HCV UPDATE Cases from the Clinic

Transcription

1 HCV UPDATE Cases from the Clinic Ari L. Bunim, M.D. Director of Hepatology New York Hospital Queens, Division of Gastroenterology Assistant Professor of Clinical Medicine Weill Cornell Medical College

2 Disclosures Advisory Board: Abbvie, Gilead, Janssen Speaker s Bureau Abbvie All of the pakents in this presentakon are actually individuals whom I have treated in the past year for chronic hepakks C virus infeckon

3 Work up for Treatment History and Physical DuraKon of Disease and Method of infeckon Last Kme used any drugs Prior treatment history, prior response to therapy Prior liver biopsy Any decompensakon of liver disease Medical comorbidikes diabetes, fakgue, depression, cryoglobulinemia, HIV, HBV, prior malignancy, proteinuria, porphyria cutanea tarda

4 Work up for Treatment Laboratory Assessment Chem 7 and Liver tests CBC with differenkal HepaKKs B S Ag, S Ab, c IgG; HAV IgG, HIV AFP HCV RNA quanktakve (within past 6 months) HCV genotype Fibrosure or Fibroscan Urine Drug Screen

5 Patient 1 66 year- old male, contracted HCV from a dirty needle in the 1970 s He was never treated prior out of fear of interferon side effects Reports some fakgue possibly related to hepakks C Other pmh: neuropathy, mild emphysema, sleep apnea MedicaKons: urso forte 500 mg bid

6 Patient 1: Labs Creat 1 AST 26, ALT 29, T bili 0.6, alb 4.4 Wbc 6.4, hgb 13.3, plt 199 HCV: geno 1b, viral load (vl) 4,614,260 IU Fibrosure 0.64 (F3- bridging fibrosis)

7 PEARL- III 3D + RBV for 12 Weeks: GT1b Treatment- naïve Non- cirrhotic Patients 100 GT 1b SVR12 (%) / / D Regimen 3D Regimen + RBV 3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin Ferenci P et al. N Engl J Med 2014;370:

8 ION- 3 Ledipasvir- Sofosbuvir for 8 or 12 Weeks in Treatment- Naïve HCV GT 1 Patients with SVR 12 (%) / / /216 LDV-SOF LDV-SOF +RBV LDV-SOF 8-Week Regimen 12-Week Regimen Kowdley, K, et al. N Engl J Med. 2014;370:

9 ION- 3 Response to Ledipasvir- Sofosbuvir Based on 8 or 12 Weeks of Therapy 8 Weeks 12 Weeks N=215 N=216 Number of Responders at End of Treatment 100% (215/215) 100% (216/216) SVR 94% (202/215) 96% (206/216) Relapse 5% (11/215) 1% (3/216) Relapse According to Baseline HCV RNA HCV RNA 6 million IU/mL 2% (2/123) 2% (2/131) HCV RNA 6 million IU/mL 10% (9/92) 1% (1/85) Harvoni Prescribing InformaKon. Gilead Sciences

10 Patient 1: Outcome Treated with 8 week course of sofosbuvir/ ledipasvir By week 4, viral load undetectable, remained undetectable at week 8, and 12 weeks aoer complekng treatment (SVR 12) No side effects from treatment

11 Patient 2 51 yo M, h/o IVDA 1980 s Originally diagnosed with non- A, non- B hepakks, then HCV in 1990 s Failed treatment with IFN in early 1990 s No other medical problems, takes no medicakon

12 Patient 2: Labs Creat 0.74 AST 40, ALT 56, T bili 0.3, alb 4.7, glob 2.9 Wbc 5.8, hgb 15.7, plt 232 HCV geno 1a, vl 749,827 Hepascore 0.58 (f2- f4)

13 Sapphire II 3D + RBV non- cirrhotic GT 1 treatment experienced Patients (%) with SVR / / /123 All GT-1a GT-1b Zeuzem S, et al. N Engl J Med. 2014;370:

14 ION- 2 Ledipasvir/Sof ± RBV GT1 treatment experienced Patients (%) with SVR Without Cirrhosis With Cirrhosis /87 19/22 89/89 18/22 86/87 22/22 88/89 22/22 LDV-SOF LDV-SOF + RBV LDV-SOF LDV-SOF + RBV 12-Week Treatment 24-Week Treatment Afdhal N, et al. N Engl J Med. 2014;370:

15 Patient 2: Outcome Treated with Abbvie 3D regimen and ribavirin 600 bid (230 lbs=104 kg) for 12 weeks No side effects from therapy Hgb: > 12.3 during treatment, liver tests normalized HCV viral load undetectable at week 4 and end of treatment

16 Patient 3 67 yo M with alcohol and HCV cirrhosis with portal hypertension History of IVDA 1960 s s Had acute hepakks with jaundice in his 20 s No history of decompensakon of his liver disease (no ascites, encephalopathy, or variceal bleeding) Treatment naïve

17 Patient 3 PMH: HTN, COPD, Schatzki s ring, pulmonary embolus s/p parkal lobectomy in 1960 s, opioid dependence MedicaKons: FluKcasone/salmeterol inhaled, Kotropium, albuterol, montelukast, amlodipine, omeperazole, lactulose, methadone

