Updates in the Treatment of Hepatitis C

Transcription

1 Disclosures Updates in the Treatment of Hepatitis C Arslan Kahloon M.D Assistant Professor of Medicine University of Tennessee, Chattanooga I have no conflicts of interest or financial sponsorship to disclose Some slides are courtesy of Clinical Care Options (an educational tool) Learning Objectives Understand the burden of the disease from hepatitis C Understand the critical role of primary care physician Review screening guidelines and education about new therapies for hepatitis C Prevalence of Hepatitis C Approximately 3 million individuals in the US are infected with hepatitis C Maybe 7 million with new estimates 170 million individuals infected worldwide Likely greater based on potential undiagnosed cases Becomes chronic in approximately 75-85% of cases Chronic Hepatitis C Is a Progressive Disease HEALTHY LIVER FIBROTIC LIVER CIRRHOTIC LIVER Chronic hepatitis C frequently has few or no symptoms and can progress without signs for decades [1] Most pts with chronic hepatitis C are asymptomatic until serious liver complications arise [2] Hepatitis C Genotypes Genotype 1 is the most common Approximately 75% of cases are genotype 1 (a or b) Approximately 25% have genotypes 2 or 3 Helpful to know genotype for treatment recommendations Duration of therapy differs based on genotype Different areas of the world have different distributions of genotypes 1. CDC. MMWR Morb Mortal Wkly Rep. 1998;47(RR-19): Heidelbaugh JJ, et al. Am Fam Physician. 2006;74:

2 Pts (%) Hepatitis C Virus (HCV) in the US: Gaps in Current Practice Primary Care Clinicians Have a Critical Role in Hepatitis C Care % US prevalence of hepatitis C infection [1] 2% Average pt load for primary care clinician [2] x 2000 pts Average primary care clinician has 40 pts with hepatitis C infection in his/her practice [2] 60 50% 43% 40 27% 20 17% 16% 9% 0 Chronic HCV Infected Diagnosed and Aware Access to Outpatient Care HCV RNA Confirmed Underwent Liver Biopsy Prescribed Achieved HCV Sustained Viral Treatment Response n = 3,500,000 1,743,000 1,514, , , , ,859 Yehia BR, et al. PLoS One. 2014;9:e Chak E, et al. Liver Int. 2011;31: Ferrante JM, et al. Fam Med. 2008;40: Focusing on Cirrhosis Rapid reduction in mortality BUT Means forever playing catch up People with cirrhosis remain at risk of HCC and must remain under surveillance they are the most expensive to treat Slide credit: clinicaloptions.com Hepatitis C Is an INFECTIOUS Virus: Treatment as Prevention Current All-Oral Therapies Highly Effective, Simple, Well Tolerated Sex between men who are HIV-positive Risk of transmission increases the risk of from mother contracting to child is low [2] HCV [3] Infection in monogamous heterosexual couples is rare [1] 1. Terrault NA, et al. Hepatology. 2013;57: Thomas SL, et al. Int J Epidemiol. 1998;27: Larsen C, et al. PLoS One. 2011;6: Shepard CW, et al. Lancet Infect Dis. 2005;5: People who inject drugs account for the majority of new cases of HCV in developed countries [4] Slide credit: clinicaloptions.com Standard Interferon (IFN) IFN 6 Mos References in slidenotes 16 IFN Ribavirin (RBV) IFN/RBV 6 Mos 42 IFN/RBV Peginterferon (pegifn) PegIFN 55 PegIFN/RBV Direct-Acting Antivirals (DAAs) PegIFN/ RBV + DAA DAA + RBV ± PegIFN All-Oral Therapy Current 95+ All Oral DAA± RBV 2

3 Prevalence of Hepatitis C Positive (%) Case 1 When and How to Screen for Hepatitis C Infection Case 1: 56-Yr-Old Woman Presenting to Primary Care A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician She is not aware of having been tested for hepatitis C infection previously CDC, USPSTF, and AASLD/IDSA HCV Screening Recommendations Population Age Recommendation One-time screening is recommended for persons born between 1945 and 1965, without ascertainment of HCV risk [1-3] Risk One-time screening is recommended for persons with these risk factors [1,3] : History of illicit injection drug use (IDU) or intranasal illicit drug use History of long-term hemodialysis Receiving a tattoo in an unregulated facility/setting Healthcare workers upon accidental exposure Children born to anti-hcv positive mothers History of transfusion with blood or organ transplantation Were ever in prison HIV infection Chronic liver disease/hepatitis with unknown cause, including elevated liver enzymes Annual screening is recommended for current IDUs and HIV-infected MSM [3] 1. Smith BD, et al. MMWR Recomm Rep. 2012;61(RR-4): US Preventive Services Task Force. HCV Screening Guidelines AASLD-IDSA. HCV Guidelines Hepatitis C Prevalence is Increased in Baby Boomers Prevalence of Hepatitis C Antibody Positivity in US Population by Sex by Yr of Birth (NHANES III) [1] Iwasaki K, et al. ISPOR Abstract PG17. Screening recommended Male Female Yr of Birth Back to Our Case Case 1 Continued Follow-up After Initial Screening A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician Routine hepatitis C antibody test: reactive 3

4 Recommended Testing Sequence for Identifying Current HCV Infection HCV antibody test Nonreactive Stop Reactive HCV RNA test Not detected No current HCV infection Detected Current HCV infection Provide care or link to care Recommendations for Additional Follow-up of Initial HCV Testing Quantitative hepatitis C RNA testing prior to initiation of antiviral therapy to document baseline viral load Testing for hepatitis C genotype all genotypes can be treated, but genotype will guide choice of antiviral therapy My approach: Ultrasound to look for portal hypertension and identify diabetes, fatty liver Additional testing as appropriate CDC. MMWR Morb Mortal Wkly Rep. 2013;62: AASLD-IDSA. HCV Guidelines Counseling for HCV-Infected Individuals Prevent Hepatitis C Transmission Avoid sharing toothbrushes, dental, shaving equipment Prevent blood contact; do not donate blood Avoid illicit drugs; avoid reusing or sharing drug paraphernalia Risk of sexual transmission is low, except for people with HIV, multiple partners, or STIs AASLD-IDSA. HCV Guidelines Reduce Progression of Liver Disease Test for conditions that accelerate fibrosis Hepatitis B and HIV infections Evaluate for advanced fibrosis Update vaccinations Avoid alcohol Fibrosis Staging in Hepatitis: What You Need to Know Assess whether pt has advanced disease Metavir Stage 0-2 No fibrosis or portal fibrosis Vs Metavir Stage 3-4 Advanced fibrosis or cirrhosis Monitor for progressive fibrosis Noninvasive strategies or biopsy APRI (AST platelet ratio index), FIB-4, FibroSure FibroScan Determines: Treatment duration Use of ribavirin Follow-up after cure Online Calculators: Case 2: 45-Yr-Old Man With Hepatitis C Infection Case 2 Ongoing Management of Hepatitis C Infection for the Primary Care Provider A 45-yr-old man visits your office Diagnosed hepatitis C RNA positive in 2011, previously treated with peginterferon and ribavirin Noninvasive markers suggest Metavir stage 2 (some fibrosis) Now expresses interest in hepatitis C therapy after hearing positive reports about new oral treatments 4

