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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

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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.

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Objectives
• Epidemiology and natural history
• Screening
• Treatment options
• Treatment outcomes
• Fibrosis evaluation

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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

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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

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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

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• 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

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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

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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

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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

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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

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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.

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Fibrosis is the key

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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

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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