CORRELATION BETWEEN VITAMIN D LEVEL AND RESPONSE TO THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C VIRAL INFECTION

Al Shaimaa Zakaria El Sayed Mohamed 1 , Neveen Ahmed Abdul Hafeez Soliman 2 , Eman Ramadan AbdEl gwad 2 and Dalia Mohamed AbdEl-Hassib 3 . 1. Resident phyisician at clinical pathology department ,Benha Fever Hospital,Ministery of Health, Egypt. 2. Professor of Clinical and Chemical Pathology,Benha Faculty of Medicine, Egypt. 3. Lecturer of Clinical and Chemical Pathology,BenhaFaculty of Medicine,Egypt. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV) which is a small, enveloped, single-stranded and positive-sense RNA virus (Rosen,2011). The hepatitis C epidemic in Egypt had began during 1960-1980, when mass campaigns were conducted to control schistosomiasis through parenteral antischistosomal therapy administered by health-care workers using improperly sterilized glass syringes (Srickland,2006). The primary route of transmission of HCV in the developing world areblood transfusions and unsafe medical procedures(Maheshwari and Thuluvath,2010). Hepatitis C virus infection usually is slowly progressive Thus,acute hepatitis is rarely daignosed as it is not clinically apparent (Wassmuth,2012).A hallmark of HCV infection is the establishment of chronic infection which is the persistence of HCV RNA in the blood for at least 6  Major changes had emerged during the last few years in the therapy of patients with chronic hepatitis C , Several direct acting antiviral agents (DAAs) including Sofosbuvir had been developed showing potent activity against HCV and improving the rates of Sustained Virological response (SVR) even in difficult-to-treat chronic hepatitis C patients (Cholongitas and Papatheodoridis,2014). Vitamin D is a fat soluble vitamin metabolized by the liver and is converted to 25 dihydroxy vitamin D which is then converted to the active form 1, 25(OH)2 vitamin D. Those with impaired liver function can have poor conversion.vitamin D has been found to have an immunological role( modulate immunity principally via regulating T-cell function).Vitamin D Receptor (VDR) has been found to be expressed on virtually every type of cell involved in immunity

Statistical analysis:-
Statistical Package for Social Sciences (SPSS) version 19 software( SPSS Inc., Chicago,USA) was used to analyze and tabulate collected data. Categorical data were presented as numbers and percentages. Quantitative data were expressed as mean and standard deviation. Chi square test (X2) was used to compare between 2 or more categorical 1893 groups. Student t-test, "Z" of Mann Whitney and U-test were used to compare means of two independent groups. Pearsons correlation analysis and Spearman Rho correlation were used to compare between quantitative variables. The accepted level of significance (predictive value) was >0.05.

Results:-
By comparing between patient and control groups,it was found that,there was statistically non significant difference as regards to both age groups(>45 and <45 years old).It also showed that 46.7% of patients are older than 45 years old (p> 0.05),and there was negative correlation between age of patients group and vitamin D levels ) Fig:1).andthere was statistically no significant difference between patients and control groups as regard togender (p > 0.05).
There was a highly significant difference of Vitamin D level between patients and control groups,(patients were lower than controls) (17.9±29.8ng/ml for patients versus 43.2±11.9ng/mlfor control)(p <0.001) (Tab:1).
there was statistically no significantdifference between male and female regarding to Vitamin D level in studied groups (p >0.05) (Tab:2).
There was a highly significant difference of PCR level between baseline time and 12 weeks(end) of treatment in patients group (p > 0.001) (Tab:3),and all cases responded 100% to treatment regardless vitamin D level (Tab:4).

Discussion:-
This case-control was intended to evaluate the relationship of 25(OH)D level and the response to antiviral therapy in chronic hepatitis C viral infection.
In this study,the mean age of our patients was 42.1± 11.6 (46.7% were older than 45 years old) and there was no significant difference between patients and control groups as regard to age in years and as regard to gender (most of patients 76.7% were males while females represented 23.3%).This was in agreement withEl-Zanaty and Way (2009) who reported that prevelance of chronic HCV in Egypt is higher among men than women and increases with age (reaching >25% among persons aged >50 years).This was also reported by El-Sadawyand coworkers(2004)whoreported that the high risk of exposure to HCV infection is among males (due to the relative increase in males outdoor activities).While this was disagreed by Zhili and colleagues (2016) who found that The frequency of HCV prevalence was significantly higher in female patients compared to males before ages 60, while the opposite result was observed after 60 years.
In this study there was a highly significant difference of Vitamin D level between patients and control groups (lower levels in patients),these outcomes were in concurrence with ElHusseinyand associates (2012)who found a significant reduction of vitamin D and its active metabolites in HCV genotype 4-infected Egyptian patients compared to control groups,and with Targherand colleagues (2007)who reported that patients with chronic liver disease of any cause have lower levels of serum 25(OH) vitamin D,this was explained by Schiefke and coworkers(2005)and Nair (2010) to be due to impaired 25-hydroxylation of vitamin D and impaired synthesis of vitamin D binding protein and impaired absorption of vitamin D due to impaired bile acid production or gut edema associated with portal hypertention.
Our study showed no significant difference between male and female regarding to Vitamin D baseline level in groups,This disagreed with Masanori and coworkers (2015)who reported lower level of vitamin D in female patients.
The present study demonstrated that there was a highly significant difference of PCR level between Baseline time and 12 weeks(end) of treatment in patients group (p > 0.001) (all patients became negative for HCV-RNA),These outcomes were in concurrence withFoster and associates (2015)who reported that sofosbuvir has been a breakthrough new medication for the treatment of patients with chronic hepatitis C and has an excellent sustained virologic response rates in patients with unfavorable baseline characteristics.

1895
Our study showed that all cases respond 100% to treatment regardless vitamin D level,this was agreed by AbdElalim and colleagues (2015) who reported that vitamin D status has no correlation with viral load and there was no significant association between vitamin D deficiency and the antiviral therapy response,while was disagreed by Petta and coworkers (2010)who reported that low vitamin D was linked to severe fibrosis and low SVR on IFNbased therapy for CHC patients.

Conclusion:-
This study revealed that chronic hepatitis C patients have low vitamin D level and respond well to antiviral treatment including the new DAA(Sofosbuvir) So vitamin D level is an independent factor not corresponding to the level of the virological response to antiviral therapy.