manag. of chronic hgv infection

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Information about manag. of chronic hgv infection
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Published on March 12, 2009

Author: essaa2000

Source: authorstream.com

Management Of Chronic Hepatitis C Genotype 4 (HCV-4) : 1 Management Of Chronic Hepatitis C Genotype 4 (HCV-4) BY Dr. MUHAMAD ESSA MANAGEMENT OF CHRONIC HEPATITIS C GENOTYPE 4 (HCV-4) : 2 MANAGEMENT OF CHRONIC HEPATITIS C GENOTYPE 4 (HCV-4) .. HCV accounts for a sizable proportion of chronic liver disease , liver disease deaths , hepatocellular carcinoma and represents the most common indication for liver transplantation (LTx) .. Six major genotypes and more than 50 subtypes of HCV have been subscribed. .. Genotype 4 (HCV-4) is predominant in AFRICA and MIDDLE EAST.. In EGYPT 15% of population are infected with HCV, 91% of which is of genotype 4 (HCV-4). MANAGEMENT OF CHRONIC HCV-4 / SCREENING AND EPIDEMIOLOGY : 3 MANAGEMENT OF CHRONIC HCV-4 / SCREENING AND EPIDEMIOLOGY …ELISA ( antibody test ) is a good and efficient screening test , if we exclude some false negative cases in acute infections and in the immunocompromised state. …In these situations the diagnosis can be made with HCV-RNA by using the amplification technique ( PCR) . …For the majority of patients , the usual approach is to test them initially by ELISA and then to use the PCR to test and assess viraemia. MANAGEMENT OF CHRONIC HCV-4 SCREENING @ EPIDEMIOLOGY (CNT.) : 4 MANAGEMENT OF CHRONIC HCV-4 SCREENING @ EPIDEMIOLOGY (CNT.) …Multiple large community-based studies in EGYPT have shown a strong association between a history of receiving parenteral anti- schistosomal therapy ( in 1960s and 1970s ) and the prevalence of anti HCV antobody (anti- HCV )”1;2;3” …Many publications suggest that parenteral anti- schistosomiasis treatment has a role in the transmission of HCV throughout EGYPT MANAGEMENT OF CHRONIC HCV-4/ SCREENING AND EPIDEMIOLOGY : 5 MANAGEMENT OF CHRONIC HCV-4/ SCREENING AND EPIDEMIOLOGY ( CONT. ) …EGYPTs mass campaigs of parenteral anti- schistosomiasis treatment may represent the worlds largest iatrogenic transmission of blood-borne pathogens.”3” MANAGEMENT OF CHRONIC HCV-4 PRETREATMENT DIAGNOSTIC EVALUATION : 6 MANAGEMENT OF CHRONIC HCV-4 PRETREATMENT DIAGNOSTIC EVALUATION Pretreatment diagnostic cosiderations ..Seropositive persons for anti_HCV in the pessence HCV_RNA and compensated liver disease are considered as potential candidates for antiviral therapy. ..Antiviral therapy is not recommended for patients with decomp_ sated liver cirrhosis or history of severe uncontrolled psychiatric disorder. ..patients with marked leucopenia or thrombocytopenia may not tolerate INF. MANAGEMENT OF CHRONIC HCV-4PRETREATMENT DIAGNOSTIC EVALUATION(CONT.) : 7 MANAGEMENT OF CHRONIC HCV-4PRETREATMENT DIAGNOSTIC EVALUATION(CONT.) Pretreatment diagnostic cosiderations(cont.) Patients with marked anaemia cardiovascular or cerebro- vascular disease or renal failure may not tolerate ribavirin cause it causes dose dependent haemolytic anaemia. Testing ALT and AST level is important although elevation of ALT and AST is not a requirement for therapy. MANAGEMENT OF CHRONIC HCV-4 VIROLOGIC TESTS FOR MONITORING THERAPY : 8 MANAGEMENT OF CHRONIC HCV-4 VIROLOGIC TESTS FOR MONITORING THERAPY Quantitative PCR for HCV-4 It is a prognostic indicator..... a baseline level for monitoring virologic response. Patients with very high PCR-RNA for HCV respond less to treatment than those with lower levels. It is important for demonstration of early virologic response ( EVR ) which