Author: Philip Bolduc, MD. New England AETC This lesson will focus on the fundamentals of treating HCV infection. Understanding the treatment of HCV mono-infection is critical to mastering care of HIV/HCV co-infection.

1. July 2017
Updated: December 2018
Lesson 1: Fundamentals of
Hepatitis C Virus Treatment
Core Competency 4: HCV Treatment

2. Lesson Objectives
At the end of this lesson, participants will be able to:
 Understand the goal of treatment
 Choose appropriate treatment settings
 Describe systems for successful treatment
 Identify patients to treat
 Evaluate patients before treatment
 Select the correct treatment regimen
 Monitor during and after treatment
 Reassess if treatment fails
 Build further knowledge
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3. Goal of Treatment
“The goal of treatment of HCV-infected persons is
to reduce all-cause mortality and liver-related
health adverse consequences, including end-
stage liver disease and hepatocellular carcinoma,
by the achievement of virologic cure as evidenced
by a sustained virologic response.1
AASLD-IDSA
https://www.hcvguidelines.org/
3

4. Current All-Oral Therapies2
Highly effective, simple, well-tolerated
Cure Rates
IFN
6 Mos
PegIFN/RBV
12 Mos
IFN
12 Mos
IFN/RBV
12 Mos
PegIFN
12 Mos
2001
1998
2011
Standard
Interferon
(IFN)
Ribavirin
(RBV)
Peginterferon
(pegIFN)
1991
PegIFN/
RBV +
DAA
IFN/RBV
6 Mos
6
16
34
42 39
55
70+
0
20
40
60
80
100
DAA +
RBV ±
PegIFN
90+
2013
All–Oral
DAA±
RBV
Current
95+
All-Oral
Therapy
Direct-Acting
Antivirals
(DAAs)
Box T, Clinical Care Options. 2017

5. Then (pre-2013) and Now
 Cure rates are much higher today, in some populations
close to 100%
 There is far less medication toxicity
 Length of treatment is shorter
 While HCV medications are expensive, the cost has
come down considerably and they have been shown to
be highly cost-effective in the long run
 Treatment depends on genotype, degree of liver damage
and prior treatment history
 Pan-genotypic medications have simplified treatment
considerably
5

6. HCV Treatment Workforce
 “All persons with current active HCV infection should be
linked to a practitioner who is prepared to provide
comprehensive management.”3
 New potent and well-tolerated hepatitis C treatments
present an opportunity to expand the number of
advanced practice practitioners and primary care
physicians trained in the management and treatment of
HCV infection.
6

7. HCV Provider by Stage of Liver
Disease1
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Child-Turcotte-Pugh Class A (score 5-6)
 GI and HCV-informed ID and primary care providers
Child-Turcotte-Pugh Class B (score 7-9)
 Hepatologists
 GI and HCV-informed ID and primary care providers in
close communication with a supporting hepatologist
Child-Turcotte-Pugh Class C (score ≥10)
 Hepatologists
For an online calculator of the Child-Pugh-Turcotte score, see:
http://www.hepatitisc.uw.edu/page/clinical-calculators/ctp

8. Help Patients Succeed
Use pharmacist, nurse or medical assistant-
based medical case management to:
 Schedule patient intakes
 Submit and track prior authorizations
 Resolve pharmacy and medication delivery
issues
 Make reminder calls for patient visits and labs
 Field patient questions
8

9. Appropriate Patients for Treatment1
 See Lesson 3.2 to review who and when to treat
 Goal should be to treat whenever possible to
reduce HCV transmission and HCV-related
morbidity and mortality
 Treatment may not be of sufficient benefit to
justify the cost if life expectancy is <12 months
9

10. Preparing for Treatment
 Approval for treatment varies by insurer. Factors may
include:
 Fibrosis stage
 Sobriety requirements
 Prescriber type: Hepatology, GI, ID, primary care
 Some states (for example, Maryland) provide and
require a certification process to prescribe HCV
medications
 A good place to start is to investigate your state’s
Medicaid HCV prior authorization process as many
have adopted a standardized form used across various
insurers
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11. Preparing Patients for Treatment
 Achieve medical stability before HCV treatment
 HCV treatment usually is not urgent; most experts prefer to control
HIV infection, cardiac disease, asthma, etc. prior to HCV treatment
 Waiting until the patient has no acute or unstable chronic
conditions avoids confounding comorbid symptoms with treatment
side effects
 Patient must be able to understand and adhere to
care plan
 HCV medications are expensive – use resources wisely by
working aggressively to resolve barriers to success before treating
11

