HCV Eradication with Direct Acting Antivirals (Daas)?

HCV eradication with direct acting antivirals (DAAs)?

Massimo LEVRERO

Dept. of Internal Medicine – DMISM Sapienza University, Rome, Italy [email protected] HCV replicative cycle and main targets for DAAs

NS5ANS5A ...asvir...asvir DaclatasvirDaclatasvir LedipasvirLedipasvir OmbitasvirOmbitasvir PPI-688PPI-688 ElbasvirElbasvir

PIPI POLPOL NNINNI POLPOL ...previ...previ ...buvir...buvir rSimeprevirrSimeprevir AsunaprevirAsunaprevir SofosbuvirSofosbuvir ParitaprevirParitaprevir DasabuvirDasabuvir /r/r BeclabuvirBeclabuvir ElbasvirElbasvir GS-9669GS-9669

Modified from: Manns & Cornberg, Lancet Infectious Diseases 2013 DAAs currently approved 2013 Triple therapy with Sofosbuvir Simeprevir Daclatasvir PEG IFN and ribavirin Nucleotide SOF and ribavirin, no Protease inh. NS5A inh. IFN polymerase inh. Gt 1, 4 Gt 1, 3, 4, 5, 6 All Gts (±3) Off-label combination of two DAAs ± ribavirin

2014 Dasabuvir

Non-Nuc Gt 1-(4) Polymerase Gt 1, 3, 4 Inh. Ledipasvir Sofosbuvir Paritaprevir/R Ombitasvir NS5A inh Nucleotide Protease inh./ NS5A inh. Ritonavir polymerase inh.

Fixed dose combination of Fixed dose combination of three DAAs ± ribavirin two DAAs ± ribavirin. DAAs currently approved 2013 Triple therapy with Sofosbuvir Simeprevir Daclatasvir PEG IFN and ribavirin Nucleotide SOF and ribavirin, no Protease inh. NS5A inh. IFN polymerase inh.- Short therapy (8-12 wks), Gt 1, 4 Gt 1, 3, 4, 5, 6 All Gts (±3) cirrhotics may need 24 wks Off-label combination of two DAAs ± ribavirin - >90% SVR 2014 - Few pills, no IFN Dasabuvir- No RBV, but not for all pts Non-Nuc- Not all regimens suitable for Gt 1-(4) Polymerase Gt 1, 3, 4 Inh. decompensated pts Ledipasvir Sofosbuvir Paritaprevir/R Ombitasvir NS5A inh Nucleotide Protease inh./ NS5A inh. Ritonavir polymerase inh.

Fixed dose combination of Fixed dose combination of three DAAs ± ribavirin two DAAs ± ribavirin. Efficacy evaluation of different DAA-containing regimens

• SOFOSBUVIR – plus Ribavirin for HCV-2 (12 wks) SVR 80-95% – plus PEG-IFN / RBV for HCV-1, HCV-3, HCV-4 naive (12 wks) SVR 80- 92% – plus Ribavirin (24 wks) for HCV-1 SVR 50%, for HCV-3, HCV-4 SVR 70- 80% – plus Simeprevir (12 wks) for HCV-1 and HCV-4 SVR > 90-95% • SIMEPREVIR – plus PEG-IFN/RBV for HCV-1 and HCV-4 ● P/R naive SVR 75-80% ● P/R experienced SVR 50-85% – plus Sofosbuvir (12 wks) for HCV-1 and HCV-4 SVR > 90-95% • DACLATASVIR – plus Sofosbuvir (12-24 wks) HCV-1 and HCV-4 SVR > 90-95

Data on patients with F0 to F4 fibrosis (under-represented) and compensated disease Efficacy evaluation of different DAA-containing regimens

• SOFOSBUVIR – plus Ribavirin for HCV-2 (12 wks) SVR 80-95% – plus PEG-IFN / RBV for HCV-1, HCV-3, HCV-4 naive (12 wks) SVR 80- 92% – plus Ribavirin (24 wks) for HCV-1er SVRall 50%, for HCV-3, HCV-4 SVR 70- ove s 80% an TT etter th – rm be plus Simeprevir (12 wks) for HCV-1 p ander fHCV-4orm SVR > 90-95% ombos • SIMEPREVIR label co ee off la –IFplusN fr PEG-IFN/RBVe for HCV-1 and HCV-4 ● P/R naive SVR 75-80% ● P/R experienced SVR 50-85% – plus Sofosbuvir (12 wks) for HCV-1 and HCV-4 SVR > 90-95% • DACLATASVIR – plus Sofosbuvir (12-24 wks) HCV-1 and HCV-4 SVR > 90-95

