Management of Hepatitis C in Baby Boomers and Older Adults

Hemant Shah MD MScCH HPTE

Clinical Practice Director, Francis Family Liver Clinic

University Health Network

@hepatoMD

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Freeport Physicians’ Education Days

Faculty: Dr. Hemant Shah

• Relationships with financial sponsors:Member of Advisory Board: GHS, Gilead, Abbvie, Janssen, Roche, Merck

Relationship with organization that funds this program: Merck

Presenter COI Disclosure

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Freeport Physicians’ Education DaysDr. Hemant Shah

Disclosure of Financial Support

This program has received financial support from the following organizations in the form of unrestricted educational grants:

Astellas, Bayer, Bayshore Home Health, Boehringer Ingelheim, Eli Lilly, GSK Canada,

Merck, Mylan, Novartis, NovoNordisk, Pfizer and Purdue

This program has received financial support from Grand River Hospital Foundation in the form of speaker honoraria. This program has received in-kind support from Grand River Hospital in the form of logistical support.

Potential for conflict(s) of interest:Dr. Hemant Shah has received funding from Merck, which is a sponsor of this program. He has a relationship with Merck, Gilead, Abbvie, Intercept and Janssen that produce products that will be discussed in this program

Dr. Hemant Shah is receiving payment from the Freeport Physicians’ Education Fund for this presentation

Freeport Physicians’ Education DaysDr. Hemant Shah

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Mitigating Potential Bias:

• Recommendations for Drug Therapy will be based on peer reviewed journal articles and published guidelines

Objectives

• Review the progress in Hepatitis C management and treatment

• Understand the approach to Hepatitis C in baby boomers and older adults

• Appreciate the nuances to management of Hepatitis C in the elderly

• Enhance your own skillset in managing Hepatitis C in your practice

Scientific Milestones in HCV

• 1975: Description of non-A, non-B hepatitis

• 1989: Identification of HCV

• 1993: HCV genome organization and polyproteinprocessing delineated

• 1997: First HCV clone constructed

• 1998: First use of IFN-α and Ribavirin therapy

• 2003: First clinical studies of HCV protease inhibitor

• 2005: Production of recombinant HCV in tissue culture

EPIDEMIOLOGY

HCV is a MAJOR global public health problem

- ~71 million people infected- No vaccine- Leading indication for liver transplant

WHO

Viral Hepatitis Deaths Globally (WHO)

WHO commitment to lead

• Ambitious goals• Canada has signed on to these goals – requires action!

WHO 2016

WHO commitment to lead

• Ambitious goals• Canada has signed on to these goals – requires action!

WHO 2016

Approximately 1% of Canadians Have HCV

• Current estimated prevalence is between 250,000 and 400,000 people

• Up to 70% undiagnosed

• ~40% of Hepatitis C cases are in Ontario

• Lack good seroprevalencedata in Canada

Adapted from Myers R, et al. Can J Gastroenterol Hepatol. 2014;28(5):243-50 andSherman, M et al. Liver Disease in Canada: A Crisis in the Making. Canadian Liver Foundation, 2013.

Regionally: Hepatitis C has the Highest Impact of all Infections

Recent History of HCV Treatment: Marching Towards Elimination of HCV

Up to 2011IFN- and RBV-based,

up to 1 year of Tx

2011 to 2014IFN + RBV + oral PI, 24–48

weeks of Tx, increased toxicity

2014 -->All oral, no IFN or RBV, 8–24 weeks of Tx, few side effects

Cure rate (% SVR12)

6%

16%

42%

54–56%

68–75%

94–99%

0%

20%

40%

60%

80%

100%

IFN 6 mos IFN 12 mos IFN + RBV 12mos

PegIFN + RBV12 mos

PI + PegIFN +RBV

LDV/SOFsingle tablet

SVR

12

(%

)

DAA regimens

Strader DB, et al. Hepatology. 2004;39(4):1147-71; Vertex Pharmaceuticals Incorporated. Incivek Product Monograph; Jacobsson I, et al. EASL 2013, poster 1425; Manns M, et al. EASL 2013, oral presentation 1413;

Lawitz E, et al. APASL 2013, oral presentation LB-02; Afdhal N, et al. N Engl J Med. 2014;370(20):1889-98; Kowdley KV, et al. N Engl J Med. 2014;370(20):1879-88.

