liveonearth (liveonearth) wrote,

Liver Diagnosis: Lab Dx II review for final

1. Know why the enzymes on a hepatic panel are not necessarily good indicators of liver function and what tests are better indicators of liver function?

--best indicators of liver FUNCTION are liver products, such as albumin, bilirubin, total protein, prothrombin time (PT), BUN and ammonia
--ALP-1 markedly increases with intra- or extrahepatic obstructive biliary dz, lower elevations with hepatocellular dz (ALP-2: bone, intestine, placenta, certain cancers)

2. What disease process is suggested when an increased ALP is greater than the increase in AST or ALT, and vice versa?
--OBSTRUCTION of biliary tree.

How would you verify that an increased in ALP originated in the liver?
--measure GGT, it is highly accurate for detecting cholestasis
--GGT is most sensitive for biliary obstruction, cholangitis, cholecystitis
--also influenced by alcohol abuse?? (course notes)
--ALP and GGT elevated together: hepatobiliary problem

3. Know the various interpretations of the AST/ALT ratio.
--"if you drink too much you land on your AST" --Dr. Miller
--if AST>ALT more than 1x: alcoholic cirrhosis, congestion, metastatic tumor
--AST>ALT more than 2-3x: alcoholic hepatitis
--AST < ALT: acute hepatitis, chronic viral hep, infectious mono (EBV)
--ratio inaccurate if AST >10x normal

4. Know how the prothrombin time (PT) as a prognostic tool in chronic liver dz.
--PROGNOSIS GOOD if PT is less than 2x normal
--if PT 2x normal or more-->likely development of acute hepatic insufficiency
--clotting factors are made in the liver
--sick liver-->clotting function declines-->bleeding time increases
--PT may be slightly elevated in chronic liver disease
--PT is markedly elevated in acute fulminant necrosis, chronic active hep, end stage liver dz

5. Know whether the cause of jaundice is pre-hepatic, hepatic, or post-hepatic based on the patterns of conjugated & unconjugated bilirubin in serum and urine.
--post-hepatic = conjugated/direct bili too high
--pre-hepatic jaundice = unconjugated/indirect bili too high
--hepatic jaundice = unconj??? bcs liver not doing its job???
--liver conjugates bilirubin
--once it's conjugated it's "direct" meaning water soluble
--when bili comes from hemolysis of RBC's it is unconjugated until it gets to the liver
--unconj/indirect must be bound to proteins for transport in blood
--unconj/indirect bili is normally 70-85% of total
--unconj/indrect increased via RBC hemolysis, poor erythropoiesis, hep, cirr, drugs
--direct/conjugated bili is normally 15-30% of total
--direct/conjugated increase dt: extrahepatic duct obstrx, mets, other intrahepatic cholestasis
--jaundice happens when total bili is over 2.5 mg/dl in serum-->deposits in skin & sclera

6. What tests are included on a typical “acute hepatitis panel?”
--AST, ALT = transaminases
--Anti-HAV = hep A antibody
--HBsAg = hep B surface antigen
--Anti-HBc = hep B core antibody
--Anti-HCV = hep C antibody

Why doesn’t the panel include testing for HDV, HEV, or HGV?
--because they are relatively rare
--HDV can't infect anyone unless they are also infected with B
--E is acquired via travel to endemic areas, and is a similar acute to A with no chronic state
--G seems to be harmless and they don't know how it is transmitted

7. What degree of elevation in AST & ALT typically occurs in acute hep? Why might unconjugated & conjugated bilirubin increase in acute hepatitis?
--AST and ALT may increase 20-100x normal levels in acute hep
--increased unconj bili dt liver's inability to extract and conjugate it
--increased conj dt leakage from hepatocytes or blockage of small bile ducts
--may have both

8. What test would confirm acute Hep A?
--anti-HAV IgM
--IgG will show up about 2 weeks after IgM and may be present for life
--IgM and IgG-->previous infection plus acute current one

