Outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection

Ossama A Ahmed,1 Mohamed A Elsebaey,2 Mohamed Hassan A Fouad,1 Heba Elashry,3 Ahmed I Elshafie,1 Ahmed A Elhadidy,2 Noha E Esheba,2 Mohammed H Elnaggar,2 Shaimaa Soliman,4 Sherief Abd-Elsalam3 1Department of Internal Medicine, Ain Shams University, Faculty of Medicine, Cairo, Egypt; 2Department of Internal Medicine, Tanta University, Tanta, Egypt; 3Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt; 4Department of Public Health and Community Medicine, Menoufia University, Shbeen El-koum, Egypt Background and aims: Treatment of hepatitis C virus (HCV) changed dramatically with the introduction of oral direct-acting antiviral drugs due to their high antiviral potency and safety profile. Sofosbuvir plus daclatasvir combination therapy was extensively investigated in HCV genotypes 1, 2, and 3, while published data regarding its real-life application in the treatment of genotype 4 is lacking. Therefore, we conducted this study to assess the outcomes and predictors of treatment response with sofosbuvir plus daclatasvir with or without ribavirin in Egyptian patients with genotype 4 hepatitis C virus infection. Patients and methods: This prospective study included 300 Egyptian patients with chronic genotype 4 HCV, treated with sofosbuvir plus daclatasvir with or without ribavirin for 12–24 weeks. Primary outcome was the number of patients who achieved sustained virologic response (SVR12), and secondary outcome was the occurrence of adverse events. Results: A total of 92.67% of all patients achieved SVR12. SVR12 rates of 96.55% and 84.54% were reported in non-cirrhotic and cirrhotic patients, respectively. SVR12 in treatment-naïve and treatment-experienced patients were 94.12% and 87.01%, respectively. A total of 19.7% of patients experienced mild adverse events. Older age, cirrhosis, and low platelet count were the predictors of treatment non-response. Conclusion: Based on this multi-center prospective study, sofosbuvir plus daclatasvir with or without ribavirin for 12–24 weeks appears to have favorable outcomes in the treatment of genotype 4 HCV-infected Egyptian patients. Older age, cirrhosis, especially Child–Pugh class B, and low platelet count are independent risk factors of treatment non-response. Keywords: hepatitis C virus, genotype 4, sofosbuvir plus daclatasvir, sustained virologic respons

Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities

Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease