Transcript Slide 1

Liver disease and how
to manage it!
Dr Allister J Grant
Consultant Hepatologist
Leicester Liver Unit
University Hospitals Leicester NHS Trust
Anatomy &Physiology
IVC
Portal Vein
Hepatic Artery
Splenic Vein
Gallbladder
CBD
SMV
Anatomy &Physiology
Liver Functions
Nutrition/Metabolic
– stores glycogen (glucose chains)
– releases glucose
– absorbs fats, fat soluble vitamins
– manufactures cholesterol
Bile Salts
– lipids derived from cholesterol
– dissolves dietary fats (detergent)
Bilirubin
– breakdown product of haemoglobin
Liver Functions
Clotting Factors
– manufactures most clotting factors
Immune function
– Kupfer cells engulf antigens (bacteria)
Detoxification
– drug excretion (sometimes activation)
– alcohol breakdown
Manufactures Proteins
– albumin
– binding proteins
Liver Function Tests
Different cells have different enzymes inside them,
depending on the function of the cell.
AST and ALT are associated with hepatocyte damage
GGT and ALP are associated with cholangiocyte
damage ie biliary disease
Aminotransferases
1. Alanine aminotransferase (ALT) and
Aspartate aminotransferase (AST)
These are enzymes that help to process
proteins.
ALT is more specific for liver disease than AST
as AST is found in more types of cell (e.g. heart,
intestine, muscle).
Alkaline Phosphatase
This enzyme level is elevated in a large number of disorders that affect the
drainage of bile e.g.
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Gallstones damaging the bile duct
Tumor blocking the common bile duct
Drug-induced cholestatic hepatitis, blocking the flow of bile in smaller bile
channels within the liver
The alkaline phosphatase is also released from damaged
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bone,
placenta, and
intestine
(isoenzymes)
For this reason, the GGT is utilized as a supplementary test to be sure that
the elevation of alkaline phosphatase is indeed coming from the liver or the
biliary tract
Other Liver “Enzymes”
3) Albumin is a major protein which is produced by the liver
In more advanced liver disease, the level of the serum albumin is
reduced.
4) Bilirubin is the main bile pigment in humans.
Bilirubin is formed primarily from the breakdown of called "haem”
from red blood cells
When elevated, bilirubin causes the yellow discoloration of the skin
and eyes- jaundice and maybe associated with dark urine.
The bilirubin may be elevated in many forms of liver or biliary tract
disease, and thus it is also relatively nonspecific.
Other Liver Enzymes
5) Gamma Glutamyl Transpeptidase is often elevated in liver
disorders but not in diseases of bone, placenta, or intestine.
However the high sensitivity and very low specificity of this test
seriously hampers its usefulness.
GGT is elevated in a whole host of liver diseases
BUT also in
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obesity
hyperlipidaemia
diabetes
congestive cardiac failure
diseases of the kidney, pancreas and prostate.
ALT elevated? (>53)
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Hepatitic illness
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Acute
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Age
Sex
Drugs
Alcohol
Travel
Contacts
Risky behaviour
Autoimmunity
Fever
AF/BP/CCF
Pregnant?
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Chronic
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Age/sex
Ethnicity
BMI
Lipids
Diabetes
Alcohol
Travel
Risky behaviour
FHx
• Autoimmunity
• Unexplained Cirrhosis
The majority of abnormal LFTs in
asymptomatic people occur in those with:
 Diabetes
or metabolic syndrome
(increased risk of NAFLD)
 Excessive alcohol intake
 Chronic hepatitis B or C
 Drugs
ALT elevated
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Hepatitic illness
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Acute
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Hep A,B,C,E
EBV, CMV, TOXO
Drugs screen?
Immunoglobulins
Autoimmune profile
Caeruloplasmin (<50)
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Chronic
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TFT
Diabetic screen
Hep B, C
Lipids
Immunoglobulins
Autoimmune profile
Ferritin
Caeruloplasmin (<50)
α-1 antitrypsin
TTG
(ACE)
ALP Elevated? (>130)
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Cholestatic Illness
(With or without jaundice)
Differentiate from bony
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Acute
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Age/Sex
Drugs/Antibiotics
FHx gallstones
Abdo Pain
Red flag symptoms
Jaundice?