is a 2-log 10 reduction in HCV-RNA level within 12 weeks of initiating therapy MANAGEMENT OF CHRONIC HCV-4VIROLOGIC TESTS FOR MONITORING THERAPY : 9 MANAGEMENT OF CHRONIC HCV-4VIROLOGIC TESTS FOR MONITORING THERAPY GENOTYPING It is a strong predictor of response to therapy and can affect the duration of therapy. In EGYPT where more than 90% of chronic HCV cases are of the genotype 4 ;treatment must be continued for 48 weeks with full dose ribavirin like patients of the genotype 1 ( it is intermediate in responsiveness between genotype 1 and genotype 2 and 3 ) MANAGEMENT OF CHRONIC HCV-4VIROLOGIC TESTS FOR MONITORING THERAPY : 10 MANAGEMENT OF CHRONIC HCV-4VIROLOGIC TESTS FOR MONITORING THERAPY LIVER BIOPSY Despite its complications and interpretation errors , it remains the gold standard for determining histological grade and stage to assess the current state of the liver and to provide prognostic information for future disease progression. The degree of liver fibrosis is an important predictor of the response to therapy. Patients with milder disease respond better to therapy Steatosis is a negative predictor of response to therapy MANAGEMENT OF CHROMIC HCV-4PRETREATMENT GIAGNOSTIC EVALUATION(CONT.) : 11 MANAGEMENT OF CHROMIC HCV-4PRETREATMENT GIAGNOSTIC EVALUATION(CONT.) PERSISTENTLY NORMAL SERUM ALT. Patients with such ALT generally do not progress histologically. they are good candidates for antiviral therapy or for monitoring without intervention ... this is determined on individual basis ; and is influenced by patients factors such as motivation , histological activity and fibrosis.. MANAGEMENT OF CHRONIC HCV-4 : 12 MANAGEMENT OF CHRONIC HCV-4 Counselling to avoid tranmission of HCV HCV patients should be counselled to avoid sharing tooth brushes and dental & shaving equipements, to cover any bleeding wound, not to donate blood and to avoid sharing syringes. Clean injection sites with alcohol swabs ,dispose safely syringes and needles after use Sexual transmission is low and there is no need to use barrier precautions. MANAGEMENT OF CHRONIC HCV-4PRETREAMENT DIAGNOSTIC EVALUATION : 13 MANAGEMENT OF CHRONIC HCV-4PRETREAMENT DIAGNOSTIC EVALUATION Approach to patient with anti-HCV If anti-HCV is +ve and ALT is initially normal.. this gives limited information and we must have 3 estimations of ALT over 6 months. If anti-HCV is +ve with normal ALT ,PCR ( qualitative HCV RNA ) should be performed. ...if HCV RNA is negative--past infection. ... if HCV RNA +ve .. no liver biopsy and no treat. but annual follow up , or treat. MANAGEMENT OF CHRONIC HCV-4PRE-TREATMENT DIAGNOSTIC EVALUATION : 14 MANAGEMENT OF CHRONIC HCV-4PRE-TREATMENT DIAGNOSTIC EVALUATION Approach to patient with anti-HCV(cont.) if the anti-HCV is +ve and there is ALT elevation... a qualitative PCR is indicated . A quantitative PCR (which is less sensitive than the qualitative ) and genotyping are only indicated when treatment is considered. Liver biopsy is not indicated in patients with normal transaminases ., but is highly recommended before considering treatment in order to determine the inflammatory activity and degree of fibrosis and to exclude other liver diseases. MANAGEMENT OF CHRONIC HCV-4PRE-TREATMENT DIAGNOSTIC EVALUATION : 15 MANAGEMENT OF CHRONIC HCV-4PRE-TREATMENT DIAGNOSTIC EVALUATION Approach to patient with anti-HCV (cont.) When it is decided not to treat ( in very mild histological disease ) , a follow up biopsy is planned 3 - 5 years to determine the evalution of the disease.. MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(1) : 16 MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(1) The