Testing for Viral Hepatitis Flashcards
What is the DDx for acute hepatocellular injury?
- Viral hepatitis (A, B, C, D, E, EBV, CMV, Parvovirus)
- Acetaminophen toxicity
- Other toxins
- Ischemia
- Autoimmune liver disease
- Wilson’s disease (can present with fulminant acute hepatitis)
- Alpha 1 anti-trypsin deficiency
Hep A,B,C,D,E…RNA or DNA?
RNA, DNA alternating
CMV EBV HSV… RNA or DNA?
DNA
Self‐limited illness (<2 months)
Jaundice, fatigue, fever, anorexia, diarrhea, dark
urine, pale stools, abdominal pain
Younger age: fewer (if any) symptoms
Spread is fecal‐oral
Poor sanitation, contaminated food and water
Hep A
Dark urine and pale stools: not able to excrete conjugated bile normally, so some is excreted in the urine (making the urine darker)
Incubation is 2-6 weeks compared to 2-6 mos for B!
hep A
Most recent outbreak associated with frozen
strawberries in smoothies from “Tropical Smoothie Cafés”. 135 infections reported.
Hep A
Hep A vaccine became available?
1995
What are the two general tests for HepA?
Total anti-HAV:
- IgM, IgG, IgA
- looks at all antibodies, so if positive, can be from an acute infection, a previous infection, or has been immunized (cannot differentiate)
- IgM anti-HAV: acute infection only
To be diagnosed for Hep A you must meet both clinical and lab criteria which are…
Clinical case definition: An acute illness with
a) discrete onset of symptoms and
b) jaundice or elevated serum aminotransferase levels
And laboratory criteria for diagnosis:
Immunoglobulin M (IgM) antibody to hepatitis A
virus (anti‐HAV) positive
Who should be vaccinated for Hep A?
All children at 1 year (12‐23 mo)
Children and adolescents ages 2‐18 years where
routine vaccination is implemented because of
high prevalence
Travelers to high/intermediate prevalence
countries
Men who have sex with men
High risk: drug users, occupational exposure
Chronic liver disease patients
Pts. receiving clotting factors
RNA virus, flaviviridae family
Estimated that only 25‐50% of infected U.S.
patients are diagnosed
High rate (75‐85%) of chronic infection
because of low spontaneous clearance
Leading indication for liver TRANSPLANT in U.S.
Hep C
What is hte natural outcome of an HCV infection?
Of every 100 persons infected with HCV, approximately
75–85 will go on to develop chronic infection
60–70 will go on to develop chronic liver disease
5–20 will go on to develop cirrhosis over a period of 20–30 years
1–5 will die from the consequences of chronic
infection (liver cancer or cirrhosis)
when is acute hep C detectable?
viral RNA: 1-3 weeks post exposure
Abs: 20-150 days (average 50)
sxs of acute hep C? who is more likely to seroconvert?
Jaundice in <20%
preceded by malaise, lethargy, myalgias, low‐grade fever, nausea, vomiting, RUQ pain
symptoms can persist from 2‐12 weeks
symptomatic patients
Three modes of transmission for Hep C?
- exposure to infected blood (IV, needle stick, dialysis)
- Sexual transmission (C MUCH less than B)
- mother to child (4% risk during pregnancy, depend on level of viremia)
What lab tests are done for HCV?
- EIA/CIA immunoassays to look for antibodies
- oraquick (fingerstick)
- RIBA (NO MORE)
- molecular assays (quantitative and genotyping)
- liver bx (not usually needed)
- routine liver fxn tests
What is the signal to cut off ratio (s/co)?
Positive antibody screens should be confirmed by another method, most commonly RNA detection
Confirmatory testing may not always be needed if the s/co ratio (the ratio of a sample’s OD to the OD of the assay cut‐off for that run) EXCEEDS specified values, which vary by test system
** Confirmatory test should be run after positive screen, especially if positive test was “weak zone”!
what HCV genotypes are MC in the us?
1a and 1 b
unfortunately 1 has been most difficult to tx w/ interferon
How long does it take to detect anti-HCV abs?
Anti‐HCV
- Usually by 4‐10 weeks post infection
- By 6 months, >97% are positive
PCR
- 1‐3 weeks
what are reasons for false negative HCV results?
Immunosuppression
Low level of antibodies
Absence of antibodies against antigens in test
*Test has antibodies derived from specific molecule components, may not align with the antibodies formed within the patient
Testing in the “window period” (~11 weeks)
what are reasons for false + HCV results?
Usually unexplained
Aged serum samples
Hypergammaglobulinemia, rheumatoid
factor
Antibodies against vector or fusion proteins
Recent immunizations (influenza vaccine)
What does a positive screening assay indicate?
How do you confirm it?
Indicates current or past infection
No differentiation between acute, chronic, or
resolved infection
Positive results should be confirmed by
supplemental test
RNA
(RIBA test is no longer available) ▪ A different screening test
How many genotypes are there?
What type is the MC in the US?
Which genotypes require alplha interferon +/- ribavarin for 24 weeks vs 48 weeks?
Six genotypes (1‐6) and ~50 subtypes
Genotype 1 is most common in U.S.
Genotypes 2, 3 have a 3x better rate of
response to alpha‐interferon ± ribavarin than genotype 1
Need only 24 weeks of above conventional therapy vs. 48 weeks for genotype 1
who should be screened for HCV?
Persons born from 1945 through 1965 (BABY BOOMERS)
Persons who have ever injected illegal drugs,
including those who injected only once many
years ago
Recipients of clotting factor concentrates made
before 1987
Recipients of blood transfusions or solid organ
transplants before July 1992
Patients who have ever received long‐term
hemodialysis treatment
Persons with known exposures to HCV, such as
health care workers after needlesticks involving HCV‐
positive blood
recipients of blood or organs from a donor who later
tested HCV‐positive
All persons with HIV infection
Patients with signs or symptoms of liver disease (e.g.,
abnormal liver enzyme tests)
Children born to HCV‐positive mothers (to avoid
detecting maternal antibody, these children should not be tested before age 18 months)
baby boomers have an HCV prevalence ____xhigher than other age groups
5x (75% of known HCV infected people)
All should be screened at least ONCE for HCV
What is hte goal for treating HCV?
sustained virologic response (undetectable viral RNA 24 wks after tx completed)
what is used to tx HCV?
Until recently, treatment was combined
Peginterferon‐alpha‐2a OR ‐2b (s.c.)
Ribavarin (oral)
what are SE of PEG/RBV?
Nausea, diarrhea
Skin rash/itch
Insomnia
Severe depression