Acute Hep B?
--HBsAg = hep B surface antigen, the earliest indicator of HBV infx appears 27-41 days after exposure
--above true if it's IgM, if IgG then could be dt prior, cleared, or chronic infx: be clear
--order anti-HBc to be sure no false neg dt window
--HBe Ag can tell you if someone resolves the infx or has chronic infx
--if antibody to surface antigen is present (>10mU/ml), and antigen is absent, indicates recovery
--90-95% of pts clear the infx, ALT normalizes, they are forever immune to HBV

What tests are used to confirm Acute Hep C?
--PCR is best, look for HCV RNA in serum, can find before immune response, but costs big $$$
--can determine genotype which helps because certain strains have more CA risk (Ib worst)
--PCR qualitative for those with positive anti-HCV to look for active infx
--PCR quantitative used to determine viral load and monitor antiviral tx
--also available: RIBA test the Anti-HCV = hep C antibody. Anti-HCV may not appear until 6 months after exposure, and levels may remain high for years after an infection, so it is not a good indicator of current infection status. (p581 Fischbach)

What must you do if the confirmatory tests are positive?
--report the infection to public health authorities within 1 working day

9. What’s the clinical significance of a positive HBsAg test?
--it means the body has mounted an immune response to the surface antigen of hep B
--if it's present after 6 months then the pt has chronic HVB infx

How do you distinguish between acute & chronic Hep B in a person with a “+” HBsAg test?
--could be IgM or IgG
--test for IgM, if positive then it's acute
--no indication if pt will resolve the infx or go to chronic state
--90-95% resolve, verified by no more antigen but antibody still present

10. Know the order of appearance of the various antigens & antibodies in a person who recovers from Hepatitis B.

11. Know the pattern for a person who develops chronic Hepatitis B and how to distinguish the replicative from the non-replicative states. Be familiar with HBV testing summary slide.

How is chronic Hep B defined?
--still have HBsAg after 6 mo
--if antibody to surface antigen is present (>10mU/ml), and antigen is absent, indicates recovery

12. What is the “core window?”
--gap between disappearance of HBsAg and appearance of anti-HBs Ab

What tests will be positive during that period?
--anti-HBc (core antibody)

13. When might you want to screen for Hep C Virus?
--pt has hx of drug injection, blood transfusions before 1992, long term dialysis, blood from infected donor, or has persistently elevated ALT

What is the significance of a positive Hepatitis C Virus ELISA test and a negative RIBA test?
--I DON'T KNOW ??? they test for the same thing
--both RIBA and ELISA detect antibodies, neither is the same as PCR which finds viral RNA

--ELISA is positive in nearly all chronic hep C cases, but may be negative in acutes because it can take 6 weeks or longer for the pt to develop antibodies
--anti-HCV may not appear until 3-6 months after exposure
--ELISA = most commonly used initial blood test for hepatitis C
--ELISA = enzyme-linked immunosorbent assay, aka EIA
--false-negative ELISAs occur in patients whose immune systems do not produce enough antibodies, such as people on hemodialysis and people with immune disorders (HIV)
--very rare: ELISA may give false-positive result in people with autoimmune disorders
--confirm ELISA with an HCV RNA test (PCR)

--RIBA = recombinant immunoblot assay also detects antibodies to HCV in serum
--RIBA can be used to confirm a positive ELISA, ex: blood donor w/o risk factors for HCV
--RIBA tests for Anti-HCV = hep C antibody
--blood banks use the RIBA to test donated blood, especially to confirm blood samples that are HCV-positive by the ELISA (does this put us at risk because of the window between exposure and appearance of antibodies????)
--another source says that ELISA is used to screen the blood supply

--Anti-HCV ELISA used for initial evaluation of all pts wth liver dz or increased ALT
--A + Anti-HCV can mean current or resolved infx
--15% of acutes clear the virus and resolve without going into a chronic state
--Use qualitative HCV RNA PCR to look for evidence or viral replication (if neg then resolved)
--CAUSES OF FALSE POSITIVES on ELISA test: autoimmune dz, polyarteritis nodosa, rheumatic fever, hypergammaglobulinemia, passive antibody transfer (ie breastmilk)
--FALSE NEGATIVE ELISA ETIO: early acute infx, immunosuppression, immunoincompetence
--new way: PCR. Look for HCV RNA in blood, qualitative and quantitative. Can diagnose before seroconversion. Also PCR allows you to know the genotype: there are six known with 50 subtypes....type Ib has the highest risk of hepatocellular cancer
--seroconversion 2-3 weeks after exposure
--PCR detects virus as early as 1-2 weeks after exposure
--PCR amplification can detect very low levels of HCV RNA in serum (100-2000 copies/ml)
--PCR not standardized among labs so use the same lab for monitoring viral load during treatment
--qualitative HCV RNA test recommended for those who test + for Anti-HCV (ELISA) to determine if infection is active or resolved
--viral load under 2 million copies/ml have better response to treatment
--viral load not "thought to" correlate with severity or prognosis (why not???)

