1. Dr. chandrasekar

2. HEPATITIS = inflammation of liver 3. HEPATITIS - causesACUTE: Viral hepatitis Non-viral infection Alcohol Toxins Drugs Ischemic hepatits Autoimmune Metabolic diseases CHRONIC: Viral hepatitis Alcohol Drugs Non-alcoholic steatohepatitis Autoimmune Heredity 4. HEPATITIS - symptomsACUTE: Malaise Muscle and join ache Fever Nausea or vomiting Loss of apetite Abdominal pain Dark urine Jaundice CHRONIC: Malaise, tiredness, weakness Weight loss Peripheral oedema Ascites 5. Hepatitis A Transmission: faecal-oral,sexual Incubation: 2-6weeks High-risk countries: Eastern Europe, Africa, Asia, South America diagnosis: AST, ALT, Igm, IgG Propylaxis:Ig inactivated vaccine 0, 6-12 6. Hepatitis B: Transmission: blood and body fluids, iv drug abusers, sexual transmission Incubation: 1-6 months Hepatitis B virus primarily interferes with functions of the liver by replicating in liver cells During HBV infection, the host immune response causes both hepatocellular damage and viral clearance prophylaxis: hbig, recombinant vaccine 0-2,1-4,4-6 7. Hepatitis C 8. Transmission: blood Incubation: 2weeks - 6months No vaccine! 35% of patients infected with HIV are also infected with hepatitis C virus 9. Hepatitis D Incubation (days 30180, mean 6090 Transmission percutaneous, prenatal, sexual Prophylaxis HBV vaccine (none for HBV carriers) Cancer +/- 10. Hepatitis E Incubation 14 -60, days Transmission faecal oral Prophylaxis vaccine Cancer none 11. Alcoholic hepatitis 12. Anesthetic Halothanec Antiandrogen Flutamide Antibiotic Isoniazid,c rifampicin, nitrofurantoin, telithromycin, minocycline,d pyrazinamide, trovafloxacine Anticonvulsant Phenytoin, carbamazine, valproic acid, phenobarbital Antidepressant Iproniazid, amitriptyline, imipramine, trazodone, venlafaxine, fluoxetine, paroxetine, duloxetine, sertraline, nefazodone,e bupropion Antifungal Ketoconazole, fluconazole, itraconazole Antihypertensive Methyldopa,c captopril, enalapril, lisinopril, losartan 13. Anti-inflammatory Ibuprofen, indomethacin, diclofenac, sulindac, bromfenac Antipsychotic Risperidone Antiviral Zidovudine, didanosine, stavudine, nevirapine, ritonavir, indinavir, tipranavir, zalcitabine Calcium channel blocker Nifedipine, verapamil, diltiazem Diuretic Chlorothiazide Norepinephrine-reuptake inhibitor Atomoxetine Oral hypoglycemic Troglitazone,e acarbose 14. Hbs Ag test 15. PREVENTION 16. Strategy to Eliminate Hepatitis B Virus Transmission Prevent perinatal HBV transmission Routine vaccination of all infants Vaccination of children in high-risk groups Vaccination of adolescents Vaccination of adults in high-risk groups 17. Hepatitis B Vaccine Composition Recombinant HBsAg Efficacy 95% (Range, 80%-100%) Duration of Immunity 20 years or more Schedule 3 Doses Booster doses not routinely recommended 18. Hepatitis B Vaccine Routine Infant Schedule Dose+ Primary 1 Primary 2 Primary 3 Usual Age Birth 1- 2 months 6-18 months* Minimum Interval - - - 4 weeks 8 weeks** 19. Hepatitis B Vaccine Contraindications and Precautions Severe allergic reaction to a vaccine component or following a prior dose Moderate or severe acute illness 20. Medical management 21. Type of hepatitis Diagnostic test TREATMENT Chronic hepatitis B HBsAg, IgG anti- HBc, HBeAg, HBV DNA Uncommon IFN-, PEG IFN- lamivudine adefovir entecavir telbivudine tenofovir Chronic hepatitis C Anti-HCV, HCV RNA Autoantibodies PEG IFN- ribavirin Telaprevird Boceprevird Chronic hepatitis D Anti-HDV, HDV RNA, HBsAg, IgG anti-HBc Anti-LKM3 IFN-, PEG IFN-c 22. Goals of Therapy in Patients With Chronic HBV Infection Eradication of infection HBsAg seroconversion Undetectable HBV DNA Prevent complications of liver disease Histologic progression to cirrhosis Decompensated liver disease Liver cancer 23. HBeAg-positive patients (wild type) HBeAg seroconversion is KEY Sustained suppression of HBV DNA to low or undetectable levels ALT normalization Reduced necroinflammation on biopsy HBeAg-negative patients (precore and core promoter mutants) HBeAg seroconversion not an endpoint Sustained suppression of HBV DNA to low or undetectable levels ALT normalization Reduced necroinflammation on biopsy 24. Lamivudine (virolam,heptavir) cytosine Nucleoside analog Different dose for HBV (100 mg) monotherapy, use 300 mg for HIV+ and never alone Well-tolerated and cheap eAg conversion rate b/t 21-28% High rates of resistance! S/E nausea,headche, fatigue ,insomnia and pancreatitis in children 25. Adefovir (adfovir,adheb) Analogue of adenosine monophosphate It is phosphorylated by cellular kinases to an active diphosphate derivative that