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Hepatitis C Nurse Workshop
Michael Smit CRNP, MS
CRNP, GI Associates, Sinai Hospital of Baltimore
Clinical Coordinator Hepatitis C Clinic
Hepatitis C Nurse Workshop

Michael Smit: I have no conflict of interest to declare.
Objectives

To identify risk factors for Hepatitis C.

To identify appropriate screening, laboratory analysis, and testing for
Hepatitis C pre, and post treatment.

Treatment for HCV
Hepatitis C Screening

Current or former injection drug users, including those who injected only once many years ago.
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Recipients of blood transfusions or solid organ transplants before July 1992 (USA).
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Chronic hemodialysis patients.

Persons who have had tattoos, body piercing.
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Children born to mothers infected with HCV.
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Persons who have used intranasal drugs.
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Prisoners and previously incarcerated persons.

Persons with HIV infection.

People with sexual partners who are HCV-infected.

In April 2014, WHO launched "Guidelines for the screening, care and treatment of persons with
hepatitis C". These are the first guidelines dealing with hepatitis C treatment produced by WHO(4)
Hepatitis C Screening

Adults born between 1945 and 1965 (“Baby Boomers”)

People born during 1945 through 1965 are 5 times more likely than other adults to
be infected. In fact, 75% of adults with Hepatitis C were born in these years.

The reasons why baby boomers have the highest rates of Hepatitis C are not
completely understood.

It is estimated that one-time testing of everyone born during 1945 through 1965
will prevent more than 120,000 deaths.(6).

Most boomers are believed to have become infected in the 1970s and 1980s when
rates of Hepatitis C were the highest.

Since people with Hepatitis C can live for decades without symptoms, many baby
boomers are unknowingly living with an infection they got many years ago.(6).
HCV Diagnostic Algorithm Based on
Serologic Testing (7)
Anti-HCV Antibody
Positive
HCV RNA
Negative
Negative
No Further
Testing†
No Active
Disease
HCV Genotype
Positive Liver Assessment/Biopsy
CBC, CMP, AFP, ETC
*If patient lacks pre-existing antibodies to HAV or HBV.
HAV=hepatitis A virus, HBV=hepatitis B virus.
† HCV RNA testing should be performed in Patients with unexplained liver disease whose anti-HCV test is negative and who
are immunocompromised or suspected of having acute HCV infection
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Hepatitis C Testing, Laboratory Analysis

Assessment of the degree of liver damage (fibrosis and cirrhosis). This can be
done by liver biopsy or through a variety of non-invasive tests.

HCV RNA – Viral Load, and Genotype.

CMP (electrolyte panel, including LFT’s), CBC, Alpha fetoprotein (AFP) is a
protein produced by the liver and yolk sac of a developing baby during
pregnancy. AFP levels go down soon after birth. (Cirrhosis and Liver cancer).

Hepatitis A antibody, hepatitis B surface antigen, hepatitis B core antibody,
hepatitis B surface antibody, HIV antibody.
Hepatitis C Testing, Laboratory Analysis:
Genotype

1. HCV RNA: the quantitative HCV RNA test measures the amount of HCV in
the blood. Such as “4,380,250 IU/ml. Known as the "viral load."
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2. Genotypes are used to identify particular strains of HCV.
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3. Genotypes help to determine treatment course.
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4. 6 different types of genotype, but up to 11 known, and subsets.

5. History of prior treatment
Hepatitis C Testing, Laboratory Analysis:
Liver Assessment

Liver Biopsy Gold standard for defining status of liver injury (Time, cost, complications)

Non-invasive methods for estimating fibrosis in HCV
May reveal advanced fibrosis or cirrhosis.


Fibroscan, Computer morphometry, Ultrasound, Magnetic resonance elastography
Commercial blood tests:

FIBROSpect II

HepaScore

HCV FIBROSURE
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Serum-based Aspartate aminotransferase-to-Platelet Ratio Index (APRI)
Metavir Score
Hepatitis C Testing, Laboratory Analysis:
Liver Assessment

Fibrosis Stage (FibroTest) Results

F0 - No fibrosis
0.00 - 0.21
F0 - F1
0.21 - 0.27
F1 - Portal fibrosis
0.27 - 0.31
F1 - F2
0.31 - 0.48
F2 - Bridging fibrosis with few septa
0.48 - 0.58
F3 - Bridging fibrosis with many septa
0.58 - 0.72
F3 - F4
0.72 - 0.74
F4 - Cirrhosis
0.74 - 1.00
Hepatitis C Testing, Laboratory Analysis:

Testing complete Results

HCV antibody, HCV RNA, Genotype, Liver assessment (FibroSure)

Ultrasound, CBC, CMP, LFT’s, AFP, TSH, Vitamin D
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Putting it together and significance for treatment.
HCV Treatment

Unlike Hepatitis B and HIV, HCV is curable.

