Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice.

Egypt has the highest hepatitis C virus (HCV) prevalence in the world. Sofosbuvir is a new highly effective drug for treatment of HCV infection. Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to fourfold reduced duration of therapy. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin in Egyptian patients with liver cirrhosis due to chronic HCV infection. We studied 2400 cirrhotic Egyptian patients with chronic HCV infection who were treated with dual therapy with sofosbuvir and ribavirin for 24 weeks. Efficacy was determined by assessment of serum HCV RNA. Any adverse events during treatment were recorded. Two thousand four hundred cirrhotic Egyptian patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks were enrolled in the study. The mean age of the studied group (± SD) was 53.9 ± 6.5 years, 1549 (64.54%) were males, all were cirrhotic patients, 3.41% were treatment-experienced, the baseline mean HCV RNA concentration was 4.33 × 106 IU/mL, and 94.37% of the patients had completed the full course of therapy. The overall SVR12 rate was 71.2%. The most common adverse events were fatigue, myalgia, headache, insomnia, and anemia. One hundred thirty-five (5.63%) patients stopped treatment permanently due to the appearance of complications that prevented continuation of treatment. The sofosbuvir and ribavirin combination is safe and effective in treatment of HCV patients with liver cirrhosis. However, further studies are needed to establish the optimal treatment regimen for those cases.

Anti-Nuclear Cytoplasmic Antibody-Associated Vasculitis: A Probable Adverse Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients.

Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide. Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase. It has shown high efficacy in combination with several other drugs and has a low reported rate of side effects. Objective: The aim of this prospective cohort study was to assess the safety of sofosbuvir-based treatment regimens used to treat chronic hepatitis C infections and to detect any side effects of sofosbuvir not previously reported. Methods: We studied treatment side effects in 3,000 patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple therapy for 12 weeks. The endpoint of the study was the end of treatment. Results: Hyperbilirubinemia occurred frequently during treatment in both groups. Treatment was discontinued in 72 cases due to hepatic decompensation and drug complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal bleeding, 85 of whom had a vasculitic skin rash. Conclusion: We report the occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV).We believe this to be the first report of sofosbuvir-induced AAV skin lesions and bleeding disorders.

Role of statins in the treatment of chronic hepatitis C virus infection.

This study assessed the clinical outcome of fluvastatin in addition to the standard regimen used now for treatment of chronic HCV in Egypt. A total of 80 patients with chronic hepatitis C virus infection fulfilled clinical, laboratory and histo-pathological criteria were ready for interferon therapy. They were divided into two groups: GI (N = 40) received standard treatment for HCV (Pegylated interferon and Ribavirin) and GII (N = 40) received standard treatment plus Fluvastatin (80 mg/daily). Six months before and after treatment liver function tests and HCV-RNA were evaluated. The results showed that addition of Fluvastatin to the standard HCV treatment (Pegylated interferon and Ribavirin) significantly increased sustained virological response (SVR) from (55%-62.5%; P < 0.01) and significantly decreased viral load in relapse patients (P < 0.001). No significant differences and correlations were found between serum levels of LDL-cholesterol and viral load before and after treatment in both groups.

Thyroid function in patients with chronic hepatitis C virus infection under interferon therapy.

The study examined 60 HCV patients with normal baseline levels of TSH. The patients received subcutaneous pegylated interferon a-2b weekly in addition to oral ribavirin. Before the start of the interferon therapy, serum TSH, thyroglobulin-Ab (TG-Ab) and antiperoxidase antibodies (TPO-Ab) were measured. Three months after interferon therapy serum levels of TSH were measured to all patients; patients with abnormal TSH were subjected to the measurements of FT3, FT4, TPO-Ab, TG-Ab, and thyroid stimulating immunoglobulin levels (TSI). After 3 months of therapy, 48 patients (80%) had normal TSH, and 12 patients (20%) had abnormal TSH. Of 12 patients with abnormal TSH 10 (16.6%) had high levels of TSH (hypothyroidism), while the other two (3.4%) had low levels of TSH (Hyperthyroidism). Of 10 patients with hypothyroidisms, 6 patients (10%) had overt hypothyroidism and 4 patients (6.6%) had subclinical hypothyroidism. All patients with abnormal TSH had significant higher levels of TG-Ab, TPO-Ab and TSI (in cases with hyperthyroidism only) than the patients with normal levels of TSH (p < 0.001), the levels of TPO-Ab only of the most patients with abnormal TSH were above the normal reference range before the start of interferon therapy. Patients with hyperthyroidism, one was presented by clinical picture of overt hyperthyroidism, and the second by subclinical hyperthyroidism. All patients with overt hypo and hyperthyroidism received medical treatment, with normalization of levels of TSH and improvement of clinical symptoms and completed their course of interferon therapy Forty patients (66.6%) responded to interferon (-ve PCR for HCV), while 20 (33.3%) did not respond, 5 had TSH abnormalities that were significantly higher than those in patient with normal TSH {5/12 (41.6%).versus 15/48 (31%); p < 0.01}.