6/18/2016. Hepatitis C

Transcription

1 Family Medicine s Role in Diagnosing and Treating Hepatitis C Daniel J. Joyce D.O. Program Director OUHSC Family Medicine Lawton June 18, 2016 Nothing to disclose Disclosure 1

2 Outline Review Hepatitis C Prevalence Discuss Risk Factors Discuss Family Medicines Role How to Diagnose What needs to be done once diagnosed Discuss Treatment My Story Do You Know what kind of people they are? 2

3 Hepatitis C World Health Organization million people are chronically infected with the Hepatitis C virus, >350,000 people dying from Hepatitis C related liver diseases each year. Hepatitis C Countries with high rates of people chronically infected with Hepatitis C are Egypt (22%) Pakistan (4.8%) China (3.2%) United States (1.8%) 3

4 Hep C Numbers 3.9 Million or 1.8% Population 2,900,000 Chronic infected 2,400,000 Undiagnosed 800,000 Diagnosed 4

5 Increasing HCV Associated Morbidity and Mortality Hepatitis C is a leading cause of liver transplants and liver cancer. Annual HCV associated mortality in the U.S. increased more than 50% from 1999 to People born during account for 73% of all HCV associated deaths. Hep c 2010: 800,00 persons with HCV-related cirrhosis 10,000 to 12,000 deaths million persons with HCV-related cirrhosis = 283,378 deaths / ~14,000/yr 5

6 Baby Boomers Account for the Majority of HCV Cases in United States 1.6 Number With Chronic HCV Infection (millions) < s 1930s 1940s 1950s 1960s 1970s 1980s CDC and USPSTF Recommend that All adults born during Receive one time testing for hepatitis C virus (HCV) without prior ascertainment of HCV risk 6

7 Hepatitis C and Primary Care Percent of Population with hep c Average panel of patients for PCP 1.6% of U. S. Population 2000 Patients 32 HCV Patients Average number each PCP has on their panel Limited Effectiveness of Current Testing Strategies Greater than 50% of persons with chronic hepatitis C do not know that they are infected. Testing based solely on elevated alanine aminotransferase (ALT) levels is estimated to miss 50% of chronic infections. 7

8 Screening for Hepatitis C Risk behaviors Injection drug use (current or ever, including those who injected once) Intranasal illicit drug use Screening for Hepatitis C Risk exposures Long term hemodialysis (ever) Getting a tattoo or Body piercing in an unregulated setting Body piercing legal in Oklahoma in 1999 Tattoo legal in Oklahoma 2006 Persons who were ever incarcerated 8

9 Screening for Hepatitis C Occupational exposure Healthcare, emergency medical, and public safety workers after needlesticks, sharps, or mucosal exposures to HCV infected blood Sexual exposure to known HCV patient Prenatal exposure Children born to HCV infected women Screening for Hepatitis C Prior recipients of transfusions or organ transplants, including persons who: Were notified that they received blood from a donor who later tested positive for HCV infection Received a transfusion of blood or blood components, or underwent an organ transplant before July 1992 Received clotting factor concentrates produced before

10 Screening for Hepatitis C In those individuals with: HIV infection Hepatitis B infection Unexplained chronic liver disease and/or chronic hepatitis including elevated alanine aminotransferase levels Solid organ donors (deceased and living) Rating: Class I, Level B How to screen 10

11 Now What? Hepatitis panel for Hep A and Hep B Hep C Viral Load Hep C Genotype CBC Comprehensive Metabolic Pt, INR HIV 11

12 Markers of End stage Liver failure Elevated Bilirubin Low platelets Decreased Coagulation factors Increased INR Low albumin Normal or slightly elevated AST/ALT 12

13 Now what? Liver Biopsy Advanced Imaging for Fibrosis Lab measure of fibrosis(fibrosure/fibrotest) 13

14 Treatment Treatment based on: Genotype(currently) Presence of Cirrhosis (compensated/decompensated) Naïve or previously treated Direct antivirals Better tolerated less side effects Treatment course 1 2 meds for weeks with >95% cure History of Hepatitis Treatment Non A, non B hepatitis was recognized in the mid 1970 s 1989 Hepatitis C Virus is identified! 1991 The first Hepatitis C treatment is approved by the FDA Intron A The United States blood supply is tested for HCV 14

