Transcript hepatitis c - Scioto County Medical Society

HEPATITIS C VIRUS INFECTION
VALERIE FLETCHER, M.D.
INFECTIOUS DISEASES
SOUTHERN OHIO MEDICAL CENTER
INTRODUCTION
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Hepatitis C virus (HCV) is the most common chronic blood-borne viral
infection in North America.
Major cause of chronic hepatitis.
Causes progressive hepatic fibrosis which leads to cirrhosis and an
increased risk of hepatocellular carcinoma.
HCV liver disease is the most common reason for liver transplantation
in USA.
THE VIRUS
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HCV is an RNA virus and a member of the Flaviviridae family, genus
Hepacivirus.
There are 6 known genotypes and more than 50 subtypes
(quasispecies).
Type 1 (75%), type 2 (10%) and type 3 (10%) are the commonest
genotypes in USA.
There is a lack of a robust T-lymphocyte response to, and a high rate
of mutations within the genotypes, thus allowing HCV to elude the
immune system-mediated clearance and so produce chronic infection.
EPIDEMIOLOGY
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Estimated 4 million people in USA infected with HCV; 2.7 million have
chronic infection.
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35,000 new cases per year.
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8000 – 10,000 deaths per year from HCV-related chronic liver disease.
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Estimated prevalence is 1.8% of population.
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Many persons with chronic HCV have yet to be diagnosed.
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A fourfold increase in the number of persons diagnosed with chronic
HCV is projected from 1990 -2015.
Management of Hepatitis C: 2002.
NIH Consensus Development
Conference Statement
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Persons aged 40 – 59 years have the highest seroprevalence.
High HCV seroprevalence rates (15 -50%) in specific populations
(homeless, incarcerated, injection drug users and persons with
hemophilia treated with clotting factors before 1992).
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70 to 90% seroprevalence in IDU.
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Source of infection unknown in many.
TRANSMISSION
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Blood transfusion before 1992.
Injection drug use.
Solid organ transplantation from infected donor.
Unsafe medical practices.
Occupational exposure to infected blood.
Infected mother to child during birth.
High risk sexual practices.
Intranasal cocaine use.
Body piercing.
IDU and HCV transmission
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HCV transmitted efficiently by contaminated needles, syringes and
other drug paraphernalia.
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Infection is rapidly acquired after initiation of use; > 50% after 5 years.
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More easily transmitted than HIV.
Perinatal Transmission
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Transmission only from women with positive HCV-RNA at delivery.
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Average rate of transmission is 6%, higher if HIV co-infection.
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No association with method of delivery and breastfeeding.
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Maternal HCV antibodies persist in uninfected infants for approximately
12 months.
Infected infants have a good prognosis.
Transmission between sex partners
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Sexual transmission occurs but is inefficient.
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Male to female transmission more efficient.
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Transmission rare between long term steady partners.
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Factors that facilitate transmission between partners unknown.
NATURAL HISTORY
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Incubation period is up to ~ 8 weeks.
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Acute infection.
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> 80% persistent infection.
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Slower progression if young age at time of infection and female gender.
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More rapid progression if HIV or HBV co-infection, alcohol use
Natural History of HCV
Course of acute HCV in HCW after needle stick injury
CLINICAL FEATURES
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The majority of infections are asypmtomatic.
Prodrome of anorexia, nausea vomiting, myalgia and malaise. Diarrhea
or constipation, low grade fever and abdominal pain may occur (tender
hepatomegaly).
Icteric phase – jaundice may occur after 5 – 10 days.
Convalescent phase.
Acute illness may be mild and subsides in 2 – 3 weeks. Fulminant
infection is rare.
LAB
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In acute infection, mild leukopenia, hyperbilirubinemia and elevated
transaminases may occur.
HCV RNA detected in blood within 1 – 3 weeks of exposure.
HCV antibodies present in 50 – 70% of patients at onset of symptoms,
and 90% at 3 months.
Alanine aminotransferase (ALT) levels decline with resolution of
symptoms, however, may fluctuate throughout the course of infection.
ALT persistently normal in up to 40% person with chronic hepatitis.
Alanine Aminotransferase
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Serum ALT testing is inexpensive and noninvasive.
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Insensitive means of monitoring disease activity.
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A single determination gives limited information, and serial
measurements recommended.
Weak association between the degree of ALT elevation and severity of
histopathological findings on liver biopsy.
Resolution of ALT elevation with antiviral therapy appears to indicate
disease response.
Chronic infection and risk of progression
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Chronic inflammation of the liver with persistence of HCV RNA > 6
months.
Sequelae include progressive liver fibrosis, cirrhosis, end-stage liver
disease and hepatocellular carcinoma.
Little evidence that viral factors (viral load, genotype) affect the risk of
progressive liver disease.
Risk of progression increased by older age at time of infection, male
gender, immunosuppression, HBV, alcohol.
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As little as 30 g/day in men (2 beers, 2 glasses of wine, or 2 mixed
drinks) and 20 g/day in women have a detrimental effect on disease
progression.
Other factors include iron overload, nonalcoholic fatty liver disease,
hepatotoxic medication and environmental contaminants may also
increase progression.
Extra-hepatic manifestations of chronic HCV
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‘Rheumatoid’ symptoms
Keratoconjunctivitis sicca
Lichen planus
Glomerulonephritis
Lymphoma
Essential mixed cryoglobulinemia
Porphyria cutanea tarda
Psychological disorders
Leukocytoclastic vasculitis
LABORATORY DIAGNOSIS
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Serologic tests to detect HCV antibodies:
- enzyme immunoassay (EIA). False negative in pts on HD,
immunodeficiency; false positive in autoimmune disorder.