12. Pretreatment Evaluation – History and
Exam:
 Evaluate symptoms and medical comorbidities
 Ask about alcohol and drug use that may impact
treatment
 Elicit information about housing or food insecurity
that may impact treatment
 Reconcile medication list
 Look for stigmata of liver disease (see Module 3)
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13. Pre-treatment Tests1
 Fibrosis staging: (see Module 3 for more details)
 AASLD-IDSA recommends combining a non-invasive serum
biomarker assay (such as FIB-4, FibroSURE, FIBROSpect II) and
elastography (vibration-controlled transient liver elastography, MR
elastography, acoustic radiation force impulse)
 Liver biopsy is reserved for situations in which discordance between
serum and elastography tests will impact clinical decisions
 May also use the biomarker assay alone and reserve elastography or
biopsy for intermediate results (i.e. F2-F3)
 Individuals with clinically evident cirrhosis do not require additional
staging (biopsy or noninvasive assessment)
 Liver ultrasound for most patients; consider CT scan if
cirrhosis present
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FIB-4 Calculator:
https://www.hepatitisc.uw.edu/page/clinical-
calculators/fib-4

14. Pre-treatment Labs4
 Any time prior to treatment:
 HCV genotype and VL (but insurers often require a VL within 6
months of treatment)
 Labs <12 weeks prior to treatment:
 HIV – 4th-generation test preferred (if not HIV infected)
 HAV Ab and HBV cAb, sAb, sAg (vaccinate if not immune)
 If HBV cAb+/sAg-, consider checking HBV DNA, especially if patient is
immunosuppressed, due to HBV reactivation risk with HCV treatment
 LFTs, INR – needed to calculate Child-Turcotte-Pugh score
 CBC (for platelets) and BMP creatinine/eGFR
 TSH if IFN to be used
 Consider AFP if HCC risk higher (cirrhotic or HBV or HDV co-infected)
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15. Influences on HCV Regimen Selection5
 Prior treatment history, whether with IFN or DAAs
 HCV genotype
 Presence or absence of cirrhosis
 If cirrhotic: compensated vs. decompensated
 Renal impairment
 Other comorbid conditions and medication
interactions
15

16. HCV Treatment in Pregnancy and
Breastfeeding4
 No DAAs are approved for use during pregnancy or breastfeeding
 Ribavirin is highly teratogenic
 Women of childbearing age need dependable contraception when taking
ribavirin and for 6 months thereafter
 Men taking ribavirin should avoid close contact with pregnant women during
treatment and for 6 months thereafter
 See Lesson 5.1 for full review of HCV management in pregnancy
 Bottom line: do not treat HCV during pregnancy
 Best to treat before pregnancy until we have data from ongoing trials in
pregnancy
 Providers can however prepare patients for treatment after completion of
pregnancy and breastfeeding
16

17. HCV Medication Classes4
Used in combinations of usually two but sometimes
three medications:
 Protease inhibitors: “previr”
 e.g., glecaprevir, grazoprevir
 NS5A inhibitors: “asvir”
 e.g., ledipasvir, pibretasvir
 NS5B nucleotide polymerase inhibitors: “buvir”
 e.g., sofosbuvir, dasabuvir
 Ribavirin
17

18. Resistance4
 There is no cross-resistance between classes
 AASLD/IDSA HCV medication recommendations tell
you when to screen for resistance prior to treatment
 These guidelines should be consulted each time a
treatment regimen is selected
 For example: treatment-naïve, non-cirrhotic genotype 1a
patients require NS5A resistance testing prior to treatment
with elbasvir/grazoprevir
 For a full review of HCV resistance, please see
https://www.hcvguidelines.org/evaluate/resistance
18

19. Laboratory Monitoring during
Treatment4
 4-week HCV VL, eGFR, LFTs for all regimens
 Plus other labs for some specific regimens – see guidelines
 HCV VL check is recommended by AASLD-IDSA and required by some
insurers, but treatment should not be stopped if the HCV VL is not done
 Consult guidelines for stopping treatment based on side effects or lab
abnormalities
 If 4-week HCV VL undetectable, continue treatment and consider
rechecking at end of treatment (recommendations are not firm)
 If 4-week HCV VL detectable, recheck at 6 weeks
 Consider stopping treatment if 6-week HCV VL has increased, particularly if
10-fold increase from 4-week level
 Consultation with an HCV expert or clinical resource such as the National
Clinician’s Consultation Center (see http://nccc.ucsf.edu/ ) is recommended
19

20. Monitoring after Treatment4
 12-week post-treatment HCV VL:
 if undetectable = SVR = 99% chance of durable cure
 24-week post-treatment HCV VL is optional; order if risk
is higher, such as:
 Viremia present on 4-week HCV VL check
 Adherence problems identified
 Patients who have received a liver transplant
 If viremia reappears at 12 or 24 weeks, consider rechecking
HCV genotype to see if patient may have been dually
infected with a different minority genotype
20

21. Additional Monitoring Post-treatment
 HCC screening with every 6-month liver
ultrasound if F3-F4 fibrosis or cirrhosis
 Also includes:
 Counseling to prevent reinfection
 Screening for reinfection
 Behavior modifications
 See Lesson 2.4 (preventing reinfection) for additional
information
21

