Change in the hepatic profile of hepatitis C virus genotype 4-infected patients with compensated cirrhosis receiving ombitasvir, paritaprevir, and ritonavir plus ribavirin: A subanalysis of the AGATE-II study.

In AGATE-II, treatment with ombitasvir coformulated with paritaprevir/ritonavir plus ribavirin (RBV) in Egyptians infected with hepatitis C virus genotype 4 resulted in high rates of sustained virologic response at post-treatment week 12. This subanalysis examined the effects of treatment in AGATE-II on liver biomarkers in patients with compensated cirrhosis. AGATE-II was a phase 3, open-label, partly randomized trial of ombitasvir/paritaprevir/ritonavir with weight-based RBV daily once in treatment-naive or treatment-experienced patients. Patients without cirrhosis received treatment for 12 weeks and patients with compensated cirrhosis were randomized 1:1 to the same regimen for either 12 or 24 weeks. Sixty patients with compensated cirrhosis were randomized to treatment for 12 weeks (n = 31) or 24 weeks (n = 29). In the 12-week arm, significant improvements were observed in biomarkers of liver injury (alanine aminotransferase: -53.7 U/L, P < 0.001; aspartate aminotransferase: -35.9 U/L, P < 0.001) and liver fibrosis (aspartate aminotransferase to platelet ratio index: -0.987, P < 0.001; fibrosis-4 index: -1.165, P < 0.001). Similar results were reported in the 24-week arm. Treatment with ombitasvir/paritaprevir/ritonavir plus RBV in hepatitis C virus genotype, 4-infected Egyptians with compensated cirrhosis resulted in improvements in certain biomarkers of liver synthetic function, injury, and fibrosis, independent of treatment duration.

Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients.

Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis.

Serious Adverse Events with Sofosbuvir Combined with Interferon and Ribavirin: Real-Life Egyptian Experience.

Viral hepatitis is a serious problem worldwide that was under-recognized till recently. The prevalence of chronic hepatitis C virus (HCV) is estimated to be 180 million people worldwide. Treatment of chronic HCV using combined pegylated interferon and ribavirin (PEG/RIBA) has long been the standard of care with modest response. In our study, we will report the real-life experience of serious adverse events (SAEs) that were reported by the National Committee for Control of Viral Hepatitis (NCCVH, Cairo, Egypt) program while treating chronic HCV using the triple therapy, sofosbuvir combined with pegylated interferon and ribavirin (PEG/RIBA/SOF), which led to premature discontinuation of treatment. This retrospective analysis included a total of 6,989 chronic HCV patients who were treated by the NCCVH. They received the triple antiviral therapy in 26 treatment centers in Egypt using PEG/RIBA/SOF for 12 weeks. Among 6,989 patients who were treated in 26 treatment centers related to NCCVH, 406 cases (5.9%) reported SAEs and prematurely stopped their treatment. Triple therapy PEG/RIBA/SOF was an important intermediate milestone between interferon-based therapy and the interferon-free all-oral direct acting antiviral agents (DAAs). Results of this study were the leading cause of discontinuation of interferon-based therapy and introduction of interferon-free all-oral treatment protocols, incorporating DAAs from different classes as soon as they gain approval.

Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients.

BACKGROUND: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. METHODS: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. RESULTS: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. CONCLUSION: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.

Study of the clinical relevance of Helicobacter pylori virulence genes to gastric diseases among Egyptian patients.

BACKGROUND AND STUDY AIMS: Helicobacter pylori infection is common in Egypt. It has been associated with gastritis, ulcers and it is a risk factor for gastric cancer. We aimed to study the correlation between the presence of H. pylori virulence factors and the histopathological and endoscopic findings in gastric biopsies. PATIENTS AND METHODS: Gastric biopsies from thirty seven patients scheduled for diagnostic endoscopy in Cairo University hospital were included in the study. All gastric biopsies were subjected to histopathological examination and PCR assay for detection of 16S rRNA gene to diagnose H. pylori infection, detection of H. pylori virulence factors by PCR for cagA and vacA genotypes and serological analysis of H. pylori (cagA, vacA, P25, and P19) IgG antibodies by immunoblot assay were done. RESULTS: H. pylori infection was detected in 23 (62.2%) cases by histopathology while 28/37 (75.7%) were positive for H. pylori 16S rRNA gene by PCR. By PCR seventeen samples out of 37 (45.9%) were positive for cagA gene and five (13.5%) for cag empty site gene. CONCLUSION: The most common vacA genotype identified was vacA s2m2 genotype in 10 (27.02%). No statistical correlation was found between IgG antibodies against different antigens of H. pylori virulence factors (cagA, vacA, p25, and p19) and the degree of gastritis except for IgG antibodies against the UreA antigen.

Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial.

