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

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

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.
Patterns of Liver Tests
Hepatitis
AST
High
ALT
High
LDH
High
ALP
High
TP
Normal
Alb
Normal
Bilirubin
High
Ammonia
Normal

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.

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

Cirrhosis
Normal
Normal
Normal
Normal to slightly high
Low
Low
High
High

Biliary Obstruction
Normal
Normal
Normal
High
Normal
Normal
High
Normal

Low albumin levels

Liver disease

Ascites

Burns (extensive)
Glomerulonephritis

Malabsorption syndromes

Crohn's disease,
Sprue

Whipple's disease)

Malnutrition
Nephrotic syndrome

Pregnancy

Hepatic Mass
Normal or high
Normal or high
High
High
Normal
Normal
Normal to high
Normal

Fulminant Failure
Very High
High
High
High
Low
Low
High
High

Passive Congestion
Slightly High
Slightly High
Slightly High
Normal to slightly High
Normal
Normal
Normal to slightly High
Normal

High Bilirubin
High ALT/ALP

High ALT

Normal

High ALP
Cholestasis

Nl ALT/ALP
Normal B2
Hemolysis
Gilbert's
Conjugation defects

<10x

ALP >3x

High B2
Drugs
Dubin-Johnson

>10x
ALP <3x
Cholestasis and/or
hepatocellular injury

ALP >3x

ALP <3x
Hepatocellular injury

rainwater@mymelody.com || 1st semester, AY 2011-2012

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

beta-gamma
bridging

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 <80% necrosis, total protein, albumin and

ammonia levels are unchanged.
2) In the absence of regeneration in cirrhosis, normal
AST, ALT, and LDH.
3) In cirrhosis, cholangioles are destroyed so B1 & B2
rise.
4) Space-occupying lesions cause isolated rise in LDH
and ALP.
5) In fulminant liver failure, there is disproportionate
rise of AST over ALT.
6) In alcoholic hepatitis, AST:ALT is 3:1

An acute, self-limited illness with fever malaise,

jaundice, anorexia, nausea.
Symptomatic infection: typical in older children and
adults with jaundice in 70%; only 30% of <6 yrs of age,
few with jaundice.
Disease may last as long as 6 months.
Fulminant hepatitis rare (<0.1%) and in those with
underlying liver disease.
Chronic infection does not occur.
Diagnostic tests: serology for HAV-specific total and
IgM antibody.
IgM HAV: from onset of disease to 4 months. Means
current or recent illness.
Total IgG (without IgM): past infection and immunity.

Hepatitis B Virus

Hepadna virus

Stable enveloped virus resists treatment with ether,

low pH, freezing and moderate heat; labile to drying
Virion characteristics:

a protein kinase around a core antigen

an envelope with a gp surface antigen

envelope antigen with different antigenic

determinants

Replication is unique:
*
virion has strict tropism for the liver
*
infected cells release large amounts of HBsAg
without DNA
*
genome can integrate into the host chromosome
virus replicates through a circular RNA
*
intermediate
Risk of superinfection or coinfection with HDV

Sequelae: chronic hepatitis, cirrhosis and hepatoma

Hepatitis B, C and D have similar epidemiology.

Hepatitis B Virus, EM

Know your A, B, C, D, E, F, G's

Hepatitis A Virus

A picorna virusfrom It. piccolo small

Enterovirus 72 with 27 nm naked icosahedral capsid

surrounding a positive SS RNA genome; very stable in
the environment

Spread by fecal-oral route

May cause asymptomatic viral shedding

HEV has similar epidemiology as HAV.

Hepatitis B Dane Particle

Hepatitis B
Surface Antigen
Particle

HAV replication
within hepatocytes

rainwater@mymelody.com || 1st semester, AY 2011-2012

Hepatitis B Virus Replication

Entry and Spread of HBV

rainwater@mymelody.com || 1st semester, AY 2011-2012

Clinical Outcomes of HBV Infection

Determinants in Acute and Chronic Hepatitis B

Worldwide Prevalence of
Chronic Hepatitis B

rainwater@mymelody.com || 1st semester, AY 2011-2012

Expected Hepatitis B
Prevalence in Various
Population Groups

Chronic HBV Infection

Serologic Markers in HBV Infection

Serology
Anti HBc
Anti Hbe
Anti HBs
HBeAg
HBsAg
Infectious Virus

Early Acute
+/+
+

Early
+
+
2+

Acute
+
+
2+

Disease state
Late Acute
+/+
+

Resolved Acute
+
+/+
-

Chronic
+
+
+
2+

Vaccinated
+
-

rainwater@mymelody.com || 1st semester, AY 2011-2012

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 people

are 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 with

the next dose in the series.
Hepatitis C Virus

A flavivirus (from L. flavus yellow) 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

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 antiHDV may persist in chronic infections.

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

rainwater@mymelody.com || 1st semester, AY 2011-2012

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 fecaloral 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 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 been

accomplished 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.

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.

rainwater@mymelody.com || 1st semester, AY 2011-2012