15 History of Hepatitis Treatment 1997 FDA approves Infergen (interferon alfacon 1) injection sometimes taken in combination with ribavirin for the treatment of chronic HCV in patients 18 years of age and older with compensated liver disease FDA approves Merck s Rebetol (ribavirin) to be used in combination with interferon alfa 2b (both pegylated and non pegylated) injections for the treatment of chronic hepatitis c in patients 3 years of age and older with compensated liver disease 1998 Schering Plough announces that the FDA has approved the combination use of Rebetol and Intron to be marketed as Rebetron for the treatment of chronic hepatitis C in patients with compensated liver disease who have relapsed following interferon therapy. History of Hepatitis Treatment 2001 Merck s Pegintron (peginterferon alfa 2b) injections are approved by the FDA and is indicated for the treatment of chronic HCV patients with compensated liver disease. For certain patients peginterferon alfa 2b may be administered with ribavirin Genetech Pegasys (peginterferon alfa 2), Copegasus. Copegasus is indicated for the treatment of chronic hepatitis C virus infection in combination with Pegasys in patients 5 years of age and older with compensated liver disease that were not previously treated with interferon alpha as well as in adults coinfected with HIV On May 13th, the FDA approves Victrelis (boceprevir) for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy, including prior null responders, partial responders, and relapsers. 15

16 History of Hepatitis Treatment 2011 May 23rd, Incivek (telaprevir) is approved by the FDA for use in combination with peginterferon alfa and ribavirin for the treatment of genotype 1 HCV infection in adults with compensated liver disease, including cirrhosis, who are treatment naïve or who have been previously treated with interferon based treatment, including prior null responders, partial responders, and relapsers November FDA approves Olysio (simeprevir) capsules to be used in combination with peginterferon alfa and ribavirin or in combination with sofosbuvir. Its efficacy is established in patients with hepatitis c genotype 1. In addition to other limitations, simeprevir isn t recommended for those that have failed previous treatment regimens that included simeprevir or other HCV protease inhibitors December FDA approves Sovaldi (sofosbuvir) tablets to be used in combination with ribavirin or with pegylated interferon and ribavirin. Its efficacy is established in patients with hepatitis c genotypes 1, 2, 3 or 4, including those with hepatocellular carcinoma awaying liver transplant and those with hepatitis c/hiv coinfection. Duration of treatment is usually weeks History of Hepatitis Treatment 2014 The FIRST once daily pill that doesn t require interferon or ribavirin, Harvoni (ledipasvir/sofosbuvir) tablets are approved by the FDA in October. This medication is indicated for the treatment of hepatitis c, genotype 1 infections Two months later, the FDA approves Viekira Pak (ombitasvir/paritaprevir/ritonavir and dasabuvir) oral combination therapy for the treatment of patients with genotype 1 HCV infection including those with compensated cirrhosis. Limitations of use include those with decompensated liver disease. 16

17 History of Hepatitis Treatment 2015 Daklinza (daclatasvir), was approved in July for use with sofosbuvir as the first 12 week, all oral treatment option for patients with chronic hepatitis C virus genotype 3. SVR rates are reduced in HCV genotype 3 infected patients with cirrhosis July, Technivie (ombitasvir, paritaprevir and ritonavir) is used in combination with ribavirin for the treatment of HCV genotype 4 infections in patients that do not have scarring and poor liver function (cirrhosis). Technivie is the first drug approved to treat genotype 4 HCV infection without interferon. History of Hepatitis Treatment 2016 On January 28th Zepatier, a combination of elbasvir and grazoprevir, with or without ribavirin earned FDA approval. Trials demonstrated sustained virologic response (SVR) rates of up to 97 percent in genotype 1 patients and up to 100 percent in patients with genotype June 28 FDA Approval? Epsclusa (sofosbuvir/ velpatasvir )has completed Phase 3 trials and have posted cure rates of 97 to 100 percent in genotypes 1 through 6. Sofosbuvir plus velpatasvir is encouraging for all genotypes but especially genotype 3 with cirrhosis, where the cure rate was 91 percent. 17

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19 teractions with Direct-Acting Antivirals and Selected Concomitant Medications Concomitant Medications Daclatasvir Ledipasvir Paritaprevir / Ritonavir / Ombitasvir + Dasabuvir Simeprevir Sofosbuvir Elbasvir/ Grazoprevir Acid reducing agents* Alfuzosin/tamsulosin Amiodarone Anticonvulsants Antiretrovirals* See HIV section See HIV section See HIV section See HIV section See HIV section See HIV section Azole antifungals* ** Buprenorphine/nalo xone Calcineurin inhibitors* Calcium channel blockers* Cisapride Digoxin Ergot derivatives Ethinyl estradiol containing products Furosemide Gemfibrozil Glucocorticoids* (inhaled, intranasal) Concomitant Medications Daclatasvir Ledipasvir Paritaprevir / Ritonavir / Ombitasvir + Dasabuvir Simeprevir Sofosbuvir Elbasvir/ Grazoprevir Herbals St. John s wort Milk thistle 0 Macrolide antimicrobials* ** Other antiarrythmics* Phosphodiesterase type 5 inhibitors* Pimozide Rifamycin antimicrobials* Salmeterol Sedatives* Statins* 19

