Optimizing Interferon Alfa Based Therapy for Chronic Hepatitis C

The hepatitis C virus was first discovered in 1989 as the major cause of chronic non-A non-B hepatitis. The hepatitis C virus is a single stranded RNA virus that belongs to the family of flaviviruses. The primary target of the hepatitis C virus are hepatocytes where viral particles replicate extremely fast with the production of 1012 viral particles per day. Worldwide 6 major HCV genotypes occur whose prevalence varies geographically. The predominant risk factor for infection is injection drug use. Other risk factors include blood transfusions before 1992, high lifetime number of sexual partners and iatrogenic transmission. Infection with the hepatitis C virus leads to a chronic infection in 55-80% of patients. A recently discovered single nucleotide polymorphism near the IL-28b gene is associated with spontaneous clearance of the hepatitis C virus. Worldwide 180 million people suffer from chronic hepatitis C virus (HCV) infection with 3-4 million people newly infected people and more than 350000 deaths each year. Although the natural history of chronic hepatitis C is highly variable, approximately 15-30% of patients infected with HCV will develop liver cirrhosis over the ensuing 3 decades. Cirrhosis can lead to the development of hepatocellular carcinoma and end stage liver disease. Consequently, chronic HCV infection is the leading indication for liver transplantation in developed countries. The primary goal of antiviral treatment for chronic hepatitis C is to prevent complications and death from HCV infection. This goal can be achieved by eradicating the virus permanently

ITPA polymorphisms are associated with hematological side effects during antiviral therapy for chronic HCV infection

Background/Objective Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. Patients and Methods This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. Results In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024). Conclusion Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently

Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts

<p>Abstract</p> <p>Background</p> <p>Baseline low platelet count (< 150,000/μL) increases the risk of on-treatment severe thrombocytopenia (platelet count < 50,000/μL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia.</p> <p>Methods</p> <p>Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy.</p> <p>Results</p> <p>Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count < 100,000/μL and rapid early platelet decline (> 30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (<it>P </it>< 0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT ≥ 100,000/μL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count < 100,000/μL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%).</p> <p>Conclusions</p> <p>For patients with CHC on antiviral therapy, baseline platelet counts < 100,000/μL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.</p

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Background: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. Methods: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. Trial registration: ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021

Rationale and design of the virological response and ribavirin dosage (VIRID) study in hepatitis.

Contains fulltext : 71257.pdf (publisher's version ) (Open Access

Current clinical care compared with new Dutch guidelines for hepatitis C treatment.

Contains fulltext : 79561.pdf (publisher's version ) (Open Access)BACKGROUND: Recently, the Dutch Association of Gastroenterology and Hepatology issued new guidelines for the treatment of chronic hepatitis C virus (HCV). These guidelines reflect the current standard of care. Before these guidelines were published and implemented we (1) studied the current clinical care of HCV patients among Dutch physicians, and (2) identified areas for future refinement in the current treatment. METHODS: We conducted a non-targeted survey among Dutch medical specialists in Gastroenterology, Hepatology and Internal Medicine who actively treat HCV patients. The questionnaire contained items about facility, duration and dosing of treatment, and side effect management using clinical vignettes followed by short questions. RESULTS: We received 49 questionnaires from treating HCV specialists. The majority (65%) of respondents treat HCV patients during regular outpatient clinics, while 35% treat these patients in a separate setting dedicated to the care of HCV patients. The majority of physicians follow the stipulated dosage regimens of pegylated interferon (88%) and ribavirin (83%). A minority (13%) exceed the advised dosage of ribavirin. Side effects such as neutropenia are mostly managed by decreasing the interferon dosage (42%). Some 35% of physicians reduce ribavirin if haemoglobin levels drop below 5.4 mmol/l, and 41% initiate erythropoietin treatment. CONCLUSION: Dutch clinical practice reflects the recently issued HCV guidelines. An important area of refinement in treatment of HCV is the management of side effects