High success rates for the use of ombitasvir/paritaprevir/ritonavir containing regimens in treatment of naïve and experienced chronic hepatitis C genotype 4: Real world results.

INTRODUCTION AND AIMS: Treatment of hepatitis C virus (HCV) genotype 4 patient with fixed dose combination of ombitasvir-paritaprevir-ritonavir plus ribavirin (OBV/rPTV/RBV) has been proven efficacy and safety in many clinical trials. The current study reports the efficacy and safety of OBV/rPTV/RBV (for treatment-naïve), and OBV/rPTV/RBV/sofosbuvir (SOF) (for treatment-experienced), in chronic HCV genotype 4 patients in real life settings. METHODS: Prospective cohort study including all adult chronic HCV genotype 4 patients who were scheduled to receive OBV/rPTV/RBV ± SOF for 12 or 24 weeks in New Cairo Viral Hepatitis Treatment Center. The primary efficacy endpoint was a virologic response at posttreatment week 12 (SVR12). Changes in hematological parameters, liver biochemical profile and fibrosis-4 index (FIB-4), as well as clinical and laboratory adverse events (AEs) across follow up visits (week 4, end of treatment [EOT], and SVR12), were recorded. RESULTS: Our study included 325 patients (age; 47.63 ± 12.63 years, 55.38% [n = 180] men). Most of the included patients (89.85%, n = 292) were treatment naïve and only 7% (n = 23) had liver cirrhosis. Overall, SVR12 was attained by 98.44% (316 of 321) of the patients; 97.15% (307 of 316) of patients who received 12 weeks of OBV/rPTV/RBV ± SOF and 100% (9 of 9) of patients who received 24 weeks of OBV/rPTV/RBV as assessed by modified intention to treat analysis. There was a significant improvement of baseline alanine aminotransferase, aspartate aminotransferase, hemoglobin, FIB-4 at SVR12 (P < 0.05). The most common reported AEs were anemia (n = 106), fatigue (n = 41) and elevated indirect bilirubin (n = 37). CONCLUSION: OBV/rPTV/RBV (±SOF) is a highly effective therapy for chronic HCV patients in real life settings.

Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals.

BACKGROUND: Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS: We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS: Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION: DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

Retreatment of chronic hepatitis C patients who failed previous therapy with directly acting antivirals: A multicenter study.

AIM OF THE STUDY: The current study aimed to evaluate the efficacy of different DAAs regimens in the treatment of chronic hepatitis C (CHC) Egyptian patients who failed to achieve SVR after their treatment with SOF-based regimens. METHODS: This was a retrospective observational multicenter study that included CHC patients that failed to achieve cure on SOF-based regimens who were re-treated using different DAAs regimen and were allocated according to national guidelines for the treatment of hepatitis C. Primary outcome was to assess the SVR12 rate among prior non-responders after retreatment with a second course of DAAs. RESULTS: Our study included 172 patients who failed to achieve SVR after treatment with SOF-based treatment regimen [age: 51.2 ± 11.3, 58.7% men]. Included patients were retreated using SOF/DCV/RBV, SOF/ r/PAR /OMB /RBV, SOF/DCV/SIM, SOF/LDV ± RBV or SIM/SOF. SVR12 was successfully attained in 95.35% (164/172) of the included non-responders. CONCLUSION: The current multicenter study proved the efficacy of various DAAs regimens issued by the National Committee for Control of Viral Hepatitis for retreatment of relapsed CHC Egyptian patients.

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens.

BACKGROUND: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres. METHODS: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report. RESULTS: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results. CONCLUSIONS: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.

After successful hepatitis C virus antiviral therapy: It looks that normal alanine aminotransferase level is not the normal.

BACKGROUND: Normal serum alanine aminotransferase (ALT) levels differ with age, gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT needs further research in different populations. Aim of this work was to monitor the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in patients with normal pretreatment ALT. METHODS: Data of 1160 CHC patients with persistent pretreatment normal liver enzymes were retrospectively analyzed. Treatment response to direct acting antiviral agents (DAAs) therapy was recorded. Changes in ALT levels before and after treatment were analyzed by patients' demographic, laboratory, and radiologic characteristics. Areas under the receiver operating characteristic curve (AUROC) of ALT after treatment were used to generate a new ALT ULN. RESULTS: Males were 568 (49%) and females 592 (51%) with a mean age of 50.7 years. After treatment, mean (±SD) of ALT levels significantly decreased from (26.3±7.8) to (19.1±10.9). This reduction was more significant in interferon-free than interferon-based regimens. ROC curve analyses suggested a new ALT ULN cut off (26.4 IU/L) in the treated patients (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7 IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612). The identified cutoffs were 16.3 IU/L (sensitivity=66.7%, specificity=47.5%, AUROC=0.499) and 15.5 IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in males and females, respectively. CONCLUSION: The current ALT ULN needs readjustment to identify new normal cutoffs in CHC patients. Posttreatment cutoffs differ according to gender, pretreatment liver affection, and treatment regimen.

Herpes Zoster reactivation in patients with chronic hepatitis C under treatment with directly acting antiviral agents: A case series.

We report a series of cutaneous Herpes Zoster (HZ) reactivation cases in patients with hepatitis C virus (HCV) infection treated with directly acting antiviral (DAA) agents. Five cases were detected among 2133 treated patients with DAAs at one of the specialized viral hepatitis treatment centers in Egypt. A control group including 2300 age and sex matched HCV patients who were previously treated with pegylated interferon and ribavirin did not show any HZ reactivation reports while on treatment. None of cases had an evidence of immunosuppression or a risk factor for HZ reactivation. The DAAs used regimens were sofosbuvir/daclatasvir in 4 cases and sofosbuvir/simeprevir in one case. HCV clearance with antiviral therapy may bring immune changes causing reactivation of other latent viral infections like HZ. A high index of clinical suspicion may be needed to guarantee early and prompt management of such cases.