Hepatitis C virus (HCV) infection is a major public health burden in Egypt, where the highest prevalence rate of HCV in the world exists. Estimates for prevalence are based upon data reported from the 2008 Egypt Demographic and Health Survey, a nationally representative sample that included participants from all major Egyptian regions, where anti-HCV antibodies prevalence was 14.7%, and viraemia was 9.8% [1] . The natural history of chronic HCV infection involves the development of liver cirrhosis in a large proportion of patients which may eventually progress to liver cell failure and hepatocellular carcinoma [2] .

At least two thirds of cirrhotic patients will develop esophageal varices during their lifetime. Severe upper gastrointestinal bleeding as a complication of portal hypertension develops in about 30% - 40% of cirrhotics. Despite the significant improvements in the early diagnosis and treatment of esophagogastric variceal hemorrhage, the mortality rate of the first variceal hemorrhage remains high (20% - 35%). Preventing first variceal hemorrhage offers the promise of reducing mortality, morbidity, and associated health care costs [3] [4] . Although many noninvasive parameters including routine liver biochemistry, esophageal wall thickness, and splenic diameter/platelet count ratio, APRI, Fibroscan of the spleen....etc. [5] [6] , where tried to predict the presence of varices, esophagogastroduodenoscopy (EGD) remains the gold standard in the diagnosis of varices and it also offers therapeutic potentials [7] .

Before 2006, Egypt did not have a comprehensive national program for control of viral hepatitis. HCV treatment program started with strong governmental support with the hope of eventual HCV eradication in Egypt. All eligible patients were treated with pegylated interferon/ribavirin (PEGIFN-RBV), with almost 100% of the patients receiving therapy for free [8] . Viral hepatitis treatment centers opened nation-wide for application of PEGIFN-RBV therapy since 2007.

A number of new treatment options have become available, with much higher efficacy (cure rates >90%) compared to the previous standard of care PEGIFN-RBV [9] . Sofosbuvir was the first direct antiviral agent (DAA) introduced in Egypt, with large scale treatment starting in October 2014.

Priority of treatment in Egypt’s HCV treatment program with new DAAs therapies is directed towards patients with stage III and stage IV hepatic fibrosis. No differentiation in treatment priority was granted based on previous treatment experience. Upper GIT endoscopy was mandatory according to the national Egyptian guidelines in the following circumstances: histologic evidence of cirrhosis by liver biopsy, fibroscan score >19.2 k・pa and Platelet count < 100,000 × 10³/dl. Exclusion criteria included a Child-Pugh class C with score ≥9, presence of ascites (except after control), patients with HCC except after successful radical intervention (4 months after resection or successful local ablation) evident by triphasic CT and presence of large risky esophageal varices (except after prophylactic treatment) [10] .

This study aimed at estimating the prevalence of varices among those patients and judging the validity of the national recommendation of upper GIT endoscopic screening before enrollment in HCV antiviral therapy and consequently assesses the work load on the endoscopic units met by this recommendation.

This study is a prospective study including patients evaluated at endoscopy units, Zagazig University Hospitals between January 1^st and December 31^st 2014 for enrollment in HCV therapy. Patients were referred to our endoscopy units from HCV treatment clinics of the National Committee for Prevention and Control of viral hepatitis centers.

The availability of a highly effective therapy, coupled with increased diagnosis and treatment and marked reduction in the new cases, has the potential to eliminate hepatitis C in Egypt within the next decades because viral hepatitis is arguably the most significant public health problem facing Egypt [11] . HCV prevalence rates in the general population are estimated at 10% to 15% in rural areas, with some age groups suffering from prevalence rates of up to 50%. As additional DAAs are approved for clinical use, clinicians may face complex choices and treatment guidelines [12] - [14] .

Newly introduced DAAs for HCV are expected to increase eligibility for treatment. Hepatologists will probably face challenges in prioritizing patients for treatment [15] [16] , and criteria for receiving therapy will be reshaped in parallel with changing therapeutic landscape [17] .

In our study, patients presenting for upper GIT endoscopy as preparation for HCV therapy had mostly borderline laboratory findings, including liver function tests. Total number of such patients increased in 2014 as compared to 2013. There was also a trend of increase in the second half of 2014. Both findings can be explained by the introduction of the new HCV therapies, with increased eligibility for treatment and the priority criteria for enrollment in the national treatment program when compared with previous policy for IFN based regimens. Besides, the effect imparted by the mass media which encouraged patients for treatment armed by the high SVR rates in the preliminary studies.

Portal hypertension is a progressive complication of cirrhosis. The management of the patient with cirrhosis and portal hypertensive gastrointestinal bleeding depends on the phase of portal hypertension at which the patient is situated, from the patient with cirrhosis and portal hypertension who has not yet developed varices to the patient with acute variceal hemorrhage for whom the objective is to control the active episode and prevent re- bleeding [3] .

