Hepatitis C: The New World of Treatment

Transcription

1 Hepatitis C: The New World of Treatment Aban 1395, NIOC Hospital Shahin Merat, M.D. Professor of Medicine Digestive Disease Research Institute Tehran University of Medical Sciences 1

2 Drugs NS5B polymerase inhibitors: Sofosbuvir (SOF), nucleotide analog Dasabuvir (DBV), non-nucleoside analog NS5A protein inhibitors: Velpatasvir (VEL) Daclatasvir (DCV) Ledipasvir (LDV) Elbasvir (EBR) Ombitasvir (OMB) NS3/4A protease inhibitor (not for Child B or C) Simeprevir (SMV) Paritaprevir-Ritanovir (PRV-r) Grazoprevir (GZR) 2

3 Interferon-Free Regimens A polymerase (NS5B) inhibitor Sofosbuvir (SOF) Dasabuvir (DBV) + One or two NS3/4/5A protease inhibitors Ledipasvir (LDV) Daclatasvir (DCV) Velpatasvir (VEL) Simeprevir (SMV) Ombitasvir (OMB) Paritaprevir-Ritanovir (PRV-r) Elbasvir (EBR) Grazoprevir (GZR) Maybe ribavirin (RBV) 1000 mg if < 75 kg 1200 mg if > 75 kg 3

4 Brands Pan genotypic: Epclusa: SOF 400mg + VEL 100mg, Gilead Sovodak: SOF 400mg + DCV 60mg, Abeidi Genotype specific: Harvoni: SOF 400mg + LDV 90mg, Gilead Zepatier, EBR 50 mg + GZR 100 mg, Merck Viekira Pak: OMB/PRV-r/DBV, Abbvie Two OMB/PRV-r on mornings, Twice daily DBV 4

5 Grouping HCV Patients Cirrhosis Non cirrhotics Compensated cirrhosis Child A Decompensated cirrhosis Child B and C up to 12, MELD up to 20 Very decompensated cirrhosis Child >12, MELD > 20 Genotype 1a/1b/2/3/4/5/6 Previous treatment failure with DAAs No/Yes 5

6 Pangenotype Treatments 6

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8 Epclusa, SOF/VEL, Giliad All genotypes (including Child A cirrhosis) SOF/VEL x 12 wk All genotypes + advanced cirrhosis SOF/VEL/RBV x 12 wk SOF/VEL x 24 wk Not indicated for egfr<30 ml/min (?) Not recommended for Child>12 or MELD>20 (?) 8

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10 Sovodak, SOF/DCV, Abeidi Branded (not a copy) Pharmacokinetic studies (better than SOF and DCV given separately) Clinical trials Only available in Iran All genotypes SOF/DCV x 12 wk All genotypes + cirrhosis SOF/DCV/RBV x 12 wk SOF/DCV x 24 wk Choice for HIV coinfection Not indicated for egfr<30 ml/min (?) Not recommended for Child>12 or MELD>20 (?) 10

11 Genotype Specific Treatments 11

12 Cautions: You should have reliable genotype testing Watch out for mixed infections Common in drug addicts (up to 40%) The lab may only report the dominant genotype I suggest you avoid these treatments 12

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14 Harvoni, Sof/Ledipasvir, Gilead Genotype 1 and 4 SOF/LDV x 12 wk Genotype 1 and 4 + cirrhosis SOF/LDV/RBV x 12 wk SOF/LDV x 24 wk Not indicated for genotypes 2 and 3 Not indicated for egfr<30 ml/min Not recommended for Child>12 or MELD>20 (?) 14

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16 Zepatier, EBR/GZR, Merck Genotype 1 If 1a check baseline NS5A polymorphisms for RAVs EBR/GZR x weeks, with or without RBV Genotype 4 EBR/GZR x 12 weeks EBR/GZR/RBV x 16 weeks If previous PEG/RBV failure, 16 weeks Not indicated for genotypes 2 and 3 Not recommended for Child B or C Can be used in renal failure 16

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18 Viekira-Pak, Abbvie Paritaprevir-Ritanovir (PRV-r), Ombitasvir (OMB) Dasabuvir (DBV) Frequently referred to as PrOD or 3D Genotype 1b Viekira-Pak x 12 wk (4 pills a day) Genotype 1a and 4 Viekira-Pak + RBV x 12 wk (9 or 10 pills a day) No DBV for genotype 4 Not indicated for genotypes 2 and 3 Not indicated for Child s B and C Plenty of interactions Can be used in renal failure (not ribavirin though) 18

19 Non-Branded Drugs Copies India Egypt Pakistan Bangladesh Smuggled (authenticity, storing conditions, expiry date ) Poor blood level (daclatasvir) Poor experience (Iraq: 50% SVR) 19

