Hepatitis C - Etiology Pathogenesis Clinical Features Diagnosis Management
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Hepatitis C is a viral infection that affects an estimated 2-3% of the world's population. It is transmitted parenterally or through exposure to infected blood or bodily fluids. Approximately 70-130 million individuals are chronically infected. While some acute cases resolve, others progress to chronic infection which can lead to cirrhosis or liver cancer over time. Diagnosis involves testing for HCV antibodies and RNA. Genotypes 1-6 exist globally. Management involves antiviral therapy with pegylated interferon and ribavirin or newer direct acting antiviral agents targeting viral proteins. Treatment aims to achieve a sustained virologic response and prevent progression of liver disease.
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Hepatitis C - Etiology Pathogenesis Clinical Features Diagnosis Management
- 1. Hepatitis C GUIDE:DR SACHIN HOSKATTI STUDENT : DR ABHAY KIRAN
- 2. Epidemiology Population prevalence : 2 – 3% of the world ’ s population 7 0 a n d 1 3 0 m i l l i o n i n d i v i d u a l s m a y b e c h r o n i c a l l y i n f e c t e d One of the top 10 causes of deathdue to infectious diseases
- 3. Hepatitis c accounted for the vast majority of non - A, non – B post - transfusion hepatitis before screening of hepatitis was started Single leading indication for liver transplantation in Europe and north America
- 4. Epidemiology
- 7. HCV Virus Discovered in 1989 small single stranded Enveloped RNA virus Family flaviviridae A single polyprotein that is processed into 10 functional proteins
- 8. E1and E2are important antigenic sites Variability may be important in persistence of infection and immunopathogenesis RNA- dependent RNApolymerase Non – structural region of the HCV genome is divided into regions NS2 to NS5 NS5A is essential for assembly of hcv into mature virions
- 9. Because of low fidelity of HCV RNA polymerase ,viral genome is very unstable 6 genotypes Genotypes 1 to 6
- 11. Pathology in 15- 40 % acute illness resolving completely In others it progress to chronic infection HCV uses variety of strategies to escape innate and adaptive immune responce
- 12. HCV induces hepatocellular injury by cell mediated immune mecha nism is supported by the following: i) It is possible that the host lymphoid cells are infected by HCV. ii) HCV-activated CD4+ helper T lymphocytes stimulate CD8+ T lymphocytes via cytokines elaborated by CD4+ helper T cells.
- 13. iii) The stimulated CD8+T lymphocytes, in turn, elaborate antiviral cytokines against various HCV antigens. iv) Further support to this T- cell mediated mechanism comes from the observation that immune response is stronger in those HCV- infected persons who recover than those who harbour chronic HCV infection.
- 14. v) There is some role of certain HLA alleles and innate immunity in rendering variable response by different hosts to HCV infection. vi) Natural killer (NK) cells also seem to contribute to containment of HCV infection.
- 15. vii) In as subset of patients, there is cross reactivity between viral antigens of HCV and host autoantibodies to liver-kidney microsomal antigen (anti-LKM) which explains the association of autoimmune hepatitis and HCV hepatitis.
- 16. Diagnostic tests Anti – HCV :doesnot identify active infection. Serum HCV RNA: 5 – 15 IU/mL . Genotyping
- 17. Genotypes in INDIA Genotype 3 : 60% Genotype 1 : 30% Genotype 4 : 6% Genotype 2,6 : 4%
- 18. Acute hepatitis C generally asymptomatic Incubation period 2 – 12 weeks (average 7weeks) HCV RNAbecomes positive within 2 weeks of exposure Anti - HCV positive within 8 – 10 weeks of exposure
- 20. MANAGEMENT SUPPORTIVE TREATMENT SPECIFIC ANTIVIRAL THERAPY IFN MONOTHERAPY[>90% SVR] ASYMPTOMATIC PATIENT- DIRECT ANTIVIRAL AGENTS SOFOSBUVIR +LEDIPASVIR[6-8WKS]
- 21. Chronic Hepatitis C Presence of HCV RNA> 6 months in serum Asymptomatic and go unnoticed 10-20 %develop cirrhosis in next 20 years
- 22. Progressive disease results in worse lab values : AST> ALT Low Serum albumin Prolonged PT Low platelet count Positive for LKM-1 antibodies
- 24. Extrahepatic manifestations Cryoglobulinaemia, Vasculitis, Lichen Planus, Porphyria Cutanea Tarda, Lymphocytic Sialoadenitis And Membranous Glomerulonephritis Non - Hodgkin ’ SLymphoma Insulin resistance and T2DM
- 25. Microscopy Mild portal tract inflammation Lymphoid aggregates or follicles Mild periportal piecemeal necrosis Parenchymal steatosis, Apoptosis and mild lobular inflammation Portal fibrosis or portal – central fibrosis Bridging necrosis - rarely Granulomas - rarely
- 26. Management - Approach HCV RNAin serum Anti HCV antibodies Liver enzymes PT Bilirubin levels HCV Genotyping HBsAg HIV Anti LKM antibodies
