5/23/2014
1
Hepatitis C
‘ An Update’
Alnoor Ramji
Gastroenterology & Hepatology
Clinical Associate Professor
Division of G...
5/23/2014
2
Disclosure of Commercial Support
• This program has NOT received financial support.
• This program has NOT rec...
5/23/2014
3
Objectives
• Epidemiology and natural history
• Screening
• Treatment options
• Treatment outcomes
• Fibrosis ...
5/23/2014
4
Estimated 170 Million Persons With
HCV Infection Worldwide
• 3-4 million newly infected each yr worldwide
Worl...
5/23/2014
5
9
HCC: hepatocellular carcinoma.
1. Remis RS. Final Report. PublicHealth Agency of Canada. 2007. Available fro...
5/23/2014
6
111. Seeff LB. Hepatology 2002;36(Suppl 1):S35-46; 2. Sherman et al. Curr Oncol. 2011;18:228-40; 3. Consensus ...
5/23/2014
7
• 312 patients with initially compensated cirrhosis of viral aetiology
Cirrhotic patients at risk of serious
m...
5/23/2014
8
15
CDC: Centers for Disease Control and Prevention
1. Hepatitis C: Proposed Expansion of Testing Recommendatio...
5/23/2014
9
Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting,
April 27-28, 201...
5/23/2014
10
0
20
40
60
80
100
SVR(%)
PegIFN/RBV
BOC or TVR +
PegIFN/RBV
38-44
67-81
Poordad F, et al. N Engl J Med. 2011;...
5/23/2014
11
Adverse Event Arm 1 (PR48); n=363 (%) Arm 2 (RGT); n=368 (%) Arm 3 (BOC/PR48); n=366 (%)
Fatigue 59 52 57
Hea...
5/23/2014
12
Virologic Response to Sofosbuvir (Nuc. Inh.) + PEG-INF
+ Ribavirin x 12 weeks Treatment: Genotype 1
Lawitz E,...
5/23/2014
13
Fibrosis is the key
5/23/2014
14
Hepatitis C: Summary
• HCV is common
• Screening for HCV is imperative
– ‘baby-boomers’ and immigrants
• Vira...
5/23/2014
15
Hepatitis C
‘ An Update’
Alnoor Ramji
Gastroenterology & Hepatology
Clinical Associate Professor
Division of ...
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  1. 1. 5/23/2014 1 Hepatitis C ‘ An Update’ Alnoor Ramji Gastroenterology & Hepatology Clinical Associate Professor Division of Gastroenterology University Of British Columbia St. Paul’s Hospital Site ramji_a@hotmail.com Fax: 604-689-2004 Company Name Relationship Abbvie Investigator, consultant BI Investigator, Consultant BMS Investigator, Consultant, Gilead Sci. Inc Investigator, Consultant, Speaker Hoffman LaRoche Investigator, Consultant, Speaker Nursing Support Janssen (J. & J.) Investigator, Consultant, Speaker Novartis Investigator Merck & Co. Investigator, Consultant, Speaker Nursing Support Vertex Pharmaceuticals Investigator, Consultant, Speaker Disclosures
  2. 2. 5/23/2014 2 Disclosure of Commercial Support • This program has NOT received financial support. • This program has NOT received in-kind support. • Potential for conflict(s) of interest: – As prior slide, nil else. Mitigating Potential Bias • The presentation was reviewed by an external reviewer for any biases.
