Presentation on theme: "How to optimize the treatment of HCV-4 patients? Nabil Antaki MD, FRCPC Aleppo, Syria Paris, January 30, 2012."— Presentation transcript:
How to optimize the treatment of HCV-4 patients? Nabil Antaki MD, FRCPC Aleppo, Syria Paris, January 30, 2012
Case Presentation A 39-year-old Syrian male was diagnosed 6 months ago with genotype 4 HCV infection discovered during screening before blood donation. He had no symptoms. BMI 27. No alcohol His physical examination revealed no abnormalities and his liver was not enlarged.
C Allele is Associated with SVR (HCV-1) Percentage SVR by Genotype of rs12979860 020406080100 C/C T/C T/T SVR Combined European Americans African Americans Hispanics n = 70 n = 14 n = 102 n = 91 n = 35 n = 433 n = 186 n = 559 n = 392 n = 30 n = 26 n = 336 P = 1.37 x 10 -28 vs T/T Ge D, et al. Nature. 2009;461:399-401.
IL28B in HCV-4 EthnicityCC (%)CT(%)TT(%)SVR(%) Stättermayer 1 n=102 98% Egyptian33.35412.757 De Nicola 2 n= 103 68% Egyptian 32% European 23631449 Asselah 3 n= 82 51%Egyptian 34% European 13%African 26.852.420.82 Antaki 4 n= 194 100% Caucasian30.455.21245 Worldwide distribution in Caucasian 385012 1. Stättermayer et al,Clin Gastro and Hepatol, 2011. 2. De Nicola et al. Hepatology 2011.3 Assellah et al. J Hepatol 2011. 4. Antaki et al. submitted article
SVR in HCV-4 stratified by IL28B genotype (rs12979860)
SVR in HCV-4 stratified by IL28B genotype (rs8099917)
Week 4 Following 4 weeks of HCV treatment, the patient presents with no anemia (Hb: 12.5 g/dL; HCT: 37.5%) and mild neutropenia (WBC: 2600 cells/mm3; ANC: 1600 cells/mm3). Neither condition requires dose reduction or addition of epoetin at this time. ALT and AST normal The patient's HCV RNA is now undetectable.
How would you manage his treatment at Week 4? A. The patient is a responder and treatment should continue for 48 weeks B. The patient achieved RVR and 24 weeks of therapy is recommended C. The patient achieved RVR but his rs12979860 genotype is CT. He should continue therapy for 48 weeks
Optimizing the response: RESPONSE GUIDED THERAPY The faster after initiating treatment, HCV RNA becomes undetectable, the higher is the SVR rate and shorter is the duration of treatment.
Impact of RVR RVR, EVR as a guide for 24 w, 36 w or 48w 358 patients Adaptive N=308 Fixed N=50 24 w RVR N=69 36 w cEVR N=79 48 w pEVR N=160 48 w Kamal et al, Hepatology. 2007
EOT and SVR rates in HCV-G4 patients with RVR & EVR Kamal et al, Hepatology. 2007 % Response
RVR in HCV - 4 66 HCV-4 patients, Peg IFN α 2a and RBV RVR achieved in 45% 26 RVR patients (86.7%) achieved an SVR when treated for 24 weeks only No relation: with baseline viral load with dose of RBV Ferenci P, et al. Gastroenterol. 2008
SVR rates in HCV-G4 patients with RVR & EVR Ferenci P, et al. Gastroenterol. 2008 0 20 40 60 80 100 ≤ 400,000400,000 - 800,000 > 800,000 SVR in Patients Achieving RVR (%) All Genotype 1 F0-F2F3-F4 By Baseline HCV RNA (IU/mL) By METAVIR Fibrosis Stage Genotype 4 86.5 90.0 81.3 82.2 85.7 80.6 70.8 83.3 66.7 81.5 88.5 79.6 75.0 n/N =61/7452/649/1037/4525/3112/1417/2412/185/697/11974/9323/2618/243/415/20
Impact of RVR and IL28B on SVR RVR achieved in 25.4 to 41% of patients. In De Nicola study: RVR 34% SVR 80% (CC100%, CT/TT 70%, p= 0.06) No RVR 66% SVR 32% (CC 75%, CT/TT 23%, p= 0.001)
Pre-treatment predictors of response Univariate analysis: 1.Fibrosis (yes 1, 2, 4; no 3) 2.Ethnicity ( yes 2, no 3) 3.IL28B CC 4.Viral load
On-treatment predictors of response Univariate analysis: 1.Fibrosis (yes 1, 2, 4 no 3) 2.Ethnicity ( yes 2, no 3) 3.IL28B CC 4.Viral load 5.RVR
predictors of response Multivariate analysis: 1.Fibrosis 2.IL28B CC 3.RVR : the strongest predictor of SVR
W 24 At Week 24 of HCV therapy, the patient is tolerating treatment and remains fully compliant. The patient's liver enzymes are normal (AST: 23 IU/mL; ALT: 19 IU/mL). His current HCV RNA is undetectable
What would you do? A. The patient should continue his current regimen through 48 weeks B. The patient should discontinue treatment and be monitored for the next 6 months to determine whether he has achieved SVR
What would you do? The patient has no advanced fibrosis His pre-treatment viral load was 900,000 IU but this is not a poor predictive factor of response if he achieves RVR Although his IL28B genotype is CT, he achieved RVR (no statistical significance in SVR between CC and CT/TT in RVR patients) Treatment was stopped at W 24
W 24 after ETR The patient returns 6 months after stopping treatment to determine whether he has achieved SVR. His liver enzymes remain within the normal range and HCV RNA remains negative, indicating that he has achieved SVR.