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HEPATITIS C UPDATE

HEPATITIS C UPDATE. ANTONIO SANCHEZ, M.D. DIVISION OF GASTROENTEROLOGY AND HEPATOLOGY UNIVERSITY OF IOWA HOSPITALS AND CLINICS. FINANCIAL DISCLOSURES I, Antonio Sanchez, disclose the following relationship(s) with manufacturers of health care products:

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HEPATITIS C UPDATE

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  1. HEPATITIS C UPDATE

  2. ANTONIO SANCHEZ, M.D. DIVISION OF GASTROENTEROLOGY AND HEPATOLOGY UNIVERSITY OF IOWA HOSPITALS AND CLINICS

  3. FINANCIAL DISCLOSURES I, Antonio Sanchez, disclose the following relationship(s) with manufacturers of health care products: Grant/Research Support: Merck, Ocera, Salix Advisory Board Panel – Bristol Myers

  4. Learning Objectives Discuss the epidemiology and natural history of chronic hepatitis C infection Review the diagnostic approach of hepatitis C Discuss current approved therapies for hepatitis C

  5. Clinical Scenario 53 y/o Caucasian man Chronic hepatitis C, diagnosed in 2000 Genotype 1b, treatment naïve HCV RNA 1,550,000 IU/ML Liver biopsy showed mild inflammation and moderate hepatic fibrosis in 2008 ( grade I, stage II)

  6. Clinical Scenario PAST MEDICAL HISTORY Hepatitis C, tx naïve Hypertension Depression, on fluoxetine 3 years ago No suicidal behavior

  7. Clinical Scenario SOCIAL HISTORY Lawyer ETOH: 1-2 beers/month Illicit drug use during 1990’s, in remission No smoking, no blood transfusions REVIEW OF SYSTEMS Fatigue Abdominal distention

  8. Clinical Scenario PHYSICAL EXAM 220 pounds – BMI 31 Abdomen- Palpable spleen. Mild ascitic fluid wave Spider angiomata on anterior chest wall LABS HB 15 g/dl, Platelet count is 90,000 Glucose 108 mg/dl ALT 150, AST 90, T BILI 2.3 , ALK PHOS 90, INR 1.4 Serum albumin 2.9 g/dl, serum creatinine 0.9 mg/dl serum sodium 137 Meq/L

  9. Clinical Scenario Risk factors for transmission - Illicit drug use during 1990’s, in remission Treatment naive Hx of depression, on treatment Works full time/ has good family support

  10. WHAT IS THE NEXT STEP IN MANAGEMENT ? 1. Recommend hepatitis C treatment 2. Repeat a liver biopsy 3. Defer hepatitis C treatment, he has decompensated cirrhosis

  11. HCV: Background 1-2% US population infected: 3 - 4 million More prevalent than HIV Men > Women -Patients not aware of infection Inversely proportional to socioeconomic status

  12. HCV worldwide EUROPE 9 M FAR EAST /ASIA 60 M USA & Canada 4 M EASTERN MEDITERRANEAN 21.3M Japan 2M SOUTH EAST ASIA 32.3 M AFRICA 32 M SOUTH AMERICA 10 M AUSTRALIA 0.2 M 170 Millions worldwide WHO, 1999

  13. Goals of Hepatitis C Treatment Eradicate hepatitis C virus ( predicted by SVR ) Prevent complications of liver disease Delay disease progression Prevent recurrence after liver transplant

  14. Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.

  15. Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.

  16. Transient Elastography . Source : www.fibroscan.com

  17. Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.

  18. Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.

  19. Predictors of Virologic Response

  20. A- Grade I B - Grade II C - DRESS Cacoub P, et al. Dermatological side effects of hepatitis C and its treatment: patient management in the era of direct-acting antivirals. J Hepatol. 2012 Feb;56(2):455-63.