  3. 3. 5/23/2014 3 Objectives • Epidemiology and natural history • Screening • Treatment options • Treatment outcomes • Fibrosis evaluation
  4. 4. 5/23/2014 4 Estimated 170 Million Persons With HCV Infection Worldwide • 3-4 million newly infected each yr worldwide World Health Organization 2008. Available at: http://www.who.int/ith/es/index.html. Accessed October 28, 2009. > 10% 2.5%-10% 1%-2.50% Prevalence of infection NA 1a, 1b 2a, 2b, 3a 1a, 1b 2a, 2b, 2c, 3a 4 5a 1b 1b, 6 1b, 3a 1b, 3a 3b 4 Fang et al. Clin Liver Dis. 1997. HCV Infection: Worldwide Genotype Distribution 1a, 1b, 2b, 3a 2a
  5. 5. 5/23/2014 5 9 HCC: hepatocellular carcinoma. 1. Remis RS. Final Report. PublicHealth Agency of Canada. 2007. Available from: http://www.phac-aspc.gc.ca/sti-its-surv-epi/model/pdf/model07-eng.pdf. Canadian Burden of HCV Modeled Non-exclusive Burden of HCV and Sequelae in Canada1 HCC: hepatocellular carcinoma. 1. Remis RS. Final Report. PublicHealth Agency of Canada. 2007. Available from: http://www.phac-aspc.gc.ca/sti-its-surv-epi/model/pdf/model07-eng.pdf. 10 HIV: human immunodeficiencyvirus 1. Ly et al. Ann Intern Med. 2012;156:271-278 Importance of Screening and Treating HCV HCV-related mortality exceeds mortality from HCV1
  6. 6. 5/23/2014 6 111. Seeff LB. Hepatology 2002;36(Suppl 1):S35-46; 2. Sherman et al. Curr Oncol. 2011;18:228-40; 3. Consensus recommendationsof the Steering Committee. Natural History of HCV HCV exposureHCV exposure Chronic infectionChronic infection Cirrhosis 20-30 yrs following infection Cirrhosis 20-30 yrs following infection Liver failure or decompensationLiver failure or decompensation Hepatocellular carcinoma3Hepatocellular carcinoma3 Acute infectionAcute infection60-75% are asymptomatic60-75% are asymptomatic 50-85% of patients50-85% of patients >20% of patients3>20% of patients3 1-4% of patients/yr 1-4% of patients/yr Liver transplant, deathLiver transplant, death 4% of patients/yr3 4% of patients/yr3 Progression To Cirrhosis Progression to cirrhosis: based on inflammation of initial biopsy. Yano. Hepatology 1996
  7. 7. 5/23/2014 7 • 312 patients with initially compensated cirrhosis of viral aetiology Cirrhotic patients at risk of serious morbidity Benvegnù L, et al. Gut 2013; 53: 744‒9 Patients at risk HCC 312 311 310 303 297 268 226 189 153 129 94 65 45 27 11 5 Variceal bleeding 312 312 312 309 301 269 237 190 163 131 97 71 44 29 13 7 Ascites 312 311 312 305 296 259 223 181 152 125 93 60 48 30 15 9 Encephalopathy 312 312 312 309 300 270 235 192 161 127 95 65 43 30 13 7 Cumulativerisk(%) Years of follow-up HCC Variceal bleeding Ascites Portal-systemic encephalopathy 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 14 *Other modes of transmission include sexual, occupational, nosocomial and vertical transmission. IDU: injection drug use. 1. Remis RS. Final Report. PublicHealth Agency of Canada. 2007. Available from: http://www.phac-aspc.gc.ca/sti-its-surv-epi/model/pdf/model07-eng.pdf. HCV Prevalence According to Exposure
  8. 8. 5/23/2014 8 15 CDC: Centers for Disease Control and Prevention 1. Hepatitis C: Proposed Expansion of Testing Recommendations, 2012. Available from: http://www.cdc.gov/nchhstp/newsroom/docs/HCV-TestingFactSheetNoEmbargo508.pdf; 2. Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm?s_cid=rr6104a1_w. CDC Recommendations (August 2012) *** InCanada : CLF suggests 1945-1975 → One-time testing during a yearly checkup or as a part of insurance blood work In the US, >75% of adults with chronic hepatitisC are baby boomers • 73.4% of HCV-related deaths were in persons 45-64 years of age Screening of those born between 1945-19651,2 Virological tests to confirm HCV infection • Anti-HCV • HCV-RNA • HCV genotype Bloodwork • CBC • Liver enzyme & function tests: • ALT,AST, GGT, alkaline phosphatase, bilirubin, INR (or PT), albumin • NormalALT is not a contraindication to treatment (⅓ have normal test results)2 • Creatinine 16 ALT : alanine aminotransferase; AST : aspartate transaminase;CBC: complete blood count; GGT: gamma-glutamyl transferase;HAV: hepatitisA virus; HAV-AB: hepatitisA antibody; HB: hepatitis B; HBsAG:hepatitis B surface antigen; HBsAb: hepatitisB surface antibody; HIV: human immunodeficiencyvirus; INR: Internationalnormalized ratio; PT: Prothrombin time 1. Myers et al. Can Gastroenterol.2012;26(6):359-75; 2. Pinette et al. Public Health Agency of Canada. Available from: http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf. Evaluation: LaboratoryTesting1,2 Abdominal ultrasound • Test for cirrhosis and exclude hepatocellular carcinoma Tests to rule out coinfections • Hepatitis A (HAV-Ab) • Hepatitis B (HBsAg, HBsAb) • HIV (Anti-HIV) Tests to exclude other causes of liver disease