Data on patients with F0 to F4 fibrosis (under-represented) and compensated disease Large body of evidence shows IFN-free therapy new combinations are highly effective in GT 1 Summary of 8 N Engl J Med studies on IFN-free therapy in GT 1 published in 2014

Trial Regimen ION-1 LDV/SOF ± RBV 96 ION-2 LDV/SOF ± RBV

ION-3 LDV/SOF ± RBV ) % (

SAPPHIRE-I PAR/r/OMB + DAS + RBV R V

SAPPHIRE-II PAR/r/OMB + DAS + RBV S PEARL-III PAR/r/OMB + DAS ± RBV PEARL-IV PAR/r/OMB + DAS ± RBV 3672/ 3826 TURQUOISE-II PAR/r/OMB + DAS + RBV

Short, well-tolerated treatment regimens 8–24 weeks NB: Summary of 8 heterogeneous Included treatment-naïve and -experienced patients Phase 3 studies and cirrhotics LDV, PAR/r, OMB and DAS are investigational agents and not approved for use in HCV by the EMA/FDA Liang J, Ghany MG. N Engl J Med 2014;370:2043–7DAS: dasabuvir; LDV: ledipasvir; OMB: ombitasvir; PAR: paritaprevir; r: ritonavir Large body of evidence shows IFN-free therapy new combinations are highly effective in GT 1 Summary of 8 N Engl J Med studies on IFN-free therapy in GT 1 published in 2014 100 96 Trial Regimen ION-1 LDV/SOF ± RBV VIR ? 80 ION-2 LDV/SOF ± RBVFECTO

R ) ION-3 LDV/SOFPER ± RBV Feld 60 J. F % © (

SAPPHIRE-I PAR/r/OMB + DAS + RBV R

V 40 SAPPHIRE-II PAR/r/OMB + DAS + RBV S PEARL-III PAR/r/OMB + DAS ± RBV 20 PEARL-IV PAR/r/OMB + DAS ± RBV 3672/ 3826 TURQUOISE-II PAR/r/OMB + DAS + RBV 0

Short, well-tolerated treatment regimens 8–24 weeks NB: Summary of 8 heterogeneous Included treatment-naïve and -experienced patients Phase 3 studies and cirrhotics LDV, PAR/r, OMB and DAS are investigational agents and not approved for use in HCV by the EMA/FDA Liang J, Ghany MG. N Engl J Med 2014;370:2043–7DAS: dasabuvir; LDV: ledipasvir; OMB: ombitasvir; PAR: paritaprevir; r: ritonavir Further DAA combos available within 2016-17 Fixed dose combination of two or three DAAs

Pangenotipic (±) Beclabuvir Polymerase Grazoprevir Pangenotipi Inh. (MK 5172) Elbasvir c (MK 8742) Daclatasvir 2nd generation 2nd generation Asunaprevir IDX 21437 protease inh. NS5A inh Protease inh. NS5A inh. or 459 Polymerase Inh.

Pangenotipi ACH-3422 c Polymerase GS 5816 Pangenotipic (?) Inh.

Sofosbuvir 2nd generation Sovaprevir ACH-3102 NS5A inh. (ACH-1625 Nucleotide Protease inh. NS5A inh. polymerase inh. Further DAA combos available within 2016-17 Fixed dose combination of two or three DAAs

Pangenotipi ACH-3422 c Polymerase GS 5816 Pangenotipic (?) Inh.

Pangenotipic (±) Beclabuvir Polymerase Grazoprevir Samatasvir Pangenotipi Inh. (MK 5172) Elbasvir(IDX) c 2nd(MK generation 8742) Daclatasvir 2nd generation 2nd generation Asunaprevir IDX 21437 NS5A inh protease inh. NS5A inh Protease inh. NS5A inh. or 459 Polymerase- Ultra-short therapy (4-8 wks) Inh.- >95% SVR for all pts. - Pangenotypic - One-pill regimen, no RBV Pangenotipi- Suitable for all disease stagesACH-3422 c Polymerase GS 5816 Pangenotipic (?) Inh.