14. What’s the significance of a positive Hep C Virus ELISA test & a negative qualitative HCV RNA test?
--positive for antibodies but negative for viral RNA means the infection has resolved, the person is not a carrier

15. What test would monitor the effectiveness of anti-viral therapy in a confirmed chronic Hep C patient?
--quantitative HCV RNA is used to monitor viral load and antiviral therapy

Why is it advisable to do HCV genotyping in this patient?
--because some strains are more likely to cause liver cancer than others (Ib bad)

16. When might you order the Hep D virus?
--when pt has hep B (HBsAg present)

Understand the difference between co-infection & super-infection for HBV & HDV and their respective test patterns.
--coinfx means both are introduced at same time
--superinfx means hep D infx happens in chronic HBV carrier

17. When might you decide to test for the Hepatitis E virus? (postabsorptive)
--pt develops hep after travel to Mexico, India, Africa, Burma, Russia
--pt has no serologic markers for hep A, B, C, EBV or CMV


--originally named "infectious hepatitis"
--does not cause chronic hepatitis or a carrier state
--rarely causes fulminant liver failure: fatality rate is about 0.1%
--outcome more severe if infx is superimposed on chronic Hep B, C, or alcohol damage
--INCUBATION period: 2-6 weeks
--TRANSmission: fecal-oral, highly contagious
--occurs all over the world, more with poor hygiene/sanitation
--populations where it is endemic may have anti-HAV antibodies by age 10
--TESTING: no antigen test is available, so antibody testing is the standard
--IgM antibodies appear in blood at onset of symptoms 99% of the time, usually 3-4 weeks after exposure, and just before liver enzymes elevate
--IgG antibodies appear weeks-months later, and may persist for years or for life, conferring lifelong immunity to Hep A Virus.
--so if a person tests + for the IgM and - for the IgG, it's an acute infection, possibly contagious, and reportable here in Oregon
--if a person tests - for the IgM and + for the IgG, the antibodies are from a previous infection (since there is no chronic state for hep A), and the person is not contagious
--if someone tests + for both IgM and IgG, they may have had a previous infection and had a reinfection
--Sx: mild or asymptomatic, fever, nausea, vomiting
--HAV accounts for 25% of clinically evident acute hep worldwide
--270,000 new cases/year in the US
--LABS: ALT may go as high as 1000
--TX: get IgG to boost resistance
--VACCINE: available for travelers, a big needle in the bum last I heard, confers immunity for a limited time period. (I got it prior to going to Chile in 1992 and am no longer immune as of 2006).