addition of the synthetic guanosine analogue ribavirin to INF was a major breakthrough in the treatment of HCV infections. Shoboshki et al. treated 180 HCV-4 patients ..in a randomised multicenter trial.... divided the into 3 groups First group received PEG-INF-alfa-2a 180 mg weekly plus ribavirin 800 mg/day for 48 weeks. ETVR = 67% SVR = 50% Second group received PEG-INF monotherapy ETVB = 59% SVR = 28% Third group was treated using the standard INF 4.5 MU MANGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(2) : 17 MANGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(2) /TIW plus ribavirin 800 mg/day ETVB = 37% SVR = 30% Patients who did not achieve a significant response at the 12th week of therapy showed no SVR. MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(3) : 18 MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(3) Diago et al. treated cases of HCV-4 He divided them into 4 groups First group treated with PEG-INF-alfa-2a plus ribavirin 1000 - 1200 mg/day for 48 weeks. SVR=79% Second group was divided into 4 subgroups PEG-INF-alfa-2a plus 800mg &1000-1200 mg RIB for 24 and 48 weeks. Patients treated with ribavirin in a dose of 800 mg for 48 weeks gave SVR-63% MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(4) : 19 MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(4) Those treated with ribavirin 1000-1200 mg for 48 weeks gave SVR= 67%. No SVR was achieved in those treated with ribavirin 800 mg/day for 24 weeks. MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(5) : 20 MANAGEMENT OF CHRONIC HCV-4PEG-INF AND RIBAVIRIN(5) In a study from KUWAIT PEG-INF-alfa-2b 100 mg/week plus ribavirin 1000-1200 mg a day SVR was 68%. From these studies .... it was concluded that high dose ribavirin that is 1000 - 1200 mg /day should be used in HCV-4 patients irrespective of the type of PEG-INF used. MANAGEMENT OF CHRONIC HCV-4MONITORING RESPONSE TO ANTIVIRTAL THERAPY : 21 MANAGEMENT OF CHRONIC HCV-4MONITORING RESPONSE TO ANTIVIRTAL THERAPY Baseline and 12th week quantitative PCR must be done EVR during the 12th week of therapy is a valuable laboratory milestone In absence EVR at the 12th week the likehood of SVR is 0 - 3% If the only goal of therapy is to achieve a SVR ; therapy can be discontinued after 12 weeks of therapy if EVR is not achieved . Histologic benefit may happed even in absence of SVR. MANAGEMENT OF CHRONIC HCV-4FOLLOW UP AFTER TREATRMENT : 22 MANAGEMENT OF CHRONIC HCV-4FOLLOW UP AFTER TREATRMENT Once treatment has been decided, routine follow up is planned. Pre-treatment baseline laboratory values should be obtained including CBC , complete metabolic panel , INR , and viral load. Patients should return 2 weeks after initiation of therapy and subsequently every 4 weeks , and routine lab studies (CBC) should be done. MANAGEMENT OF CHRONIC HCV-4FOLLOW UP AFTER TREATMENT(CONT.) : 23 MANAGEMENT OF CHRONIC HCV-4FOLLOW UP AFTER TREATMENT(CONT.) And also at these 4 weeks interval to monitor for signs of adverse effects due to the drugs The decision to continue treatment after the week 12 would then be determined based on EVR , tolerance to drugs , lab. profile and the pretreatment assessment of the severity of liver disease. Once the course of treatment is completed , a quantitative PCR must be obtained to document the end of the ETR. The same test should be done later after 6th&12th month to evaluate SVR. MANAGEMENT OF CHRONIC HCV-4CONTRAINDICATION TO INF THERAPY : 24 MANAGEMENT OF CHRONIC HCV-4CONTRAINDICATION TO INF THERAPY Severe uncontrolled psychiatric or depressive disorder . Decompensated liver cirrhosis ,marked leucopaenia ,thrombocytopaenia or anaemia. Patient with severe concurrent disease such as severe hypertension , poorly controlled DM, COPD, cardiovascular disease, renal failure, kiney ;heart; or lung transplant recipient , autoimmune hepatitis, untreated hyperthyroidism,pregnancy ,under 3 years of age and hypersensitivity to one of the drugs used in the treatment of HCV. MANAGEMENT OF CHRONIC HCV-4CONTRAINDICATIONS FOR INF THERAPYSPECIAL PRECAUTIONS : 25 MANAGEMENT OF CHRONIC HCV-4CONTRAINDICATIONS FOR INF THERAPYSPECIAL PRECAUTIONS Care must be taken in : Age older than 70 years , neutropaenia (neutrophil count less than 1500 cells /ul), thrombocytopaenia (less than 85000 /ul) , organ transplantation ,history of autoimmune disease and the presence of thyroid antibodies. MANAGEMENT OF CHRONIC HCV-4ADVERSE EFFECTS TO THERAPY : 26 MANAGEMENT OF CHRONIC HCV-4ADVERSE EFFECTS TO THERAPY The side effects tend to be more severe in the initial weeks of treatment. they are neutropenia , thrombocytopaenia , depression , hypothyroidism and hyperthyroidism , irritability , concentration and memory disturbances ,visual disturbances , fatigue , muscle aches , headach , nausea and vomiting , skin irritation , low grade fever , weight loss , insomnia , hearing loss , tennitus , interstitial fibrosis. MANAGEMENT OF CHRONIC HCV-4ADVERSE EFFECTS TO THERAPY : 27 MANAGEMENT OF CHRONIC HCV-4ADVERSE EFFECTS TO THERAPY Those typically associated with ribavirin include : haemolytic anaemia , fatigue ,itching , rash , sinusitis , birth defects and gout. Deaths reported in association with therapy include suicide , myocardial infarction , sepsis and stroke Ribavirin is contraindicated in pregnancy , so contraception is a must , even if the HCV affects either the male or the female partner. MANAGEMENT OF CHRONIC HCV-4HCV AND SCHISTOSOMIASIS : 28 MANAGEMENT OF CHRONIC HCV-4HCV AND SCHISTOSOMIASIS Dual infections of schistosomiasis and viral infections display significant influences on the host immune reactions. It also has impact on response to antiviral therapy. Thus screening for active schistosomisis and treating it prior to initiating INF/RIBAVIRIN therapy is mandatory. MANAGEMENT OF CHRONIC HCV-4FACTORS ASSOCIATED WITH RESPONSE TO INF AND RIBAVIRINRELAPSERS AND NON-RESPONDERS : 29 MANAGEMENT OF CHRONIC HCV-4FACTORS ASSOCIATED WITH RESPONSE TO INF AND RIBAVIRINRELAPSERS AND NON-RESPONDERS Relapsers patients in whom HCV-RNA is undetectable during and arround the end of therapy but reappears again after completion of therapy...........they are likely to respond and relapse again with subsequent courses of the same therapy. If relapse occurs after therapy with the standard INF , PEG-INF /ribavirin must be started with SVR expected to be arround 40% - 50%. MANAGEMENT OF CHRONIC HCV-4FACTORS ASSOCIATED WITH RESPONSE TO INF AND RIBAVIRIVRELAPSERS AND NON-RESPONDERS : 30 MANAGEMENT OF CHRONIC HCV-4FACTORS ASSOCIATED WITH RESPONSE TO INF AND RIBAVIRIVRELAPSERS AND NON-RESPONDERS NON-RESPONDERS to previous course of standard INF,, re-treatment with PEG-INF/RIBAVIRIN can increase the frequency of responsiveness to approximately 20 %. Expectations for responsiveness to re-treatment are lower in patients with genotype 1 , cirrhosis , high baseline PCR-RNA level and black ethnicity. Such factors in addition to patient's tolerance to previous therapy and the severity of the underlying liver disease , should be taken into consideration whem making idividualized decisions about re-treatment of prior non-responders. THANK YOUessaa2000@hotmail.com : 31 THANK YOUessaa2000@hotmail.com

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