Unit 16. liver diseases.

 Overload – pre hepatic

haemolysis.
 Hepatic – poisonings,
infections, loss of liver cells.
 Post hepatic - blockage of bile
ducts.
Jaundiced patient
 History: family history, contacts,
immigrant status, occupation, sexual
practices, drug use, alcohol etc
 Physical examination: stigmata, systemic,
auscultation, gall bladder problems.

 Laboratory investigations, abdominal X

ray, Ultrasound.
Hepatocellular disease with
“prodrome” – no jaundice!
 Anorexia,
 Nausea,
 Malaise,
 Abdominal pain,
 Liver tenderness,
 Faeces: pale, may float.
 Urine: dark.
Liver functions:
 Protein homeostasis
 Carbohydrate homeostasis
 Lipid homeostasis
 Erythrocyte: make and destroy
 Waste: metabolize and excrete
 Digestion: make bile salts
 Blood clotting factors made
 Speciality proteins made and destroyed.
Liver function tests
 s-AST and s-ALT indicate
hepatocellular damage
 s-bilirubin and s-ALP indicate
cholestasis
 In chronic disease s-albumin is
measured.
LFT: serum transaminases, ALT
and AST.
 Clinically sensitive but not clinically specific
 Both are found in many tissues.
 s-ALT is more increased in liver disease than s-
AST
 s-ALT has fewer false positive results.
 Increased by overload of liver, infections, shock,
severe hypoxia, acute and chronic cardiac failure
Distribution of ALT and AST in
normal human adult tissue
ALT AST
Serum 1 1
Lung 44 500
Spleen 75 700
Kidney 1200 4550
Heart 450 7800
Skeletal muscle 300 4950
Liver 2750 7100
LFT: serum bilirubin
 Breakdown product from haem.
 Insoluble in water, transported bound to albumin
 Liver makes it into mono and diglucuronide
(“direct” or conjugated bilirubin)
 Conjugated bilirubin is secreted into the bile
 Altered in the gut to stercobilin (urobilin)
 Normal is <17 umol/L but jaundice is seen when
bilirubin is >40 umol/L
Serum alkaline phosphatase
 Membrane transport protein
 Increases in blood in cholestasis
 Increases in cancer and cirrhosis
 Also found increased in diseases of the
bone, small intestine, kidney and the
placenta.
Serum gamma glutamyl
transferase
 Microsomal enzyme
 Increased in cholestasis but is somewhat
increased in all liver diseases
 Ethanol and Phenytoin etc users have
increased serum levels of gamma glutamyl
transferase [GGT].
Serum albumin
 Transport protein
 Most abundant protein made by
the liver
 Low levels in chronic liver
disease, starvation and shock.
Prothrombin time:
 Liver made clotting protein
decreased in liver disease.
 Increased prothrombin time may
be the first sign of liver damage
 Short half life – the only LFT that
gives the “current” situation
Serum globulins or total protein
 In hepatitis there is broad spectrum
(polyclonal) increase in serum gamma
globulins.
 In autoimmune hepatitis similar broad
gamma band is seen on serum protein
electrophoresis.
 Could be estimated by s-protein and/or s-
albumin.
Liver function tests summary:
 Cell damage = s-ALT (or s-AST) increased
 Bile blocked = s-bilirubin, s-ALP, s-GGT
increased
 Serial tests for monitoring and prognosis.
 s-GGT increase may indicate
hepatocellular enzyme induction by drugs
or alcohol.
Rarer liver function tests:
 Alpha foetoprotein; usually used as a
cancer marker but also increases in liver
regeneration.
 Alpha-1-antitrypsin: juvenile cirrhosis.
Serum ceruloplasmin
 Anti inflammatory protein – increased in
inflammation.
 Decreased in Wilson’s disease
 Increased tissue and urinary copper
 Leads to juvenile cirrhosis
 1 in 30,000 Europeans
 Liver serology, tertiary LFTs
Virus . Test Indication
A IgM anti-HAV Acute infection
IgG anti-HAV Prior infection
B HBsAg, anti-HBs Acute infection
HBc, anti-HBc Prior infection
HBV DNA Detection, response to therapy
Anti-HBe Response to therapy
 Liver serology (continued)
Virus Test Indication
C Anti-HCV Previous infection