--look for: HBsAg (first antigen), HBeAg (replicative antigen), Anti-HBc (immune response, IgM and total M&G), Anti-HBe (good prognosis for resolution), Anti-HBs, and HBV DNA
--outer envelope contains Hep B surface antigen: HbsAg which is detectable in serum
--viral center contains double stranded DNA and DNA polymerase
--2 "core" antigens surround the viral genome: HBcAg and HBeAg (the "e" is for "exportable")
--HBeAg is detectable in serum (c is not bcs surrounded by HBsAg)
--FIRST indicator of HBV infx: HBsAg, the surface antigen, appears 27-41 days after exposure and 7-26 days before biochemical abnormalities, peaks as ALT rises and may persist during acute illness. Disappears 12-20 weeks after onset of Sx in 90-95% of cases. If HBsAg persists more than 6 MONTHS it is defined as a CHRONIC HBV infection.
--HBsAg is used as a diagnostic screen for HBV infection however 10% may present with illness after the surface antigen has cleared. TO BE SURE test for anti-HBc IgM, the initial antibody to the core antigen. The infection may clear or may become chronic from a + at this stage.
--if HBeAg is present, the pt is highly contagious due to active HBV replication. HBeAg appears within 1 wek after HBsAg. In acute cases that resolve, HBeAg is present for 3-6 weeks then disappears before HBsAg. Use to determine RESOLUTION of infection. If it persists over 20 weeks suggestive of progression to chronic HBV with active viral replication.
--Anti-HBc IgM appears 2-4 weeks after HBsAg appears, and is replaced with IgG in about 6 months. Anti-HBcAb IgG remains for life but does not correlate with resolution of infection, as it will be present in individuals who have chronic infection as well as those that resolve.
--Anti-HBc present in absence of HBsAg and anti-HBs: confirms recent acute (2-16 weeks)
--Anti-HBe appears only if HBeAg disappears, and remains detectable for years. Indicates decreasing infectivity and good prognosis for resolution of acutes.
--90-95% recover from acutes, confirmed by presence of Abs w/o HBsAg, conferring immunity
--appearance of antibodies may take wks/mos after HBsAg has disappeared and ALT HAS NORMALIZED
--the gap between the disappearance of HBsAg and appearance of anti-HBsAb (2-6 weeks) is known as the "core window" or serologic gap.
--30-50% loose antibodies in 7 years after immunization and require a booster. I got the shots when I worked ski patrol in the early 90's and still had Ab's when tested in 2006.
--THE MOST SENSITIVE AND SPECIFIC ASSAY FOR EARLY EVALUATION IS: PCR. Measures HBV replication even when HBeAg is not detectable. This is how you measure "viral load". People with HBV DNA > 200 pg/mL are less likely to respond to interferon therapy.
--after HBsAG appears there will be 7-26 days before biochemical abnormalities (elevated transaminases)
--HBsAg peaks as ALT rises, may persist during illness
--HBsAg disappears 12-20 weeks after onset of sx in 90-5% of cases
--if it doesn't disappear then you have a chronic infection
--Anti-HBc = hep B core antibody
--core antigen is inside envelope of virus and not detectable in serum
--HBe Ag = so called "exportable" antigen
--while HBe antigen is present, HBV is replicating and the pt is highly contagious
--time period between disappearance of surface antigen and appearance of antibody (2-6 wks) is "core window"

--non-enveloped, positive-sense, single-stranded RNA virus
--causes 1% of the acute hepatitis cases in US
--Trans: fecal-oral
--S/Sx resolve over approx 6 wks
--exception: infx in pregnant woman can lead to fulminant hepatic necrosis
--fatality rate in pregnant woman 20% in third trimester
--Locations: N. Africa, Egypt, Mexico, India, Burma, Russia
--testing is indicated after travel to these locations
--serological markers for Hep A, B, C, EBV, and CMV are ABSENT
--not recognized as unique disease agent in humans until 1980

--chronic hepatitis is defined as more than 6 month with histological documentation of liver inflam and necrosis
--Hep B, C, and B&D cause chronic infx
--#1 cause of hepatitis worldwide: B
--#1 cause of hepatitis in the US: alcohol
--NON-VIRAL causes of hepatitis: chronic alcoholism, Wilson's dz, alpha 1-antitrypsin deficiency, drugs and other hepatotoxins, various autoimmune dzs
--posts on hepatitis A, B, C, D, E follow this one
--mild hep = limited to portal tracts, lymphocytes, macrophages, occasional plasma cells, neuts and eos, with liver architecture preserved but individual hepatocytes necrotic, diffuse granular cytoplasm, ground glass hepatocytes

--Hep G Virus is found in 1-2% of blood donors and has no know pathogenic activity
--HGV has been found in the sera of Hep C patients and terms and "innocent bystander" virus
--transmission of G uncertain
--causes 0.3% of the acute hepatitis in US
--infection persists for many years
--ALT is persistently abnormal
--serologic assays under development
--can be detected by RT-PCR
Tags: diagnosis, hepatitis, labs, liver, nd2

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