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manag of hoh responders

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Information about manag of hoh responders
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Published on March 12, 2009

Author: essaa2000

Source: authorstream.com

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Slide 1: TREATMENT OF NON-RESPONDERS BY DR, MUHAMAD ESSA ARMANT FEVERS HOSPITAL MANAGEMENT OF NON RESPONDERS byDR. MUHAMAD ESSAARMANT FEVERS HOSPITAL : MANAGEMENT OF NON RESPONDERS byDR. MUHAMAD ESSAARMANT FEVERS HOSPITAL Definitions of response to treatment : Definitions of response to treatment MANAGEMENT OF NON RESPONDERS : MANAGEMENT OF NON RESPONDERS NULL RESPONDERS >1-log decline in HCV RNA on treatment. Partial Response > or = 2-log decline in HCV RNA at week 12 ..but undetectable level is never achieved. Slow Response persistent viraemia at week 12 but undetectable at week 24. MANAGEMENT OF NON RESPONDERS : MANAGEMENT OF NON RESPONDERS Rapid reduction in the viral load after initiation of therapy indicates a higher SVR. Patients with RVR r more likely 2 have SVR. If no EVR is achieved ..discontinue treat. and these r called non responders. MANAGEMENT OF NON RESPONDERSEmerging Treatments : MANAGEMENT OF NON RESPONDERSEmerging Treatments There r many non responders on the current therapy of INF and Ribavirin. Newer formulations of INF with less toxicity , more convenient means of administration and improved efficacy are being tested. The most promising is agents that target viral enzymes required for HCV replication (STAT-C ). MANAGEMENT OF NON RESPONDERSEmerging Treatments : MANAGEMENT OF NON RESPONDERSEmerging Treatments NOVEL INTERFERON-BASED FORMULATIONS INTERFERON ALFACON-1 (CONSENSUS INTERFERON) Synthetic INF Has minimal efficacy in the treat. of non-responders to prior combination therapy of peg-INF and ribavirin. It is given in a daily dose 9 - 15 microgram/day plus ribavirin(1000-1200 mg) for 48 weeks. only 5% and 10% of the non responders achieved SVR. Emerging Treatments : Emerging Treatments NOVEL INTERFERON-BASED FORMULATIONS Albumin interferon alfa-2b (albinterferon) Is a cecombinant protein consisting of INF alfa-2b bound to albumin. Has longer half life thence reduced frequency of administration. It was administered to non-responders in a dose of 1800 microgram/ every 2 weeks plus ribavirin SVR was impressive 50%. Emerging Treatments : Emerging Treatments STAT-C agents It targets the virus directly by inhibiting viral-specific enzymes... such as the NS3/4A serine protease and the NS5B RNA-dependent RNA-polymerase. The emmergence of resistent mutations is a threat to its use. Emerging Treatments : Emerging Treatments Protease inhibitors Telaprevir is a selective inhibitor of the NS3/4A serine protease. It is being evaluated in combination with peg- INF and also with peg INF and ribavirin . This tripple therapy gave complete EVR in 70%...and 85% had undetectable HCV-RNA 12 weeks after discontinuation of therapy all these data in genotype 1. Emerging Treatments : Emerging Treatments POLYMERASE INHIBITORS VALOPICITABINE (NM283) AND R1626...gave promising results in non-responders , but the frequency of haematological and gastrointestinal complications put further study of these drugs on hold Emerging Treatments : Emerging Treatments CYCLOPHILLIN INHIBITORS Cyclophillin B is a cofactor for HCV NS5B polymerase , which is involved in HCV replication , so they have anti viral activity. and is being evaluated now Although the treat. was well tolerated in many trial , yet the increased incidence of hyperbilirubinemia and thrombocytopenia in patients on DEBIO-25.. this needs further investigation. conclusion : conclusion The management of patients with chronic hepatitis C who do not respond to conventional therapy remains a challenge., a trial of peg INF plus ribavirin ia a reasonable option those who fail to respond to a course of peg INF plus ribavirin represent a greater challenge . and there is no standardized approach to manage these patients. Neither re-treatment with higher doses of peg INF and/or ribavirin nor a longer duration of therapy has demonstrated sufficient improvement in SVR rates . conclusion(2) : conclusion(2) In addition , the use of maintenance therapy for non-resp.to prior treat. has not demonstrated that low-dose peg INF slowsthe progression of disease . newer formulations of INF are currently under development. the most promising therapy appears to be the STAT-C agents

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