Shortened 8 Weeks Course of Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients, With Chronic Hepatitis C Infection.

Recently, sofosbuvir and the fixed-dose combination of sofosbuvir/ledipasvir were approved for the treatment of chronic hepatitis C virus infection in adolescents, criteria being 12 years old and above or weighing at least 35 kg. Here we present the results of a pilot single cohort of 10 consecutive adolescent patients with chronic hepatitis C virus and treated with dual sofosbuvir/daclatasvir therapy for a response-tailored duration of 8 weeks for those who achieved very rapid virologic response (vRVR) and 12 weeks for those who did not. All patients achieved vRVR at week 2 and completed the shortened 8 weeks course. All patients (10/10) (100% [confidence interval 72.25-100%]) achieved sustained vRVR at week 12 post-treatment with good tolerability and no serious adverse events. These data could provide support to our suggested response-tailored protocol of dual therapy with sofosbuvir/daclatasvir in adolescents particularly for shortened duration in those who achieved vRVR. Further larger randomized controlled studies are recommended.

Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection.

OBJECTIVES: Dual sofosbuvir/daclatasvir (SOF/DCV) therapy is currently recommended by the European Association for Study of Liver (EASL) as an option for the treatment of chronic hepatitis C virus (HCV) infection in adults for all genotypes; however, it is still not considered for patients younger than 18 years old. We aimed to test safety and efficacy of SOF/DCV in adolescent patients 12 to 17 years old with chronic HCV, genotype 4 infection. METHODS: We conducted a prospective, uncontrolled, open-label multicenter study. A total of 30 chronic HCV-infected adolescents, aged from 12 to 17 years old were included and treated with dual SOF/DCV for 12 weeks. Patients were monitored throughout the treatment and follow-up period for safety and efficacy outcome measures including the sustained virologic response 12 (SVR12) rate. RESULTS: The intention-to-treat (ITT) SVR12 rate was 29 of 30 (96.7%; 95% confidence interval [CI] 83.3%-99.4%). The only patient who did not achieve SVR12 was lost to follow-up after showing viral negativity at the end of treatment (EOT) visit. Whereas all the remaining 29 patients (100%, 95% CI 88.3%-100%) who completed the follow-up visits achieved SVR12. All patients showed normalized liver enzymes with normal hematological, liver and renal function tests at the end of the study. No fatalities or treatment-emergent serious or severe adverse events were reported throughout the study. CONCLUSIONS: SOF/DCV combined therapy could be a safe and effective treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4 infection. (See Video, Supplemental Digital Content, http://links.lww.com/MPG/B348).

Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian patients with chronic hepatitis C: a real-world experience.

BACKGROUND: Simeprevir plus sofosbuvir (SIM/SOF) regimen was recommended by professional guidelines for certain patients with HCV genotype 1 infection and there is lack of data about this regimen in patients with genotype 4 infection. AIM: To evaluate the efficacy and safety of this regimen in Egyptian patients with chronic HCV genotype 4 infection in the real world. METHODS: Multicentre observational study included 583 patients with HCV genotype 4 infection who began 12 weeks of treatment with SIM plus SOF. Demographic, clinical and virological data as well as adverse outcomes were collected. Treatment naïve patients were 342 (59%) of all included patients, 45% of patients had severe fibrosis (F3 and F4) while 55% had mild fibrosis (F1 and F2) and the primary outcome was sustained virological response (SVR). RESULTS: The overall SVR rate was 95.7% (558 out of 583 patients). In total, SVR12 in naïve patients with mild fibrosis score (F1 and F2) was achieved in 98.9% (94/95) for F1 and 98.1% (105/107) for F2, while naïve patients with severe fibrosis (F3 and F4) achieved SVR of 97.7% (86/88) for F3 and (42/52) 80.8% for F4. SVR in patients with previous interferon treatment achieved in 100% (45/45) for patients with F1 and 98.7% (74/75) for F2. While 94.7% (72/76) in experienced patients with F3; and 88.9% (40/45) for F4 achieved SVR12. Notable side effects included rash in 21 patients, photosensitivity in 18 patients, pruritus in 44 patients and hyperbilirubinemia in 42 patients. CONCLUSIONS: A 12-week regimen of simeprevir/sofosbuvir was efficacious and well tolerated by treatment-naïve and treatment-experienced patients with chronic HCV genotype 4.

A randomized trial of 24 versus 48 weeks of peginterferon alpha-2a plus ribavirin in Egyptian patients with hepatitis C virus genotype 4 and rapid viral response.

