HEPATITIS C THE HIDDEN VIRUS

Fawn Mumbulo, FNP-student2013 SUNY-IT NUR 652

(RSC, 2009)

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)

GLOBAL PREVALENCE OF HCV-SPECIFIC ANTIBODIES

(Nature Medicine, 2013)

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

Etiology is 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)

EXTRAHEPATIC MANIFESTATIONS o Hematologic

o Mixed cryoglobulinemiao Aplastic anemiao Thrombocytopeniao Non-Hodgkin’s b-cell

lymphomao Dermatologic

o Porphyria cutanea tardao Lichen planuso Cutaneous necrotizing

vasculitiso Renal

o Glomerulonephritiso Nephrotic syndrome

o Endocrineo Hypothyroidismo 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)

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)

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.)

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

Social & Environmental Considerations

(CDC, 2012; Foster, 2009; Hagan, 2011; Sockalingam, Link, & Abbey, 2011; Zickmund, 2008)

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 test then 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)

EIA antibody test

EIA negative

High risk (hemodialysis, IV drug users,

immunocompromising disease)

HCV RNANAT (PCR)

test

Positive HCV RNA (NAT-

PCR)

Active HCV infectionRefer to

Specialistfor Management

&Treatment

Negative HCV RNA

(NAT-PCR)No

further testing

No further testing

EIA positive

HCV RNANAT (PCR)

test

NegativeHCV RNA

(NAT-PCR)

False positive

EIANo further

testing

Previously infected

with HCV - has clearedMonitor liver

panels every

RIBA test can be done to sort out

possible scenarios

Positive RIBA test

Previously had HCV &

cleared

Negative RIBA test* EIA test was a false

positiveNegative for

HCV

Positive HCV RNA(NAT-PCR)

Cureently has HCVRefer to Specialit for

Management & Treatment

Acute HCV infection

Monitor ALT levels periodically for 6

months

Chronic HCVperform genotyping & measure vial load to guide duration of

treatment (Usually done by

specialist)

Monitor therapyHCV RNA(NAT-PCR)

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

GUIDELINES & COMPLICATIONS

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

Management Treatment

(Dhawan, 2013; Ghany, Strader, Thomas, & Seeff, 2009)

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 IFN to 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)

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: 1st test 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)

F/U, CONSULTo 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

Monitor Frequently During & After Treatment

(Dhawan, 2013; Mogul & Schwarz, 2012; U.S. Department of Veterans Affairs, 2013)

EDUCATION 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

Prevention of Liver Disease Progression

(CDC, 2013; fpnotebook.com, 2013; Mayo Clinic, 2013; Mogul & Schwarz, 2012)

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)

o The most common risk factors for contracting HCV are all of the following except:a) Baby boomersb) Illicit drug usersc) Blood transfusion before 1992 d) wrestling

The first symptoms if they occur will present within _____ of exposure?a) 6 monthsb) 1 yearc) 6 weeksd) 4-12 weeks

If you received clotting factors before what date, you may be at risk of HCV?a) 1988b) 1987c) 1992d) 1995

All of the following are contraindicated for HCV therapy except:a) Uncontrolled depressionb) Pregnancyc) HTNd) STD’s

Counseling needs to be done if the patient with HCV experiences the following:a) Social isolation, stigmatismb) Fear of transmitting HCVc) Suicidal ideationsd) All of the above

An infant born to a mother with HCV is preferred to be tested at what age?a) 1-2 monthsb) 6 monthsc) 18 monthsd) 2 years

Interferon side effects include:a) Urinary retentionb) Sleep disturbancesc) Tachycardiad) Depression

All of the following about mothers with HCV are false except:a) Cannot breast feedb) Cannot have vaginal birthsc) Cannot be treated during pregnancyd) C-sections increase the risk of transmission to the infant

What percentage will people with HCV go on to develop liver cirrhosis?a) 10%b) 13%c) 85%d) 20%

If a patient is anti-HCV positive, what is the next step:a) Order a genotyping testb) Tell the patient that they have HCV & send them to a hematologistc) Order a NAT (HCV RNA)d) Do another anti-HCV test in 2 months

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