Introduction Chronic liver disease secondary to liver cirrhosis from chronic HCV infection is a leading cause of morbidity


Introduction
Chronic liver disease secondary to liver cirrhosis from chronic HCV infection is a leading cause of morbidity & mortality and a major public health problem in Egypt. Both quantitative and qualitative platelet defects are frequently seen in patients with chronic liver disease, with thrombocytopenia is the most common haematological abnormality in patients with liver cirrhosis 1.

Thrombocytopenia can be used as a part of non-invasive tests of portal hypertension, and as a prognostic parameter in patients with end-stage liver disease. Also, alterations in platelet morphology can be used in the diagnostic assessment of these patients 2.
Mean platelet volume (MPV) is considered a marker of platelet activation and function. MPV values were increased in patients with non-alcoholic fatty liver disease, intrahepatic cholestasis of pregnancy, chronic hepatitis, and liver cirrhosis 3, 4.

Recently, MPV and MPV/platelet count (PC) ratio were proposed as markers for the diagnosis of HCC in patients with chronic liver disease 5.

MPV was associated with greater fibrosis histological scores and necro-inflammatory activity, especially in patients with chronic hepatitis B virus (HBV) infection & primary biliary cirrhosis. Moreover, MPV was an independent, very short-term (i.e., 4weeks) prognostic indicator in patients with HBV-related acute-on-chronic liver failure 6.

In cirrhotic patients, increased MPV was noted in patients with spontaneous bacterial peritonitis, emphasizing the role of MPV as a possible marker of inflammation. However, there are no enough data on the possible association between either clinical features or prognosis of cirrhotic patients and MPV 7.

Aim of the work
In this study we aimed at evaluating the association between MPV and clinical features, complications & severity of cirrhosis in Zagazig university hospitals.

Patients & Methods:
This study was carried out in Internal Medicine Department & out-patient clinic of Zagazig University Hospitals. One hundred and fourteen patients with cirrhosis of various grades of severity & various presentations were enrolled in our study. Liver cirrhosis was diagnosed on the basis of instrumental findings (ultrasonographic, endoscopic) & clinical findings (shrunken liver, splenomegaly, variceal bleeding, presence of ascites &/ or hepatic encephalopathy). The patients were grouped according to Child-Pugh score with Child-A patients have compensated cirrhosis while Child-B & C patients had decompensated cirrhosis. All patients were evaluated according to age, sex, smoking status, history of encephalopathy, history of bleeding varices, Ultrasonographi findings, presence of DM, HTN, ascites, splenomegaly, INR, MPV, Platelet count, serum total bilirubin, albumin, ALT, AST, creatinine, FIB4, MELD & CHILD scores. We evaluated the association of MPV values with the disease clinical features, complications & severity according to Child, MELD & Fib-4 scores. Blood samples were taken by venipuncture and platelet counts & MPV were measured using ((((EDTA blood in Advia 2120 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) ))))) within 2 hours of blood withdrawal. Normal values for MPV were 7.1–11.5 femtolitre (Fl).
Informed consent was obtained from each patient or first degree relative
Statistical analysis
The collected data were computerized and statistically analyzed using SPSS program (Statistical Package for Social Science) version 20. Qualitative data were represented as frequencies and relative percentages. Chi square test (?2) and Fisher exact was used to calculate difference between qualitative variables as indicated. Quantitative data were expressed as mean ± SD (Standard deviation) for parametric and median and range for non-parametric data. One-way ANOVA F-test and Kruskal-Wallis Test were used to calculate difference between quantitative variables in more than two groups in normally normal and non-parametric variables respectively. Pearson’s and Spearman’s correlation tests were used for correlating normal and non-parametric variables respectively. The (+) sign was considered as indication for direct correlation i.e. increase frequency of independent lead to increase frequency of dependent & (-) sign as indication for inverse correlation i.e. increase frequency of independent lead to decrease frequency of dependent, also we consider values near to 1 as strong correlation & values near 0 as weak correlation. The significance Level for all above mentioned statistical tests done. With a threshold of significance is fixed at 5% level (P-value). P value of >0.05 indicates non-significant results. P value of ?0.05 indicates significant results.

Results
Table I. Demographic data among child classes of the studied patients:
Child class Total
n= 114
A
n= 27 B
n= 54 C
n= 33 Age, years 47.8 ± 14.9 55.8 ± 12.2 60.7 ± 10.2 55.3 ± 12.9
Sex Male No. 15 30 15 60
% 55.60% 55.60% 45.50% 52.60%
Female No. 12 24 18 54
% 44.40% 44.40% 54.50% 47.40%
Smoking Yes No. 6 12 9 27
% 22.20% 22.20% 27.30% 23.70%
No No. 21 42 24 87
% 77.80% 77.80% 72.70% 76.30%
Hx of HE Yes No. 0 15 30 45
% 0.00% 27.80% 90.90% 39.50%
No No. 27 39 3 69
% 100.00% 72.20% 9.10% 60.50%
Hx of bleeding OV Yes No. 0 30 27 57
% 0.00% 55.60% 81.80% 50.00%
No No. 27 24 6 57
% 100.00% 44.40% 18.20% 50.00%
DM Yes No. 9 15 15 39
% 33.30% 27.80% 45.50% 34.20%
No No. 18 39 18 75
% 66.70% 72.20% 54.50% 65.80%
HTN Yes No. 3 9 0 12
% 11.10% 16.70% 0.00% 10.50%
No No. 24 45 33 102
% 88.90% 83.30% 100.00% 89.50%
Ascites No No. 27 30 6 63
% 100.00% 55.60% 18.20% 55.30%
Ascites No. 0 24 27 51
% 0.00% 44.40% 81.80% 44.70%
Spleen Splenomegaly No. 3 24 21 48
% 11.10% 44.40% 63.60% 42.10%
SplenectomyNo. 0 3 3 6
% 0.00% 5.60% 9.10% 5.30%
No No. 24 27 9 60
% 88.90% 50.00% 27.30% 52.60%
Focal lesion Single No. 0 3 3 6
% 0.00% 5.60% 9.10% 5.30%
Multiple No. 0 0 3 3
% 0.00% 0.00% 9.10% 2.60%
No No. 27 51 27 105
% 100.00% 94.40% 81.80% 92.10%
. Data are expressed in Mean & SD or absolute value and percentage OV: eosophageal varices ….HE: hepatic encephalopathy…… HTN: hypertension…….DM: Diabetes Mellitus.

Table II: Correlation between (MPV) & other Variables:
MPV
r p
age (yrs) +.062 .712
INR +.462 .003
Platelet count -.319 .051
T. Bilirubin +.433 .007
albumin -.449 .005
ALT +.260 .115
AST +.297 .071
Creatinine+.189 .256
FIB4 +.353 .030
MELD +.424 .008
CHILD SCORE +.361 .026
MPV: mean platelet volume……. R: correlation co-efficient ……. AST: aspartate aminotransferase……… ALT: alanine aminotransferase…… MELD: Model for End-stage Liver Disease
Table III: relation between (MPV) in each Child class & other Variables
MPV
Child A Child B Child C
r p r P r p
age (yrs) .350 .356 -.263 .293 -.364 .270
INR .261 .497 .103 .686 .670 .024
Platelet count .067 .865 -.111 .662 -.273 .417
T. Bilirubin .450 .224 .285 .251 .296 .377
albumin -.310 .417 -.082 .745 -.500 .117
ALT -.683 .042 .482 .043 .536 .089
AST -.736 .024 .574 .013 .451 .164
CREAT -.160 .682 .125 .621 .251 .457
Fib-4 .400 .286 .238 .342 .164 .631
MELD .538 .135 .220 .380 .547 .082
CHILD SCORE .365 .334 -.002 .995 .768 .006

Figure.1 Box-plot diagram of MPV values of the patients in each child class, p= .109

Figure.2: Correlation analysis indicates significant correlation between (MPV) & Child score, r=+.361, p= .026
Discussion
Mean platelet volume (MPV) is a part of a routine complete blood count. MPV has been investigated in various clinical fields including inflammatory conditions, stroke, cardiovascular & chronic liver diseases. Only few studies evaluated the relationship between MPV & established cirrhosis regarding clinical features, complications & severity of cirrhosis 8.
High MPV values have been associated with worse histological fibrosis stage in patients with chronic viral hepatitis & NAFLD compared to controls due to a possible role of larger, activated platelets in the formation of micro-thrombi causing obliteration of both the portal vascular bed & intra-hepatic vessels leading to parenchymal extinction and progression of liver disease 9.

On the basis of these findings we deemed it of interest to assess whether elevated MPV values may be associated with clinical features, complications & severity of cirrhosis.
Our study included 60 males & 54 females with mean age 55 years old. Child-A patients were 27, Child-B patients were 54 while Child-C patients were 33 in number. Smokers were 24% of our patients while 76% were non-smokers. DM was present in 34% of patients while 66% of patients were non-diabetics. Focal lesions were found as ultrasonograghic finding in 8% of patients only.

We found that there was an increase in MPV values with the increase in values of Child-Pugh (positive correlation co-efficient). Also, there was significant relation between Child score values in Child-C patients & MPV.

Even when we assessed the correlation between different features of decompensation & MPV values, we found that MPV values had positive correlation with presence of high serum bilirubin, high INR & low serum albumin in addition to advanced age.

We also observed that MPV values were significantly higher in patients with more severe liver disease according to MELD & Fib-4 scores, indicating that MPV values were significantly different between patients with less advanced cirrhosis and those with severely decompensated cirrhosis.

Lastly, MPV values did not show any association with either platelet count nor kidney dysfunction in cirrhotic patients in our study.

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