Sofosbuvir 2nd generation Sovaprevir ACH-3102 NS5A inh. (ACH-1625 Nucleotide Protease inh. NS5A inh. polymerase inh. Factors impacting response to HCV treatment: before 2015

Viral factors Host factors

Baseline viral load Age Age Gender Race

HCV genotype Prior Genetics response to (IL28B, IP10, etc) HIV/HCV treatment HIV/HCV Cirrhosis co-infection Transplant Obesity DAA baseline Hepatic resistance Hepatic decompensation Diabetes/insulin resistance HBV/HCV co-infection Pharmacokinetics and DDIs Factors impacting response to HCV treatment: after 2015

Viral factors Host factors

HCV Cirrhosis genotype

Post OLT status Post- treatment DAA RAVs

Pharmacokinetics and DDIs Efficacy of SOF + SMV ± RBV in real-world settings

HCV-TARGET TRIO Prospective Observational Cohort Study: Prospective Observational Cohort Study: 2330 pts (51 US sites) 955 pts enrolled SOF + PR : 384 SOF + PR SOF + RBV : 667 SOF + RBV SOF + SMV : 784 SOF + SMV + RBV SOF + SMV + RBV : 228

GT1 GT1a GT1b SOF + SMV SOF + SMV + 100 RBV 89 92 100 86 87 87 86 83 85 80 80 80 )

% 60 (

) 60 2 % 1 (

R 40 4 V R S

V 40 S 20 20 n = 132 85 36 0 0 All Pts Tx-Naive Tx-Exp’d Tx-naive SMV + SOF ± Pts Pts RBV 1. Jensen DM, et al. AASLD 2014. Abstract 45. 2. 2. Dieterich D, et al. AASLD 2014. Abstract 46. HCV TARGET: analysis by subgroups

Adjusted* SVR4, % Genotype 1 Patients Genotype 1 Patients Treated With SOF + SMV + Treated With SOF + SMV RBV Overall 87 86 Treatment history •Naive 87 89 •Experienced 86 85 Genotype •1a 82 84 •1b 93 92 Cirrhosis status •Noncirrhotic 90 89 •Cirrhotic 83 85 Genotype and cirrhosis status •Genotype 1a noncirrhotic 87 88 •Genotype 1a cirrhotic 80 82 *Adjusted•Genotype for cirrhosis 1b status, noncirrhotic genotype, previous treatment experience,94 previous decompensation, and93 previous triple therapy failure •Genotype 1b cirrhotic 88 87 Jensen DM, abs #45 HCV TARGET: analysis by subgroups

Adjusted* SVR4, % Genotype 1 Patients Genotype 1 Patients Treated With SOF + SMV + Treated With SOF + SMV RBV Overall 87 86 Treatment history •Naive 87 89 •Experienced e86eded 85 not ne Genotype RBV n GT1a •1a 82 r than 84 s better •1b rforms 93 92 1b per Cirrhosis statusGT •Noncirrhotic 90 89 •Cirrhotic 83 85 Genotype and cirrhosis status •Genotype 1a noncirrhotic 87 88 •Genotype 1a cirrhotic 80 82 *Adjusted•Genotype for cirrhosis 1b status, noncirrhotic genotype, previous treatment experience,94 previous decompensation, and93 previous triple therapy failure •Genotype 1b cirrhotic 88 87 Jensen DM, abs #45 PTV/RTV/OMV + DSV + RBV in GT1

PEARL-IV1 PEARL-III1

RBV-free + RBV

* 97 99,5 ) ) % % (

(

2 2 1 1 R R V V

90 S

S 99

185/ 97/ 207/ 209/ 205 100 209 210

GT 1a GT 1b Treatment-naïve Treatment-naïve

*RBV-free arm did not meet non-inferiority vs RBV-containing arm; Ombitasvir, paritaprevir, RTV + dasabuvir are not approved Ferenci P, et al. N Engl J Med 2014;370:1983–92. for use in HCV by the EMA; EMA: European Medicines Agency; RTV: ritonavir PTV/RTV/OMV + DSV + RBV in GT1

PEARL-IV1 PEARL-III1

RBV-free + RBV

* 97 T1a than GT 99,5 better t forms b 1b perf T1 ) ) GT d % ed

% de ( ed

( ee e n be 2 2 ht b igh 1 1 mig V R R RB R V V

90 S

S 99

185/ 97/ 207/ 209/ 205 100 209 210

GT 1a GT 1b Treatment-naïve Treatment-naïve

12 wks 24 wks

94.2 95.9 96.6 100 94.4 100 95.2 95.0 98.5 100 94.3 97.1 94.7 97.1 93.9 100 86.7 88.6 80.5

