13 - liver panel - hepatitis profile

7/23/2019 13 - Liver Panel - Hepatitis Profile

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[email protected] || 1stsemester, AY 2011-2012

13 - Liver Panel and Hepatitis Profile

Liver Disease

Inflammatory Conditions:

1. Acute Hepatitis

2. Fulminant Hepatitis

3.

Chronic Hepatitis

Cirrhosis

Neoplastic Lesions

Non-neoplastic Lesions

Cholestatic Conditions

Liver Function Tests

Tests for hepatocyte integrity

Liver enzymes

Tests for liver synthetic capacity

Total serum protein

Serum albumin

Clotting factors Serum ammonia

Tests for bilirubin metabolism

Indirect bilirubin

Tests for biliary obstruction

Alkaline phosphatase

Direct bilirubin

Gamma-glutamyl transferase

Aminotransferases

AST is found in most tissues; ALT is confined to the

liver and kidneys.

AST is 80% mitochondrial.

AST and ALT require B6 (pyridoxal).

ALT>AST in acute or chronic hepatitis.

ALT is more specific in non-alcoholics.

Chronic ALT elevation in fatty liver and chronic

hepatitis.

Lactic Dehydrogenase

Catalyzes oxidation of lactate to pyruvate.

Total LDH rises in liver disease:

Very high in SOL

2-3x in viral hepatitis

Slight in biliary obstruction

Liver LDH isoenzyme: LD5

Albumin

Most abundant serum protein

17-20 days half-life

15 gms formed daily

May fall in non-hepatic severe acute or chronic

inflammatory condition

Drugs that can increase albumin measurements:

anabolic steroids, androgens, growth hormone, and

insulin.

Low albumin levels

Liver disease

Ascites

Burns (extensive)

Glomerulonephritis

Malabsorption syndromes

Crohn's disease,

Sprue

Whipple's disease)

Malnutrition

Nephrotic syndrome

Pregnancy

Patterns of Liver Tests

Hepatitis Cirrhosis Biliary Obstruction Hepatic Mass Fulminant Failure Passive Congestion

AST High Normal Normal Normal or high Very High Slightly High

ALT High Normal Normal Normal or high High Slightly High

LDH High Normal Normal High High Slightly High

ALP High Normal to slightly high High High High Normal to slightly High

TP Normal Low Normal Normal Low NormalAlb Normal Low Normal Normal Low Normal

Bilirubin High High High Normal to high High Normal to slightly High

Ammonia Normal High Normal Normal High Normal

High Bilirubin

High ALT/ALP

High ALT

Normal

High ALPCholestasis

3xALP 10x

ALP >3xALP


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Predominant Hepatocellular

Acute hepatitis

Chronic hepatitis

Anoxia

Drugs: aspirin, chlordiazepoxide, chlortetracyline,

cytotoxics, ferrous sulfate, isoniazid, methotrexate,

paracetamol, phenytoin, propylthiouracil

Predominant Cholestasis

Intrahepatic: hepatitis, tumor, cholangitis

Extrahepatic: cholelithiasis, tumor, biliary

stricture/atresia

SOL: tumors, cysts, granuloma, abscess

Drugs: carbamazepine, chlorpromazine,

chlorpropramide, erythromycin, indomethazine,

phenothiazine, steroids, tolbutamide

Cirrhosis

Hepatocellular & Cholestasis

Acute cholestatic

hepatitis

Chronic active hepatitis

Prolonged biliary

obstruction

Decompensated cirrhosis

Severe Liver Disease

1.

Plasma albumin

2. Vitamin-K dependent clotting factors

3. Plasma urea

4. Blood ammonia

General Principles

1)

Liver injury and necrosis increases AST, ALT and LDH.

Secondarily, alkaline phosphatase, GGT, direct and

indirect bilirubin also rise.

If


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Entry and Spread of HBV

Hepatitis B Virus Replication


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Clinical Outcomes of HBV Infection

Determinants in Acute and Chronic Hepatitis B

Worldwide Prevalence ofChronic Hepatitis B


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Serologic Markers in HBV Infection

Disease state

Serology Early Acute Early Acute Late Acute Resolved Acute Chronic Vaccinated

Anti HBc +/- - - +/- + + -

Anti Hbe - - - - +/- - -

Anti HBs - - - - + - +

HBeAg - + + - - + -

HBsAg + + + + - + -

Infectious Virus + 2+ 2+ + - 2+ -

Expected Hepatitis B

Prevalence in Various

Population Groups

Chronic HBV Infection


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Hepatitis B Carrier

Hepatitis B carrier: infection with HBV longer than 6

months.

Chronic infection: 2% to 6% of persons over 5 years of

age; 30% of children 1-5 years of age; and up to 90%

of infants .

In the United States, an estimated 1.25 million peopleare chronically infected with HBV.

HBV Vaccine

HB vaccine protects against chronic HBV infection for

at least 15 years.

Booster doses of hepatitis B vaccine are not

recommended routinely.

Immune memory remains intact indefinitely following

immunization.

People with declining antibody levels are still

protected against clinical illness and chronic disease.

If the vaccination series is interrupted, resume withthe next dose in the series.

Hepatitis C Virus

A flavivirus (from L.flavusyellow) with a SS (+) RNA

genome

170,000,000 people worldwide and 4,000,000 in the

United States are infected with HCV.

Major cause of post-transfusion hepatitis (5% to 10%

of transfusions); chronic hepatitis in 50-85% of cases.

