Sofosbuvir in combination with ribavirin or simeprevir: real-life study of patients with hepatitis C genotype 4.

BACKGROUND: The discovery of direct-acting antiviral agents (DAA) is an outstanding achievement of modern medicine in the current century. The current study aimed to explore the effectiveness and safety of two regimens sofosbuvir (SOF) in combination with either ribavirin (RBV) or simeprevir (SMV) in chronic hepatitis C (CHC) genotype (GT) 4 patients in Egypt. METHODS: A total of 201 patients, treatment-naïve and experienced, with CHC GT4 infection were allocated into two groups based on the type of the regimen used. All eligible patients were treated orally with SOF plus daily oral weight-based RBV (24 weeks; group 1), or SOF plus daily oral SMV (12 weeks; group 2). RESULTS: In the patients who received SOF/RBV therapy for 24 weeks, a sustained virological response (SVR12) was achieved by 89% (90/101) of all patients, 92% (49/53) of naïve patients and 85% (41/48) of experienced patients. In the SOF/SMV group, the SVR12 rate was 92% (92/100) for overall patients, 93% (70/75) of naïve patients and 88% (22/25) of experienced patients. Adverse events (AEs) were reported in 70% of patients in the SOF/RBV group and 42% patients in the SOF/SMV group. The most common AEs in both groups were fatigue, headache, nausea, and dyspnea. CONCLUSIONS: The present comparative study suggests that both SOF/RBV and SOF/SMV combination regimens are highly effective in CHC GT4 treatment. However, the two-DAA regimen (SOF/SMV) may offer well-tolerated treatment, with a shorter duration and better safety compared to SOF/RBV.

Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin: large real-life results of patients with chronic hepatitis C genotype 4.

BACKGROUND AND AIM: Clinical studies evaluating the efficacy of daclatasvir (DCV) for treatment of chronic hepatitis C virus (HCV) genotype 4 (GT4) infection are scarce. This study aims to evaluate the efficacy and safety of DCV plus sofosbuvir (SOF) with or without ribavirin (RBV) for treatment of Egyptian patients infected with HCV GT4. METHODS: Between April 2016 and March of 2017, a large cohort of 946 patients with chronic HCV GT4 was enrolled for completing the treatment. Patients were classified into two groups: group 1 (easy to treat) was treated with a dual therapy of SOF/DCV daily for 12 weeks and group 2 (difficult to treat) was treated with a triple therapy of SOF/DCV/RBV daily for 12 weeks. Efficacy and safety of the treatments were estimated, and baseline characters associated with sustained virological response at 12 weeks post-treatment (SVR12) were investigated. RESULTS: Among the patient's cohort, SVR12 was achieved by 94% (891/946) in the overall patients, by 95% (718/758) in the easy-to-treat group, and by 92% (173/188) in the difficult-to-treat group. The most common adverse events recorded were fatigue, headache, nausea, asthenia, and gastrointestinal troubles. No patient discontinued treatment due to severe adverse events. CONCLUSION: The findings from the present study suggested that SOF/DCV (with or without RBV) regimen exhibited high effectiveness, was well tolerated in the treatment of chronic HCV GT 4, and revealed itself as a better option for patients with advanced liver disease, making the eradication of HCV a more realistic target to achieve.

Retreatment Efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/Ritonavir + Ribavirin for Hepatitis C Virus Genotype 4 Patients.

BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens. METHODS: A total of 113 treatment-experienced patients were allocated for the completion of their treatment period. The enrolled patients were treated orally with SOF plus a fixed dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients' tolerability. The primary end point was a sustained virological response (HCV RNA < 15 IU/mL), observed 12 weeks after the end of the treatment (SVR12). RESULTS: Among all patients, the treatment-experienced patients with SOF plus OBV/PTV/r + RBV had a higher SVR12 rate (97%; 109/113). Further, SVR12 was achieved by 98% (81/83) of non-cirrhotic patients and 93% (28/30) of cirrhotic patients. Additionally, the most common adverse events reported included fatigue, headache, insomnia, nausea, and dyspnea. CONCLUSIONS: The recent multi-targeted regimen of SOF plus OBV/PTV/r + RBV was well tolerated and achieved excellent SVR rates among retreatment-experienced Egyptian patients with prior DAA treatments failure, thus providing an alternative regimen for the retreatment of difficult-to-cure HCV GT4 patients.

Blastocystis subtypes isolated from irritable bowel syndrome patients and co-infection with Helicobacter pylori.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease presenting clinically by abdominal pain with alteration of bowel habits. Although IBS has uncertain etiology, chronic gut inflammation due to persistent exposure to an infectious agent including Blastocystis sp. was proposed. The aim of this study was to detect the prevalence of Blastocystis sp. subtype (ST) isolated from stool of IBS patients and to assess Blastocystis sp. and H. pylori co-infection in IBS patients from Beni-Suef Governorate, Egypt. Stool samples were collected from 115 IBS patients, following Rome III criteria. All stool samples were microscopically examined by wet mount and permanent trichrome stain, cultured on Jones' medium with further sequencing of positive Blastocystis isolates and screened for detection of H. pylori coproantigen. Blastocystis sp. was the predominant parasite in IBS patients; it had statistical significant association with both rural residence (OR = 10) and flatulence (OR = 8.2). There was a predominance of Blastocystis sp. ST3 (81%) followed by ST1 (19%). Blastocystis culture results (19.1%) were superior than microscopy (16.5%). The majority of Blastocystis-positive IBS patients (72.7%) were co-infected with H. pylori with statistical significance; however, H. pylori was higher in Blastocystis-negative IBS patients (47/64) than in Blastocystis-positive IBS patients (17/64). Interestingly, IBS is usually associated with gut dysbiosis, while the most prevalent parasite in our IBS patients was Blastocystis sp., which is frequently found in asymptomatic individuals. Whether Blastocystis sp. is a cause or a consequence of IBS still needs further investigation, with a particular focus on correlation of IBS with different Blastocystis sp. subtypes and gut microbiomes.

Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4.

BACKGROUND: Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. OBJECTIVE: In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4. SUBJECTS AND METHODS: A total of 120 adult individuals aged 30-68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques. RESULTS: Approximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment - insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms. CONCLUSION: The data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.