Gastric varices are less prevalent than esophageal varices and are present in 5% - 33% of patients with portal hypertension with a reported incidence of bleeding of about 25% in 2 years, with a higher bleeding incidence for fundal varices [3] . In our series, gastric varices were reported in 2.6% and 3% of screened and follow up patients respectively.

Our figures are less than the rates reported previously from the Egyptian literature that ranged from 12.5% to 13.3%, and that is because our patients, in one hand were none bleeders and in the other hand were at earlier stages of cirrhosis when compared to patients with acute variceal hemorrhage including patients with Child C cirrhosis and HCC in the previous studies [18] [19] .

A substantial number of screened patients (68.4%) had esophageal and gastric varices mostly detected for the first time. A small proportion of those patients had history of previous endoscopy with medical treatment for portal hypertension. Endotherapy in the form of band ligation for esophageal varices and variceal injection for gastric varices was performed. The decision for endoscopic intervention for our cases coincided with the current guidelines [20] . In fact, endoscopic treatment of grade III varices and grade II varices with risky signs will reduce the frequency of 1^st variceal bleeding and that is why we endoscopically treated these patients.

Detection of such large number of patients with varices points to a large gap in our follow-up strategies in HCV-positive patients. However, detection of such large number of patients at earlier stages will shift management of varices from bleeding to prophylactic measures which probably may improve the general wellbeing and survival in HCV cirrhotic patients.

The presence of varices correlates with the severity of liver disease; while in the previous international studies only 40% of Child A patients had varices; about 85% of Child C patients had varices [4] . In the current study about 65.9% and 69.5% of screened patients with Child A and B had varices respectively. These figures are consistent with similar higher rates reported from the Egyptian literature [21] [22] , and can be explained by the noncompliance of cirrhotic patients with the scheduled endoscopic screening in cirrhotics [20] and the bad reputation of IFN based therapies, were a large proportion of Egyptian patients canceled evaluation for IFN based therapies and were waiting the oral drugs. However, this study confirmed parallel increase [4] in the severity of varices (represented with increased grade) with advanced liver disease. This was noticeable by the higher prevalence of risky varices (grade II and III) in Child B patients compared to Child A patients, although the difference was not statically significant (p = 0.25).

The observable trend for increased numbers of subjects requiring endoscopic evaluation prior to HCV treatment has many implications. First of all, workload is increasing on endoscopy units which are already loaded with many patients of portal hypertension and varices due to the high prevalence of chronic liver diseases in Egypt [18] [19] [23] , and this is obvious by the four fold rise in pre-treatment endoscopic assessments and overall endoscopic examinations during 2014 in comparison to 2013. Second; more cases eligible for endotherapy are detected earlier with shifting of workload from advanced to earlier stages of CLD. A program for follow-up of endoscopically-detected early cases of varices should be established parallel to HCV treatment program in line with established guidelines. This will ultimately reduce the frequency and complications of variceal bleeding. Also, the effect of newer therapies on portal hypertension and its complications should be noted, yet recent report from Austria showed potential beneficial effect of interferon free regimens for HCV cirrhotic liver on portal hypertension with improved liver stiffness, platelet count, serum albumin and bilirubin levels, as well as prothrombin time [24] .

Increased eligibility for therapy will generally increase the burden on national resources. This will probably lead to some prioritization strategy, which may be included in the enrollment criteria for therapy. Presence of varices together with other parameters points to advanced CLD and hence gives priority for initiation of oral HCV therapy, particularly with shortage of liver transplantation in Egypt. However, due to the short period from its introduction till now, our understanding of its effects on the course of chronic liver disease and portal hypertension together with the side effects profile is not yet clear.

This study had some limitations. The first of all, it is a single center study. The second is the lack of follow up of patients who received new oral therapies and studying its effect on the natural history of varices.

According to the results of this study screening endoscopy for early cirrhotic patients awaiting oral anti-HCV therapy is valid, because a substantial proportion of these patients had varices, and it seems that varices are higher in patients with Child B cirrhosis when compared with patients with Child A cirrhosis. Endoscopic work burden is expected to rise with increased demand on newer oral regimens. More cases eligible for endotherapy are detected earlier with shifting of workload from advanced to earlier stages of CLD.

In conclusion, screening endoscopy for early cirrhotic patients awaiting oral anti-HCV therapy is valid. Endoscopic work burden is expected to rise with increased demand on newer directly acting antiviral regimens.

Salem Y.Mohamed,Bassim A.Gaballah,Mohamed H.Emara, (2015) Validity of Upper Gastro-Intestinal Endoscopic Screening in HCV Cirrhotic Patients Awaiting Antiviral Therapy. Open Journal of Gastroenterology,05,191-199. doi: 10.4236/ojgas.2015.512029