Chronic
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Family Hx
Metabolic syndrome
Recurrent Fever
Itch/lethargy
Dry eyes/mouth
Colitis
Pain
SOB/Resp symptoms
CCF
Liver ALP Elevated
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Cholestatic Illness
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Acute
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CBD stones/Gallstones
Tumours 1º or 2º
Pancreatic pathology
Drugs
Infiltration
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Chronic
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PBC
Sclerosing Cholangitis
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NASH
α-1 antitrypsin
Sarcoid
Amyloid
HIV
Drug Induced Cholestasis
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Intrahepatic Hepatocellular
Cholestasis
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Intrahepatic Ductular cholestasis
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Ductopenic
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Granulomatous
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Allopurinol
Antithyroid agents
Augmentin
Azathioprine
Barbiturates
Captopril
Carbamezepine
Chlorpromazine
Chlorpropamide
Clindamycin
Clofibrate
Diltiazem
Erythromycin estolate
Flucloxacillin
Isoniazid
Lisinopril
Methyltestosterone
Oral contraceptives (containing estrogens)
Oral hypoglycemics
Phenytoin
Trimethoprim-sulfamethoxazole
Investigation of Cholestasis
Raised ALP
Check GT
if isolated rise
Dilated
bile ducts
1) Stop alcohol
Consider
MRCP
ERCP
Other imaging
2) Stop hepatotoxic drugs
3) Advise weight loss if BMI>25
Non-dilated
bile ducts
4) Recheck LFT’s after an interval
Persistently raised ALP
Full liver screen
Diagnosis madeTreat disease
Non diagnostic Ixconsider
Liver biopsy
Isolated raise in Bilirubin (>22)
 Differential
Gilberts vs Haemolysis
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GilbertsUnconjugated hyperbilirubinaemia
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HaemolysisUnconjugated hyperbilirubinaemia
splenomegaly, anaemia ,
DCT, haptoglobin, reticulocyte count, film
Disease Progression
100%
Liver function
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B
Cirrhosis
Liver Failure
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Years
C
Mrs W
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48 year old ♀ admitted from a surgical clinic with
jaundice and unwell
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Unwell for 6 wks after holiday in Mexico
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Hx of xs alcohol 30u/wk
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No previous jaundice
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USS normal size liver and spleen – biliary tree normal
OE
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Jaundice
Drowsy
Agitated/Irritable
Doesn’t obey
commands
No stigmata of CLD
Asterixis (Liver Flap)
No spleen
No ascites
Mrs W
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U&E
ALP
 ALT
 Bili
 Alb
normal
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FBC
Normal
107
736
363
24
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INR
3.7
Causes of Acute Liver Failure
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Drugs
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Paracetamol (UK)
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INH
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Halothane
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Ecstacy
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Wilsons Disease
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Autoimmune Hepatitis
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Reye’s Syndrome
Viral
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Hepatitis A
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Hepatitis B
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Hepatitis E
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Non-A Non-B
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Cardiovascular
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Ischaemic hepatitis
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Budd Chiari
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Acute Fatty Liver of Pregnancy
Cirrhosis
Expanded Portal Tracts
(Blue)
Signs of Chronic Liver Disease
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None
 Asterixis/Flap
 Relative hypotension
 Oedema
 Jaundice/No jaundice
 Large/Small liver
 Splenomegaly
 Gynecomastia
 Testicular atrophy-loss of secondary sexual
characteristics
 Impotence
Decompensation in Cirrhosis
Means the development ofAscites
Hepatic Encephalopathy
Portal hypertension (variceal haemorrhage)
The Development of Ascites
50% of compensated
cirrhotics develop
ascites over 10yrs
50% of cirrhotics with
ascites will die within 2
yrs
Encephalopathy
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1
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 Grade
Constructional apraxia
Poor memory – number connection test
Agitation/ irritability
Reversed sleep pattern
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• Lethargy, disorientation
• Asterixis
 Grade
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• Drowsy, reduced conscious level
 Grade
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• Coma
Decompensation in Cirrhosis
Means the development ofAscites
Hepatic Encephalopathy
Portal hypertension (variceal haemorrhage)
Portal
Circulation
Oesophageal varices
Management of Bleeding Varices
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Prevention
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Prophylactic Antibiotics
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Resuscitation
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Endoscopy -
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Pharmacotherapy- Terlipressin
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Balloon Tamponade
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TIPS
Band Ligation
Sclerotherapy
Management of Bleeding Varices
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Prevention
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Prophylactic Antibiotics
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Resuscitation
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Endoscopy -
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Pharmacotherapy- Terlipressin
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Balloon Tamponade
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TIPS
Band Ligation
Sclerotherapy
Oesophageal varices
Bleeding Gastric Varices
Variceal Bander
Variceal Band Ligation
Management of Bleeding Varices
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Resuscitation
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Endoscopy -
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Pharmacotherapy-
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Balloon Tamponade
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TIPS
Band Ligation
Sclerotherapy
Terlipressin 2mg qds i.v
Management of Bleeding Varices
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Resuscitation
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Endoscopy -
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Pharmacotherapy- Terlipressin
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Balloon Tamponade
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TIPS
Band Ligation
Sclerotherapy
The END
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