BACKGROUND: In Egypt, chronic hepatitis C virus (HCV) infection occurs in around 10% of the population (about 8 million individuals), and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and mortality. Although HCV genotype 4 constitutes about 20% of HCV infections worldwide, the prevalence in Egypt is more than 90%. We assessed the efficacy and safety of the two direct-acting antiviral drugs ombitasvir, an NS5A inhibitor, and paritaprevir, an NS3/4A protease inhibitor dosed with ritonavir, plus ribavirin in treatment of chronic HCV infection in Egypt. METHODS: AGATE-II was a phase 3, open-label, partly randomised trial in patients with chronic HCV genotype 4 infection recruited from five academic and hepatology centres in Egypt. Patients were HCV treatment-naive or treatment-experienced with interferon-based regimens. Eligible patients were aged 18 years or older, and had been chronically infected with HCV genotype 4 for at least 6 months with a plasma HCV RNA concentration of more than 1000 IU/mL at screening. Patients without cirrhosis were assigned to receive 12 weeks of 25 mg ombitasvir, 150 mg paritaprevir, and 100 mg ritonavir orally once daily plus weight-based ribavirin. Patients with compensated cirrhosis were randomly assigned (1:1) to receive the same treatment for either 12 weeks or 24 weeks. Randomisation was stratified by previous pegylated interferon and ribavirin treatment experience using a web-based interactive response technology system and computer-generated schedules prepared by personnel from the funder's statistics department. Investigators were masked to randomisation schedules and were informed of each patient's assigned treatment by the interactive response technology system immediately after allocation. The primary endpoint was the proportion of patients with a sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the last dose of study drug (SVR12). All patients who received at least one dose of study drugs were included in the primary and safety analysis. This study is registered with ClinicalTrials.gov, number NCT02247401. FINDINGS: Between Nov 4, 2014, and March 16, 2015, we screened 182 patients with HCV infection, of whom 160 were eligible for inclusion; 100 patients were assessed as not having cirrhosis and were given 12 weeks of treatment, and 60 patients assessed as having cirrhosis were randomly assigned to the 12-week treatment group (n=31) or the 24-week treatment group (n=29). 94 (94%; 95% CI 88-97) of 100 patients in the without cirrhosis group, 30 (97%; 84-99) of 31 patients in the cirrhosis 12-week treatment group, and 27 (93%; 78-98) of 29 patients in the cirrhosis 24-week treatment group achieved SVR12. The most common adverse events in patients without cirrhosis were headache (41 [41%]) and fatigue (35 [35%]). Fatigue occurred in nine (29%) patients in the cirrhosis 12-week treatment group and 11 (38%) patients in the cirrhosis 24-week treatment group, and headache occurred in nine (29%) patients in the cirrhosis 12-week treatment group and in 10 (35%) patients in the cirrhosis 24-week treatment group. Adverse events were predominantly mild or moderate in severity, and laboratory abnormalities were not clinically meaningful. No patients discontinued treatment because of an adverse event. One serious adverse event in the group without cirrhosis was attributed to study drugs by the investigators; the patient had deep venous thrombosis. INTERPRETATION: Ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12 weeks achieved SVR12 in a high proportion of patients and was well tolerated in Egyptian patients with HCV genotype 4 infection with or without compensated cirrhosis. Extension of treatment to 24 weeks in patients with cirrhosis did not improve the proportion of patients achieving SVR12. A shorter duration regimen could be useful to address the significant burden of HCV genotype 4 infection in patients with compensated cirrhosis. FUNDING: AbbVie.

Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4.

BACKGROUND AND STUDY AIMS: Worldwide, Egypt has a high prevalence of adult hepatitis C virus (HCV) infection. Serum alanine aminotransferase (ALT) activity is most commonly measured to assess hepatic disease. The revision of the definition of the normal limits for the ALT level is advisable. The aim of this work was to compare the histopathological changes in the liver tissue biopsies of HCV-infected patients, clinically presenting with ALT levels below normal, based on the conventional, previously used upper limit of normal (ULN) of ALT (40U/L for men and 30U/L for women) with the proposed new ULN (30U/L for men, and 19U/L for women). PATIENTS AND METHODS: This is a retrospective cross-sectional study. A total of 668 cases of chronic hepatitis C genotype 4 were included. Patients were classified according to grades of histological activity and fibrosis stages (by the Metavir scoring system). They were also classified into normal and high groups according to the old and new cutoffs of both aspartate transaminase (AST) and ALT levels. RESULTS: The results of our study showed that the serum AST level in our study showed a better correlation with the histopathological changes in liver biopsy rather than ALT, especially when using the old cutoff of the ULN for AST. The serum ALT level in our study (both the old and the new cutoffs) did not show a significant correlation with the histopathological status in the liver biopsies of our patients. CONCLUSION: This study concluded that the old cutoff of the ULN AST is a better predictor of fibrosis.