BUT Treatment uptake more important than SVR rate

SVR in individuals SVR in the population

Thomas Lancet 2010

Improved therapy of no benefit unless treatment rates increase

Natural History of HCV Infection

Adapted from 1. Alter HJ, et al. Semin Liver Dis. 2000;20:17-35and 2. Myers RP, et al. Can J Gastroenterol Hepatol. 2015;29(1):19-34.

Patients with HCV exposure

20%–40% spontaneously clear the virus and recover

60%–80% have persistent (chronic) infection

10%–20% have chronic, nonprogressive hepatitis

10%–20% have severe, progressive hepatitis

60%–80% havevariable progression

• All of these patients are infectious and can transmit the disease• There is no reliable way to predict the course and severity of disease

All chronically infected patients should be considered candidates for treatment2

Curing Hepatitis C Saves Lives

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Adapted from van der Meer AJ, et al. JAMA. 2012;308(24):2584-93.

SVR, sustained virologic response.

All-cause mortality in HCV

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

The Many Faces of Hepatitis C…

SCREENING AND DIAGNOSIS

Signs and Symptoms Are Not Usually Helpful for Identification of HCV

▪Most patients with HCV infection (60% to 75%) are asymptomatic• If a patient does exhibit symptoms, they may already have advanced liver

disease

▪ Liver enzyme tests (e.g., ALT, AST): patients with HCV often have normal liver enzymes

▪HCV-specific screening is crucial

Adapted from Wong T, et al. CMAJ. 2006;174:649-59;

Centers for Disease Control and Prevention. www.cdc.gov/hepatitis/resources/professionals/pdfs/abctable.pdf; and Seeff LB. Hepatology. 2002;36(Suppl 1):S35-46.

ALT, alanine transaminase; AST, aspartate transaminase.

Mode of Hepatitis C Acquisition

• North America:

• 60% IVDU

• 15% Sexual

• 10% Transfusion (pre-1992)

• 5% Nosocomial/Health-care work/Perinatal

• 10% Unknown

• Worldwide

• Use of contaminated medical products

CDC Viral Hepatitis C. http://www.cdc.gov/hepatitis/index.htm

Factors Associated with High Risk of HCV

Adapted from Wong T, et al. CMAJ. 2006;174:649-59.

Category Risk Factors

Demographic • Birth between 1945 and 1975• Living or having lived in an endemic area• Children born to a mother with HCV infection• Undiagnosed liver disease

Exposurerisks

• Injection drug use• Contaminated blood/blood products/organ transplantation before 1992 in Canada• High-risk sexual behaviour• Incarceration• Needlestick or sharp injuries• Reuse/sharing of contaminated equipment in areas with high HCV prevalence• Nonsterile contaminated tattooing or body-piercing equipment• Sharing personal items contaminated with blood with an HCV-infected person• Sharing contaminated intranasal cocaine equipment

Comorbidities • Hemodialysis• Hepatitis B virus infection • HIV infection

Groups to Prioritize for HCV Screening

▪ Birth between 1945 and 1975

▪ Any history of injection drug use

▪ Living or having lived in an endemic area

▪ Contaminated blood or blood products or organ transplantation before 1992 in Canada

▪High-risk sexual behaviour

Adapted from Wong T, et al. CMAJ. 2006;174:649-59.

Recent Canadian Screening Guidelines Miss The Mark

How It Was Done1. How good is the test?

