Hepatitis C  The Hidden Virus

1. Hepatitis C The Hidden Virus Fawn Mumbulo, FNP-student 2013 SUNY-IT  NUR 652 (RSC, 2009)

2. Hepatitis C Incidence & Prevalence • Incidence: CDC (2013) estimates that approximately 17,000 new HCV infections occurred in 2007 • Acute HCV is rarely identified or reported due to asymptomatic until chronic • Prevalence: According to the CDC (2013) approximately 3.2 million people in the U.S. have chronic HCV • Most prevalent in baby boomers (born between 1945-1965) – likely infected during the highest rates of occurrence 1970-1980’s • Forty percent of HIV patients have co-infections of HCV (route of transmission is almost identical to HIV) • Global Prevalence: • Exposure occurs differently by country • Foreign-born persons who live in the U.S. whom countries where HCV is an endemic (greater than 1 million new immigrants enter the U.S. annually) • The WHO has formed a Global Hepatitis Program to assist member countries in achieving control of HCV • Lack of access to screening, care, & treatment limit the use of therapies with deaths from preventable cirrhosis & liver cancer that continue to rise (Averhoff, Glass, & Holtzman, 2012; fpnotebook, 2013; Shivkumar, Peeling, Jafari, Joseph, & Pant Pai, 2012)

3. Global Prevalence of HCV-Specific Antibodies (Nature Medicine, 2013)

4. Etiology & Pathophysiology • HCV – viral disease that involves inflammation of the liver. It is the most common blood-borne infection in the U.S. Transmitted from contaminated blood • Etiologyis a single-stranded RNA virus of the Flaviviridae family • There are 6 types: Genotype 1-6 • Pathophysiology • HCV replicates in the hepatocytes through a dependent RNA polymerase process • Lymphocytes recognize infected cells initiating an immune response • Viral clearance is associated with cytotoxic T lymphocytes & helper T cells • Rapid evolution of a mutated process happens - the virus is a moving target to the immune system – making it difficult to develop a vaccine • Damage to the liver parenchyma is mediated by inflammatory cytokines • Inflammatory mediator activate stellate cells in the liver parenchyma – leading to varying degrees of hepatic fibrosis (CDC, 2011-2012; fpnotebook, 2013; O’Shea, 2011)

5. Extrahepatic Manifestations • Hematologic • Mixed cryoglobulinemia • Aplastic anemia • Thrombocytopenia • Non-Hodgkin’s b-cell lymphoma • Dermatologic • Porphyria cutanea tarda • Lichen planus • Cutaneous necrotizingvasculitis • Renal • Glomerulonephritis • Nephrotic syndrome • Endocrine • Hypothyroidism • Diabetes mellitus • Ocular • Corneal ulcer • Uveitis • Vascular • Necrotizing vasculitis • Polyarteritis nodosa • Neuromuscular • Weakness/myalgia • Peripheral neuropathy • Arthritis/arthralgia • Autoimmune Phenomena • CREST syndrome • Neuropsychiatric • Depression • Psychosis (Hepatitis C New Drug Research and Liver Health, 2013)

6. Risk Factors • Persons born from 1945-1965 should be tested, regardless of risks • Illegal drug users who have injected or used intranasal drugs • Patients who had clotting factor concentrates before 1987 • Patients who have had blood transfusions prior to 7/1992 • Long term hemodialysis patients • Foreign-born people where HCV is an epidemic in their country • Known exposures to HCV - recipients of blood or organs from a donor later tested positive for HCV • All patients with HIV infection • Patients with S/S of liver disease • Healthcare workers-needle sticks, other sharps, or mucosal exposure • Acquiring unregulated tattoo’s or body piercings • Incarceration patients • Sex with an HCV infected person • Persistently elevated levels of alanine aminotransferase (ALT) (Campos-Outcalt, 2012; CDC, 2012; Mahajan, Liu, Klevens, & Holmbertg, 2013; Mogul & Schwarz, 2012)

