is a potential prognostic index for liver diseases due to chronic hepatitis C virus infection


1 Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission01-May-2017
Date of Acceptance01-Nov-2017
Date of Web Publication23-Jan-2021

Correspondence Address:
MSc Mennat-Allah M El Sawaf
Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University Hospital, El Geish Street, Tanta, Gharbia Governorate
Egypt
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DOI: 10.4103/tmj.tmj_68_17

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  Abstract 


Background Red cell distribution width (RDW) is a marker of red blood cell size heterogeneity. Increased RDW is associated with liver diseases, but it has not been studied in patients with hepatitis C virus (HCV).
Aim To determine if RDW is a potential prognostic index for liver diseases due to chronic HCV infection.
Patients and methods A total of 95 patients with liver diseases due to chronic HCV infection and 20 healthy controls were enrolled in this cross-sectional study. Patients comprised 20 patients with chronic HCV, 52 patients with HCV-related cirrhosis, and 23 patients with HCV-related hepatocellular carcinoma (HCC). HCV antibody, PCR of HCV, HBsAg, complete blood count, liver function tests, and RDW were assessed. Child–Pugh score were calculated in patients with cirrhosis and those with HCC.
Results RDW was significantly increased in patients with HCV-related liver cirrhosis and patients with HCV-related HCC compared with patients with chronic HCV infection and healthy controls (P≤0.05). Moreover, RDW was higher in patients with chronic HCV infection than in healthy controls, but it did not achieve statistical significance (P>0.05). In patients with cirrhosis and patients with HCC, RDW was positively correlated with total bilirubin and Child–Pugh score and negatively correlated with hemoglobin concentration, platelet counts, and serum albumin.
Conclusion RDW was increased in patients with HCV-related liver cirrhosis and patients with HCV-related HCC and was correlated with higher Child–Pugh score. RDW could be a valuable prognostic index for chronic liver diseases due to HCV infection.

Keywords: chronic hepatitis C, hepatocellular carcinoma, liver cirrhosis, red cell distribution width


How to cite this article:
El Sawaf MAM, Ali LA, El Bendary AS, Negm OE. Red blood cell distribution width is a potential prognostic index for liver diseases due to chronic hepatitis C virus infection. Tanta Med J 2019;47:102-6

How to cite this URL:
El Sawaf MAM, Ali LA, El Bendary AS, Negm OE. Red blood cell distribution width is a potential prognostic index for liver diseases due to chronic hepatitis C virus infection. Tanta Med J [serial online] 2019 [cited 2021 May 17];47:102-6. Available from: http://www.tdj.eg.net/text.asp?2019/47/3/102/307635




  Introduction Top


Hepatitis C virus (HCV) infection is a major cause of liver diseases and increases the rates of morbidity and mortality all over the world [1]. Chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) are frequent complications in patients infected with HCV [2].

Red cell distribution width (RDW), a part of an electronic complete blood count, is a measure of variation in the size of circulating red blood cells (RBCs). Higher RDW values demonstrate greater variation in size. RDW has been reported as a prognostic marker in various diseases including coronary artery disease, congestive heart failure [3], cerebrovascular accidents [4], pulmonary hypertension [5], and peripheral artery disease [6].

Regarding liver diseases, increased RDW has been described in patients with alcoholic or nonalcoholic fatty liver disease and other types of liver diseases such as HCC and primary biliary cirrhosis [7]. Lou et al. [8], reported that RDW values were significantly increased in patients with chronic hepatitis B and were associated with increased morbidity and mortality.

This study aimed to determine if RDW is a valuable prognostic factor for chronic liver diseases due to HCV infection.


  Patients and methods Top


Study design and patients

This was a cross-sectional study conducted in Egypt during the period from May 2015 to November 2015. A total of 95 patients with liver diseases due to chronic HCV infection admitted at the Department of Tropical Medicine and Infectious Diseases in Tanta University Hospital and 20 age-matched and sex-matched healthy controls were enrolled in this study. Patients were divided into 20 patients with chronic HCV, 52 patients with HCV-related cirrhosis, and 23 patients with HCV-related HCC.

Diagnosis of chronic hepatitis C was based on persistence of HCV antibodies and HCV-RNA in the serum of the patients for at least 6 months. Liver cirrhosis was diagnosed based on clinical, laboratory, and radiologic data. HCC was diagnosed according to the European Association for the Study of Liver (EASL) guidelines established in 2012 [9]. Healthy volunteers with normal liver functions, negative hepatitis viral markers, and normal ultrasound imaging finding were enrolled as controls.