2. What are the benefits?

3. What are the harms?

4. What is the cost-effectiveness?

Issues• Misinterpreted the Test

• Used old literature

• Equated spontaneous clearance with ‘false positive’

• Under-value benefits

• Assume very low rate of cirrhosis → misinterpret 20 year vs life-time risk

• Value of SVR → ignore liver and non-liver benefits

• Over-value harms

• Screening with no treatment → Now we can treat most…and by end of year ALL

• Cost – without mentioning cost of no treatment

• Didn’t recognize changing treatment environment

• Cost effectiveness has already been established (Wong et al CMAJ 2015)

Barrett, Feld, Janssen, Shah, Sherman CMAJ 2017

HCV Antibody Prevalence in Ontario (n=10,006) – Supports Boomer Screening

Bolotin S, Feld JJ, Garber G, Wong WWL, Guerra FM, et al. (2018) Population-based estimate of hepatitis C virus prevalence in Ontario, Canada. PLOS ONE 13(1): e0191184. https://doi.org/10.1371/journal.pone.0191184https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191184

CASL Consensus Guidelines – Baby Boomer Testing Recommendations• To increase the identification of the large proportion of persons

living with undiagnosed HCV, we recommend that screening be both risk-based and target the birth cohort of individuals born from 1945-1975, which currently encompasses the majority of persons chronically infected with HCV in Canada. (Class 2a, Level C)

Key Laboratory Tests for Diagnosing HCV

Test Methods Implications of Positive Test

Anti-HCV antibody

• Serum test• Point of Care Test

• Indicates exposure to hepatitis C• Does not imply active infection• Confirm status by testing for HCV RNA

HCV RNA • Serum Test• Dried Blood Spot

• Presence of HCV infection• If positive, request identification of

genotype

Adapted from British Columbia Ministry of Health. Viral Hepatitis Testing. 2012.

RNA, ribonucleic acid.

Simple Algorithm for HCV Screening

Anti-HCV antibody

Anti-HCV negative

Adapted from Wong T, et al. CMAJ. 2006;174(5):649-59 and Pinette GD, et al. Primary Care Management of Chronic Hepatitis C: Professional Desk Reference 2009.

*Consider checking HCV RNA in patients who are at high risk of infection or immunocompromised.

Anti-HCV positive

Check HCV RNA + genotype

HCV RNA positiveHCV RNA negative

Repeat HCV RNAin 6 months

Refer to experienced colleague

Not infected*

To include in referral:• HCV RNA and genotype

• CBC, INR, bilirubin, ALT, AST• Ultrasound results

CBC, complete blood count; INR, international normalized ratio.

After a Positive HCV RNA

Additional Tests to Provide Supporting InformationTypes of Investigations Individual Tests

Bloodwork • CBC• Liver enzyme and function tests

• ALT, AST, GGT, alkaline phosphatase, bilirubin, INR (or PT), albumin• Normal ALT is not a contraindication to treatment (one-third have normal test results)2

• Creatinine

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

• Various

Adapted from Myers RP, et al. Can J Gastroenterol. 2012;26(6):359-75 and Pinette GD, et al. Public Health Agency of Canada. http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf.

GGT, gamma-glutamyl transpeptidase; HAV-Ab, hepatitis A antibody; HBsAb, antibody to hepatitis B surface antigen; HBsAg, hepatitis B surface antigen; PT, prothrombin time.

Key Elements of Patient Education for Newly Diagnosed Hepatitis C in Primary Care

▪Chronic condition that progresses slowly, but can also present as advanced liver disease

▪Virus is carried by the blood and is transmissible to others• Avoid sharing razors, toothbrushes, nail cutters

• OK to share cutlery, eat from same dish, kiss/hug

▪High risk sexual behaviour increases risk

▪Goal of treatment is cure of hepatitis C

▪Treatment prevents complications and transmission of virus

Other Important Points for Counselling Patients

▪Avoid/limit exposure to alcohol 2-4 drinks per week

▪Strict alcohol abstinence recommended if F3-4

▪Maintain a healthy lifestyle

▪Coffee is the best natural supplement

▪ If cirrhotic - annual influenza vaccine, one-time pneumococcal vaccine, hepatocellular carcinoma surveillance

▪Vaccinate if patient is non-immune for HAV and HBV

TREATMENT

Treatment is Effective – Genotypes 1 to 6

SOF/LDV

EBV/GZP

SOF/VEL

GLE/PIB

SOF/VEL/VOX

Access to Treatment

• Access for all!• No fibrosis restrictions

• No sobriety restrictions

• No upper age limit (lower limit 18yrs)

• All patients with chronic HCV are eligible for treatment• Limited use codes – very easy!

