Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine CME Conference March 10 13, 2016 Disclosures: Hep C Update N. Randy Kolb, MD Speakers has received Funding from Gilead Science for investigator sponsored research related to the care of patients with Hepatitis C and B. The speakers have attested that their presentation will be free of all commercial bias toward a specific company and its products. The speakers indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices. This activity was funded in part by an educational grant from Gilead Science at the Pittsburgh CME Conference, which had no control over the content.
Hepatitis C update N. Randall Kolb M.D. Program Director UPMC Shadyside Family Medicine residency March 13, 2016 1 Disclosure Dr. Kolb has received Funding from Gilead Science for investigator sponsored research related to the care of patients with Hepatitis C and B. No conflict of interest exists. This activity was funded in part by an educational grant from Gilead Sciences., Inc. at the Pittsburgh CME Conference, which had no control over the content. 2 Which is correct regarding Hepatitis C in the US? A. Hepatitis C is the second leading indication for liver transplant (following Chronic Hepatitis B) B. Hepatitis C screening is recommended by USPSTF with an A rating C. Hepatitis C is the most common blood borne disease D. Most patients with Chronic active Hepatitis C will eventually develop life threatening complications (cirrhosis, HCC) 3 1
Which is correct regarding Hepatitis C screening? Screen all patients born 1945 1965 once with anti HCV blood test A. if + check liver enzymes, if more than 2x normal refer for liver biopsy B. if + get HCV RNA test, if both +, refer for liver biopsy C. and screen all adults with risk factors by anti HCV antibody test, if + get HCV RNA test D. is not recommended by USPSTF 4 Which is correct regarding Hepatitis C treatment? A. Current treatment for HCV leads to >15% of patients discontinuing therapy because of serious side effects B. Treatment protocols are based on stage of liver disease, genotype and prior treatment C. Treatment of patients with prior failures is not recommended because of the poor success even with a different agent D. Provisions in the ACA require health plans to offer treatment for all active hepatitis C patients 5 Learning goals Screen appropriate patients for Hepatitis C Counsel patients who screen positive for Hepatitis C and implement an appropriate work up Recognize patients who are candidates for antiviral treatment of Hepatitis C and sources of current information on treatment 6 2
What is your current practice? A. Do not care for Hepatitis patients B. Care for patients but no organized system to screen C. Screen for Hepatitis C and refer positive patients D. Screen and evaluate and refer chronic hepatitis C patients E. Screen, evaluate, treat and refer complicated patients such as decompensated cirrhosis, or treatment failures 7 Hepatitis C background About 3% world wide Most common reason for liver transplantation Surpassed HIV as cause of death in 2007 (US). Increased incidence in baby boomers up to 4.3% Additional cohort of people at risk because of percutaneous exposure and risky sexual behaviors 8 Hepatitis C Background Identified 1989 is a flavivirus like dengue, zika and yellow fever Six genotypes with different responses to treatment Chronic inflammation leads to fibrosis and cirrhosis Over decades can decompensate especially with alcohol use Hepatocellular cancer (HCC) can develop in patients with cirrhosis 9 3
Acute Hepatitis C Only 20 30% have symptoms Diagnose in patients with acute hepatitis who have negative serology for Hep A and B By six months after exposure 97% have positive anti HCV HCV RNA is positive soon after exposure 10 Chronic Hepatitis C 120% 100% 80% 60% infected, 100% 40% Chronic, 85% liver disease, 60% 20% 0% cirrhosis, 15% infected Chronic liver disease cirrhosis Die Die, 2% 11 Higher incidence groups IVDU most common risk factor rising incidence in non urban counties since 2006, source of a new cohort up to 90% prevalence in some groups of IVDUs 18.1% rate in PA state prisoners (2004 2012) 8 9% in hemodialysis patients 12 4
Risk factors in HCV+ persons Ever injected drugs (even once) On hemodialysis Persistently elevated ALT HIV infected H/o blood components or organ transplant (before 1992) 13 Risk factors continued Sexual transmission 15 20% US HCV patients Multiple partners and h/o other STI MSM HIV pos. partner, group sex and non IV drug use increase risk Vertical transmission esp. with prolonged rupture of membranes, HIV + 14 Low risk factors Breastfeeding Rare transmission among heterosexual couples (no anal sex, no sex or condoms during menses, no sharing toothbrushes) Risk from transfusion 1 in 1,390,000 in US 15 5
Screening guidelines CDC Adults born from 1945 1965 should be tested once Are currently or ever injected drugs Ever on long term hemodialysis Prior recipients of blood transfusions, blood components, or organ transplant before July 1992 Children born to HCV positive mothers* USPTF Adults born from 1945 1965 due to potential blood transfusion pre 1992 or other risk factors for exposure decades earlier Past or current injection drug use Long term hemodialysis Received blood transfusion before 1992 Born to HCV infected mother 16 CDC Received clotting factor concentrates produced before 1987 Persistently abnormal alanine aminotransferase levels HIV infection Prior recipients of transfusions or organ transplants that was notified blood from donor later tested positive for HCV infection Healthcare, emergency medical, and public safety workers after needle sticks, sharps, or mucosal exposures to HCV positive blood* USPTF Incarceration Intranasal drug use Getting an unregulated tattoo or other percutaneous exposures 17 Screening algorithm 18 6
Interpretation of results Anti HCV HCV RNA Interpretation Neg Neg no infection Pos Pos acute or chronic HCV Pos Neg resolved Neg Pos early acute, immunocompromised 19 Interpretation of results For persons who might have been exposed to HCV within the past 6 months, testing for HCV RNA or follow up testing for HCV antibody is recommended. For persons who are immunocompromised, testing for HCV RNA can be considered. To differentiate past, resolved HCV infection from biologic false positivity for HCV antibody, testing with another HCV antibody assay can be considered. Repeat HCV RNA testing if the person tested is suspected to have had HCV exposure within the past 6 months or has clinical evidence of HCV disease, or if there is concern regarding the handling or storage of the test specimen. Source: CDC. Testing for HCV infection: An update of guidance for clinicians and laboratorians. MMWR 2013;62(18). 20 Screening rationale No prospective clinical trials of screening, however: For multiple risk factors NNS is <20. Optimal frequency of repeat screens unknown For age cohort one time screen regardless of risk (difficult to recall remote history) Reduced risk of harm using non invasive determination of liver disease stage New DAA agents with higher effectiveness and lower side effects 21 7
65 yo seen for minor illness. A reminder to screen for Hep C pops up. What is next step? A. Order HCV antibody test w reflex HCV RNA B. Ask risk factors (e.g. IVDU, sexual practice, PMH transfusion) if negative inform low risk, no need for further testing C. Order liver enzyme panel D. Ask risk factors (e.g. IVDU, sexual practice, PMH transfusion) and order HCV antibody test w reflex HCV RNA 22 Results are Anti HCV +, HCV RNA what is next step? You asked about risk factors: He is monogamous w wife, no IVDU, no ETOH, tattoos, had blood transfusion 30 yrs ago A. Inform negative no further testing needed B. Inform no active disease, instruct to not share toothbrush or razor, use condoms C. Order liver enzymes and Hep C genotype test D. Inform negative, enter reminder for annual Hep C test 23 Risk reduction Knowledge of HCV+ promotes decreased alcohol use and sharing needles. Conflicting evidence how effective counseling regarding long term risk reduction such as long term alcohol or acetaminophen use. Immunizations for Hep A and B 24 8
Cascade of care 25 Cascade of Care for HCV Infection within the US VA Number with HCV Infection n=224,658 Diagnosed with HCV n=180,489 (80%) Linked to care n=160,794 (72%) Antiviral treatment n=43,544 (19%) Achieved SVR n=22,159 (10%) Percent of estimated with HCV infection 100 80 60 40 20 0 Comparison of Cascade of HCV Care in 2013 and 2014 78 80 69 72 VHA 2013 VHA 2014 Diagnosed with HCV Linked to HCV care 17 19 Treated with HCV antivirals The VA has diagnosed the majority of patients with HCV (80%) and linked them to HCV care (72%) 7 10 The largest gap in care remains the initiation of antiviral treatment SVR Case 2 1. 65 yo presents for acute visit with fatigue, muscle aches and dark urine. Depression screen is positive and further evaluation finds moderate depression. SH: He lost job 2 months ago at Agway. Admits to using heroin twice last month with his son. He is embarrassed and though he feels sad and hopeless he insists he will not use again. 27 9
What is best next step for lab testing? A. Order Anti HCV test B. Order Anti HCV and HCV RNA PCR tests C. Ask him to return in six months to be screened for hepatitis C D. Order bilirubin, liver enzymes, acute hepatitis A&B panel and Anti HCV and HCV RNA tests 28 What tests if Hepatitis C screen is positive? Goals: 1. If active, HCV only or also HIV or Hepatitis B? 2. Any evidence of cirrhosis? 3. HCV genotype? HCV RNA level (PCR) viral load HIV antibody (ELISA) Hepatitis B surface antigen and antibody AST, ALT, Platelet count Fibrosis Assessment Liver imaging: RUQ US HCV genotype 29 Initial evaluation History Complete list medications and supplements, e.g. OTC PPI PMH severe psychiatric disease (not contra indicated in DAA therapy, was issue in INF based treatments) IVDU, number sexual partners, ETOH Previous evaluation for Hep C, estimated time when acquired ROS fatigue, MSK sx, cirrhosis sx 30 10
Initial evaluation Exam Nutritional status Dilated veins (portal HTN), spider nevi, palmar erythema Jaundice, gynecomastia Palpable purpura, blisters and vesicles Enlarged liver, spleen 31 Assess priority for treatment Cost prohibitive: 3.5 million patients at about $100,000 per course is $350 billion. Most insurers will authorize only high priority pts. Priority based on stage of liver disease Metavir stage of fibrosis and cirrhosis Decompensated liver disease Presence of HCC Presence of renal or autoimmune disease Patient readiness to complete treatment 32 Assess readiness to treat Many of the factors which increase risk of Hep C also create barriers to care e.g. IVDU, homelessness, incarcerated The Psychosocial Readiness Evaluation and Preparation for Hepatitis C Treatment (PREP C) is a free interactive online tool that enables you to provide a thorough assessment of a patient s psychosocial readiness to begin Hepatitis C treatment, and make a treatment plan to improve treatment readiness. PREP C.org 33 11
Assess stage of fibrosis 34 Assess stage of fibrosis 35 Assess stage of liver disease Many payers require estimate of Metavir stage Fibrotest FibroScan Liver biopsy generally not required Ultrasound poor for fibrosis, may help identify HCC 36 12
Case 3 42 yo heard about Hepatitis C treatment from friends and came to office wanting to be tested. He used IVD when 20, none for last 22 years. Uses 5 6 drinks/week ETOH. No travel, no sexual contact with HCV + partner, no blood transfusions. His screening blood test result: Anti HCV +, HCV RNA + 37 What is next step in evaluation A. Refer for liver biopsy B. Order CBC and CMP and calculate probability of fibrosis C. Order CBC and CMP and either Fibrotest or Fibroscan D. Order CBC, CMP, HIV, liver US, Fibrotest or Fibroscan 38 Assess eligibility for treatment Determine genotype Must evaluate for decompensated liver disease Know other chronic conditions and medications which might affect drugs used to treat Hepatitis C Determine satisfactory psychosocial situation to complete course Complete prior authorization for medications 39 13
Attitude of FM program directors 40 CDC Any physician who manages a person with hepatitis C should be knowledgeable and current on all aspects of the care of a person with hepatitis C; this can include some internal medicine and family practice physicians as well as specialists such as infectious disease physicians, gastroenterologists, or hepatologists 41 Case 4 60 y.o. HIV negative with Genotype 1b Treatment naive Has cirrhosis: FIB4>3.25 and F4 score on Fibrosure test Child Turcotte Pugh: class A (not decompensated) Liver ultrasound showed cirrhotic morphology no masses 42 14
Which is correct regarding Hepatitis C in the US? A. Hepatitis C is the second leading indication for liver transplant (following Chronic Hepatitis B) B. Hepatitis C screening is recommended by USPSTF with an A rating C. Hepatitis C is the most common blood borne disease D. Most patients with Chronic active Hepatitis C will eventually develop life threatening complications (cirrhosis, HCC) 43 Which is correct regarding Hepatitis C screening? Screen all patients born 1945 1965 once with anti HCV blood test A. if + check liver enzymes, if more than 2x normal refer for liver biopsy B. if + get HCV RNA test, if both +, refer for liver biopsy C. and screen all adults with risk factors by anti HCV antibody test, if + get HCV RNA test D. is not recommended by USPSTF 44 Which is correct regarding Hepatitis C treatment? A. Current treatment for HCV leads to >15% of patients discontinuing therapy because of serious side effects B. Treatment protocols are based on stage of liver disease, genotype and prior treatment C. Treatment of patients with prior failures is not recommended because of the poor success even with a different agent D. Provisions in the ACA require health plans to offer treatment for all active hepatitis C patients 45 15
http://hcvguidelines.org/ 46 16