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HCV treatment in Australia:

a new role for GPs

Dr David IserThe Alfred & St. Vincent’s Hospitals

15th October 2016

Disclosures

I have received honoraria for presentations and/or

consultancies from:

AbbVie

BMS

Gilead

Janssen

MSD

Roche

HCV: a new role for GPs

Why treat HCV?

Evolution of HCV Therapy

The bad old days of interferon

The new wonder drugs

Assessing your patient

HCV genotype

Assessment of liver disease

Where to get help

HCV is common (Aust ~230,000)

Gower E et al. J Hepatol 2014;61:S45–S57

Viraemic prevalence

0.0–<0.75%

0.75–<1.25%

1.25–<1.75%

1.75–<2.5%

≥2.5%

Estimated global viraemic infections:

80 (64–103) million people

The health burden is growing

Sievert W et al J Gastroenterol Hepatol 2014; 29 (S1):1-9

HCV is expensive

Sievert W. et al J Gastroenterol Hepatol 2014; 29 (S1):1-9

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Curing HCV improves outcomes

Van der Meer A, JAMA 2012 (530 patients with Ishak 4-6, median follow up 8.4 years, death in 13/192 with SVR, 100 non-SVR)

Without cure

Without cure

Without cure

Without cure

With cure

With cure

With cure

With cure

Liver failure All-cause mortality

Liver-related death or transplant Hepatocellular carcinoma

?Tested for HCV

Referred to

specialist

Offered

treatment

Willing to undergo

treatmentReceive

treatment

But barriers to treatment exist

Barriers in Australia (Care cascade)

Kirby Institute 2015

Aust: all diagnosis, no treatment . . .

2013 estimates

Dore GJ et al. J Viral Hepat 2014;21(S1):1–4

6

5

4

3

2

1

00 20 40 60 80 100

Diagnosis rate (%)

Tre

atm

en

t ra

te (

%)

France

Germany

Austria

England

Spain

Czech

Republic

Egypt

Turkey

Brazil

Portugal

Belgium

Switzerland

Denmark

Canada

Australia

Sweden

Some terminology

HCV antibody (Ab) indicates exposure to HCV

HCV PCR detects RNA and indicates current infection

Pegylated interferon (pegIFN) is an old HCV treatment

Direct-acting antivirals (DAAs) are the new treatments

Sustained virological response (SVR) indicates that HCV

RNA is not detectable after treatment finishes

SVR12 means no HCV 12 weeks after finishing = CURE

The evolution of HCV treatment

1992 1998 2003 2013 2014

interferon

(sIFN)

sIFN

+ RBVpegIFN

+ RBV

pegIFN

+ RBV

+ BOC/

TVR

pegIFN

+ RBV

+ SMV

0

10

20

30

40

50

60

70

80

90

100

2016

IFN-free,

all-oral

DAA

2006

liver biopsy optional, retreatment possible

SV

R r

ate

(%

)

Short-

duration,

Pan-

genotypic

2017?

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Pegylated interferon (pegIFN) sub cut injection weekly

Ribavirin tablets twice daily

Treatment for up to 48 weeks!!!

Lots of side effects

2006: HCV treatment with pegIFN

0%

20%

40%

60%

80%

100%

1 Manns M et al. Lancet 2001; 2 Fried MW et al. N Eng J Med 20023 Hadzyannis SJ et al. Ann Intern Med 2004

76%80%

63%

52%56%

46%

54%

42%

82%

Overall Gt 1 Gt 2/3

2006: pegIFN + RBV results

1 Manns 2 Fried 3 Hadzyannis

SV

R r

ate

2006: treatment was complicated . . . 2006: GP’s role in HCV treatment

Hepatitis Treatment Centre of Excellence

2016: a new DAA dawn DAAs via PBS since 1st March

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Where the DAAs act

Polymerase

inhibitors Protease Inhibitors

NS3 4A NS5A NS5B

NS5A

Inhibitors

NS4B

- buvir- previr - asvir

How to remember the names . . .

Nucs

Non-nucs

Three important questions

Does my patient have hepatitis C?

HCV antibody (Ab) indicates exposure to HCV

Up to 45% of people will clear HCV without treatment

If HCV PCR is positive, the person still has HCV

Which HCV genotype is present?

Single blood test

Can be requested by GPs (covered by MBS)

Australia has mainly GT 1 or GT 3

Does my patient have cirrhosis?

Tricky . . .

HCV genotypes in Australia

Data from >10,000 patients at VIDRL in MelbourneVictorian Infectious Diseases Reference Laboratory (data on file)

GT: genotype

54%

5%

37%

2% 2%

GT 1

GT 2

GT 3

GT 4

GT 5

GT 6

GT 1 24%

GT 1a 39%

GT 1a/b 8%

GT 1b 29%

Gower E et al. J Hepatol 2014; 61:S45–S57

How long is treatment?

Treatment for most people with HCV being treated in

primary care is for:

12 weeks

If the person has cirrhosis, treatment may be for 24 weeks

nb: people with cirrhosis should be referred to a liver

specialist

Assess Start Monitor 12 weeks Test for cure

SVR12TreatmentTests

DAA regimens* on the PBS

97 98 96 9894 9696 98 100 99

90 88

0

20

40

60

80

100

119

123

126

131

124

126

41

42

301

301

65

66

100

101

59

63

9

10

105

109

23

26

* These results are from separate clinical trials and not from head-to-head comparisons

SV

R12 (

%)

LDV/SOF

(Harvoni)DCV

+ SOF

+ RBV

DCV+SOF

(Daklinza

Sovaldi)

AbbVie 3D

(Viekira Pak)

SOF+RBV

(Sovaldi)

GT 1 GT 2 GT 3

8w 12w TN TE 1a 1b 12w 24w NC Cirr 12w 16wLDV/SOF

(Harvoni)

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Which treatment?

Several options

Mainly determined by HCV genotype

Occasionally by drug-drug interactions

Sometimes determined by patient or doctor preference

GPs should focus on patients with:

Genotype 1 or 3

No cirrhosis

Fewer co-morbidities & normal renal function

Genotype 1

Genotype 1a

Ledipasvir/ sofosbuvir (Harvoni®)

Single pill daily

Few adverse effects

Few significant drug-drug interactions

SVR rate of up to 98% (similar success rate for Genotype 1b)

Genotype 1b

Ombitasvir/paritaprevir/rit + dasabuvir (Viekira Pak ®)

3 morning pills and 1 evening pill (daily pack)

Few adverse effects

More drug-drug interactions (ritonavir boosting)

SVR rate of almost 100%

Genotype 3

Genotype 3

Sofosbuvir (Sovaldi ®)

in combination with

Daclatasvir (Daklinza ®)

Daily pill (60mg)

Few adverse effects

Few drug-drug interactions

SVR rate of ~95% with sofosbuvir in genotype 3

Genotype 2 is treated with Sofosbuvir + ribavirin

Genotypes 4,5 and 6 only pegIFN + ribavirin + SOF (PBS)

Drug-drug interactions

Need to check HCV treatment compatible with patient’s

other medications

Important contra-indicated medications:

Amiodarone

Carbamazepine

Phenytoin

Beware:

Statins

High dose PPIs

www.hep-druginteractions.org How to assess cirrhosis

Pre-test probability

Older patients, longer Hx of HCV, alcohol, GT 3

Clinical signs

Spider naevi, leukonychia, splenomegaly, jaundice

Investigations

Low platelets, low albumin, raised bilirubin

APRI (AST to Platelet Ratio Index)

FibroScan ® (where available)

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Linking with a specialist

Linking with Specialist Care

Who can prescribe these new treatments?

States and territories may have specific requirements about prescriber eligibility for the new medicines in their jurisdiction.

For the PBS subsidy, where state or territory requirements allow, gastroenterologists, hepatologists, or infectious disease physicians experienced in the treatment of chronic hepatitis C infection are eligible to prescribe the new medicines.

All other medical practitioners, including general practitioners (GPs), are also eligible to prescribe under the PBS, provided that is done in consultation with one of the specified specialists experienced in the treatment of chronic hepatitis C infection. For example, a GP must consult with one of the specified specialists by phone, mail, email or videoconference in order to meet the prescriber eligibility requirements.

http://www.pbs.gov.au/info/publication/factsheets/hep-c/factsheet-for-patients-and-consumers

www.hepvic.org.au

www.hepchelp.org.au Referral for ‘specialist consultation’

Primary Care consultation request FINAL Page 1 of 2

Note: All fields below are mandatory

ATTENTION OF:

Hospital: Department (Gastroenterology or ID):

Dr (if known): Fax: Email:

GP DETAILS

GP name: Provider no:

GP address:

GP contacts: Phone: Fax: Email:

PATIENT DETAILS

Patient Name UR no (if known):

Patient Date of Birth Gender: Male Female

Pregnant or nursing female: Yes * No N/A

FibroScan® Date: ____/____/_____ Median liver stiffness (kPa): _______ Is it >12.5:

Yes * No

IQR/med (%): ________

APRI score

Online APRI Calculator Date: ____/____/_____ Result: _________

Is i t >1.0:

Yes * No

*If ANY apply, please refer to a specialist for clinical review

Hepatitis C History Intercurrent conditions

Likely year of acquisition: Diabetes: Yes No

Year of chronic hepatitis C diagnosis: Obesity (BMI>30): Yes No

Known cirrhosis: Yes * No Immunosuppressed: Yes No

Hepatic decompensation (ascites, encephalopathy, variceal bleeding): Yes * No Hepatitis B: Yes * No

Any previous treatment with Direct Acting Antivirals for HCV: Yes No HIV: Yes * No

*If ANY apply, please refer to a specialist for in person clinical review Alcohol >40g / day: Yes No

LABS (OR ATTACH COPY OF RESULTS)

Test Date Result Test Date Result

HCV genotype INR

Viral load Creatinine

ALT eGFR

AST Hb

Total bil irubin Platelets

Albumin β HCG

Primary Care Consultation Request - Initiation of Hepatitis C Treatment in Victoria

www.mja.com.au

Thompson AJ et al. Med J Aust 2016; 204 (7): 268-272.

New strategies & models of care

Elimination strategies

Treatment as Prevention (TAP) study

Nurse-led models of care

Treatment in prisons

Treatment in primary care

Treatment in NSP/OST settings

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Summary

DAAs are the new standard of care for HCV

All-oral DAA therapy for HCV is now available for

anyone in Australia with HCV via PBS

Very well tolerated and highly effective (95+%)

Some limitations and barriers to treatment still exist

New models of care are needed to provide treatment to

everyone with HCV

GPs will be integral to eliminating HCV

Thank you

Health Ed

Hepatitis Victoria

Prof Margaret Hellard, Dr Joe Doyle, Dr Brett Sutton (Burnet)

Prof Alex Thompson (St. Vincent’s Hospital)

A/Prof John Lubel & Dr Stephen Bloom (Eastern Health)

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