80 ) % (

60 2 1 R

V 40 S

20 81/ 71/ 28/ 23/ 17/ 13/ 65/ 59/ 124/115/ 67/ 51/ 33/ 33/ 125/102/ 33/ 31/ n/N = 86 74 29 23 18 13 75 62 140 121 68 51 35 34 132 105 41 33 0 Naive Relapser Partial Null GT1a GT1b CC CT TT Responder Responder HCV Subtype IL28B Genotype Factor P Value IL28B TT genotype .021 Previous null response to pegIFN/RBV .038 GT1a HCV .046

Fried MW, et al. AASLD 2014. Abstract 81. HCV Gt 3: still a difficult genotype SOF + RBV x 24 weeks (VALENCE) LDV/SOF + RBV x 12 weeks (ELECTRON-2) SOF + DCV x 12 weeks (ALLY-3)

100 100 95 97 97 94 92 89 83 87 83 73 % 69

, 62

2 58 1 R V S

87/92 21/21 73/75 38/39 12/13 5/5 11/19 85/98 25/28 32/34 10/12 29/47 16/22 9/13 10/12 SOF + PEG-IFN + RBV x 12 weeks (TN: PROTON/ELECTRON Treatment-experienced Non-cirrhotic LDV/SOF + RBV for 12 weeks and SOF + DCV for 12 weeks are not EMA-recommended treatment regimens for GT 3 Zeuzem S, et al. N Engl J Med 2014;370:1604-14; Gane E, et al. EASL 2014; Oral #6; Gane E et al. NEJM 2013;368:34–44; Lawitz E et al. Lancet Infect Dis 2013;13:401–408; Gane E et al. AASLD 2014, Poster #LB-11; Lawitz E et al. AASLD 2013, Oral #LB-4; Nelson M et al. AASLD 2014, Oral #LB-3. HCV GT 3: still a difficult genotype in cirrhotic patients

SOF + RBV x 24 weeks (VALENCE) LDV/SOF + RBV x 12 weeks (ELECTRON-2) SOF + DCV x 12 weeks (ALLY-3) aying = disma 100 97 97 100 wks) = 100 95 92 V (12 w 94 + DCV 87 89 SOF + 83 83 s) and 80 (24 wk ? 73 + RBV ( ded ? 69 SOF + need 62 % S 58 BV RB , 60 -IFN + 2 PEG-I 1 OF + P ated R S a 40 S evalu V to be e S V to V + RBV 20 DCV SOF + 87/92 21/21 73/75 38/39 12/13 5/5 11/19 85/98 25/28 32/34 10/12 29/47 16/22 9/13 10/12 0 SOF + PEG-IFN + RBV x 12 weeks (TN: PROTON/ELECTRON Treatment-experienced Non-cirrhotic LDV/SOF + RBV for 12 weeks and SOF + DCV for 12 weeks are not EMA-recommended treatment regimens for GT 3 Zeuzem S, et al. N Engl J Med 2014;370:1604-14; Gane E, et al. EASL 2014; Oral #6; Gane E et al. NEJM 2013;368:34–44; Lawitz E et al. Lancet Infect Dis 2013;13:401–408; Gane E et al. AASLD 2014, Poster #LB-11; Lawitz E et al. AASLD 2013, Oral #LB-4; Nelson M et al. AASLD 2014, Oral #LB-3. LDV/SOF efficacy in compensated Gt1 cirrhosis

12 wks of LDV/SOF 24 wks of LDV/SOF 12 wks of LDV/SOF + RBV 24 wks of LDV/SOF + RBV

100 100 100 100 96 98 96 98 97 96 98 92 90 80 ) %

( 60

2 1 R

V 40 S

20 n = 118 204 133 58 47 45 33 36 71 159 100 22 0 Total Treatment Naive Treatment Experienced Bourlière M, et al. AASLD 2014. Abstract 82. LDV/SOF efficacy in compensated Gt1 cirrhosis ilures) g PI fail cluding 12 wks of LDV/SOF ts (inc 24 wks of LDV/SOF hotic pt 12 wks1 c ofir rLDV/SOFh + RBV 24 wks of LDV/SOF + RBV TE GT in V ng RBV ion 98 100 addin 98 100 uratio 98 100 100 96 a 96 m97ent du 96 92 g treatm 90 tending 80 or ext %) to ≥96% ) (90% % VR ( 60 SV ses 2 creas 1 inc R