Cure defined as achieving of a sustained virologic response (SVR) following
completion of treatment.

Persistent absence of HCV RNA by PCR assay at a specific time after antiviral
therapy completion (6 mos).

24 weeks post treatment completion, although studies have shown assessment of
serum HCV RNA 12 weeks is now as sensitive.

Results of SVR:

Normalization of ALT levels
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Improvement in inflammation and fibrosis
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Improvement in quality of life
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Reduction in the risk of developing hepatocellular carcinoma
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Reduction in the risk of liver-related morbidity and mortality
HCV Treatment Timeline
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1997 FDA approves Infergen (interferon alfacon-1)
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Interferon and Pegylated Interferon.

Interferon is similar to a protein your body makes to fight off infection.

Pegylated interferon is a long-acting form of interferon that’s administered as
an injection. Used with Ribavirin.

These treatments have significant side effects, and many people with HCV
were not able to take it or stopped therapy due to these side effects.

In US newer meds have replaced Interferon and its use is expected to
decrease in other countries as all-oral treatment options become available.

Ribavirin (RBV) Is used in combination with interferon, which increases the
chances of eliminating the virus from your body, never monotherapy.
HCV Treatment Timeline

May 2011 Protease inhibitors Boceprevir, Telaprevir were approved as
direct-acting antivirals (DAAs). Called triple therapy because it was used in
combination with Peg-IFN/RBV therapy.

December 2013 Polymerase inhibitors Sofosbuvir (brand name SOVALDI), It
works by blocking a specific protein the Hepatitis C virus needs to
grow. Sofosbuvir, a once-daily pill, was approved to treat HCV genotypes 1, 2,
3 and 4. For GT2 and GT3 an interferon-free regimen with ribavirin.

October 2014 The first combination pill to treat Hepatitis C, GT1 an all-oral
treatment regimen. Ledipasvir/sofosbuvir (brand name HARVONI) directacting antivirals (DAAs), which interfere with the enzymes the hepatitis C
virus needs to multiply.
HCV Treatment Timeline

December 2014 Combination medicine, which can be given with or without
ribavirin GT1B. Ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets
(brand name VIEKIRA PAK)

July 2015 TECHNIVIE for the treatment of HCV genotype 4 and DAKLINZA for
the treatment of HCV genotype 1 & 3. Technivie was approved for use in
combination with ribavirin for the treatment of HCV Gt 4 in patients without
scarring and cirrhosis. This is the first treatment option for people with
genotype 4 that does not require co-administration of interferon.

Daclatasvir (Daklinza) Class of drugs called direct acting anitvirals or DAAs –
was approved for use with sofosbuvir (Sovaldi) to treat HCV genotype 3
infections. Daklinza is the first drug that demonstrated safety and efficacy in
treating HCV GT 3 without the need of interferon or ribavirin.
HCV Treatment Timeline

January 2016 Zepatier, a combination of elbasvir and grazoprevir, with or
without ribavirin earned FDA approval. (SVR) rates of up to 97 percent in
genotype 1 patients and up to 100 percent in patients with genotype 4.
(11).
HCV Treatment DAA’s
•
•
•
•
2013 Less side
effects
High cure rate
Need RBV GT 2, 3
Peg RBV GT 1, 4
Sovaldi
Zepatier
Harvoni
Sovaldi
•
•
•
•
2014 Less side
effects
High cure rates
No INT RBV
GT 1,4,5,6
Harvoni
•
•
•
•
2016 Less side
effects
High cure rate
May Need RBV
NS5A assay for
GT1a
Zepatier
Daklinza
•
•
•
2016 Less side
effects
With Sovaldi
For GT 1, 3
Daklinza
HCV Treatment
Adverse Reactions


Adverse effects are common with IFN and
ribavirin combination therapy. Approximately
75% of patients experience one or more of
adverse effects.
Adverse effects of IFN include the following:

Hematologic complications (ie, neutropenia,
thrombocytopenia)
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Neuropsychiatric complications (ie, memory and
concentration disturbances, visual disturbances,
headaches, depression, irritability)

