الفهرس 
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Abstract
Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial.
Hepatitis C virus (HCV) infection promotes liver fibrogenesis by direct and indirect mechanisms through chronic inflammation. chronic infection with hepatitis C virus (HCV) induces the progression of liver fibrosis, which results in the development of cirrhosis and hepatocellular carcinoma (HCC).
Liver fibrosis is the essential factor in the management of HCV disease. Its assessment is crucial to make therapeutic decisions and determine the adequate follow up of the patients. Hence, the fibrosis stage is one of the main predictive factors to become complicated once the virus is eradicated. Consequently, fibrosis regression has become a new surrogate goal of HCV therapy.
Accurate evaluation of hepatic fibrosis has become the primary goal in managing the progression of CHC because its morbidity and mortality are linked to cirrhosis and its complications.
Although liver biopsy (LB) is considered the standard for determination of the stage of fibrosis, it has disadvantages such as invasiveness, expensiveness, risk of complications, and potential for sampling errors.
Various non-invasive serum biomarkers and imaging methods for evaluating liver fibrosis have recently developed as alternatives to liver biopsy to determine the degree of liver fibrosis.
A positive impact has been made by the advent of direct acting antiviral (DAA) agents, which have a success rate of over 90% in achieving sustained virologic response (SVR), or virologic cure, including in patients with decompensated cirrhosis.
Successful HCV eradication was associated with regression of fibrosis; this is likely attributed to the significant improvement in liver histology.
However, patients with advanced hepatic fibrosis and comorbid conditions continue to be at high risk of disease complications and require continued monitoring after successful therapy.
Indeed, the degree of fibrosis regression varies, and liver-related complications remain in some patients despite having achieved SVR.
Therefore, predicting HCC and liver fibrosis progression is clinically crucial.
Noninvasive markers such as serum angiopoietin-2 (Ang-2) are being sought as an alternative for detecting liver fibrosis. Ang-2 is believed to be involved in both the angiogenesis and the inflammatory pathways in pathological situations.
Ang-2 is increased in viral hepatitis and its concentrations could be valuable marker of hepatic inflammation, disease progression, and response to therapy. In fact, Ang-2 serum levels were significantly higher in advanced stages of liver fibrosis.
In this study, we can affirm that Ang2 levels are predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs.
The present study was held to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs.
This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals.
Patients who did not achieve SVR, had a history of liver transplantation, HCC, decompensated liver disease (Child C) or another liver disease, had missing clinical information, were co-infected with HIV or hepatitis B virus, had renal dysfunction, did not undergo paired pelvi-abdominal ultrasound or FibroScan examination at baseline and at SVR12 were excluded from the study.
All patients were subjected to the following:
1. Full history taking with stress concerning the hepatology system.
2. Clinical evaluation including
a. Symptoms: abdominal distension, lower limb edema and bleeding (hematemesis and melena)
b. Signs: jaundice, hepatomegaly, splenomegaly, signs of portal hypertension and liver decompensation.
3. Laboratory investigations including
a. Routine investigations:
• HCV-RNA PCR
• Complete blood picture
• Alpha-fetoprotein
• Serum urea and creatinine
• Child-Pugh score
b. Liver function tests and liver enzymes including serum alanine transaminase (ALT), serum aspartate transaminase (AST), serum albumin, serum bilirubin, and INR.
c. Measurement of serum Angiopoeitin-2 (Ang2) by ELISA.
d. Non-invasive fibrosis markers: FIB-4 index and APRI score
4. Abdominal and Pelvic ultrasonography.
5. Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients.
Statistical analysis of data obtained from the present study revealed the following results:
• Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy.
• There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12.
• The liver size, the spleen size and portal vein diameter were also significant after DAA therapy.
• There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant.
• There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages.
• Overall, serum Ang-2 levels significantly decrease after DAA therapy.
• In F0, F1, F2 & F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost.
• Baseline Ang-2 and WBCs, AST, ALT, total bilirubin,, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated.
• There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment.
• Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy.
• Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline.
• Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy.
• Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy.