1. Hepatitis C in Primary Care
Mary Alice Walker, FNP Family Nurse Practitioner, Penobscot Community Health Care
Kathryn Cunniff, PharmD Primary Care Pharmacist, Penobscot Community Health Care

2. Disclosures
The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:
Mary Alice Walker: No relationships to disclose
Kathryn Cunniff: No relationships to disclose

3. Session Objectives Recognize ways to increase hepatitis C screening
Formulate a workflow to schedule, assess, and treat patients
Introduce key resources and review medications
Practice a patient case
Review data and outcomes at PCHC

4. Overview of Penobscot Community Health Care (PCHC)
Established in 1998
Federally Qualified Health Center
16 practice sites
100 Primary Care Providers
40 Psychiatric Providers
18 Pharmacists
13 Dentists
7 Physical Therapists
3 Chiropractors
In 2017, 65,000+ patients
Majority uninsured or underinsured
4 integrated pharmacies

5. Increasing Hepatitis C Screening
The CDC’s 2020 goal for hepatitis C is to reduce the rate of acute HCV infections to 0.25 cases per 100,000 U.S. population.
The rate of acute HCV infections reported to the CDC in 2015 was 0.81 cases per 100,000 US population. (Target for 2015 was 0.66)

6. Why Screening for HCV is Important
Chronic HCV can progress to cirrhosis and eventually liver failure and/or HCC
DEATH ~1%−5%
of patients infected with HCV will die from the consequences of chronic HCV infection
LIVER TRANSPLANT #1
HCV is #1 cause of liver transplant
HEPATOCELLULAR CARCINOMA ~1%−5%
of patients with HCV-related cirrhosis will develop HCC annually
CIRRHOSIS 5%−20%
of patients infected with HCV over a period of 20−30 years
HCV Infection Has Serious Clinical Consequences1
Notes
Chronic HCV can progress to cirrhosis and eventually liver failure or HCC.2,3 Approximately 1% to 5% of patients with HCV-related cirrhosis will develop HCC each year3
HCV infection is the leading cause of liver transplants2
For approximately 1% to 5% of all patients infected with HCV, chronic infection results in death2
Almost 20,000 deaths were associated with HCV in 20154
References
Razavi H, El Khoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):
Centers for Disease Control and Prevention. Hepatitis C FAQs for health professionals. Updated January 27, Accessed January 17, 2018.
Mutimer D, Aghemo A, Diepolder H, et al; European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60(2):
Centers for Disease Control and Prevention. Surveillance for viral hepatitis—United States, Updated June 19, Accessed January 17, 2018.
CHRONIC LIVER DISEASE ~60%−70%
of patients with HCV
Almost 20,000 deaths were associated with HCV in 2015
AbbVie Inc. AbbVie Standards of Care. The Importance of Screening to Help Manage the Growing Burden of Hepatitis C Virus. Sept Accessed March 2018

7. Recommendations for One-Time Hepatitis C Testing
All patients born between 1945 and 1965
Risk Behaviors
Injection-drug use
Intranasal illicit drug use
Risk Exposures
Patients on long-term hemodialysis
Patients with percutaneous/parenteral exposure in an unregulated setting (ie. tattoos, piercings)
Healthcare personnel after a needle stick
Children born to HCV-infected mother
Patients who have received transfusions or organ transplants prior to 1992
Patient’s with a history of incarceration
IV drug use to include those who injected only once
AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Date accessed: 2/28/18

8. Recommendations for One-Time Hepatitis C Testing
Other Conditions and Circumstances
HIV infection
Sexually active persons about to start PreP for HIV
Unexplained chronic liver disease and/or chronic hepatitis, including elevated ALT levels
Solid organ donors
AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Date accessed: 2/28/18

9. Recommendation for HCV Testing for Persons with Ongoing Risk Factors
Annual HCV testing is recommended for persons who
Inject drugs
HIV-infected men who have unprotected sex with men
Periodic testing should be offered to any patients with ongoing risk factors for HCV exposure
AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Date accessed: 2/28/18

10. % of Individuals Infected With HCV
20s-50s vs
Injection Drug Use Is the Most Common Mode of Transmission of HCV in the United States
HCV Can Spread in Many Ways
Most common modes of HCV transmission
Injection drug use
Receipt of donated blood, blood products, or organs (prior to 1992 in the United States)
Needlestick injuries in health care settings
A mother infected with HCV can transmit the virus to her baby
Less common modes of transmission
Sex with a person infected with HCV
Sharing personal items contaminated with infectious blood, such as razors or toothbrushes
Prevalence
Populations With High Rates of HCV Infection 90 20 40 60 80
100 %
% of Individuals Infected With HCV 50
Onset % 35 % 29 %
Injection Drug Use Is the Most Common Mode of Transmission of HCV in the United States1
Notes
According to the CDC, an estimated 2.7 to 3.9 million people in the United States have chronic hepatitis C1
Some populations have extremely high infection rates2
An estimated 90% of IDUs, who have used continuously over 10 years, are infected
About half of people who use injection drugs for less than 10 years are infected
Other populations with high rates of infection include those who have been homeless or incarcerated
Although the most common mode of transmission of HCV is IDU, the disease can be spread in many other ways1
Other common modes of transmission include1:
Receipt of donated blood, blood products, or organs (prior to 1992 in the United States)
Needlestick injuries in health care settings
Transmission of the virus from a mother infected with HCV to her baby
Less common modes of transmission include1:
Sex with a person infected with HCV
Sharing personal items contaminated with infectious blood, such as razors or toothbrushes
The US Preventive Services Task Force recommends regular screening for people who currently use injection drugs3
References
Centers for Disease Control and Prevention. Hepatitis C FAQs for health professionals. Updated January 27, Accessed January 17, 2018.
Edlin BR. Perspective: test and treat this silent killer. Nature. 2011;474(7350):S18-S19.
US Preventive Services Task Force. Understanding Task Force Recommendations: Screening for hepatitis C virus infection in adults. Published June Accessed January 17, 2018.
Prisoners
IDU >10 year
IDU <10 years
Homeless Persons 
The US Preventive Services Task Force recommends regular screening for people who currently use injection drugs

11. Hepatitis C Genotypes
Schafer J, Short W. Ask The Experts: Updates and Challenges in Managing Patients with Hepatitis C Virus Infection American Society of Health-Systems Pharmacists. Accessed April 19, 2018.

12. Genotypes in North America

13. Implementations at PCHC
EHR “Pop-up” alert for all patients born between and 1965
This patient population should be screened for hepatitis C per CDC recommendations
This was added to our EHR in 2017
Data to follow
Patients enrolling in one of our Medication Assisted Treatment (MAT) Programs are screened
This patient population has a history of substance use disorder and should be screened for hepatitis C
Data are still in collection

14. Formulate a Workflow to Connect Patients to Treatment
Review resources and medications

15. Hepatitis C Antibody (+): Now what?

16. Additional Labs Within12 weeks prior to starting antiviral therapy:
Complete Blood Count (CBC)
International Normalized Ratio (INR)
Hepatic function panel and fibrosis score
Calculated eGFR
Quantitative HCV RNA (Viral Load)
HCV Genotype and subtype – any time prior to treatment
HIV and RPR
All patients should be assessed for:
HBV coinfection with HBsAg testing
Evidence of prior infection with anti-HBs and anti-HBc testing
Vaccinate when appropriate
Direct Acting Antivirals used to treat hepatitis C have a Black Box Warning with the risk of re-activating hepatitis B infections

17. PCHC’s Workflow Patient w. Active Viral Infection
PCP places a referral in the EHR for infectious disease
Referrals Flags Clinical Pharmacist
Patient chart is reviewed by the clinical pharmacist and a hepatitis C pharmacy consult is posted in the chart
Pharmacist schedules patient with Mary Alice Walker, FNP or indicates a specialist consult is needed
Patient is seen in the Primary Care Office
Additional labs are ordered if needed
Once all results are obtained, the appropriate course of therapy is chosen
Pharmacist Completes the PA process for Medication
PA submitted to insurance
Application is filled out with patient for free medication
Medication Approved
Patient is scheduled to meet with the pharmacist

18. Monitoring Labs After 4 Weeks of Treatment
CBC
Creatinine level
Calculated glomerular filtration rate (eGFR)
Hepatic Function Panel
Quantitative HCV viral load

19. Pharmacist’s Role Initial consult at first medication fill
Review of prescription and OTC medication use
Common side effects and management strategies
Encourage adherence to regimen, and identify potential barriers
Phone check-in at weeks 2, 4, 8, and 12 if indicated
Assess adherence and any adverse reactions
Schedule patient for follow up labs
Coordinate medication refills
Track outcomes once patient has completed therapy

20. Resources Clinical Sources Pharmacy Sources AASLD and IDSA Guidelines
Centers for Disease Control and Prevention (CDC)
Project ECHO
NovaMed Education – HCV Clinician Toolbox
Fibrosis 4 (FIB 4) Score Calculator
Pharmacy Sources
University of Liverpool – HEP Drug Interactions
CoverMyMeds
Gilead’s Support Path Program

21. Harvoni Epclusa Mavyret Vosevi Medications (ledipasvir/sofosbuvir)
Genotype 1a, or1b
1 tablet once daily – 8 or 12 week regimen
Genotype 4, 5, 6
1 tablet once daily – 12 week regimen
Harvoni
(ledipasvir/sofosbuvir)
Genotypes 1, 2, 3, 4, 5, 6
Epclusa
(sofosbuvir/velpatasvir)
3 tablets once daily WITH food – 8 or 12 week regimen
Mavyret
(glecaprevir/pibrentasvir)
Treatment experienced, patients who previously failed other regimens
Vosevi
(sofosbuvir/velpatasivr/
voxilaprevir)

22. Patient Case
Work together to solve the following case

23. Patient: JM 34 year old white male
Patient tested positive for hepatitis C in November of 2015.
2010 through 2011: Patient used IV and intranasal drugs for approximately one year
2012: patient tested negative for hepatitis C
2015 patient had a tattoo done on right leg
Patient has never been treated for hepatitis C
Patient medications:
ranitidine 150 mg twice daily
Suboxone 8-2 mg film daily
What counseling should be provided to this patient?
What labs are indicated for this patient?

24. Counseling & Lab Orders
Patient counseling
Discuss ways to reduce liver disease progression and how to prevent transmission
Encourage abstinence from alcohol and offer support if needed
Labs
HIV co-infection
Hepatitis A and B history
CBC
INR
Hepatic function panel
Calculated eGFR
Quantitative HCV RNA (viral load)
HCV genotype and subtype
Staging of hepatic fibrosis (ie. FIB-4, or liver elastography)
Additionally:
Vaccinate for Hep A and B if patient is not immune
Vaccinate against pneumococcal infection in cirrhotic patients

25. Patient: JM 34 year old white male continued
Lab Results:
HIV – nonreactive
CBC: Platelets: 200
INR: 1.0
Hepatic Function Panel:
AST: 45 [H], ALT: 55 [H], albumin: 4.6 g/dL, T. Bili: mg/dL, Alk Phos: 66 U/L
eGFR:>60 min/hr
Hepatic panel
Hep B Core total IGG and IGM (-)
Hep B surface antibody (+)
Hep B surface antigen (-)
Hep A antibody total (+)
Viral Load: 1,450,000 IU/mL
Genotype: 3a
Fibrosis Score:
FIB-4: 1.52
(> 1.45 = inconclusive)
US Elastography: mild/moderate F2-F3
What should this patient’s treatment plan look like?