Flu-like symptoms
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Metabolic complications (ie, hypothyroidism,
hyperthyroidism, low-grade fever)
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Gastrointestinal complications (ie, nausea,
vomiting, weight loss)
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Dermatologic complications (ie, alopecia)
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Pulmonary complications (ie, interstitial fibrosis)

Adverse effects of ribavirin include the
following:

Hematologic complications (ie, hemolytic anemia)

Reproductive complications (ie, birth defects)

Metabolic complications (ie, gout)
HCV Treatment
Adverse Reactions

Harvoni Headaches, Insomnia, Nausea, Diarrhea, Fatigue
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Viekira Pak Fatigue, Nausea, Pruritus, Insomnia, Weakness
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Daklinza Nausea, Decreased Appetite, Difficulty Sleeping, Headache,
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Fatigue, Flu-like illness, Fever, Itching, Dry skin
HCV Treatment
Contraindications and Cost

New Medications Harvoni, Viekira Pak, Daklinza

1. PPI’s, Statins, Amiodarone, Seizure Meds, St John’s Wort etc

2. Renal restrictions (GFR, Creatinine), Compensated, Decompensated
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3. Prior treatment

Cost Factor
HCV Treatment
SVR

Monitoring Post treatment Labs

HCV RNA at week 4, 12, 24, 1 year

CBC(or full blood count), CMP, liver function testing (ALT, AST, Alk Phos)
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Ultrasound or CT-Scan if F3, F4.
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Antibody not helpful post treatment
HCV Special Considerations

Testing NS5A Resistance

New Meds, pangenotype meds Epclusa

Advanced cirrhosis

HIV coinfection

Gender Men increase in progression of F3 and F4 (20 yrs)

Genotype 3 rapid progression

Genotype 1 and 3 higher relapse rate
HCV Summary

130–150 million people globally have chronic hepatitis C infection

HCV infection one of the main causes of chronic liver disease

HCV Screening, and Identify High Risk Populations
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HCV Testing to Evaluate for Best Treatment Options

Support and Monitor during Treatment, Post Treatment Monitor for SVR

Recognize Barriers to Treatment, and Prevention Measures.
QUESTIONS???
References

1. National Institutes of Health Consensus Development Conference Statement:
Management of hepatitis C 2002 (June 10-12, 2002) Gastroenterology.
2002;123(6):208299. [PubMed]

2. Centers for Disease Control and Prevention. Recommendations for prevention
and control of hepatitis C virus (HCV) infection and HCV-related chronic disease.
MMWR Recomm Rep. 1998;47:139. [PubMed]

3. Choo Q.L. et al. Isolation of a cDNA clone derived from a blood-borne non-A,
non-B viral hepatitis genome. Science. 1989;244(4902):359?62. [PubMed]

4. WHO Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J,
et al. Global and regional mortality from 235 causes of death for 20 age groups in
1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
Lancet 2012;380:2095-2128
References

5. Hepatology. 2015 Jan; 61(1): 77?87.
Published online 2014 Jul 28. doi: 10.1002/hep.27259
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6. www.cdc.gov/hepatitis/HCV
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7.Ghany MG, et al. Hepatology. 2009;49:1335-1374
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8. www.hepatitiscentral.com/hcv/genotype/explained
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9. http://emedicine.medscape.com/article/177792-treatment
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10. http://hepc.liverfoundation.org/treatment/the-basics-about-hepatitis-ctreatment/advances-in-medications/
References
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11. http://www.hepatitiscentral.com/medications-to-treat-hepatitis-c-a-timeline/
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12. http://www.ncbi.nlm.nih.gov/pubmed/22212587
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13..http://www.medscape.com/viewarticle/775855_3
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14. http://www.who.int/mediacentre/factsheets/fs164/en/
15. www.news.emory.edu/stories/.../hepatitis c testing...at.../index.html
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16. https://depts.washington.edu/.../presentations/.../ion3ledipas
17. Kowdley K, et al. N Engl J Med. 2014;370:1879-88
18. www.daklinzahcp.bmscustomerconnect.com/ALLY-1
19. http://www.healio.com/hepatology/hepatitis-c/news/online/%7Bb69f9d74-01d9-47c3903d-b003271bf53c%7D/ally-1-transplant-patients-those-with-cirrhosis-achieve-svr12-withdaclatasvir-sofosbuvir
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