• HCV RNA positive x 2 more than 6 m apart (exclude spontaneous clearance)

• GI, ID or “provider experienced in HCV treatment”

A simple approach to treatment for patients up to compensated cirrhosis

Regimen Genotype Duration

(weeks)

Pills

per

day1a 1b 2 3 4 5 6

SOF/LDV

(Harvoni)8-12 1

ELB/GZV

(Zepatier)12 1

SOF/VEL*

(Epclusa)12 1

GLE/PIB*

(Mavyret)8-12 3

G3 cirrhosis treated differently:SOF/VEL need to add RBVGLE/PIB must use 12 weeks

1. Confirm infection – RNA + genotype2. Identify cirrhosis – APRI >1.5, FIB-4 >3.253. Exclude drug interactions – www.hep-druginteractions.org4. Start!

If you treat 1000 patients this way…

Action Number of Patients Cured Not Cured

Treat First Line 1000 950 50

Treat Second Line 50 45 5

TOTAL TREATMENTS ADMINISTERED: 1050

OVERALL CURE RATE: 99.5%

STRIVING TOWARDS ELIMINATION

Focus (Priority Populations)

DRAFT CanHepC Blueprint 2019

Hepatitis C in the Older Adult

• Toxicity of interferon-based treatments severe in adults

• Historically under-represented in clinical trials

• Provider attitudes around treatment of older adults often biased towards non-treatment

HCV Infection Duration Impacts Risk

Healthy Liver Cirrhosis Liver Cancer

Slowly progressive over decades of infection

1-4%/yr20%

Does this mean 80% do not have consequences?

(at 20 yrs of infection)

No!

Cirrhosis risk 41% at 30 yrs…lifetime risk 50-60% or higher

Thein Hepatol 2008

Fibrosis Progression Accelerates by Age

Pros/Cons of Treating Older Adults

PROS

• Usually treating more advanced liver disease

• Prevent more accelerated fibrosis

• Can facilitate other interventions (chemo, transplant, surgery, etc)

CONS

• Many individuals with Hepatitis C at elder age are non-progressors

• Elderly may experience more side effects with treatment

• Concern about decreased efficacy in older adults

Efficacy in Older Adults

97 9699 9898 97

100 100

0

10

20

30

40

50

60

70

80

90

100

SOF/LED 3D GZP/EBV SOF/VEL

SVR from clnical trials

<65 years >65 years

• Comparable SVR to younger individuals

• Includes individuals who are 75 and older (small numbers)

• Similar rates of adverse events and drug discontinuations

Jhaveri et al. Drugs Aging. Feb 2018

RESOURCES FOR TREATMENT

Additional Resources

• ECHO Ontario Liver• 16 week curriculum, sessions Mondays 12-1:30• Covers NAFLD, AFLD, Hep B, Hep C, DILI, Other Topics• Accredited by CFPC and FREE• www.echoontario.ca

• ENDHepC• 1-day hepatitis roadshow that comes to your clinic• Education for HCPs and patients, testing for patients, free fibroscans

• Hepatology Update• Friday September 27, 2019, one-day CME

• Hepatitis C Workshops• 1-day intense training on treatment• Twice a year (spring and fall)

Summary

• Hepatitis C is a significant underdiagnosed public health issue

• Screening is important to identify individuals eligible for treatment

• Treatment is effective across the age spectrum

• Hepatitis C treatment is very much in the domain of primary care expertise