7. Clinical Findings & Screening • Signs & symptoms of acute HCV may present 4-6 wks after infected, most likely patient’s will have no S/S until years later when the disease presents as cirrhosis • Presentation will depend on the virus replication itself, 1 in 5 patients self clear the virus • For every 100 people infected 75-85 will develop chronic HCV, 60-70 develop chronic liver disease, 5-20 develop cirrhosis, and 1-5 will die of cirrhosis or liver cancer (CDC, 2011). • If symptoms present they are non-specific to HCV such as, fatigue, anxiety/depression, flu-like symptoms, aches/pains, loss of appetite, weight loss, poor memory/concentration, liver pain, jaundice • Screening for HCV should be done in all patient’s who are at risk and birth cohort screening (1945-1965) • Screening tests include the ELISA-2, it detects seroconversion 1-6 wks after exposure with the sensitivity/specificity being 99%, note that false negative tests - if patient is immunocompromised • Anti-HCV antibody is present in 70% patient at onset of symptoms, 90% at 3 months, and most cases by 6 months post-exposure. • Interval screening should be done to patients who continue to have risk factor (CDC, 2013; fpnotebook, 2013; Mahajan et., al. 2013; Moyer, 2013; Poll, n.d.)

8. Social & Environmental Considerations • Social isolation & poor quality of life: • Fatigue & misunderstanding affect social networks(don’t look sick-therefore is not sick) • Employment & financial issues (out of pocket costs for treatment-stigmatization at work  work loss) • Fear of transmitting disease (less intimate relationships, limiting exposure to body fluids) • Lifestyle & emotional difficulties (loss of friends) • Isolating effects of social stigmatization (judgment-ETOH, IV drug use, inappropriate behaviors) • Stigmatization within provider-patient relationship (communication issues, abandonment, misdiagnosis, poor care d/t knowledge deficits) • Suicide associated with psychosocial burden, co-infected HIV, depression, depression 2nd to IFNx therapy • With injectable exposure to HCV infected blood is relatively stable in the environment • IV illegal drug users • Shared used syringes • Drug preparation equipment • Drug cookers • Filtration cotton • Rinse water • The HCV can survive outside the body at room temperature on environmental surfaces for up to 4 days. • Clean affected area with diluted household bleach-one part bleach to 10 parts water. • HCV survives temperatures up to 145-158 degrees Fahrenheit (CDC, 2012; Foster, 2009; Hagan, 2011; Sockalingam, Link, & Abbey, 2011; Zickmund, 2008)

9. Laboratory Testing • Blood work for an assay for HCV antibody • Nonreactive HCV antibody • If positive follow up with a NAT (HCV RNA) • NAT results give a quantitative measure of viral load or a qualitative assessment of the presence/absence of the virus • In order to distinguish a true positivity from a biologic false positivity - testing with a 2nd HCV antibody assay can be done – it is unlikely that there would be two biologic false positivity's • If the screening test is positive & the confirmatory testthen begin education on disease process, transmission prevention, treatment options, caring for their liver, and modifying risky behaviors • Liver biopsies are not recommended only to clarify current status of the liver, identify features in order to make therapy decisions, and to reveal advanced fibrosis or cirrhosis • All past or present acute HCV are reportable nationally to health departments • Differential Diagnosis • Autoimmune chronic active hepatitis • Alcoholic liver disease (CDC, 2013; Ghany, Strader, Thomas, & Seeff, 2009)

10. (meddean.luc.edu/lumen/MedEd/orfpath/virhepc.htm)

11. Guidelines & Complications Management Treatment • Vaccinate for HBV & HAV • Discontinue all ETOH • Use protective barriers during sexual intercourse • Monitor patient for cirrhosis & hepatocellular carcinoma • Children 2-17 years old will be treated the same as adults (weight based doses) • Contraindications for therapy: • Renal, heart, or lung transplants, uncontrolled depression, autoimmune conditions that are exacerbated with INF & ribavirin, untreated thyroid disease, pregnant or unwillingness to comply with contraceptives, uncontrolled diseases (HTN, heart failure, coronary heart disease, diabetes, COPD), less than 2 yrs old, and hypersensitivity to drug therapy • Combination therapy of 3 medications are ribavirin, interferon (IFN), and protease inhibitors (boceprevir & telaprevir FDA-2011)Effective in fewer than 50% of patients with HCV genotype 1 (most common genotype in U.S.) • Adjustments in treatment • Coinfections • HIV, HBV • End-stage renal disease • Illegal drug users • ETOH abuse • Different genotypes (Dhawan, 2013; Ghany, Strader, Thomas, & Seeff, 2009)