  21. Drug Interactions – Boceprevir and Telaprevir

  22. QUEST-1: SVR by Subgroup 152/ 183 54/ 90 54/ 77 11/ 40 105/ 147 36/ 74 105/ 117 29/ 56 72/ 77 29/ 37 114/ 150 32/ 76 24/ 37 4/ 17 Fibrosis Genotype IL28B genotype I. Jacobson et al, Abstract 1425. EASL, April 2013

  23. Sofosbuvir + Simeprevir ± RBVCOSMOS Cohort 2- Gen 1, Naive and NR, F3-F4 100% 94% 93% 93% 93% 100 90 80 70 60 SVR12 rate (%) 50 40 30 20 10 N=15 N=80 N=27 N=14 N=24 0 All patients SOF+SIM+RBV SOF+SIM SOF+SIM+RBV SOF+SIM 12 weeks 24 weeks (Lawitz et al., Lancet 2014 Nov 15;384(9956):1756-65. )

  24. Sofosbuvir + Simeprevir ± RBVTARGET 2.0- Genotype 1, Real-life, US Without RBV With RBV 93% 92% 90% 89% 89% 87% 87% 86% 85% 86% 85% 83% 84% 82% Adjusted SVR4 Overall Cirrhosis No cirrhosis Genotype 1a Genotype 1b Naive Experienced (Jensen et al., AASLD 2014)

  25. Ledipasvir • Once-daily, oral, 90-mg NS5A inhibitor Sofosbuvir • Once-daily, oral, 400-mg NS5B inhibitor Sofosbuvir/Ledipasvir FDC (HARVONI) • Once-daily, oral, fixed-dose (90/400 mg) combination tablet • Single-tablet regimen for hepatitis C FDC, fixed-dose combination.

  26. www.hcvguidelines.org

  27. Drug Interactions – Harvoni and Viekira www.hcvguidelines.org

  28. SPECIAL POPULATIONS

  29. Sofosbuvir/Ledipasvir ± RBVGen 1 Rx-experienced patients withcompensatedcirrhosis 100% 98% 96% 100 90% 90 80 70 60 SVR12 rate (%) 50 40 30 20 10 0 12 wk No RBV 12 wk +RBV 24 wkNo RBV 24 wk+RBV (Bourlière et al., AASLD 2014)

  30. Sofosbuvir/Ledipasvir + RBVGenotype 1,4 decompensatedcirrhosis LDV/SOF + RBV 12 Weeks LDV/SOF + RBV 24 Weeks SVR12 rate (%) N=52 N=47 N=30 N=27 N=22 N=20 Overall CPT B CPT C 6 subjects excluded because received transplant while on study: (2 CPT B/24 week; 1 CPT 2/12 week; 3 CPT C/24 week 3 subjects had not reached SVR12 timepoint Source: Flamm SL, al. 65th AASLD. 2014: Abstract 239.

  31. Hepatitis C and Liver Transplantation Hepatitis C indication for liver transplant Virologicrecurrence after LT is universal – 100 % 30% ofHCV-infected recipients develop cirrhosis from hep C recurrenceby 5th postop year Proportion increasing withduration of follow-up

  32. Recurrent Hepatitis C after LT By 5th postoperative year 30% cirrhosis Accelerated courseof liver injury Cholestatic fibrosing hepatitis C Associated withhigh levels of viremia Subsequent rapid allograft failure Gane E. The natural history and outcome of liver transplantation in hepatitis C virus infected recipients. Liver Transpl 2003;9(Suppl 3):S28–34

  33. Watt K, Veldt B, Charlton M A Practical Guide to the Management of HCV Infection Following Liver Transplantation. American Journal of Transplantation 2009; 9: 1707–1713

  34. Hepatitis C Treatment - After Liver Transplantation Audrey C, et al. Safety and Efficacy of Protease Inhibitors to Treat Hepatitis C After Liver Transplantation: a Multicenter Experience. J Hepatol. 2013 Aug 29.

  35. Sofosbuvir/Ledipasvir + RBVSOLAR-1- Genotype 1, post-transplant HCV recurrence LDV/SOF + RBV 12 Weeks LDV/SOF + RBV 24 Weeks SVR12 (%) N=5 N=55 N=56 N=26 N=25 N=26 N=18 N=3 F0–F3 CPT A CPT B CPT C Source: Reddy KR, al. 65th AASLD. 2014: Abstract 8.

  36. HIV+HCV CoinfectionERADICATE Trial Sofosbuvir-Ledipasvir in GT1 Source: Osinusi A, et al. 65th AASLD. 2014: Abstract 84.

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