Diagnostic Tests:

1) Antibody assay for anti-HCV

a) Screening EIA

b)

Recombinant immunoblot assay

2)

Nucleic acid test (NAT)

3) Viral genotyping (prognostic tool)

4)

Liver biopsy

Positive anti-HCV (IgG) within 15 weeks of exposure

and 6 weeks of illness.

Passively acquired antibodies in newborns may last

for 18 months.

Positive RT-PCR within 2 weeks of exposure

(incubation period 2-24 weeks). False negative due to

intermittent presence of virus in blood.

Genotype 1: less responsive to treatment.

HCV Infection

Viremia 1 to 3 weeks after transfusion, and lasts for 4

to 6 months

Antibody to HCV is not protective.

Antibody does not indicate activity of illness.

Hepatocyte dead from

exhaustion due to

repeated budding of

HCV

No PEP* for HCV

Early diagnosis and treatment.

Intervention with antivirals when HCV RNA first

becomes detectable.

A short course of interferon early in the course of

acute hepatitis C has a higher rate of resolved

infection.

* post-exposure prophylaxis

Survival of Hepatitis Virus

HAV: can live outside the body for months,

depending on the environmental conditions.

HBV: can survive outside the body at least 7 days and

still be capable of transmitting infection.

HCV:can survive outside the body and still transmit

infection for 16 hours, but not longer than 4 days.

Coinfection with HIV and Hepatitis C Virus

Hepatitis C is more serious in HIV +ve persons.

Coinfection leads to liver damage more quickly.

Coinfection with HCV may also affect the treatment

of HIV infection.

Hepatitis D Virus

Viriod: consists of the genome (RNA, which is not

translated and has no protein), and a delta antigen

(surrounded by HBsAg envelope).

Historically classified as a virus. Delta agent is cytotoxic.

The Delta agent.

Picorna-like virus. RNA genome is very small (1700

nucleotides), single stranded and circular.

Cause of 40% of fulminant hepatitis.

Can replicate only in HBV-infected cells.

HDV is replication defective and cannot propagate in

the absence of another virus. In humans, hepatitis D

virus infection only occurs in the presence of hepatitis

B infection.

A patient can acquire hepatitis D virus infection at the

same time as the hepatitis B virus (co-infection).

Or at any time after during hepatitis B virus infection

(super-infection).

HDV Infection

HDV super-infection should be suspected in a patient

with chronic hepatitis B whose condition suddenly

worsens.

A particularly aggressive acute HBV infection (+ IgM

anti-HBc) should suggest HDV co-infection (fulminant

in 5%).

Super-infection with HDV in a patient with hepatitis B

is diagnosed by the presence of anti-HDV. IgM anti-

HDV may persist in chronic infections.


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HBV-HDV Coinfection: Typical Serological Course

HBV-HDV Super-Infection: Typical Serological Course

HBV, HCV and HDV

Hepatitis C virus exhibits stronger inhibitory action in

the reciprocal inhibition seen in co-infection with HBV

and HCV. HDV is the dominant virus in HBV/ HDV co-infection

and in triple co-infection.

Levels of HBV-DNA and HCV-RNA are lower in co-

infections than in single infections.

Hepatitis E Virus

HEV causes hepatitis E, or enterically transmitted

non-A non-B hepatitis (ET-NANBH). Also called fecal-

oral non-A non-B hepatitis, and A-like non-A non-B

hepatitis.

Hepatitis E is clinically indistinguishable from hepatitis

A disease. Symptoms include malaise, anorexia,

abdominal pain, arthralgia, and fever.

HEV is transmitted by the fecal-oral route.

Waterborne with person-to-person spread.

Food-borne transmission possible.

The infective dose is not known.

The incubation period: 2 to 9 weeks. The disease

usually is mild and resolves in 2 weeks, leaving no

sequelae.

The fatality rate is 0.1-1% . In pregnant women the

fatality rate approaches 20%.

Hepatitis E Virus

HEV Infection

Diagnosis of HEV is based on the epidemiological

characteristics of the outbreak and by exclusion of

hepatitis A and B viruses by serological tests.

Confirmation requires identification of the 27-34 nm

virus-like particles by immune electron microscopy in

feces of acutely ill patients.

Hepatitis F Virus

Round 27-37 nm Virus-Like Particles (VLP).

Genome: double stranded DNA with 20 bk.

Originally thought to be a mutant strain of HBV.

The virus was seen in the cytoplasm of hepatocytes

only in one experimental monkey.

Sequencing of the entire viral genome has not beenaccomplished to this date.

(Deka et al. J. Of Virology, 68(12):7810-15,1994)

HFV Infection

Infection is sporadic and enterically transmitted.

Viral antigens (feces) and elevation of transaminases

appear in 20 days.

The liver shows an acute hepatitis.

The disease in humans may assume a fatality course

in around 20% of the cases.

HFV antigen has been detected by ELISA in 66% of

cases.

Hepatitis G Virus

GB was a 34 year-old surgeon who contracted

hepatitis.

"GB agent" in his serum has been passaged in

monkeys over the years.

It is known to be distinct from other human hepatitis

viruses (A, B, C, D, E).

The "GB agent" contains two flavivirus sequences

related to, but distinct from, HCV.

Single-strand RNA virus of Flaviviridae family

27% homology with HCV, 95% with GBV.

A transfusion-transmitted hepatitis. (Also sexually and

from mother to infants.)

HGV Infection

HGV co-infection is observed in 6% of chronic HBV

infections and in 10% of chronic HCV infections.

Unclear if HGV is actually pathogenic in humans ( no

viral replication in liver.)

Diagnostic tests: Anti-HGV, HGV RNA by PCR.

13 - liver panel - hepatitis profile

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