26. Determining a Treatment Plan
Choose medication
Determine length of treatment
Identify potential drug interactions
Create a plan to have frequent contact with the patient
i.e. phone calls or clinic visits
After 4 weeks of therapy:
Monitor labs: CBC, SCr, eGFR, hepatic function, and viral load
Additional viral load testing
Consider at end of treatment
To ensure cure draw 12 weeks following completion of therapy

27. Patient: JM 34 year old white male
Appropriate Therapies
Guidelines suggest:
Mavyret x 8 weeks
Epclusa x 12 weeks
Insurance generally directs treatment options

28. Medication Comparison
Mavyret 300/120 mg
3 Tablets WITH food daily
8 -12 weeks of treatment
Serious drug interaction with atazanavir or rifampin
CI in severe hepatic impairment (Child-Pugh C)
Can be used in eGFR < 30 or ESRD
Similarities
Pan-genotypic
Risk of reactivating HBV
Adverse Reactions: Headache and Fatigue
Epclusa
400/100 mg
1 Tablet +/- food daily
12 weeks of treatment
Serious drug interaction w. amiodarone
Can be used in Child-Pugh class A, B, or C
Not recommended in eGFR <30 mL/min

29. Potential Drug Interactions
Mavyret interactions
Epclusa interactions
Acid reducing agents may decrease concentrations of glecaprevir
H2-receptor antagonists may decrease velpatasvir concentrations
Ranitidine may be administered simultaneously with or 12 hours apart from Epclusa
Doses should not exceed the equivalent of famotidine 40 mg twice daily

30. Patient Monitoring Plan
Check-ins and Monitoring
Pharmacist calls after 2 weeks of treatment
Patient is scheduled for a clinic visit after 4 weeks of treatment
Labs drawn
Pharmacist calls when each refill is ready
Patient is scheduled for a clinic visit upon treatment completion
Reminded of future labs
Schedule labs for 4 weeks, end of treatment, and 12 weeks following treatment
Cure = Sustained virologic response (SVR) 12 weeks following final dose of medication

31. Penobscot Community Health Care
Data and Outcomes

32. PCHC’s Hepatitis C Clinic at Brewer Medical Center
Since integrating hepatitis C treatment into our primary care setting in 2017
We have treated 38 patients
14 of which we have SVR results
All are considered cured of hepatitis C
We currently have 11 patients on treatment
As we continue to grow our program we hope to reach more patients in our community

33. Patient Panel
Average patient age: 47
Age range:

34. PCHC's Insurance Coverage Among the Hepatitis C Population
The above data is reflective of patients who have received or are receiving treatment.

35. Genotypes

36. Medication Use

37. Barriers to Treatment Uninsured Lost to follow up
High cost of labs
High cost of medications
Application available through the pharmaceutical companies
Lost to follow up
Unreliable means of communication and transportation
Multiple co-morbidities
Mental health
Substance use disorder
Hepatic complications

38. Screening Baby Boomers
Prior to EHR prompt
After EHR prompt
From November 2016 to February 2017
75,037 patient visits
29,607 unique patients
Total patients screened: 324
From October 2017 to December 2017
70,333 patient visits
27,509 unique patients
Total patients screened: 643
PCHC was able to nearly double screening efforts by implementing an EHR prompt
We are now implementing a screening process for patients admitted to our buprenorphine/naloxone program
This will help us identify additional patients at risk for hepatitis C

39. Questions?

40. References:
CDC. Testing for HCV infection: An update of guidance for clinicians and laboratorians. MMWR 2013;62(18).
CDC. Hepatitis FAQs for health professionals. Updated January 27, 2017.
Mutimer D et al. J Hepatol. 2014;60(2):392‐420.
CDC. Surveillance for viral hepatitis—United States, Updated June 19, 2017.
1. CDC. Hepatitis C FAQs for health professionals. Updated January 27, Edlin BR. Nature. 2011;474(7350):S18-S US Preventive Services Task Force. Understanding Task Force Recommendations: Screening for hepatitis C virus infection in adults. Published June 2013
AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Accessed March 7, 2018.
Harvoni [package insert]. Foster City, CA. Gilead Sciences, Inc
Epclusa [package insert]. Foster City, CA. Gilead Sciences, Inc
Mavyret [package insert]. North Chicago, IL. AbbVie Inc
Vosevi [package insert]. Foster City, CA. Gilead Sciences Inc. 2017