12. Tx Side Effects of Antiviral Therapy • Seventy five percent experience 1 or more of the following side effects when taking IFN: • Neutropenia, thrombocytopenia, memory & concentration disturbances, visual disturbances, HA, depression, irritability, flulike symptoms, hypo/hyperthyroidism, low-grade fever, N/V, weight loss, alopecia, interstitial fibrosis • Ribavirin adverse effects: • Hemolytic anemia, birth defects, gout • Granulocyte-stimulating factor and erythropoietin can be used to counteract hematologic effects of IFN and ribavirin (eltrombopag FDA approved-2012) • Treatment can be delayed for 8-12 wks to allow for spontaneous resolution • Development of depression during therapy caused by alterations in serotonin metabolism can lead to psychosis • the greatest risk of depression developing is in the first 12 weeks of immunotherapy • Monitor suicidal ideation for 12 months post IFNto ensure resolution of neuropsychiatric symptoms (suicidal ideation peak between 8-12 wks into therapy) • Upon completion of IFN therapy serotonin abnormalities improve at the 6 month period, which correlate with resolution of depression • Continue anti depressive and/or anti psychotic agents for 2-3 months after treatment is discontinued to minimize relapses (Dhawan, 2013; Ghany et al, 2009; Sockalingam, Link, & Abbey, 2011)

13. Pregnancy/Children Considerations • Approximately 6 in every 100 infants born to HCV mothers become infected during or near delivery time • C-section does not decrease the risk of transmission • Infants are at greater risk of transmission if the mother is co-infected with HIV • There is no study that suggests HCV is transmitted through breast feeding, although if nipples are cracked or bleeding then breast feeding should be discontinued • Spontaneous clearance of HCV before age 24 months & as late as 7 yrs of age can happen • Development of cirrhosis or liver failure from chronic HCV occurs in 1-2% of children • Screening infants & children: • 1sttest should be at18 mo. of age-anti-HCV IgG, if the test is + then • HCV RNA levels should be measured at 1, 2, 3 mo. • If at the 1st mo. + then obtain HCV genotype • Treatment for children is controversial d/t HCV progresses slowly in childhood, & serious complications from chronic HCV is rare (AHRQ, 2010; CDC, 2013)

14. F/U, Consult Monitor Frequently During & After Treatment • Weeks 2, 4, then every 1-2 months • Hgb • Hct • WBC w/diff • Platelet ct • Creatinine • Weeks 4, 12, 24 during treatment, at the end of treatment, and 6 months after treatment ends • HCV RNA by quantitative and/or qualitative assay • Monthly after treatment starts • ALT, then every 1-2 months • Pregnancy test if applicable, then every 6 months • Week 12, then every 12 weeks • TSH • Blood glucose • Monitor pt. with cirrhosis for HCC (hepatocellular carcinoma), esophageal varices, & decompensated liver • Vaccinations for HAV & HBV before a decompensated liver manifests in order to mount an immune response • Referrals: • Gastroenterologist, infectious disease, or hepatologist for tx of HCV • Psychiatrist for depression, coping strategies, support systems or any other mental illnesses • Surgeon if liver transplant is warranted • HCV children are seen by a pediatric hepatologist yearly • Serum measurements, aminotransferase, total & direct bilirubin, albumin, HCV RNA levels, CBC, & coags (Dhawan, 2013; Mogul & Schwarz, 2012; U.S. Department of Veterans Affairs, 2013)

15. Education Prevention of Liver Disease Progression • Cirrhosis in 5 yrs after onset of infection (20% in 20yrs) • Hepatocellular carcinoma (2-4% if cirrhosis present, 5 yrs 7%, 10 yrs 14%) • Associations: DM II, Sjogren's syndrome, lymphoma, glomerulonephritis, porphyria cutanea tarda, lichen planus, cutaneous necrotizing vasculitis • Avoid ETOH  decreases the response to interferon therapy • Avoid hepatotoxins (drugs that are metabolized in the liver) • Maintain low fat diet • Vaccinate with Hep A, B • Prevent transmission • Do not share razors/toothbrushes • Cover skin lesions • Do not donate blood products, organs, or semen • Use protective devices for intercourse • Counseling for various psycho-social issues that arise • HCV is not transmitted by sneezing, hugging, holding hands, coughing, sharing eating utensils or drinking glasses, or through food or water • Check with a health care professional before taking new prescriptions or OTC drugs that can potentially damage the liver • HCV patients should not be excluded from work, school, play, child care-as long as there is no blood-blood contact • There is no legal requirement to disclose HCV to sexual contacts or to child care/schools, although the CDC recommends it • Stop using illicit drugs, cautious about body piercing/tattooing (CDC, 2013; fpnotebook.com, 2013; Mayo Clinic, 2013; Mogul & Schwarz, 2012)