BACKGROUND AND AIM: Little data is available regarding the 24-week therapy with pegylated interferon and ribavirin in Egyptian patients with hepatitis C virus (HCV) genotype 4 infection. We aimed to investigate the efficacy of 24-week versus 48-week peginterferon alpha-2a plus ribavirin therapy in patients with HCV genotype 4 infection with with rapid virological response. METHODS: This trial included 102 patients with HCV genotype 4 infection and low viral load. They were treated with peginterferon alpha-2a (180 microg/week) plus ribavirin. Patients (87/102) with a rapid virological response were randomized for a total treatment duration of 24 weeks (group A: 43) or 48 weeks (group B:44). Virological responses (EVR: early virological response, EOTR: end of treatment response, and SVR: sustained virological response) were assessed for each group. RESULTS: In group A, EVR was achieved in 37/43 (84%) patients, while EOTR was achieved in 34/43 (79%) patients and SVR in 30/43 (70%) patients. In group B, on the other hand EVR was achieved in 38/44 (84%) patients, while EOTR was achieved in 35/44 (80%) patients and SVR in 32/44 (73%) patients. No significant difference in SVR rates was observed between the two groups. The rate of adverse events was higher in group B, with lower adherence rates than group A. CONCLUSIONS: In patients with chronic HCV genotype 4 infection with rapid virological response and low viral loads, a 24-week peginterferon alpha-2a plus ribavirin therapy is as effective as a 48-week therapy with lower rate of adverse events.

A prospective randomized trial of sham, single-dose Stretta, and double-dose Stretta for the treatment of gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent disorder that often requires long-term medical therapy or surgery. Radiofrequency (RF) energy delivery (Stretta procedure) has been shown in several studies to improve GERD symptoms and quality of life for approximately two-thirds of patients. The authors proposed that increasing the dose of Stretta would further improve the response to this therapy. METHODS: For this study, 36 patients were randomized into three groups. In group A, 12 patients underwent a single session Stretta procedure. In group B, 12 patients under went a sham Stretta procedure (mirror of the active procedure in all aspects except there was no deployment of the electrodes). In group C, 12 patients underwent a single Stretta treatment followed by repeat Stretta if GERD health-related quality of life (HRQL) was not 75% improved after 4 months. For each patient, 56 RF lesions were created per session. The principal outcome was GERD HRQL improvement. The secondary outcomes were medication use, lower esophageal sphincter (LES) basal pressure, endoscopic grade of esophagitis, and esophageal acid exposure by pH probe. RESULTS: The Stretta procedure was completed successfully for all the patients in both active treatment groups. At 12 months, the mean HRQL scores of those off medications, the LES basal pressure, the 24-h pH scores, and the proton pump inhibitor (PPI) daily dose consumption were significantly improved from baseline in both Stretta groups (p\0.01). The double Stretta was numerically but not significantly better than the single Stretta for mean HRQL, mean 24 h pH, mean LES pressure, and PPI use. Seven patients in the double Stretta treatment group had normalized their HRQL at 12 months compared with 2 patients in the single-treatment group (p = 0.035). The sham patients had a small but statistically significant decrease in their daily PPI dosages (p\0.05) and mean HRQL scores (p\0.05). No serious complications (bleeding, perforation, or death) occurred. However, two patients experienced significant delayed gastric emptying after the second Stretta treatment. CONCLUSIONS: The Stretta procedure significantly reduced GERD HRQL, use of PPI drugs, esophageal acid exposure, LES pressure, and grade of esophagitis compared with the sham procedure. The double Stretta therapy had numerically superior outcomes for most parameters and a significantly more frequent normalization of HRQL scores compared with the single Stretta.

Effects of Dual Sofosbuvir/Daclatasvir Therapy on Weight and Linear Growth in Adolescent Patients with Chronic Hepatitis C Virus Infection.

Negative effects on growth indices had been reported in children treated with interferon for chronic viral hepatitis. Forty chronic hepatitis C virus-infected adolescents, 12-17 years of age, were treated with sofosbuvir/daclatasvir therapy for 12 weeks. The intent-to-treat sustained virologic response rate at 12 weeks after end of treatment was 39/40 (97.5%). Unlike interferon-based therapy, we did not detect significant negative effects on linear growth or weight. Contrarily, a trend to increased appetite and insignificant weight gain was observed, but further larger studies are needed to confirm. See Video-Abstract, http://links.lww.com/ASAIO/A381.

Effects of dual sofosbuvir/daclatasvir therapy on, chronic hepatitis C infected, survivors of childhood malignancy.