18 Patient 3: Labs Creat 0.9 AST 88, ALT 56, alk phos 173, T bili 0.6, alb 3.7, glob 3.7 Wbc 6.1, hgb 13.3, plt 106, INR 1.1 HCV geno 1a, VL 976,670 IL- 28 TT genotype

19 Turquoise II 3D + RBV GT 1 cirrhosis Patients (%) with SVR D + RBV x 12 Weeks D + RBV x 24 Weeks / / / /121 67/68 50/51 Overall GT1a GT1b 3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin Poordad F, et al. N Engl J Med. 2014;370:

20 Turquoise II GT 1a SVR 12 based on prior treatment Patients (%) with SVR D + RBV x 12 Weeks D + RBV x 24 Weeks /64 52/56 14/15 13/13 11/11 10/10 40/50 39/42 No Prior Treatment Prior Relapser Partial Responder Null Responder Poordad F, et al. N Engl J Med. 2014;370:

21 ION- 1 Ledipasvir/Sof ± RBV GT 1 treatment naive Patients (%) with SVR Without Cirrhosis With Cirrhosis /179 32/33 178/178 33/33 181/182 31/32 179/179 36/36 LDV-SOF LDV-SOF + RBV LDV-SOF LDV-SOF + RBV 12-Week Treatment 24-Week Treatment Afdhal N, et al. N Engl J Med. 2014;370:

22 Patient 3 MedicaKon interackons 3D: salmeterol, flukcasone, amlodipine (dose modificakon) Sof/ledipasvir: omeprazole Gave pakent 12 weeks of sofosbuvir/ ledipasvir Held the omeprazole for 12 weeks

23 Patient 3: Outcome By week 4, HCV viral load was undetectable PaKent went on to have SVR weeks aoer complekon: albumin increased to 4.1, plt inc to 120

24 Patient 4 71 year old male born in HaiK No other known HCV risk factors Treated with telaprevir/peg IFN and ribavirin Therapy complicated by reknal hemorrhages, treatment conknued Had virologic breakthrough Other pmh HTN (takes losartan, HCTZ, and amlodipine)

25 Patient 4: Labs Creat 0.80 AST 112, ALT 92, alk phos 85, T bili 0.9, alb 3.5, glob 3.8 Wbc 4.85, hgb 12.3, plt 196 HCV geno 1a, vl 1,427,177 IU Fibrosure 0.84 (F4- cirrhosis)

26 ION- 2 Ledipasvir/Sof ± RBV GT1 treatment experienced Patients (%) with SVR Without Cirrhosis With Cirrhosis /87 19/22 89/89 18/22 86/87 22/22 88/89 22/22 LDV-SOF LDV-SOF + RBV LDV-SOF LDV-SOF + RBV 12-Week Treatment 24-Week Treatment Afdhal N, et al. N Engl J Med. 2014;370:

27 Patient 4: Outcome Last seen post treatment week 4 Has SVR 4, HCV undetectable since week 8 (wk 4 was < 15 IU detected) AST 25, alt 18, alk phos 86 Albumin 4.1, glob 3.5 Side effects: weakness 1 st two days of therapy and occasional headaches

28 Patient 5 58 yo Chinese male Infected with HCV from a kidney transplant in China in 2012 Other pmh includes DM, HTN, CKD MedicaKons Prednisone 5 mg qd, tacrolimus 3.5 mg bid, mycophenolate mofekl 500 bid, sitaglipkn, acarbose, insulin glargine, hydralazine, losartan, isosorbide mononitrate, calcitriol, neuronkn, aspirin, vitamin d

29 Patient 5: Labs Sodium 137, k 5.5, bun 49, creat 1.47 (GRF 58), gluc 186 AST 84, ALT 132, alk phos 94, T bili 0.4, alb 4.3, glob 2.2 Wbc 6.6, hgb 13.1, plt 180 HCV geno 3b, vl 3,810,628

30 VALENCE: Sofosbuvir + RBV for 24 Wks in GT3 IFN- Naive/Ineligible/Tx Failures SVR12 (%) Genotype Noncirrhotic Cirrhotic Noncirrhotic Cirrhotic Naive Zeuzem S, et al. AASLD Abstract /92 12/13 87/100 27/45 Treatment Experienced

31 Patient 5: Treatment Sofosbuvir 400 mg for 24 weeks Ribavirin what dose to use? Post kidney transplant with creat clr 58 Started 200 mg bid and increased to 400 mg bid aoer 2 weeks Week 6, hgb dec from 12 to 10 so reduced ribavirin to 400 qam, 200 qpm Week 12, hgb dec to 9; started epoekn alfa 40,000 unit sq qwk; cont riba 600/day Hgb remained in 9 s to end of treatment

32 Patient 5: Outcome Week 2: HCV viral load decreased to 36 IU Week 4: HCV viral load undetectable HCV viral load remained undetectable 12 weeks aoer therapy complekon (SVR 12)