16. What’s New in Research? • Screening • Studies have been shown to prove that a onetime anti-HCV antibody test for everyone age 20-69 in the U.S. is cost effective, as compared to the treatment cost of chronic HCV & end stage liver disease • There are quicker & easier assays that have not been approved by the FDA for use in the U.S. • Studies are being done on new & improved easy point of care testing for HCV anti-antibody tests • Prevention • Should focus on transmission & education • Such as needle exchange programs • Substance abuse clinics • Sex & drug education in middle & high schools • Increasing referrals when patients have anti-HCV + & NAT (HCV RNA +) • Treatment • New antiviral combinations for HCV are being studied to eradicate HCV genotype-1 • HCV vaccination • Unsuccessful research has proven that due to the protective immunity of mutational HCV research strategies have switched from sterilizing immunity to immunity that is capable of preventing chronic disease & infection • Despite failed research to encompass a vaccine to sterilize the HCV, new research suggests that development of a prophylactic HCV vaccine is in the near future • (Beaumont & Roingeard, 2013; Hagan & Schinazi, 2012; Coffin, Scott, Golden, & Sullivan, 2012; Liang, 2013)

17. The most common risk factors for contracting HCV are all of the following except: • Baby boomers • Illicit drug users • Blood transfusion before 1992 • wrestling • The first symptoms if they occur will present within _____ of exposure? • 6 months • 1 year • 6 weeks • 4-12 weeks • If you received clotting factors before what date, you may be at risk of HCV? • 1988 • 1987 • 1992 • 1995 • All of the following are contraindicated for HCV therapy except: • Uncontrolled depression • Pregnancy • HTN • STD’s • Counseling needs to be done if the patient with HCV experiences the following: • Social isolation, stigmatism • Fear of transmitting HCV • Suicidal ideations • All of the above

18. An infant born to a mother with HCV is preferred to be tested at what age? • 1-2 months • 6 months • 18 months • 2 years • Interferon side effects include: • Urinary retention • Sleep disturbances • Tachycardia • Depression • All of the following about mothers with HCV are false except: • Cannot breast feed • Cannot have vaginal births • Cannot be treated during pregnancy • C-sections increase the risk of transmission to the infant • What percentage will people with HCV go on to develop liver cirrhosis? • 10% • 13% • 85% • 20% • If a patient is anti-HCV positive, what is the next step: • Order a genotyping test • Tell the patient that they have HCV & send them to a hematologist • Order a NAT (HCV RNA) • Do another anti-HCV test in 2 months

19. References • AHRQ, (2010). Hepatitis C. in: Sexually transmitted diseases treatment guidelines. Retrieved from website http://www.guideline.gov/content.aspx?id=25593&search=hepatitis+c • Arshad, M., El-Kamary, S. S., & Jhaveri, R. (2011). Hepatitis C virus infection during pregnancy and the newborn period-are they opportunities for treatment? Journal of Viral Hepatitis, 18, 229-236. doi: 10.1111/j1365-2893.2010.01413.x • Averhoff, F. M., Glass, N., & Holtzman, D. (2012). Global Burden of hepatitis C: Considerations for healthcare providers in the United States. Clinical Infectious Diseases, 55(S1), S10-S15. doi: 10.1093/cid.cis361 • Beaumont, E., & Roingeard, P. (2013). Prospects for prophylactic hepatitis C vaccines based on virus-like particles. Human Vaccines and Immunotherapeutic, 9, 1-7. • Campos-Outcalt, D. (2012). Hepatitis C: New CDC screening recommendations. The Journal of Family Practice, 61(12), 744-746. • CDC, (2011). Sexually transmitted diseases (STDs). Retrieved from website http://www.ced.gov/std/treatment/2010/hepc.htm • CDC, (2012). Hepatitis C information for the public. Retrieved from website http://www.cdc.gov/hepatitis/c/ • CDC, (2013). Testing for HCV infection: An update of guidance for clinicians and laboratorians. Retrieved from websitehttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a5.htm

