Real-world safety and effectiveness of retreatment of Egyptian chronic hepatitis C patients not responding to NS5A inhibitor-based therapies.

The aim of this study was to assess the efficacy and safety of two protocols for retreatment of a cohort of Egyptian patients with chronic hepatitis C (CHC) who relapsed after NS5A inhibitor-based therapy. We conducted a prospective cohort study to assess the safety and efficacy of 12 weeks' retreatment with either combination of sofosbuvir/daclatasvir/simeprevir plus ribavirin (SOF/DCV/SMV/RBV, n = 45) or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin (SOF/OBV/PTV/r/RBV, n = 163) in patients who had previously failed NS5A inhibitors-based regimens. The primary end point was SVR 12 weeks after the end of treatment (SVR12). Safety follow-up data were recorded for 60 weeks after the end of treatment. Two hundred-eight patients were included in the study. Of them, 53.4% of patients were females and 40.4% had liver cirrhosis. The most common prior drug combinations were sofosbuvir/daclatasvir (n = 94) and sofosbuvir/daclatasvir plus ribavirin (n = 109). The overall SVR12 rates were 98.1%. In SOF/DCV/SMV/RBV group, 95.6% achieved SVR12, while in SOF/OBV/PTV/r/RBV group, the SVR12 rates were 98.8%. SVR12 was higher in cirrhotic patients (84/84) than noncirrhotic (120/124), P value = .0149. Regarding the safety outcomes, anaemia and fatigue were significantly higher in SOF/OBV/PTV/r/RBV group. Hepatocellular carcinoma (HCC) was reported in eight (3.8%) patients (four in each group). Of them, death was confirmed in four patients. Retreatment of Egyptian CHC relapsed patients with either sofosbuvir/daclatasvir/simeprevir plus ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin is highly effective and well-tolerated for both noncirrhotic and compensated cirrhotic patients. Incidental de novo HCC and hepatic decompensation are comparable in the two groups.

Surveillance and impact of occult hepatitis B virus, SEN virus, and torque teno virus in Egyptian hemodialysis patients with chronic hepatitis C virus infection.

OBJECTIVES: Egypt ranks first regarding the prevalence of hepatitis C virus (HCV) infection. Many patients have concomitant diseases like kidney disorders requiring hemodialysis, a procedure carrying the hazard of transmitting other hepatitis viruses. The purpose of this study was to investigate for occult hepatitis B virus (HBV), SEN virus (SENV), and torque teno virus (TTV) among chronic HCV patients on maintenance hemodialysis to identify their impacts. METHODS: A total of 325 hemodialysis patients were enrolled and divided into two groups based on HCV RNA testing results. Blood samples were collected before hemodialysis. Sera were tested for hepatitis B core antibodies (anti-HBc) and hepatitis B surface antibodies (anti-HBs) using ELISA. HBV, SENV, and TTV DNA were detected by PCR. The serum alanine aminotransferase (ALT) level was measured. RESULTS: Anti-HBc and HBV DNA were detected in 73.1% and 50.8% of group 1 versus 36.4% and 22.6% of group 2. The serum ALT level was higher in group 1 than group 2. SENV was detected in 11.5% of group 1 versus 8.2% of group 2. TTV was detected in 29% of group 1 versus 27% of group 2. CONCLUSIONS: There is an increased prevalence of occult HBV in our locality among chronic HCV patients undergoing hemodialysis. The existence of SENV and TTV viremia has no clinical impact.

Deep-sequencing study of HCV G4a resistance-associated substitutions in Egyptian patients failing DAA treatment.

PURPOSE:  To study resistance-associated substitutions using next-generation sequencing in Egyptian hepatitis C virus-infected patients failing direct-acting antiviral treatment. METHODS:  The current study describes three cases of treatment failure in patients referred to Zagazig Viral Hepatitis Treatment Center (ZVHTC), Sharkia Governorate, Egypt. RAS were identified and characterized using deep sequencing. The first patient had breakthrough while receiving a daclatasvir (DCV)+sofosbuvir (SOF) regimen, patient 2 relapsed after treatment with DCV+SOF+ribavirin (RBV), and patient 3 relapsed after DCV+SOF therapy. A serum sample was collected from each patient at failure and sent to Vall d'Hebron Research Institute at Hospital Universitari Vall d'Hebron in Barcelona (Spain) for deep-sequencing study to identify and characterize the RAS present in the samples. RESULTS:  The following were identified: L28M, L30S and L28M+L30S in patient 1, L30R in patient 2, and R155C, D168E, L28M, L30H, L30S, L28M+L30H, and L28M+L30S in patient 3. CONCLUSION: To the best of our knowledge, this is the first report from Egypt of patients failing DAA-based therapy, describing the associated RAS. This information will be of help to understand the natural history of HCV in Egyptian patients and guide the proper choice of retreatment protocols.

Prevalence of occult hepatitis C virus infection in patients who achieved sustained virologic response to direct-acting antiviral agents.

The reappearance of HCV infection months or years after sustained virologic response (SVR) may be due to the persistence of HCV in tissue cells in spite of being undetected in serum. This situation is known as occult hepatitis C infection (OCI). We aimed to assess the prevalence of OCI in Egyptian patients with chronic hepatitis C (CHC) who achieved SVR after treatment with direct-acting antiviral agents (DAA). We carried out a cross-sectional study at the Advanced Center for Liver Diseases of Zagazig University Hospitals and Al-Ahrar Viral Hepatitis Treatment Center, Sharkia Governorate, Egypt. One hundred and fifty adult patients with CHC, who achieved SVR 12-24 weeks after end of treatment with sofosbuvir/daclatasvir ± ribavirin (139 patients, 92.67%), sofosbuvir/ledipasvir ± ribavirin (eight patients, 5.33%), sofosbuvir/simeprevir (two patients, 1.33%), and ombitasvir/ paritaprevir/ritonavir + ribavirin (one patient, 0.67%), according to the Egyptian National Committee for Control of Viral Hepatitis, were included in the study. We tested these patients for HCV RNA in peripheral blood mononuclear cells (PBMCs) immediately after confirmation of SVR12-24 weeks. Statistical analysis was performed by means of the Shapiro-Wilk test, Mann-Whitney U test, Chi-square test, and Fisher's exact test. Seventeen patients (11.33%) were positive for PBMNCs HCV RNA. The prevalence of OCI was highest in patients treated with simeprevir/sofosbuvir (2/2 patients). There is a substantially high prevalence of OCI after treatment with DAAs. We recommend dual testing for HCV RNA in both serum and PBMCs at the end of treatment of HCV infection with DAAs and during validation of the SVR following the initial response.