HCV RNA Presence of viral replication

D Total anti-HDV Acute or chronic infection

E Anti-HEV Infection
 Hepatitis:
Haemolytic(pre) Hepatocellular Cholestasis (post)
s-bilirubin >75 s-bilirubin late s-bilirubin
nonconjugated conjugated.
u-bilirubin 0 u-bilirubin u-bilirubin
b-reticulocytes s-ALT, AST s-ALT, AST
b-Hb decreased s-ALP up later s-ALP increased
b-haptoglobin decreased
s-LD may increase
Gilbert’s disease:
 Defective conjugation.
 Benign or very mild disease.
 Most obvious in infections, operations,
when fasting.
 Quebec 1 in 60 “pure laine”.
 Differential diagnosis confusion.
Prehepatic jaundice
 Unconjugated hyperbilirubinaemia
 Newborn: HbF replaced

by HbA
 s-bilirubin > 300 umol/L then blood
transfusion to avoid brain damage
 Glucose-6-phosphatase deficiency,
membrane defects, severe trauma, sepsis
Hepatic jaundice
 s-bilirubin, ALT, AST, ALP increased.
 Poisonings or vial.
 Commonest poisonings:
Tylenol (Acetaminophen),
Carbon tetrachloride,
Phenytoin (Dilantin),
Valproate,
Halothane,
Plant and fungi.
15 year old woman suicidal, took
pills 2 hours ago
 s-bilrubin 15 umol/L (2-17)
 s-ALT 100 U/L (<35)
 s-ALP 100 U/L (<100)

What next?
 Viral hepatitis transmission, after
Botticelli 1486:
Transmission Viral hepatitis
Venus sexual B and D
Giant clam Shellfish,water A and B

Sea Blood B
Wind salivary B, Epstein-Barr
Pregnant neonate B
Mosquito needles, blood supply B and C.
Hepatitis tests for:
 Prodrome: s-ALT, u-urobilinogen.
 Bilirubin increases and s-AST, s-ALT
remain increased until cure.
 No u-urobilinogen until recovery.
 During cholestatic phase faeces is pale and
floats.
 Diagnosis by serology.
Hepatitis A
 Single strand RNA
 Transmission: faecal-oral
 Incubation period: 2-4 weeks
 North America: children
 Diagnosis: s-IgM against hepatitis A
 Death rate: 1 in 5,000
 No chronic hepatitis results.
 Vaccine available.
15 year old boy boarding school,
‘flu. Pain in right upper quadrant
 p-bilirubin 17 umol/L (<17)
 p-ALT 325 U/L (<35)
 p-ALP 100 U/L (<100)
 p-Albumin 39 g/L (30-50)
 p-Protein 65 g/L (60-85)

What indicates hepatitis A?

How do you confirm this?
Hepatitis B
 DNA virus,
 Transmission: by body fluids
 Incubation: 2-6 months
 World wide prevalence: 5-6%
 Neonates at most risk.
 Diagnosis: s-HBsAg
 Vaccine exists, hands on health, day care workers
should have it.
 Leads to recovery or carrier state and/or liver
cancer eventually.
Hepatitis C
 Transmission: in North America by blood
 Incubation: 7 weeks
 Mild illness but 85% get chronic liver disease
 s-ALT and s-AST fluctuate widely
 Screen by s-ALT, anti-HCV
 High rate of spontaneous mutation so no vaccine
likely.
 Liver cancer likely.
HCV
Hepatitis D
 Transmission: in some cases, at least, sexual
 Requires co-infection with HBV for replication
 First noted in Italy, pockets of it exist in Russian
and Sweden
 IgG, A, M anti HDV (total)
 Goes to severe liver disease
.
HDV
40 year old man returned from
vacation in southern Italy.
 5 days of increasing jaundice.
 p-bilirubin 200 umol/L (<17)
 p-ALT 2,640 U/L (<35)
 p-ALP 500 U/L (<100)
 p-protein 66 g/L (60-80)
 p-albumin 37 g/L (35-50)

Indicators of severity?
Diagnosis?
Hepatitis E
 Transmission: faecal-oral
 Major epidemic in Far East and India

 Diagnosis by antibodies to HEV antigens.

 May be fatal to pregnant women

 Epstein-Barr virus (EBV):
 Infectious mononucleosis, Transmission: is
oral, “kissing disease”
 Incubation period: is 28 days.
 Mild hepatitis with the usual prodrome
 Laboratory tests: Monospot (heterophil IgM
antibodies), EBV titre, nuclear, capsid and
early antigen antibodies.
Cytomegalovirus:
 Herpes type
 80% of adults show evidence of infection
 Serological Test for cytomegalovirus – not
conclusive. Rapid screen exists. IgM levels in
primary infections
 Hepatitis is mild and does not progress to chronic
disease.
 A problem in pregnancy, could cause CNS
damage to foetus.
Treatment of viral hepatitis:
 Nothing really works.
 Alpha interferon is being tried but has to be
taken continuously.