The exclusion criteria were as follows: (a) blood transfusion 4 months before admission; (b) renal impairment; (c) malignant diseases other than liver cancer; (d) hematological diseases; (e) coronary artery disease; (f) congestive heart failure; (g) cerebrovascular accidents; (h) pulmonary hypertension; (i) peripheral artery disease; and (j) coinfection with hepatitis B virus.

All participants gave their informed written consents, and the study was approved by the Research Ethics Committee of the Faculty of Medicine, Tanta University, Tanta, Egypt. All authors had access to the study data and reviewed and approved the final manuscript.


  Methods Top


All participants in the study were subjected to the following:
  1. Full history taking and through clinical examination.
  2. Laboratory investigations, including HCV antibody, PCR of HCV, HBsAg, complete blood count, liver function tests, blood urea level, and serum creatinine.
  3. RDW was performed using Erma PCE-210 hematology analyzer. Normal range of RDW in human RBCs is 11.6–14.5% (for adults).
  4. Child–Pugh score was assessed in patients with cirrhosis and patients with HCC [10],[11].
  5. Radiological imaging including abdominal ultrasonography and triphasic computed tomography for diagnosis of HCC.


Statistical analysis

Statistical analysis was carried out using SPSS, version 15, for Microsoft Windows (SPSS, Chicago, Illinois, USA). The statistical data are reported as the mean±SD, frequencies (number), and percentages when appropriate. A comparison of numerical variables between the study groups was performed using one-way analysis of variance test followed by post-hoc Tukey’s multiple comparison test when data were normally distributed. Student’s t test used to compare independent samples from two groups when the samples were normally distributed. Pearson’s correlation was used to quantify the association between continuous variables. To compare categorical data, the χ2 test was performed. P values less than 0.05 (two-tailed) were considered statistically significant.


  Results Top


A total of 95 patients, including 20 patients with chronic HCV, 52 patients with HCV-related liver cirrhosis, 23 patients with HCV-related hepatocellular, and 20 healthy controls were enrolled in this study. The demographic and laboratory profile of the studied participants are summarized in [Table 1].
Table 1 Demographic and laboratory profile of the studied groups

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There were significant differences between the studied groups regarding total bilirubin, aspartate aminotransferase, alanine aminotransferase, and international normalized ratio, as there were significant increases in these parameters in patients with HCV-related cirrhosis and HCV-related HCC when compared with patients with chronic hepatitis C infection and healthy controls (P≤0.05), but there were insignificant differences when patients with chronic hepatitis C were compared with healthy controls. Moreover, there was significant difference between the studied groups regarding serum albumin, as there were significant decreases in this parameter in patients with HCV-related cirrhosis and HCV-related HCC when compared with patients with chronic hepatitis C infection and healthy controls (P≤0.001), but there were insignificant differences when patients with chronic hepatitis C infection were compared with healthy controls ([Table 1]).

There were significant difference between the studied groups regarding hemoglobin concentration and platelets count. There were significant decreases in these parameters in patients with HCV-related cirrhosis and HCV-related HCC when compared with patients with chronic hepatitis C infection and healthy controls (P≤0.05) ([Table 2]).
Table 2 Complete blood count of the studied groups

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In the current study, there were significant differences between the studied groups regarding RDW. There were significant decreases in these parameters in patients with HCV-related cirrhosis and HCV-related HCC when compared with chronic hepatitis C patients and healthy controls (P≤0.05). RDW was higher in patients with chronic HCV infection as compared with healthy controls, but it did not achieve statistical significance (P>0.05) ([Table 3]).
Table 3 Red cell distribution width of the studied groups

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In patients with HCV-related liver cirrhosis, there were significant positive correlations between RDW and total bilirubin (r=0.346) (P=0.020) and Child–Pugh score (r=0.283) (P=0.042) and a significant negative correlations with hemoglobin concentration (r=−0.311) (P=0.025), platelets count (r=−0.596) (P=0.006), and serum albumin (r=−0.421) (P=0.021) ([Table 4]).
Table 4 Correlation between red cell distribution width with different parameters

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However, in patients with HCV-related HCC, significant positive correlations between RDW and total bilirubin (r=0.422) (P=0.045) and Child–Pugh score (r=0.614) (P=0.002) and significant negative correlations with hemoglobin concentration (r=−0.261) (P=0.047), platelets count (r=−0.485) (P=0.030), and serum albumin (r=−0.28) (P=0.031) were detected ([Table 4]).