20. References • CDC, (2013). Hepatitis C FAQs for health professionals. Retrieved from website http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm • CDC, (2013). Surveillance for viral hepatitis-United States, 2011. Retrieved from website http://www.cdc.gov/hepatitis/Statistics/2011Surveillance/Commentary. htm#hepC • Coffin, P. O., Scott, J. D., Golden, M. R., Sullivan, S. D. (2012). Cost-effectiveness and population outcomes of general population screening for hepatitis C. Clinical Infectious Diseases, 54(9), 1259-1271. doi: 10.1093/cid/cis011 • Dhawan, V. K. (2013). Hepatitis C treatment & management. Retrieved from http://www.emedicine.medscape.com/article/177792-treatment • Foster, G. R. (2009). Quality of life considerations for patients with chronic hepatitis C. Journal of Viral Hepatitis, 16, 605-611. doi: 10.1111/j.1365-2893.2009.01154.x • fpnotebook, (2013). Hepatitis C. Retrieved from website http://www.fpnotebook.com/GI/Lvr/HptsC.htm • Fox, R. K. (2013). Staying informed: Anticipating new regimens with direct acting antiviral for hepatitis C. Retrieved from website http://www.hepatitis.va.gov/provider/topics/DAA- update.asp • Ghany, M. G., Strader, D. B., Thomas, D. L., Seeff, L. B. (2009). Diagnosis, management, and treatment of hepatitis C: An update. Hepatology, 49(4), 1335-1374

21. References • Hagan, H. (2011). Agent, host, and environment: Hepatitis C virus in people who inject drugs. Journal of Infectious Diseases. Retrieved from http://www.natap.org/2011/DCV/110411_01.htm • Hagan, L. M., & Schinazi, R. F. (2012). Best strategies for global HCV eradication. Liver International, 1478-3223. doi: 10.1111/liv.12063 • Hepatitis C New Drug Research and Liver Health. (2013). Conditions outside the liver. Retrieved from http://www.hepatitiscnewdrugresearch.com/conditions-outside-the-liver.html • Kronen, M. R. (2008). Flaviviridae. Retrieved from website http://www.stanford.edu/group/virus/flavi/2008/flavi.html • Liang, T. J. (2013). Current progress in development of hepatitis C virus vaccines. Nature Medicine, 19(7), 869-878. doi: 10.1038/nm.3183 • Mahajan, R., Liu, S. J., Klevens, R. M., Holmberg, S. D. (2013). Indications for testing among reported cases of HCV infection from enhanced hepatitis surveillance sites in the United States, 2004-2010. American Journal of Public Health, 103(8), 1445-1449. • Mayo Clinic, (2013). Hepatitis C. Retrieved from website http://www.mayoclinic.com/health/hepatitis-c • MedlinePlus, (2012). Hepatitis C. Retrieved from http://www.nlm.nih.gov/medlinplus/ency/article/000284.htm • Mogul, D. & Schwarz, K. B. (2012). Hepatitis C viral infection in children. Clinical Liver Disease, 1(3), 77-80. doi: 10.1002/cld.64

22. References • Moyer, V. A. (2013). Screening for hepatitis C virus infection in adults: U.S. preventive services task force recommendation statement. Annals of Internal Medicine, 159(5), 349-357. • Nature Medicine. (2013). Global prevalence of HCV-specific antibodies. Retrieved from http://www.nature.com/nm/journal/v19/n7/fig_tab/nm.3184_F.html • O’Shea, R. S. (2011). Hepatitis C. Retrieved from http://www.cleavelandclinicmeded.com/medicalpubs/diseasema nagement/hepatology/hepatitis-C/ • Poll, R. (n.d.). The role of the community nurse in hepatitis C diagnosis and treatment. British Journal of Community Nursing, 14(7), 292-296. • RSC. (2009). New hep C breakthrough. Retrieved from http://www.rsc.org • Sockalingam, S., Links, P. S., & Abbey, S. E. (2011). Suicide risk in hepatitis C and during interferon-alpha therapy: A review and clinical update. Journal of Viral Hepatitis, 18, 153-160. doi: 10.1111/j1365-2893.2010.01393.x • United States Department of Veterans Affairs. (2013). Hepatitis C quicknotes. Retrieved from website http://www.hepatitis.va.gov/provider/guidelines/quicknotesHCV-pda-print.asp • Zickmund, S. L. (2008). Mental health and hepatitis C. Caring Ambassadors Program, Inc. Retrieved from website http://www.hepcchallenge.org/choices/pdf/Chapter_21- Sec_04_OL.pdf