Parathormone enhances eryptosis in patients with end stage renal disease treated by hemodialysis.

INTRODUCTION: Parathormone (PTH) and phosphorus, which are considered as uremic toxins, are associated with reduced red cell survival, yet with unproven mechanism. We aimed to assess the relation between PTH and phosphorus levels and eryptosis in patients with CKD5d treated by hemodialysis. METHODS: In a cohort of 85 patients with CKD5d treated by conventional hemodialysis, the percent of annexin V-binding RBCs was assessed by flow cytometry to indicate the percent of eryptotic RBCs. FINDINGS: The median percent of annexin V-binding RBCs was 2.3 (1.4-4.7)%. On linear regression analysis, PTH was independently associated with the percent of annexin V-binding RBCs (ß = 0.003; 95% CI: 0.002-0.004; p < 0.001). The percent of annexin V-binding RBCs differed significantly in patients with low PTH (<150 pg/mL; 27/85, 31.8%), target PTH (150-600 pg/mL; 32/85, 37.6%), and high PTH (>600 pg/mL; 26/85, 30.6%) groups (1.24 [0.65-1.85]; 2.46 [1.73-4.05]; and 4.82 [3.45-5.61]%, respectively; p < 0.001). Considering the tertiles of the percent of annexin V binding RBCs, PTH increased significantly from 85 (50.6-273) in the 1st to 298.3 (172.8-606.8) in the 2nd and 827.6 (357.4-1171.3) pg/mL in the 3rd tertiles (p < 0.001). Phosphorus and calcium levels as well as the CaxPh product were similar among the three tertiles (p > 0.05). DISCUSSION: Patients with CKD5d express high rates of eryptosis. PTH excess in those patients may result in further eryptosis enhancement, and this represents a potential pathogenic mechanism linking hyperparathyroidism with the anemia of CKD.

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.

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.