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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
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: Grant/Research Support: Merck, Ocera, Salix Advisory Board Panel – Bristol Myers
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
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)
Clinical Scenario PAST MEDICAL HISTORY Hepatitis C, tx naïve Hypertension Depression, on fluoxetine 3 years ago No suicidal behavior
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
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
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
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
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
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
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
Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
Ghany, MG, Strader, DB, Thomas, DL, Seeff, LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
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.
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
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. )
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)
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.
Drug Interactions – Harvoni and Viekira www.hcvguidelines.org
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)
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.
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
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
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
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.
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.
HIV+HCV CoinfectionERADICATE Trial Sofosbuvir-Ledipasvir in GT1 Source: Osinusi A, et al. 65th AASLD. 2014: Abstract 84.