Managing Hepatitis C in Vermont Module 4: Linkage to Care and Treatment Basics

Welcome to the HCV Linkage to Care and Treatment Basics Module Please take this brief pre-module quiz Click here for brief pre-module quiz or use this web address: https://forms.gle/VRZY6RWKcvPEKLEs8

This module works a lot better in “presentation” mode Above, go to “Slide Show” then hit “From Beginning” and click-through

Outline Who is a good treatment candidate and when should treatment be deferred? Linking care to VT HCV Treatment providers, and what information they need Navigating the landscape of medication coverage Basics of treatment: Common medications and how they work How long to expect treatment to last Using HCV Guidelines as a guide What patients for side-effects and lab testing while on treatment Testing for cure What to tell patients who have been cured, and those who have not been cured, and how to monitor each

Outline Who is a good treatment candidate and when should treatment be deferred? Linking care to VT HCV Treatment providers, and what information they need Navigating the landscape of medication coverage Basics of treatment: Common medications and how they work How long to expect treatment to last Using HCV Guidelines as a guide What patients for side-effects and lab testing while on treatment Testing for cure What to tell patients who have been cured, and those who have not been cured, and how to monitor each

Who is a good treatment candidate and when should treatment be deferred? Cure of HCV is a very good thing! >70% risk reduction in liver cancer, and >90% risk reduction in liver-related mortality Increased physical, emotional, and social health The current standard of care is to treat ALL chronically HCV infected patients except: Those with a short life expectancy Patients who are unable to adhere to the treatment regimen Patients who are pregnant or breast feeding. There are insufficient safety data for HCV in these groups and HCV treatment should be delayed. From https://www.hcvguidelines.org/evaluate/when-whom

Who is a good treatment candidate and when should treatment be deferred? What about in Persons Who Inject Drugs (PWID)? HCV prevalence in PWID approaches 70% Injecting drugs causes 70% of new HCV infections There is no effective HCV vaccine Treatment of PWID is important both for the patient as well as HCV transmission prevention Treatment as prevention! HCV treatment for PWID works best in a multidisciplinary fashion including social work, opioid replacement therapy, needle-exchange programs, and committed medical providers

Cost of NOT achieving HCV cure Cost of managing: Compensated cirrhosis Decompensated cirrhosis Hepatocellular carcinoma Liver transplant (~$600,000) Razavi et al. Chronic HCV disease burden and cost in the United States. Hepatology 2013.

‘Bring your friends’ approach may optimize treatment and prevention outcomes in PWID Treat all members of an individual’s injection network Optimize treatment outcomes (Peer support) Reduce risk of reinfection (reduce reservoir of HCV in a network) Courtesy of Shruti Mehta, Johns Hopkins

Who is a good treatment candidate and when should treatment be deferred? What about in Persons Who Inject Drugs (PWID)? PWID who do not share needles, and always use clean syringes, are good candidates for HCV treatment Patients who are actively injecting drugs and sharing needles with others may be poor HCV treatment candidates given high risk of re-infection, though could become good candidates if: They and their cohort of co-users are all treated simultaneously They are linked to needle exchanges and stop sharing needles They can achieve abstinence

Outline Who is a good treatment candidate and when should treatment be deferred? Linking care to VT HCV Treatment providers, and what information they need Navigating the landscape of medication coverage Basics of treatment: Common medications and how they work How long to expect treatment to last Using HCV Guidelines as a guide What patients for side-effects and lab testing while on treatment Testing for cure What to tell patients who have been cured, and those who have not been cured, and how to monitor each

Linking care to VT HCV Treatment providers, and what information they need Currently, many VT healthplans require the involvement of a subspecialty HCV provider, either from Infectious Diseases or Gastroenterology As HCV treatment becomes easier and increasingly less expensive, likely in the future subspecialist involvement will not be universally required Primary Care Professionals should obtain basic information and labs so that the subspecialist can get the patient on HCV treatment right away

What information HCV specialists need (within last 6 months) Labs Other Info HCV viral load and genotype ALT, AST, bilirubin, alkaline phosphatase, albumin Creatinine Complete blood count Prothrombin time (PTT) HIV serology Hepatitis B surface antibody, surface antigen, and core antibody Hepatitis A total antibody Cirrhosis or not? (see Module 3) HCV treatment naïve or experienced? Ensure not pregnant if a woman of child-bearing age Medication list Health plan

Where are HCV Treatment Specialists in Vermont?

Central Vermont Medical Center University of Vermont Medical Center Dartmouth-Hitchcock Medical Center Rutland Regional Medical Center

Outline Who is a good treatment candidate and when should treatment be deferred? Linking care to VT HCV Treatment providers, and what information they need Navigating the landscape of medication coverage Basics of treatment: Common medications and how they work How long to expect treatment to last Using HCV Guidelines as a guide What patients for side-effects and lab testing while on treatment Testing for cure What to tell patients who have been cured, and those who have not been cured, and how to monitor each

Navigating the landscape of HCV medication coverage Although HCV drug costs have come down significantly, HCV drugs remain expensive When the new HCV drugs came out, most health plans had “fibrosis restrictions,” limiting drug coverage to patients with more advanced fibrosis For instance in 2016 in Vermont, Medicaid required patients have F2 fibrosis or higher to qualify for HCV treatment However, the landscape is quickly changing…

Who is eligible for treatment? An Improving Landscape

2014 No Medicaid fibrosis restrictions F1 restriction F2 restriction F4 restricton

Are there HCV patients in your panel newly eligible for treatment? 2018 No Medicaid fibrosis restrictions F1 restriction F2 restriction F3 restriction F4 restricton Are there HCV patients in your panel newly eligible for treatment?