BACKGROUND: Childhood cancer survivors are potentially at a higher risk of infection with hepatitis C virus (HCV). The effects of all-oral direct-acting antiviral therapy (DAA) on both the HCV infection as well as the state of cancer remission have not been well investigated in this population. AIM: To test the effects of dual sofosbuvir/daclatasvir (SOF/DCV) therapy in the treatment of chronic HCV in survivors of hematologic malignancy in pediatric age group. METHODS: We conducted a prospective, uncontrolled, open-label multicenter study. A total of 20 eligible, chronic HCV, genotype-4, infected children who had been in continuous complete remission from hematologic cancer (leukemia/lymphoma) for at least one year were included in the study. All patients were treated with combined SOF/DCV for 12 wk. Patients were monitored throughout the study till 12 wk after end of treatment for safety and efficacy outcomes including the sustained virologic response 12 (SVR12) rate, hematological indices, liver and kidney functions. RESULTS: The intent-to-treat SVR12 rate was 20 of 20 (100%; 95%CI: 84%-100%). All patients showed normalized liver enzymes from week-4. All hematological indices, liver and kidney functions were kept normal throughout the study. No fatalities or treatment-emergent serious or severe adverse events were reported throughout the study. CONCLUSION: SOF/DCV combined therapy could be used safely and effectively in the treatment of chronic HCV genotype-4 infection in leukemia/lymphoma treated children. No relapses were detected during treatment and throughout the follow up period for either the original malignant disease or the HCV infection.

Hematopoietic stem cell mobilization into the peripheral circulation in patients with chronic liver diseases.

OBJECTIVE: The present study was aimed to investigate and compare the kinetics of bone marrow-derived hematopoietic stem cells (BMHSC) migration in the peripheral blood and liver in response to liver injury in patients with chronic liver disease (CLD). METHODS: In all, 45 CLD patients staged with Child-Pugh A, B and C and 15 healthy participants were evaluated for the concentration of circulating BMHSC by a flow cytometric analysis of CD133(+) /CD34(+) cells. In addition, homing BMHSC and hepatic progenitors were assessed by the immunohistochemical detection of CD133(+) and OV6(+) cells in liver biopsy specimens from Child-Pugh A and B patients. RESULTS: No significant difference in the percentage of circulating CD133(+) /CD34(+) cells was observed among all groups of patients. In liver tissues, OV6(+) cells increased significantly in Child-Pugh B cases (P < 0.05), while CD133(+) cells were distributed sparsely in the periportal region in Child-Pugh A and B patients. OV6(+) cells were significantly correlated with CD34(+) cells but not with CD133(+) cells in Child-Pugh A and B patients (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: Various degrees of severity in CLD neither evoked the mobilization of BMHSC into the circulation nor triggered their homing into liver tissue, thus excluding extrahepatic stem cell-mediated repair. The recovery process seems to be dependent on proliferating endogenous liver progenitors (OV6(+) cells).

Hepatitis C virus (genotype 4)-associated mixed cryoglobulinemia vasculitis: effects of antiviral treatment.

OBJECTIVE: Type II mixed cryoglobulinemia (MC) is a systemic vasculitis usually associated with hepatitis C virus (HCV). The present trial was performed to investigate the efficacy of therapy with pegylated interferon alfa-2a (PEG-IFN alfa-2a) plus ribavirin in patients with HCV-related MC vasculitis and evaluate the factors associated with clinical remission of MC. METHODS: A total of 46 consecutive patients with HCV-related Type II MC received PEG-IFN alfa-2a (standard dose 180 mg/week) subcutaneously plus oral ribavirin (800-1,200 mg/day) for 48 weeks. The response to treatment was analyzed by comparing clinical, immunologic, and virologic parameters at the initial evaluation with those observed at the end of follow-up. Logistic regression was used to assess the factors associated with clinical remission. RESULTS: A total of 22 patients (48%) had a sustained virologic response and were complete clinical responders. Serum cryoglobulin disappeared in 26 of 46 patients (56%), and complement levels normalized in 70% of the patients. In univariate analysis, factors associated with complete clinical response were early virologic response at 4 weeks [OR 1.4 (95% CI 0.1-17.1)], proteinuria [OR 1.4 (95% CI 0.2-8.2)] and the fibrosis score [OR 1.09 (95% CI 0.6-1.9)], peripheral neuropathy [OR 0.9 (95% CI 0.1-6.5)], arthralgia [OR 0.7 (95% CI 0.1-3.9)], sicca syndrome [OR 0.6 (95% CI 0.1-3.2)], cryoglobulin [OR 0.2 (95% CI 0.07-1.09)], and purpura [OR 0.1 (95% CI 0.01-1.3)]. In multivariate analysis, only cryoglobulinemia was independently associated with complete clinical response. No patient had side effects for which discontinuation of therapy was required. CONCLUSION: The results indicated that treatment with PEG-IFN alfa-2a plus ribavirin can achieve a complete clinical response in patients with HCV-related MC. Complete clinical response correlates with the eradication of HCV.