V 40 S

20 n = 118 204 133 58 47 45 33 36 71 159 100 22 0 Total Treatment Naive Treatment Experienced Bourlière M, et al. AASLD 2014. Abstract 82. 2014: HCV guidelines, recommendations & anti HCV drugs approval by International agencies

EMA APPROVAL ViekirakViekirak SovaldiSovaldi OlysioOlysio DaklinzaDaklinza HarvoniHarvoni ExvieraExviera

EASL WHO EACS guideline guideline guideline s s s

Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec

AASLD AASLD EASL RECOM EASL RECOM RECOM MENDA RECOM MENDA MENDA TIONS MENDA TIONS TIONS 1 TIONS 2

FDA APPROVAL ViekiraViekira SovaldiSovaldi && OlysioOlysio HarvoniHarvoni PackPack EASL AND AASLD-IDSA RECOMMENDATIONS

Indications to All treatment-naïve and Treatment is treatment -experienced patients with recommended for patients compensated disease due to HCV with chronic HCV infection should be considered for therapy (IA) (A1) IFN free DAA will expand the pool of treatable patients

Mild Severe Decomp HCV chronic disease spectrum Currently treated IFN free DAA will expand the pool of treatable patients

Mild Severe Decomp HCV chronic disease spectrum Currently treated

- By enrolling new patients at the extreme of the spectrum - By enforcing need for mass screening for HCV Factors affecting treatment choice

Urgency of Disease Probability Inability to HCV stage/type of SVR tolerate P/R clearance

Expectancy for newer regimens

HCV related Costs and Patient’s extrahepatic availability of Comorbidity preference disease drug (s) Factors affecting treatment choice

Urgency of Disease Probability Inability to HCV of stage/type of SVR tolerateility P/R clearanceilabi nd ava sts an Expectancy Co (s) for newer drug regimens HCV related Costs and Patient’s extrahepatic availability of Comorbidity preference disease drug (s) Factors affecting treatment choice of lability d avail an Urgency of Diseases ts Probability Inability to Co HCVs ) stage/type of SVR ug ( tolerate P/R dru clearance n HCV act o Expectancy l imp for newer will regimens ication HCV related Costs and ad er Patient’s extrahepatic availability of Comorbidity preference disease drug (s) Current EU market prices for available DAAs (for 12 weeks of treatment)

Sofosbuvir * Simeprevir * Daclatasvir * € 38-60,000 € 18-40,000 € 24-30,000 Triple therapy with Nucleotide Protease inh. NS5A inh. DAA, PEG IFN and polymerase inh. ribavirin Gt 1, 4 Gt 1, 3, 4, 5, 6 All Gts (±3) € 24-66,000

SOF (24 wk) and ribavirin, no IFN € 76-120,000 Multigenotipic Ledipasvir Off-label combination Sofosbuvir € 48,000 of two DAAs ± ribavirin NS5A inh Nucleotide € 42-100,000 polymerase inh. FDC of two DAAs Fixed dose combination of € 48,000 two DAAs ± ribavirin. Evaluation of Health Outcomes from LDV/SOF Treatment of Patients with Early vs. Advanced Liver Fibrosis

Initiating LDV/SOF treatment at F0-F1 and F2 rather than F3-F4 reduces lifetime costs of treatment, and has a lower cost per SVR

COST PER SVR LIFETIME COSTS

95000 105000 90878 99376

95000 85000 82152 82399 85128 85000 83546

75000 75000

Initiating LDV / SOF treatment in F0-F1 or F2 as opposed to F3-F4 results in substantial savings per successfully treated patient (cost per SVR) and lifetime costs.

Ahmed A, AASLD, 2014, #1751 EASL recommendations 2014

In principle, all patients with chronic HCV infection are candidate to treatment,but in a situation of limited availability: • F3-F4: Priority • F2: Reasonable • F0-F1: Debatable

Informed deferral of treatment for patients with mild disease

EASL Recommendations on Treatment of Hepatitis C, April 2014 EASL recommendations 2014

In principle, all patients with chronic HCV infection are candidate to brosis 3/F4 Fib treatment,but in a situation of limitedWith F3 availability: nts W t Patien atment • F3-F4: Priority CV Trea y for HC Priority • F2: Reasonableghest P ave Hig • F0-F1:Ha Debatable

Informed deferral of treatment for patients with mild disease

EASL Recommendations on Treatment of Hepatitis C, April 2014 Chronic HCV infection: an extrapolation of the Italian status

0.9-1.2 million infected

15% detected (∼150,000)