- recombinant immunoblot assay (RIBA)
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Target amplification technique to detect HCV RNA (molecular assay)
- polymerase chain reaction (PCR). A positive test confirms HCV
infection.
HCV TESTING
EIA
Positive
Negative
Measure HCV RNA by PCR
Negative
Low risk
Positive
High risk
Consider treatment
for HCV infection
RIBA
Negative
No further workup
Positive
Previous infection and clearance
LIVER BIOPSY
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Provides useful information about the degree of fibrosis in HCV infected
patients. This information is important in management decisions.
Is not used for diagnosis of HCV infection.
Used for assessment of severity of inflammation, presence of fibrosis,
evaluate possible concomitant disease processes, assess therapeutic
intervention.
Liver Histology
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Activity (necro-inflammation) – severity and progress. May fluctuate
with disease activity or therapeutic intervention.
Fibrosis implies possible progression to cirrhosis. In mild cases, is
limited to portal and periportal area. More advanced changes defined
by ‘bridging fibrosis’.
Cirrhosis
Fibrosis Scoring Methods
KNODELL
METAVIR
ISHAK
NONE
0
0
0
PORTAL FIBROSIS (SOME)
1
1
1
PORTAL FIBROSIS (MOST)
1
1
2
BRIDGING (FEW)
3
2
3
BRIDGING (MANY)
3
3
4
INCOMPLETE CIRRHOSIS
4
4
5
ESTABLISHED CIRRHOSIS
4
4
6
The problems associated with liver biopsy
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Cost
Complications –pain, major bleeding, pneumothorax, inadvertent
biopsy of kidney or colon, perforation of gall bladder.
Patient aversion
Physician aversion
Specimen size – degree of fibrosis more accurately determined in larger
specimens
Lack of specific findings.
MANAGEMENT – Baseline evaluation
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CBC
ALT
TSH
ANA
HCV genotype
HCV quantitative viral load
Liver biopsy (recommended)
AFP (if cirrhosis present)
Pregnancy test
MANAGEMENT
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Previously untreated patients with detectable HCV RNA, persistently
elevated ALT and liver biopsy specimen showing fibrosis (or at least
moderate necrosis and inflammation) are at high risk of disease
progression and are candidates for therapy.
Pegylated interferon (PEG-INF) combined with ribavirn is currently the
best therapy.
Treatment associated with significant side effects.
Several predictors of treatment response have been identified, eg HCV
genotype.
An absence of serum HCV RNA 6 months after therapy has been
discontinued predicts sustained viral eradication.
MANAGEMENT
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PEG-INF 180µg sc weekly and ribavirin 800 – 1200mg po daily x 24 -48
weeks.
Genotypes 2 and 3 associated with better response, and treated for 24
weeks. SVR ~ 76%
Genotypes 1, 4, 5. 6 are less responsive to therapy; if there is early
virological response after 12 weeks, therapy is continued for a total of
48 weeks. SVR ~ 50%
Independent predictors of favorable response are non-1 genotype,
lower levels of HCV RNA and lower BMI. Other factor are age, race,
gender, and presence of cirrhosis.
Side effects of Pegylated interferon
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Flu-like syndrome – fever, headache, chills, myalgia, fatigue
Gastrointestinal – nausea, anorexia, diarrhea
Neuropsychiatric – depression, irritability
Skin – alopecia, pruritus, rash, dry skin
Bone marrow – anemia, neutropenia
Cardiovascular – arrhythmia, cardiomyopathy, CHF, angina
Endocrine – hypothyroidism, hyperthyroidism, gynecomastia, DM
exacerbation
Liver – liver failure, jaundice
Musculoskeletal – arthritis, muscle weakness and cramps
Reproductive – amenorrhea, impotence, uterine bleeding
Other – respiratory, urinary, vision, hearing disturbances, injection site
reaction
Side effects of Ribavirin
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Neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia
Teratogenic, embryocidal
Depression, suicidal ideation
Pulmonary toxicity
Nausea, vomiting, colitis, pancreatitis
Hypothyroidism, hyperthyroidism
Myocardial infraction, arrhythmia
Hypersensitivity reaction, rash
Contraindication to combination therapy
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Hypersensitivity to drugs
Pregnant women
Men whose partners are pregnant
Hepatic decompensation
Neonates and children
Autoimmune hepatitis
Hemoglobinopathies
Barriers to treatment
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Neuropsychiatric illness
Alcohol use
Active illicit drug use
Cost
Poor adherence to therapy
Adverse effects
HCV AND HIV COINFECTION
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All patients with HIV should be screened for HCV.
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Treatment of co-infected persons individualized.
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The course of HCV may be accelerated in HIV co-infection.
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HCV co-infection may be associated more rapid progression of HIV.
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PEG-INF may cause a fall in CD4 cell count.
End of treatment responses and sustained virologic responses (SVR) in
HCV/HIV coinfection treated with INF/PEG-INF and ribavirin (APRICOT)
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HIV+ patients on HAART have decreased liver related mortality.
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Combination therapy is poorly tolerated.
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Lower SVR.
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Drug interactions.
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Protease inhibitors may be associated with hepatotoxity; NRTI
associated with pancreatitis, lactic acidosis and mitochondrial toxicity.
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Clinician comfort level low.
Adjunctive therapy
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Hepatitis B vaccine series - if non-immune
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Hepatitis A vaccine series
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Contraception during therapy and for 6 months afterwards
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Counseling - avoidance of alcohol and drug, use of condoms to
prevent transmission and other STDs.
Support groups