  9. 9. 5/23/2014 9 Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring, MD. SVR(%) IFN 6 mos PegIFN/ RBV 12 mos IFN 12 mos IFN/RBV 12 mos PegIFN 12 mos 2001 1998 2011 Standard IFN RBV PegIFN 1991 DAAs PegIFN/ RBV/ DAA IFN/RBV 6 mos 6 16 34 42 39 55 70+ 0 20 40 60 80 100 The Advancing Present 2014 90 PegIFN/ RBV/ DAA Or DAA+RBV Impact of SVR on All-Cause Mortality by Genotype • VA clinical case registry (N=16,864) • SVR associated with improved survival among HCV genotypes 1, 2 and 3 BackusL, et al. 61st AASLD; Boston,MA; October 29-November 2, 2010; Abst. 213. G: Genotype HR: Hazard Ratio CI: Confidence Interval G1 HR (95% CI) P value G2 HR (95% CI) P value G3 HR (95% CI) P value Unadjusted 0.45 (0.39-0.52) <0.001 0.50 (0.38-0.65) <0.001 0.30 (0.22-0.40) <0.001 Adjusted 0.67 (0.56-0.79) <0.001 0.63 (0.45-0.86) 0.004 0.45 (0.32-0.65) <0.001
  10. 10. 5/23/2014 10 0 20 40 60 80 100 SVR(%) PegIFN/RBV BOC or TVR + PegIFN/RBV 38-44 67-81 Poordad F, et al. N Engl J Med. 2011;364:1195-1206. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. The Present: SVR Rates With Boceprevir or Telaprevir in Genotype 1 Treatment-Naive Patients Triple Therapy for upto 48 Weeks F0-2 F3-4 52-62
  11. 11. 5/23/2014 11 Adverse Event Arm 1 (PR48); n=363 (%) Arm 2 (RGT); n=368 (%) Arm 3 (BOC/PR48); n=366 (%) Fatigue 59 52 57 Headache 42 45 43 Nausea 40 46 42 Anemia 29 49 49 Dysgeusia 18 37 43 Chills 28 36 33 Pyrexia 32 33 30 Insomnia 32 31 32 Alopecia 27 20 28 Decreased Appetite 25 26 24 Pruritis 26 23 25 Neutropenia 21 25 25 Influenza Like Illness 25 23 22 Myalgia 26 21 24 Rash 22 24 23 Irritability 24 22 22 Depression 21 23 19 Diarrhea 19 19 23 Dry Skin 18 18 22 Dyspnea 16 18 22 Dizziness 15 21 17 Most Common Treatment-Related Adverse Events* *Reported in >20% of patients in any treatment arm and listed by decreasing overall frequency 85% of patients have treatment shortened to 24 weeks total Virologic Outcomes Jacobson I, et al. EASL 2013. Abstract 1425. Reproduced with permission. 18/ 31 n/ N = 5/ 17 188/ 229 80 60 40 20 0 100 HCVRNAUndetectable(%) No cirrhosis Cirrhosis 82 53 58 29 SMV + P/R P/R 60/ 113 Virologic Response to Simeprevir (2nd gen. protease Inh.) + PEG-INF + Ribavirin x 24 weeks Treatment: Genotype 1
  12. 12. 5/23/2014 12 Virologic Response to Sofosbuvir (Nuc. Inh.) + PEG-INF + Ribavirin x 12 weeks Treatment: Genotype 1 Lawitz E, et al. EASL 2013. Abstract 1411. Reproduced with permission. SVR12(%) 92 80 100 80 60 40 20 0 No Cirrhosis Cirrhosis 252/273 43/54 SVR According to Fibrosis Level SVR12(%) 89 96 100 100 80 60 40 20 0 GT 1 GT 4 GT 5,6 261/292 27/28 7/7 SVR According to Genotype n/N = 0 20 40 60 80 100 SVR(%) PegIFN/RBV X 24 wks 70-80% 97% Poordad F, et al. N Engl J Med. 2011;364:1195-1206. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. Virologic Response to PEG-INF + RBV vs. Sofosbuvir + RBV (all-oral) in Genotype 2 and 3 Treatment- Naive Patients Geno 2 SOF+RBV X 12 wks 92-94% Geno 3 SOF+RBV X 24 wks Gane E, et al. J Hepatol. 2013;58(suppl 1):S3. Abstract 5. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.
  13. 13. 5/23/2014 13 Fibrosis is the key
  14. 14. 5/23/2014 14 Hepatitis C: Summary • HCV is common • Screening for HCV is imperative – ‘baby-boomers’ and immigrants • Viral eradication / cure in 70-90% • Viral eradication has a mortality benefit
  15. 15. 5/23/2014 15 Hepatitis C ‘ An Update’ Alnoor Ramji Gastroenterology & Hepatology Clinical Associate Professor Division of Gastroenterology University Of British Columbia St. Paul’s Hospital Site ramji_a@hotmail.com Fax: 604-689-2004

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