5% referred for care (∼ 50,000)

260.000 infected to be treated? 2% to 3% ● 15.000 - 20.000* urgent treated (∼ 30,000) ● 60.000* within 18 months

* Documento GdL Epatite C AIFA-MinSal-ISS-SIMIT-AISF-EPAC-CNT Aprile 2014 Chronic HCV infection: an extrapolation of the Italian status

0.9-1.2 million infected 3- 15% detectedin 2013 ed TT in receiv(e∼150,000) have r atients free Gt 1 pa for IFN 4,000 G sing f 5% referred for than 4 arehou Less 14: wa care (∼ 50,000)

260.000 infected to be treated? 2% to 3% ● 15.000 - 20.000* urgent treated (∼ 30,000) ● 60.000* within 18 months

* Documento GdL Epatite C AIFA-MinSal-ISS-SIMIT-AISF-EPAC-CNT Aprile 2014 Chronic HCV infection: an extrapolation of the Italian status

0.9-1.2 million re infected000/cur t € 50,0 lians at 000 Ital 15% detected g 300,0 n. treating 5 billio (∼150,000) ost of t ld be 15 this The co woul years, t ver 3 y s year ov 5% referred d rforug s each y get for 50,000 S budcareg (∼ 50,000) cure 5 the NHS ing to 1/5 of th Aim orb ≥ 1 260.000 infectedld abso to be treated? woul 2% to 3% ● 15.000 - 20.000* urgent treated (∼ 30,000) ● 60.000* within 18 months

* Documento GdL Epatite C AIFA-MinSal-ISS-SIMIT-AISF-EPAC-CNT Aprile 2014

HCV THERAPEUTIC OPTIONS FROM AN ECONOMIC PERSPECTIVE

•Maximal cures Treat all identified cases with an •Minimal side effects optimal DAA (IFN-free) regimen •High adherence •Allows treatment by PCP

•Reduces cure rate •Maximizes side effects Treat first with regimens that •Lowers adherence include IFN to capture easy cures •Requires specialist and use DAA-only for Tx failures •Requires 2nd Tx for some •Only reduces cost by 20% •Raises major ethical issue

•Saves money but defers >costs Prioritize cases to spread costs; •Reduces early cures/ 2nd trans only treat those with stage >2 •Staging adds costs/Bx risk fibr. •Risks missing fibrosis progress •Severe cases harder to cure SVR associated with reduced 5-Yr risk of death and HCC in all populations

• SVR on IFN-based therapy was associated with substantial benefit vs no SVR – 62% to 84% reduction in all-cause mortality, 90% reduction in liver transplantation, 68% to 79% reduction in HCC

5-Yr Risk of All-Cause 5-Yr Risk of HCC Death by SVR by SVR SVR No SVR

25 ) 25 % ) (

% s (

20 r 20 s Y

r 5 Y

r 5

e t r 15 15 13.9 f e t 11.3 A

f 10.5 C A 10.0 10.0 9.3 C

d 10 10 H a

e h t

D 5.3 i 4.5 s 5 3.6 5 W t

2.9 P s

1.3 t 0.9 0 P 0 General Cirrhotic HIV- General Cirrhotic HIV- Pts Coinfected Pts Pts Coinfected Pts Hill AM, et al. AASLD 2014. Abstract 44. Deaths due to HCC or liver decompensation after P/R treatment in 440 patients with HCV cirrhosis

Di Marco V, submitted SVR Prevents Development of Insulin Resistance

25 P = .007 P = .1 P = .04

) 20% 20 % ( 17% R

I 16%

o v 15 SVR o N

Non-SVR e d

f 10

o 8%

s 7% 7% e t a 5 R

17/23021/124 6/78 15/94 11/152 6/30 0 Overall HCV GT 1/4 HCV GT 2/3

Aghemo A, et al. Hepatology. 2012;58:1681-1687. HCV THERAPEUTIC OPTIONS FROM AN ECONOMIC PERSPECTIVE

•Maximal cures Treat all identified cases with an •Minimal side effects optimal DAA (IFN-free) regimen •High adherence •Allows treatment by PCP do we can what w be lw•Reducesays b cure rate y not al robably •Maximizes side effects will pro Treat first with regimens that •Lowers do !! adherence ould•Requires specialist include IFN to capture easy curest we sh and use DAA-only for Txwh failuresat •Requires 2nd Tx for some •Only reduces cost by 20% •Raises major ethical issue

HCV Hepatologist

HCV