20 Drugs No Longer Indicated Boceprevir Telaprevir Peg-Interferon Simeprevir (?) SOF/RBV Very soon PrOD Harvoni Zepatier 20

21 Important Contraindications SOF egfr <30 ml/min (?) LDV/DCV/VEL Amiodarone: Contraindicated Important drugs with mild to moderate interaction: (Not contraindicated, just caution. Might need dose adjustment) Digoxin Clopidogrel (Plavix, Osvix) Citalopram Statins (atorvastatin, lovastatin ) Calcium channel blockers (Amlodipine, Nifidipine, Diltiazem) Anticonvulsants Azole antifungals (fluconazole, ketoconazole ) Glucocorticoids Macrolides (azithromycin, clarithromycin, erythromycin ) Rifampin Antiretrovirals (efavirenz, atazanavir ) 21

22 Follow-Up Minimum: Check HCV PCR (qualitative) 12 weeks after end of treatment Determines SVR Recommended: Check viral count at week 4, and 12 weeks after end of treatment Unlike PEG/RBV, slow response does not indicate poor SVR Positive counts in early weeks might indicate lack of compliance Viral count is almost always negative by the end of week 1; some patients may find this encouraging and have better compliance Check creatinine, AST, ALT at weeks 4, 8, 12, and 12 weeks after end of treatment If also using ribavirin Check Hgb at weeks 2, 4, 8, 12 22

23 Important Notes Coadministration with Amiodarone Contraindicated, even within 3 months of use Coadministration with Digoxin Caution: may increase blood level of digoxin and cause toxicity Caution in patients with severe bradycardia May need to admit and observe for first 48 hours Pregnancy/Lactation Not recommended (no data) Renal failure RBV not recommended or use very low doses with extreme caution Instead, use the 24 week version for treating cirrhosis egfr >30 ml/min No dose adjustment for SOF/DCV egfr <30 ml/min SOF/DCV not recommended although it has been successfully used with same dosage refer to expert 23

24 Notes on Chirrotic Patients If too advanced (Child score > 12 or MELD > 20) treatment might not help, even if successful Even after successful treatment, risk of HCC remains high continue HCC surveillance Watch the renal function if advanced cirrhosis 24

25 Treatment Notes: No dosage adjustment for: Previous failure with PEG/RBV Concomitant immune suppression or autoimmune disease HIV coinfection not on ART HIV coinfection on ART Might need some adjustment of HIV medicine OR Might need to use Sovodak 400/90 (eg with efavirenz) or Sovodak 400/30 (eg with atazanavir) Refer to expert if: Previous failure with daclatasvir- or ledipasvir-containing regimens Cirrhosis with MELD score > 20 or Child s score >12 Renal failure (egfr <30 ml/min) 25

26 HBV coinfection Recent concerns about reactivation of HBV during treatment with DAAs For all patients check: HBs Ag, anti-hbc antibody, anti-hbs antibody HBs Ag positive: Consider starting tenofovir or entecavir Especially if HBV DNA is detected HBs Ag negative: HBs Ag negative and anti-hbc antibody positive: Check HBV DNA at weeks 4, 8 and 12 treat if appropriate HBs Ag negative and anti HBs antibody negative Vaccinate for HBV (treatment of HCV can continue) 26

27 Problem Patients Evidence not conclusive yet Renal Failure (egfr < 30 ml/min, hemodialysis) ELB/GZR (genotypes 1 and 4), PrOD (genotype 1b) Growing evidence that SOF/LDV (genotypes 1 and 4) or SOF/DCV (all genotypes) can be used Advanced cirrhosis (Childs >12, MELD>20) Treatment might not help, need OLT SOF/LDV x 24 week (genotypes 1 and 4) SOF/DCV x 24 week (all genotypes) SOF/VEL x 24 week (all genotypes) Non responders to previous DAA-containing treatment Determine RAV (?) SOF/DCV/RBV x 24 weeks (all genotypes) SOF/VEL/RBV x 24 weeks (all genotypes) Wait for new drugs 27

28 What we do in DDRI Under current Evidence All patients with LSM < 12 Kpa (non cirrhotics) SOF/DCV x 12 weeks All patients with LSM 12 Kpa (compensated cirrhosis) SOF/DCV/RBV x 12 weeks SOF/DCV x 24 weeks if cannot tolerate RBV (eg thalassemia) Decompensated cirrhosis (Child s B and C, including MELD > 20) SOF/DCV x 24 weeks + close follow-up Renal failure SOF/DCV x 12 weeks with weekly follow-up Renal failure and cirrhosis SOF/DCV x 24 weeks with weekly follow-up Failures of previous DAA-containing regimens SOF/DCV/RBV x 24 weeks 28

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