  Discussion Top


RDW reflects changes in the size of circulating erythrocytes (anisocytosis) and is routinely performed with automated blood counts in laboratories. RDW facilitates diagnosis of various types of anemias, especially microcytic (caused by iron deficiency) and macrocytic (caused by vitamin B12 or folic acid deficiencies) [12].

Regarding liver disease, RDW can be considered as an inflammatory marker for multiple liver conditions such as chronic hepatitis, alcoholic liver disease, nonalcoholic liver disease, liver cirrhosis, and primary HCC [8].

In the present study, there was a significant increase in RDW in patients with HCV-related liver cirrhosis and HCV-related HCC versus patients with chronic hepatitis C infection and healthy controls. This was in agreement with Luo et al. [13], and Hu et al. [14], who found that RDW values were higher in patients with HCC and those with liver cirrhosis due to hepatitis B virus infection compared with patients with chronic hepatitis B.

In our study, RDW was higher in patients with chronic hepatitis C infection versus healthy controls but did not achieve statistical significance, which may be owing to the relatively small sample size. Lou et al. [8], and Huang et al. [15], found that RDW was significantly elevated in patients with chronic hepatitis B infection compared with healthy controls.

Many mechanisms have been described for explanation of increased RDW in liver diseases [16]. Inflammatory cytokines [16] may inhibit RBCs maturation and speed up newer and larger reticulocytes release in the peripheral blood leading to higher RDW values [17]. Moreover, impaired renal function in patients with liver diseases may cause increase in RDW [18].

Halifeoglu et al. [19], demonstrated that folic acid levels were lower in patients with liver diseases when compared with healthy controls. Folic acid deficiency in patients with liver diseases could influence hematopoiesis, leading to increase heterogeneity of erythrocytes. Moreover, accelerated RBCs destruction due to hypersplenism may increase the release of large immature erythrocyte into the peripheral blood leading to higher RDW [20].

In the present study, in patients with HCV-related liver cirrhosis and HCV-related HCC, there were significant positive correlations between RDW and total bilirubin and Child–Pugh score and significant negative correlations between RDW and hemoglobin concentration, platelets count, and serum albumin. Consistent with our results, Hu et al. [14], found that RDW was positively correlated with serum bilirubin and Child–Pugh score and negatively correlated with platelet counts, serum albumin concentration, and hemoglobin concentration in patients with HBV-related liver cirrhosis and in patients with HCC.Increased RDW in patients with HCV-related liver diseases was correlated with higher Child–Pugh score and with other conventional prognostic factors for liver diseases such as serum albumin, serum bilirubin, and platelet counts.

The half-lives of serum bilirubin, platelets, and serum albumin is 10 h, 4 days, and 10–20 days, respectively, so these parameters may reveal recent changes in the liver disease status. In contrast, the erythrocyte half-live is ∼120 days. RDW may reflect the disease status for a longer duration. Thus, RDW could be a more stable index parameter compared with other well-established indices [14].

In conclusion, this study revealed that RDW is elevated in HCV-related liver cirrhosis and HCV-related HCC and increased RDW was correlated with higher Child–Pugh score. RDW could be a more stable prognostic index for liver diseases due to chronic HCV infection compared with other well-established indices as it reflects the disease status for a longer period.

To the best of our knowledge, this is the first study that assessed RDW in HCV-related liver diseases. Our study was a cross-sectional analysis with a relatively small sample size, so further prospective studies including larger cohort are needed to confirm our findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Huang R, Yang C, Wu K, Cao S, Liu Y, Su R et al. Red cell distribution width as a potential index to assess the severity of hepatitis B virus-related liver diseases. Hepatol Res 2014; 44:464–470.  Back to cited text no. 15
    
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Xu WS, Qiu XM, Ou Q, Liu C, Lin JP, Chen HJ et al. Red blood cell distribution width levels correlate with liver fibrosis and inflammation. Medicine (Baltimore) 2015; 94:612.  Back to cited text no. 16
    
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Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009; 133:628–632.  Back to cited text no. 17
    
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Halifeoglu I, Gur B, Aydin S, Ozturk A. Plasma trace elements,vitamin B12, folate, and homocysteine levels in cirrhotic patients compared to healthy controls. Biochemistry (Mosc) 2004; 69:693–696.  Back to cited text no. 19
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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