Portal hypertensive enteropathy before and after variceal obliteration: an endoscopic, histopathologic and immunohistochemical study.

AIM: To study portal hypertensive enteropathy (PHE) before and after the obliteration of esophageal varices. METHODS: 30 patients with portal hypertension and esophageal varices were included. Band ligation was performed for every patient until the obliteration of esophageal varices. Enteroscopy and biopsies from gastric, duodenal and jejunal mucosa were taken at the beginning of the study and after variceal obliteration. Morphometric measurement of mean vascular areas and estimation of tissue vascular endothelial growth factor (VEGF) were also completed. RESULTS: The number of patients with enteropathy increased from 6.6% before obliteration to 46.7% after variceal obliteration (p< 0.001). Angiogenesis, vascular ectasia and blood extravasation were the main histopathological findings and all increased significantly after variceal obliteration. The mean vascular area of ectatic vessels in the gastric, duodenal and jejunal biopsies also increased after variceal obliteration. The mean VEGF in the gastric, duodenal and jejunal biopsies increased after variceal obliteration. The mean corpuscular volume (MCV) and hemoglobin (Hb) concentration were significantly lower after variceal obliteration. CONCLUSION: the portal hypertensive enteropathic changes increased in frequency and severity after esophageal variceal obliteration with a probability of causing anemia.

Barrett's esophagus: prevalence and risk factors in patients with chronic GERD in Upper Egypt.

AIM: To determine the prevalence and possible risk factors of Barrett's esophagus (BE) in patients with chronic gastroesophageal reflux disease (GERD) in El Minya and Assuit, Upper Egypt. METHODS: One thousand consecutive patients with chronic GERD symptoms were included in the study over 2 years. They were subjected to history taking including a questionnaire for GERD symptoms, clinical examination and upper digestive tract endoscopy. Endoscopic signs suggestive of columnar-lined esophagus (CLE) were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BE was diagnosed by pathological examination when specialized intestinal metaplasia was detected histologically in suspected CLE. pH was monitored in 40 patients. RESULTS: BE was present in 7.3% of patients with chronic GERD symptoms, with a mean age of 48.3 +/- 8.2 years, which was significantly higher than patients with GERD without BE (37.4 +/- 13.6 years). Adenocarcinoma was detected in eight cases (0.8%), six of them in BE patients. There was no significant difference between patients with BE and GERD regarding sex, smoking, alcohol consumption or symptoms of GERD. Patients with BE had significantly longer esophageal acid exposure time in the supine position, measured by pH monitoring. CONCLUSION: The prevalence of BE in patients with GERD who were referred for endoscopy was 7.3%. BE seems to be associated with older age and more in patients with nocturnal gastroesophageal reflux.

Assessment of platelet activation in coupled schistosomiasis and viral hepatitis infection: contribution to complexity of course and development of complications.

This study assessed platelet activation and its possible contribution to the pathogenesis of liver cirrhosis (LC), hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). Forty-five patients with LC caused by dual schistosomiasis and viral hepatitis infections were enrolled in the study, 15 had LC only, 15 were complicated with HCC, and 15 were complicated with PVT, in addition to 15 healthy controls. Platelet morphological parameters including platelet count, platelet crit, mean platelet volume (MPV) and platelet distribution width (PDW), as well as platelet activation as evidenced by measuring soluble platelet selectin (sP-selectin) level and the release of beta-thromboglobulin (beta-TG), transforming growth factor beta-1 (TGF-beta1) and platelet derived growth factor-AA (PDGF-AA) were evaluated. The results obtained revealed significant reduction in platelet count, platelet crit and MPV while PDW was significantly increased in all LC patients in comparison to controls. sP-selectin, beta-TG, TGF-beta1 & PDGF-AA revealed significant increase in all diseased groups when compared to control group. Patients complicated with HCC or PVT demonstrated significant increase in the aforementioned parameters in comparison to patients with LC only. Patients with PVT showed significant increase versus HCC patients. These findings indicate that platelet activation is a prominent feature in LC and its serious complications HCC & PVT. This activation can play an important role in the pathogenesis of LC, HCC & PVT in patients with mixed schistosomiasis and viral hepatitis infections. Such patients need careful medical attention and effective treatment. Stabilization of the activated platelets and the dual suppression of PDGF & TGF-beta1 could be new therapeutic strategies against LC and its sequels.