 Isolate the patient.

 Universal (body fluid) precautions.
 Supportive care.
Post hepatic jaundice
(Cholestasis)
 Gallstones can partly or fully block the bile
duct.
 Complete block: s- bilirubin and s-ALP
increased, no u-urobilinogen, faeces pale
and float.
 Partial block: s-ALP increased but s-
bilirubin could be normal
 Increased s-conjugated bilirubin.
60 year old man jaundiced with
no pain.
 Weight loss, pale faeces, drinker, no drugs
 p-bilirubin 250 umol/L (<17)
 p-ALT 90 U/L (<35)
 p-ALP 900 U/L (<100)

Diagnosis?
What further tests?
Outcomes of hepatitis
 Complete recovery or
 Acute hepatic failure or
 Chronic hepatic damage.
 Etiology of chronic active
hepatitis:
Auto HBV HCV Unknown
-immune
USA 20 27 21 32 %

UK 58 6 4 32
Australia 30 36 4 30
Italy 2 49 15 34
France 28 17 2 53
Iraq 5 92 0 3
Chronic hepatic damage:
 Alcoholic fatty liver
 Chronic active hepatitis following
virus infection.
 Autoimmune disease
 May progress to cirrhosis.
35 year old woman had hepatitis
9 months before. Results now:
 p-bilirubin 45 umol/L (<17)
 p-ALT 350 U/L (<35)
 p-ALP 400 U/L (<100)
 p-protein 115 g/L (60-85)
 p-albumin 30 g/L (30-50)

Evidence for CAH?

What additional laboratory work?
 Probable causes of jaundice in
different age groups:
1-30yrs 30-60yrs >60yrs
Hepatitis 80 30 5%
Cancer - 10 45
Gall stones 5 15 25
Drugs 2 5 10
Alcohol 3 30 10
Other 10 10 5
Cirrhosis
 Terminal event in liver disease.
 Not reversible.
 30% of alcoholics get it.
 Multiple childbirth may be factor in autoimmune
hepatitis, primary biliary cirrhosis.
 No good markers for early stage.
 Diagnosis by biopsy.
 Little or no treatment that works is known
(Too) Late cirrhosis
 Increasing jaundice
 Mental changes, flapping tremour asterixis.
 Ascites
 Bleeding
 Terminal liver failure
 Immune suppression
 Itching (bile salts).
Cirrhosis
50 year old labourer, vomited
blood lifting a beam.
 Blood haemoglobin 102 g/L (125-175)
 Haematocrit 0.4 (0.4-0.52)
 Urine: tea coloured
 Faeces: occult blood positive
 Serum bilirubin, ALT, ALP increased
 Serum protein decreased.
 History of alcohol abuse.
Rarer causes of cirrhosis
 Wilson’s disease.
 Haemochromatosis.
 Alpha-1-antitrypsin deficiency.
Boy dies from liver failure.
 Serological tests all negative
 Liver copper much increased (found at
autopsy)

What laboratory investigations on his

younger sister?
Hepatic failure
 Electrolyte imbalances, s-Na, Ca, glucose
decreases, severe acidosis.
 Renal failure, toxins?
 b-ammonia increased
 s-albumin decreased
 p-Clotting factors decreased
 Recovery may take weeks.
Summary
 Severe acute liver damage may progress to
liver failure
 s-bilirubin, s-ALT and albumin followed
over time
 Cirrhosis is end point
 LFT little or no use in late stages
 Biopsy needed to diagnose late stages.
Liver cancers:
 Primary – hepatoma caused by hepatitis B
or C, aflatoxin, steroids,
haemochromatosis.
 Secondary – spread from other cancers
 Screening markers: s-AFP and ultrasound
each 6 months.
 s-GGT spread to liver from colon e.g.
60 year woman, breast cancer
was treated, now has bone pain:
 s-bilirubin 7 umol/L (<17)
 s-ALT 40 U/L (<35)
 s-ALP 900 U/L (<100)
 s-GGT 30 U/L (<30)

Explain these results?

What laboratory work next?
Let your liver live

with clean living.