competitively inhibits hepatitis b virus At 10 mg/d dose, no HIV activity Side effects: renal toxicity, Fanconis Syndrome,lactic acidosis , hepatomegaly 26. Tenofovir (tavin,tenof) Analogue of adenosine -5 monophosphate not approved for HBV Perhaps more potent than Adefovir 300 mg once daily after meals S/E: nausea,vomitting, diarrhoea,osteomalcia 27. Entecavir (Baraclude guanosine Nucleoside analogue Inhibits viral DNA polymerase and hence its replication Fda approved from 2005 for chronic hepatitis b Should be taken in empty stomach S/E: head ache, fatigue, nausea , dizziness 28. Telbivudine Thymidine analogue which is phosphorylated to an active triphosphate form that inhibits hepatitis b viral DNA Treat chronic hepatitis b S/E: head ache, nausea, vomitting , increase cpk 29. RIBAVARIN Synthetic analogue of guanosine Inhibits the synthesis of viral m-RNA and DNA by depleting intracellular nucleotide reserves . Oral ribavarin (800-1200mg/day) + subcutaneous interferon alfa 2 b (3 million units 3 times weekly s.c) is effective treatment against hepatitis c viral infections S/E: worsening of respiration with copd , anemia, hypotension, Potential mutagenic, carcinogenic and teratogenic 30. Interferons (cytokines ) One of the bodys important defenses against viral infection Antiproliferative and immuno regulatory effects Alpha, beta and gamma Sc, i.m, i.v, or intra lesionally Uses :chronic hepatitis b, chronic hepatitis c( 3mU three times weekly 31. S/E Nausea Vomitting Head ache , myalgia Long time use bone marrow depression , rashes, alopecia, insomnia, depression Higher dose may cause miscarriage 32. Peg-interferon probablyA complex of polyethylene glycol with IFN Long acting form of IFN, once weekly HAS improved outcomes in chronic hepatitis b and c presumably from more sustained blood levels of IFN(longer t ) Peg IFN 2a and 2b are given s.c Cons: Many side effects, expensive, not for decompensated cirrhosis No data in HIV+, lower response than in HIV- 33. Side Effects of Peg IFN Depression ranging from mild to suicidality Irritability, aggressive behavior Worsening of mania Fatigue Insomnia Myalgias, fever, flu-like symptoms Hair loss Cytopenias 34. Newer drug development Serine protease inhibitors Polymerase inhibitors Helicase inhibitors Antisense therapy siRNA Toll-like receptor agonists Therapeutic vaccination Cyclosporine analog Improved Ribavirin and Interferon 35. Serine protease inhibitors Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection boceprevir was adequately absorbed, with the most effective mode of administration appearing to be a three-times-daily regimen. In phase I clinical trials, monotherapy with boceprevir led to a distinct viral load reduction. In phase Ib combination trials of boceprevir with PEGylated IFNalpha2b and ribavirin, the reduction in viral replication was further increased http://www.ncbi.nlm.nih.gov/pubmed/19197796 36. Cyclosporine analog Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter NTCP Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins. http://www.ncbi.nlm.nih.gov/pubmed/16143140 http://www.ncbi.nlm.nih.gov/pubmed/24375637orter NTCP. 37. Toll-like receptor agonists GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. http://www.ncbi.nlm.nih.gov/pubmed/23415804 38. A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice. http://www.ncbi.nlm.nih.gov/pubmed/23306359 39. siRNA Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosome Targeted delivery of siRNA against hepatitis B virus by preS1 peptide molecular ligand RNAi for Treating Hepatitis B Viral Infection 40. miravirsen a microRNA targeting drug for Hepatitis C, SPC3649 which entered Phase II clinical trials in 2010. The drug targets miR-122, a host factor necessary for viral replication of the Hepatitis C virus in host liver cells; because miravirsen targets a host factor rather than the virus itself, there are no indications of the virus developing reistance http://www.journal-of-hepatology.eu/article/S0168-8278(13)00656-9/fulltext 41. Helicase inhibitors Leading compounds for STAT-C target the HCV nonstructural (NS)5B polymerase and NS3 protease, however, owing to the constant threat of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase domain of the HCV NS3 protein. The HCV helicase uses energy derived from ATP hydrolysis to separate based-paired RNA or DNA. recently discovered compounds that inhibit HCV helicase catalyzed reactions and HCV cellular replication, and new methods to monitor helicase action in a high- throughput format. http://www.futuremedicine.com/doi/abs/10.2217/fvl.09.7 42. Thank you