22. Chronic HBV/HCV Co-infected
Patients Require Extra Monitoring4
 HCV can suppress HBV in vivo, so HBV may flare when HCV is
treated
 More common in HBV sAg+ patients, but also can occur in isolated
HBV cAb+ patients from latent cccDNA
 Risk is much lower in HIV co-infected patients who are on tenofovir,
lamivudine, or emtricitabine
 Stage chronic HBV patients with eAg/eAb/ALT/VL before
treatment for HCV (along with the fibrosis assessment), then
check ALT and HBV VL during and immediately after HCV
treatment
 Treat if HBV treatment criteria are met (see Resources)
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23. If Treatment Is Deferred1
 Annual assessment of fibrosis progression – labs
and vibration-controlled transient elastography or
equivalent testing
 HCC screening with liver ultrasound every 6
months in patients with advanced fibrosis
(METAVIR F3 or F4)
 Work to resolve barriers to treatment
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24. When Treatment Fails
 DAA resistance and re-treatment strategies are areas of
ongoing research; consult AASLD-IDSA guidelines7
 General approach – do two of the following8:
 Switch regimen
 Add ribavirin
 Lengthen treatment
 Consider NS5A resistance testing
 With all patients, assess adherence and work to resolve
adherence barriers
 May also wait for new therapies if re-treatment is not urgent
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25. Key Points
 Non-hepatologists can and should provide HCV
treatment to confront the HCV epidemic
 The AASLD-IDSA HCV Guideline website is the
definitive source for treatment recommendations
 Other websites provide helpful clinical tools and
opportunity to practice and reinforce knowledge
 The main challenge in HIV/HCV co-infection
treatment is managing drug interactions
25

26. References
1. AASLD-IDSA. When and in whom to initiate HCV therapy. Recommendations for testing, managing, and treating
hepatitis C. http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy. Accessed December 31,
2018.
2. Box TD. Hepatitis C Update for Primary Care. Clinical Care Options. February 21, 2017. Accessed July 7, 2017 at
http://review.clinicaloptions.com/Hepatitis/Treatment%20Updates/Primary%20Care.aspx
3. AASLD-IDSA. HCV testing and linkage to care. Recommendations for testing, managing, and treating hepatitis C.
http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care. Accessed December 31, 2018.
4. AASLD-IDSA. Monitoring patients who are starting hepatitis C treatment, are on treatment, or have completed
therapy. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-
report/monitoring-patients-who-are-starting-hepatitis-c-treatment-are-treatment-or-have. Accessed December 31,
2018.
5. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org.
Accessed December 31, 2018.
6. AASLD-IDSA. Retreatment of Persons in whom prior therapy has failed. Recommendations for testing, managing,
and treating hepatitis C. http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed.
Accessed December 31, 2018.
7. Feld JJ. How I manage patients with HCV after DAA treatment failure. Clinical Care Options Hepatitis.
http://review.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20Resistance%20Alert/Clinical%20Thoughts
/CT2.aspx. Posted 11/19/2016. Accessed April 17, 2017.
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27. Resources
 Hepatitis C Online: Module 5: Treatment of Chronic Hepatitis C
Infection.
 Slide presentations
http://www.hepatitisc.uw.edu/browse/all/lectures
 Case studies
http://www.hepatitisc.uw.edu/go/treatment-infection
It is essential to practice what you have learned right away, so take the time to complete these
cases before moving on.
 Hepatitis C Online: Child-Turcotte-Pugh Calculator
http://www.hepatitisc.uw.edu/page/clinical-calculators/ctp
 Hepatitis B Web Study. https://www.hepwebstudy.org
 Live expert support: National Clinicians Consultation Center
http://nccc.ucsf.edu/ or call (844) HEP‐INFO or (844) 437-4636
Monday – Friday, 9 a.m. – 8 p.m. ET
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28. Authors and Funders
 This presentation was prepared by Philip J. Bolduc, MD (New
England AETC) for the AETC National Coordinating Resource
Center in July 2017 and updated December 2018.
 This presentation is part of a curriculum developed by the
AETC Program for the project: Jurisdictional Approach to
Curing Hepatitis C among HIV/HCV Co-infected People of
Color (HRSA 16-189), funded by the Secretary's Minority
AIDS Initiative through the Health Resources and Services
Administration HIV/AIDS Bureau.
28

29. Disclaimer and Permissions
 Users are cautioned that because of the rapidly changing
medical field, information could become out of date
quickly.
 You may use or present this slide set and other material
in its entirely or incorporate into another presentation if
you credit the author and/or source of the materials.
 The complete HIV/HCV Co-infection: An AETC National
Curriculum is available at: https://aidsetc.org/hivhcv
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