- 27. Liver biposy Unique extra information is available with biopsy like grading of fibrosis and necroinflammation Calculation of fibrosis 1. AST/Platelet ration Index ( APRI ) : 80 -90% accuracy 2. Transient elastography ( Fibroscan ) Normal = 4-6 kilo-pascals Cirrhosis = 12 – 14 kilo pascals
- 28. Indications for treatment All patients Psychiatry patients may worsen with IFN treatment In cirrhotics :Avoid IFN
- 29. Peg IFN – a ( ONCEA WEEK ) & RIBAVAR ( DAILY ) Peg IFN – a 1. Half life :3 – 8 hours 2. Peak Sr Conc :7 – 12 hour after injection 3. Cleared from blood :< 24 hours RIBAVARIN 1. Guanosine analogue 2. Inhibition of guanyltransferase and methytransferase capping enzymes 3. Induce mutation affecting HCV replication 4. <65kg :800mg 5. 65-85kg :1000mg 6. >85kg :1200mg
- 30. PEGIFN a : 180 microgm/week Genotype 1 1. 48 week therapy 2. < 75 kg : 1000 mg 3. >75kg : 1200 mg Genotype 2 and 3 1. 24 week therapy 2. 800mg / day
- 31. Ribavirin Most common adverse effect is hemolysis. Reduction of Hb% upto 2-3 gm% isseen Reduction of haematocrit upto 10% Risk of usage in patients with stroke / CAD / Hemoglinopathies. Increase in anemia on ribavirin usage, Epo can be supplemented Reduction of dose of ribavirin upto 60% of planned doseis acceptable
- 32. PegIFN types pegIFN alpha 2a pegIFN alpha 2b 40 kilodalton molecule 12 kilodalton molecule Dose is weight independent Dose is weight dependent 180 microgram / week + 800 mg Ribavirin 1.5 microgram / kg / week + 1000 mg Ribavirin • BETTERTOLERABLE • GOOD COMPLIANCE
- 33. Side effects – IFN alpha Flu like symptoms Seizure Acute psychosis autoimmune diseases Bacterialinfections Hyperthyroidism and thyroiditis Proteinuria Cardiomyopathy IFNantibodies Neuroretinitis ILD Sarcoidosis
- 34. Haemolytic anaemia, Myalgia, Hyperuricaemia, Dyspepsia, Monitored for haemoglobin, leucocytes and platelets, AST,ALT, albumin, bilirubin every 4 weeks. Uric acid and thyroid function at 1 to 3 - monthly intervals. Risk of teratogenicity, need for contraception up to 6 months after completing treatment. Side effects – Ribavarin
- 35. PEG- IFN plus RBV Non - responders or relapses to either standard IFNplus RBVor PEG- IFN monotherapy. PEG- IFN plus RBV retreatment Lessvalue if low SVRinprevious full course of PEG- IFN plus RBV. Treatment should be stopped if no early viral response with re - treatment
- 38. Sofosbuvir nucleotide NS5B polymerase inhibitor Can be given in cirrhotic patient excreted by the kidneys and not recommended for patients with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2
- 39. Sofosbuvir and ledipasvir fixed drug combination of an NS5B polymerase inhibitor and an NS5A inhibitor Daily once tablet containing 400 mg of sofosbuvir and 90 mg of ledipasvir Biliary excretion of unchanged ledipasvir is the major route of elimination.
- 40. Sofosbuvir and velpatasvir fixed drug combination of the NS5B and a second‐generation NS5A inhibitor Once dialy tablet containing 400 mg of sofosbuvir and 100 mg of velpatasvir
- 41. Ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (PrOD) combination comprises a tablet containing 75 mg of paritaprevir 12.5 mg of ombitasvir, 50 mg of ritonavir 250 mg of dasabuvir
- 42. Two tablets of paritaprevir–ombitasvir–ritonavir are taken once daily. One tablet containing 250 mg of dasabuvir is taken twice daily Paritaprevir is an NS3–4A protease inhibitor Ombitasvir is an NS5A inhibitor Dasabuvir is a non‐nucleoside NS5B polymerase inhibitor.
- 43. Grazoprevir and elbasvir Grazoprevir -protease inhibitor elbasvir - NS5A inhibitor One tablet containing 100 mg of grazoprevir and 50 mgof elbasvir is taken once daily
- 44. Daclatasvir NS5A inhibitor The combination of sofosbuvir and daclatasvir has activity against genotypes 1– 6 Dosage-60mg No dose adjustment of daclatasvir is required in advanced liver disease or for patients with renal failure. Almost 90% of daclatasvir is eliminated in faeces
- 45. Simeprevir is a protease inhibitor one capsule containing 150 mg No dose adjustment of simeprevir is necessary in moderate renal impairment
- 46. Pibrentasvir and glecaprevir Glecaprevir (formerly ABT‐493) is a pangenotypic NS3–4A protease inhibitor Pibrentasvir (formerly ABT‐530) is a Pangenotypic NS5A inhibitor Pibrentasvir shows potent activity against genotypes 1–6 once daily as three 100 mg/40 mg pills for a total dose of 300 mg/120 mg. The drugs are excreted primarily by biliary excretion
- 55. Prevention Safe blood transfusion Safe injections Education Preventing injecting drug use Clean needle programmes Treatment forms part of attempts to control the disease and to prevent transmission
- 56. Other co‐morbid conditions or modifiable factors, particularly alcohol, obesity, and coinfection with hepatitis B and HIV should be addressed Screening of undiagnosed individuals Improving the cascade of linkage to care Future vaccination
- 57. References Sherlock’s Diseases Of The Liver And Biliary System Harrison's Principles Of Internal Medicine Robbins basic of Pathology
- 58. THANK YOU