20 Recommended Follow up for Patients Who Achieve a Sustained Virologic Response (SVR). For patients who do not have advanced fibrosis (ie, those with Metavir stage F0 F2), recommended follow up is the same as if they were never infected with HCV. Rating: Class I, Level B Assessment for HCV recurrence or reinfection is recommended only if the patient has ongoing risk for HCV infection or otherwise unexplained hepatic dysfunction develops. In such cases, a quantitative HCV RNA assay rather than an anti HCV serology test is recommended to test for HCV recurrence or reinfection. Rating: Class I, Level A Surveillance for hepatocellular carcinoma with twice yearly ultrasound examination is recommended for patients with advanced fibrosis (ie, Metavir stage F3 or F4) who achieve an SVR. Rating: Class I, Level C A baseline endoscopy is recommended to screen for varices if cirrhosis is present. Patients in whom varices are found should be treated and followed up as indicated. Rating: Class I, Level C Assessment of other causes of liver disease is recommended for patients who develop persistently abnormal liver tests after achieving an SVR. Rating: Class I, Level C Recommended Monitoring During Antiviral Therapy Clinic visits or telephone contact are recommended as clinically indicated during treatment to ensure medication adherence and to monitor for adverse events and potential drug drug interactions with newly prescribed medications. Complete blood count (CBC), creatinine level, calculated glomerular filtration rate (GFR), and hepatic function panel are recommended after 4 weeks of treatment and as clinically indicated. A 10 fold increase in alanine aminotransferase (ALT) activity at week 4 should prompt discontinuation of therapy. Any increase in ALT of less than 10 fold at week 4 and accompanied by any weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or international normalized ratio should also prompt discontinuation of therapy. Asymptomatic increases in ALT of less than 10 fold elevated at week 4 should be closely monitored and repeated at week 6 and week 8. If levels remain persistently elevated, consideration should be given to discontinuation of therapy. Rating: Class I, Level B 20

21 Test of Cure Quantitative HCV viral load testing is recommended after 4 weeks of therapy and at 12 weeks following completion of therapy. Antiviral drug therapy should NOT be interrupted or discontinued if HCV RNA levels are not performed or available during treatment. Quantitative HCV viral load testing can be considered at the end of treatment and 24 weeks or longer following the completion of therapy. Rating: Class I, Level B Recommended Monitoring for Patients in Whom Treatment Failed to Achieve a Sustained Virologic Response Recommended Monitoring for Patients in Whom Treatment Failed to Achieve a Sustained Virologic Response Disease progression assessment every 6 months to 12 months with a hepatic function panel, complete blood count (CBC), and international normalized ration (INR) is recommended. Rating: Class I, Level C Screening for hepatocellular carcinoma with ultrasound examination every 6 months is recommended for patients with advanced fibrosis (ie, Metavir stage F3 or F4). Rating: Class I, Level C Endoscopic screening for esophageal varices is recommended if cirrhosis is present. Rating: Class I, Level A Evaluation for retreatment is recommended as effective alternative treatments become available. Rating: Class I, Level C 21

22 Hepatitis C Patients Persons with current (active) HCV infection should receive education and interventions aimed at reducing progression of liver disease and preventing transmission of HCV. Rating: Class IIa, Level B Abstinence from alcohol and, when appropriate, interventions to facilitate cessation of alcohol consumption should be advised for all persons with HCV infection. Rating: Class IIa, Level B 22

23 Hepatitis C Patients Evaluation for other conditions that may accelerate liver fibrosis, including HBV and HIV infections, is recommended for all persons with HCV infection. Rating: Class IIb, Level B Evaluation for advanced fibrosis using liver biopsy, imaging, and/or noninvasive markers is recommended for all persons with HCV infection, Rating: Class I, Level A 23

24 Hepatitis C Patients Vaccination against hepatitis A and hepatitis B is recommended for all susceptible persons with HCV infection. Rating: Class IIa, Level C Vaccination against pneumococcal infection is recommended to all patients with cirrhosis. Rating: Class IIa, Level C Hepatitis C Patients All persons with HCV infection should be provided education on how to avoid HCV transmission to others. Rating: Class I, Level C 24

25 What topics should be discussed with patients who have HCV infection? Patients should be informed about the low but present risk for transmission with sex partners. Sharing personal items that might have blood on them, such as toothbrushes or razors, can pose a risk to others. Cuts and sores on the skin should be covered to keep from spreading infectious blood or secretions. What topics should be discussed with patients who have HCV infection? Donating blood, organs, tissue, or semen can spread HCV to others. HCV is not spread by sneezing, hugging, holding hands, coughing, sharing eating utensils or drinking glasses, or through food or water. Patients may benefit from a joining support group. 25

26 Take Home Recognize some of Your Patients Have Hepatitis C Good Primary Care can slow progression Primary Care can Treat Useful Internet Links Patient Links