Navigating the landscape of HCV medication coverage On January 1, 2018, Vermont Medicaid dropped all fibrosis restrictions for HCV treatment Most but not all other health plans in VT have followed suit There are now many chronically HCV infected patients in Vermont who have access to HCV treatment who did not previously, and should be linked to care

Outline Who is a good treatment candidate and when should treatment be deferred? Linking care to VT HCV Treatment providers, and what information they need Navigating the landscape of medication coverage Basics of treatment: Common medications and how they work How long to expect treatment to last Using HCV Guidelines as a guide What patients for side-effects and lab testing while on treatment Testing for cure What to tell patients who have been cured, and those who have not been cured, and how to monitor each

HCV Treatment Multiple highly-effective regimens Selection may be guided by health plan restrictions Treatment range: 8-12 weeks All patient groups have a >95% virologic cure rate with 1st line agents www.hcvguidelines.org

HCV Treatment Let’s look at where and how 1st line HCV drugs work… www.hcvguidelines.org

HCV Viral Structure NS3/4a Protease NS5A Transcription co-factor NS5B RNA polymerase HCV Viral Structure

Harvoni Epclusa Zepatier Mavyret HCV Viral Structure NS3/4a Protease NS5A Transcription co-factor NS5B RNA polymerase Grazoprevir Glecaprevir Ledipasvir Velpatasvir Elbasvir Pibrentasvir Sofosbuvir Harvoni Epclusa Zepatier Mavyret HCV Viral Structure

HCV Treatment in Vermont in 2019 made easy Genotype 1a Mavyret Epclusa Harvoni Zepatier Genotype 1b 12-16 weeks 8-12 weeks Genotype 2 Genotype 3 8-12 weeks 12 weeks Genotype 4 Harvoni Zepatier Genotype 5 Genotype 6 Harvoni

HCV Treatment: The Bible www.HCVguidelines.org These HCV guidelines are the current standard of care and should always be consulted before starting HCV treatment.

What patients on treatment can expect regarding side-effects The main side effects are: Headache Fatigue These are usually mild and rarely limit the patient’s ability to complete treatment

Drug-Drug interactions with HCV Treatment Many drugs interact with HCV medications and may need to be stopped or modified Acid suppressive medications, such as PPIs and H2 blockers, can significantly decrease HCV med absorption These medications are best stopped during HCV treatment. If that is not possible, talk with an HCV specialist. Birth control also often an issue, requires careful selection of HCV medications This website is an excellent resource to check HCV medication drug- drug interactions: https://www.hep-druginteractions.org/

What patients on treatment can expect regarding lab testing Labs should be drawn every 4 weeks while on treatment, including: HCV RNA viral load The HCV RNA viral load should drop precipitously. However, if it goes to 0 while on treatment that does NOT mean the patient is cured yet Complete blood count Creatinine, AST, ALT, Alk Phos, and total bilirubin If 4 week viral load is undetectable and other labs look good, in non- cirrhotic and non-co-infected, HCV therapy compliant patients, it is reasonable to NOT get week 8 and 12 labs as they are unlikely to be abnormal.

Testing for cure A negative HCV RNA viral load 12 weeks AFTER the end of treatment is called a sustained virologic response (SVR, or SVR12) Patients who achieve SVR12 are very likely to be cured of their HCV infection All patients should have SVR12 checked In patients with cirrhosis, an HCV RNA viral load should also be checked at 24 weeks after treatment, because of late recurrences Cirrhotic patients need SVR12 and SVR24

What to tell patients who have been cured Congratulations! However…. They are not immune from HCV and can easily get it again via injection drug use, sex, or other methods of body fluid sharing (via toothbrushes, razors, nailclippers) They will always have a positive HCV antibody (serology). Thus they will always “screen positive” on an HCV test. The only way to know if they are re-infected with HCV is to obtain an HCV RNA viral load In patients at high-risk for HCV re-infection (in particular persons who inject drugs), an HCV RNA viral load at least once yearly is indicated to monitor for re-infection

What to tell patients who have not been cured despite HCV treatment 2-5% of patients receiving HCV therapy will not be cured with the 1st round of therapy Cure is still very likely with a 2nd round of a different type of HCV therapy These patients need to see a Hepatologist or Infectious Diseases physician with expertise in HCV care

Treating HCV: Key Points Most patients with HCV can and should be treated and cured Treatment for HCV follows strict guidelines as outlined at www.HCVguidelines.org Be sure to check for drug-drug interactions before starting HCV therapy, especially acid-suppressing medications and birth control Patients need routine lab monitoring while being treated for HCV, and a test of cure 12 weeks after therapy is complete Patients who have been cured can be re-infected and must be counseled on how to avoid this

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