5 HCV Treatment: Get to Know Your Pt Case 2: Initial Workup HCV genotype? Presence of cirrhosis? Previous HCV therapy? Helps tailor: Treatment options Treatment duration Need for ribavirin Key Resource: Parameter Coinfections HCV genotype HCV RNA Transient elastography Finding HAV negative, HBV negative, HIV negative 1a 3,500,000 IU/mL 8.4 kpa (significant fibrosis, F2) Parameter Finding WBC 3500 cells/mm 3 Hemoglobin 14 g/dl Platelets 155/ L INR 1.0 Albumin 3.8 mg/dl Total bilirubin 1.2 mg/dl AST 68 IU/L ALT 64 IU/L Alkaline phosphatase 115 IU/L Creatinine 1.2 mg/dl Pathway Through HCV Therapy Liver biopsy required Lots of follow-up on treatment A yr of feeling lousy with injections Who Should be Treated? Short answer: Everyone! Except those with short life expectancies who cannot be remediated by treating HCV, by transplantation, or by other directed therapy Immediate treatment is assigned the highest priority, which includes patients with: Advanced fibrosis Compensated cirrhosis Liver transplant recipients Severe extrahepatic hepatitis C High risk of transmission Hepatitis C Online When to Refer to an Experienced Hepatitis C Treater Many Options in 2017: Current All-Oral Regimens for Hepatitis C Infection No Need to Refer Refer According to Provider Experience Refer No advanced fibrosis Compensated cirrhosis Decompensated cirrhosis (any ascites) Hepatitis C reinfection Renal impairment If required by insurance Prior treatment with HIV coinfection (refer to peginterferon/ribavirin provider with experience treating HIV) Active substance use Recurrent hepatitis C infection after liver transplantation Regimen Approved Genotypes Grazoprevir/elbasvir 1, 4 Ombitasvir/paritaprevir/ritonavir 4 Ombitasvir/paritaprevir/ritonavir + dasabuvir Sofosbuvir + daclatasvir 1, 3 Sofosbuvir/ledipasvir 1, 4, 5, 6 Simeprevir + sofosbuvir 1, 4 Sofosbuvir/velpatasvir 1, 2, 3, 4, 5, 6 1 Effective options for every genotype Single-pill formulations or 2-pill combinations Effective for all genotypes 5

6 HCV Treatment in 2017 Many highly effective, highly tolerable options All-oral therapy for all Most pts receive: 12 wks of treatment 1 pill, once per day Ribavirin-free therapy Pts with previous pegifn/rbv treatment easy to cure Adverse Events and Drug Drug Interactions Adverse Events Newer hepatitis C medications do not have same adverse events as interferon and are generally well tolerated Discuss most common adverse events and management strategies in pre-education session Headaches: nonpharmacologic management strategies, limits of OTC pain relievers and liver disease Anemia: still a concern when ribavirin needed Encourage pts to report bothersome or unusual adverse events Pretreatment: Look for Potential Drug Drug Interactions Review all herbals/supplements, prescription and OTC meds, including contraceptives and proton pump inhibitors Ask about PRN usage of other drugs Consult with clinical pharmacist when possible Key Resource: Recommended Follow-up After Hepatitis C Treatment Post-treatment Follow-up Characteristic No advanced fibrosis (Metavir stage F0-F2) Advanced fibrosis (Metavir stage F3 or F4) Ongoing hepatitis C risk or unexplained hepatic dysfunction Persistently abnormal liver tests Follow-up No hepatitis C follow-up Twice-yearly ultrasound surveillance for hepatocellular carcinoma If compensated cirrhosis (F4) also test for varices using baseline endoscopy Test for recurrence or reinfection with quantitative hepatitis C RNA assay Test for other causes of liver disease No virologic cure Test for disease progression every 6-12 mos with hepatic function panel, CBC, and INR Consider retreatment options AASLD-IDSA. HCV Guidelines

7 Goal Is Elimination of Hepatitis C Infection Key Points 2030 WHO Targets 90% Diagnosed 80% Treated 65% Reduced Mortality Monitoring and Evaluation National Planning WHO. Towards the elimination of hepatitis B and C by Mitruka K, et al. MMWR Morb Mortal Wkly Rep. 2015;64: Provider Education Capacity Assessment Improve Treatment Access Secure Political Commitment Partnership Development All pts born should be screened for hepatitis C infection Know risk-based screening recommendations Virtually all pts with hepatitis C infection should be treated, regardless of genotype and fibrosis Prevents morbidity, progression of fibrosis, hepatocellular carcinoma Many pts can be treated in primary care setting Must refer pts with decompensation (ascites) Current treatments include pangenotypic and ribavirin-free options > 95% rate of cure for most genotypes Most therapies are 12 wks, ribavirin free, all oral, once daily 7