Hepatitis C E learning summary - Clinical features and treatment

E learning summary on Hepatitic C

1. E - LEARNNG Hepatitis C Moderators - Dr Akhila Paga - Dr Geeta C Presented by - Dr Mohammed Ameen

2. Hepatitis C Most common cause of Cirrhosis worldwide Most frequent indication for Liver transplantation before 2013. Transfusion related hepatitis Initially, non-A non-B Hepatitis . Discovered – 1988 RNA virus Family – Flaviviridae Genus - Hepacivirus

3. Which protein of the Hepatitis C virus is essential for viral entry into host cells? a) Core protein b) NS3 protease c) NS5B polymerase d) Envelope glycoprotein E2

4. d) Envelope glycoprotein E2

5. Life cycle of HCV

6. Which of the following host proteins make HCV infective? Immunoglobulins LDL and VLDL Fibrin Elastin

7. b) VLDL and LDL HCV is found in three forms Bound to VLDL, LDL ( Infective – Lipo-viro partcle ) Bound to Immunoglobulins Free virion

8. 3. Which viral protein is the target of direct-acting antiviral drugs (DAAs) in the treatment of Hepatitis C? a) Core protein b) NS3 protease c) p7 d) Envelope glycoprotein E2

9. b) NS3 protease

10. 4. Which of the following is the most common genotype of Hepatitis C virus in India? a) Genotype 1 b) Genotype 2 c) Genotype 3 d) Genotype 5

11. C) Genotype 3 is most commonly found genotype of HCV in India. Bad prognosis. Faster progression to steatosis Genotype 1 – most common in North America Genotype 2 – Associated with acute flare of symptoms

12. 5. Which of the following markers is first elevated in the serum during acute Hepatitis C i nfection ? a) Alanine transaminase (ALT) b) Aspartate transaminase (AST) c) HCV RNA d) Anti HCV antibody level

13. C) HCV RNA - within 7 to 21 days after viral transmission. Increase in serum ALT levels 4 to 12 weeks after infection, indicative of hepatic injury, up to more than 10 times the upper limit of normal.

14. 6. Which of the following regarding perinatal transmission of Hepatitis C is true? the risk of perinatal transmission of HCV infection is more than HBV infection. Mothers with a high serum level of HCV RNA are more likely to transmit HCV to their infants. The use of antiretroviral therapy (ART) in HCV-HIV coinfected mothers does not decrease the risk of perinatal transmission of both HIV and HCV. A higher risk of HCV transmission with vaginal delivery as opposed to cesarean.

15. b) Mothers with a high serum level of HCV RNA are more likely to transmit HCV to their infants. This is true, explains why infants born to mothers with HCV-HIV coinfection are at higher risk of HCV infection. The use of antiretroviral therapy (ART) in HCV-HIV coinfected mothers may decrease the risk of perinatal transmission of both HIV and HCV. Comparatively, risk if perinatal transmissions higher in HBV No evidence of mode of delivery affecting the risk of transmission of HCV

16. Natural course of Hepatitis C

17. 7. Which of the following factors is associated with an increased risk of Hepatitis C progression to cirrhosis? a) Female gender b) Age less than 40 years c) Obesity d) HIV coinfection

18. Factors associated progression of hepatic fibrosis in Chronic HCV infection Not associated Age > 40 years Alcohol consumption HBV Coinfection HIV Coinfection Immunosuppressed state Insulin resistance Obesity Marijuana Schistosomiasis Smoking White race Viral Genotype Viral Load D) HIV Coinfection

19. 8. Which of the following is a common extrahepatic manifestation of chronic Hepatitis C infection? a) Interstitial nephritis b) Rheumatoid arthritis c) Guillain-Barré syndrome d) Cryoglobulinemia

20. d) Cryoglobulinemia

21. 9. Which of the following endocrine disorder is commonly associated with Hepatitis C infection? Diabetes Mellitus Hypothyroidism Addisons disease Pheocromocytoma

22. a) Diabetes Mellitus Hepatitis C is associated with insulin resistance Viral interaction with IRS pathway Chronic inflammatory state Hepatitis Altered lipid metabolism Diabetes Mellitus is an independent risk factor for progression of Cirrhosis to HCC in Hepatitis C.

23. 10. Which of the following factors influences the choice of treatment regimen for Hepatitis C? a) Patient age b) Patient gender c) HCV genotype d) HCV viral load

24. HCV genotype Though few DAAs are pan genotype, some regimens are only recommended for certain HCV genotypes and subtypes. Treatment of Hepatitis C Interferon Pegylated Interferon Ribavarin – oral guanasine analog DAAs

25. DIRECT ACTING ANTIVIRALS (DAAs) NS3/4A Protease Inhibitors (- previrs ) Simeprevir Grazoprevir Paritaprevir Glecaprevir Voxilaprevir NS5A Inhibitors (- asvirs ) Daclatasvir Ombitasvir Elbasvir Ledipasvir Velpatasvir Pibrentasvi r NS5B Polymerase Inhibitors (- buvirs ) Nucleoside - Sofosbuvir Non Nucleoside - Dasabuvir

26. 11. Which laboratory parameter is monitored to assess response to Hepatitis C treatment? a) Serum ALP levels b) ALT, AST levels c) Hepatitis C viral load d) Serum Bilirubin

27. c) Hepatitis C viral load Response to the treatment in terms of viral load is determined by RVR – absence of detectable viral RNA 4 weeks after therapy EVR – detectable viral RNA levels but decline by > 2 log by 12 weeks of treatment. SVR - absence of detectable viral RNA 12 - 24 weeks after therapy ETR – undetectable viral RNA at the end of treatment

28. 12. Which of the following is true of a sustained viral response (SVR) after hepatitis C treatment? An improvement in quality of life is not associated with SVR SVR may lead to improvement of elastography fibrosis score SVR is defined as the absence of detectable virus in the blood 48 weeks after completion of therapy In patients with cirrhosis, SVR eliminated the risk of developing HCC

29. b) SVR may lead to improvement of elastography fibrosis score. SVR is associated with regression of fibrosis and reduction in hepatic inflammation during therapy. Evident improvement in elastography fibrosis scores after DAA therapy . Quality of life improves with SVR. SVR reduces, but does not eliminate the risk for HCC

30. Invasive Non Invasive APRI FibroSure Transient Elastography ( FibroScan ) Fibrosis Scoring Systems

31. 13. Which of the following is currently the first-line treatment for chronic Hepatitis C infection? a) Interferon monotherapy b) Ribavirin monotherapy c) Direct-acting antiviral (DAA) therapy d) Combination therapy with interferon and ribavirin

32. c) Direct-acting antiviral (DAA) therapy

33. 14. Which of the following is a recommended treatment regimen for chronic Hepatitis C genotype 1 infection? a) Sofosbuvir / Ledipasvir for 8 weeks b) Sofosbuvir / Velpatasvir for 12 weeks c) Peginterferon alfa /Ribavirin for 24 weeks d) Simeprevir / Daclatasvir for 6 weeks

34. b) Sofosbuvir / Velpatasvir for 12 weeks

35. 15. Which of the following drugs used in the treatment of Hepatitis C causes Hemolytic anemia? Sofusbuvir Velpatasvir Ribavarin Peg INF alpha 2a

36. C) Ribavarin causes dose-dependent hemolytic anemia. Weight based dose; the patient’s Hb level must be monitored during treatment. Side effects of Ribavarin Hemolytic anemia Hyperuricemia Dyspepsia Depression

37. 16. What is the duration of treatment for chronic Hepatitis C genotype 3 infection with sofosbuvir and ribavirin? 4 weeks 8 weeks c) 12 weeks d) 24 weeks

38. C) 12 weeks Type 3 genotype – most common in India

39. DAA Regimen in Decompensated Cirrhosis

40. Case 1 A 45-year-old male presents to the clinic with complaints of fatigue, nausea, and abdominal discomfort for the past few weeks. He has a history of injectible drug use but denies any recent drug use. On examination, he is jaundiced with hepatomegaly. Laboratory tests reveal elevated liver enzymes (ALT and AST) and positive Hepatitis C antibody. What is the most appropriate next step in the management of this patient?   a) Start treatment with direct-acting antiviral therapy immediately. b) Repeat Hepatitis C antibody test to confirm the diagnosis. c) Perform Hepatitis C viral load (HCV RNA) test to confirm active infection. d) Refer the patient for liver biopsy to assess the extent of liver damage .  

41. C) Hepatitis C viral load (HCV RNA) test to confirm active infection.

42. Case 2 A 40-year-old man presents with a history of intravenous drug use and complains of fatigue and weight loss. He has a known diagnosis of HIV infection with a CD4 count of 200 cells/mm3. Laboratory tests reveal elevated liver enzymes and positive anti-HCV antibodies. Which of the following direct-acting antiviral regimens is recommended for the management of his HCV-HIV coinfection ? Grazoprevir / Elbasvir Sofosbuvir / Velpatasvir Ledipasvir / Sofosbuvir Glecaprevir / Pibrentasvir

43. B ) Sofosbuvir / Velpatasvir In patients with HCV-HIV coinfection , the choice of direct-acting antiviral (DAA) regimen should take into account both the efficacy against HCV and potential interactions with antiretroviral therapy (ART) for HIV . Sofosbuvir / Velpatasvir is a preferred regimen for HCV-HIV coinfected patients Pangenotypic Minimal interactions with ARTs