Hepatology

YESPA ¾ STUDY GROUP

rteka1@student.monash.edu
Things we will cover:
1. LFT interpretation
2. Viral hepatitis
3. Alcoholic liver disease
4. Non-alcoholic fatty liver
disease
5. Autoimmune hepatitis
6. Wilson’s disease
7. Hereditary haemochromatosis
8. Budd-Chiari syndrome
9. Acute liver disease
10.Chronic liver disease
11.Hepatocellular carcinoma
12.Benign hepatic tumours
13.Biliary tract disease
2
LFT interpretation
FOR MONASH EXAMS

3
LFT components and their derivation:
Component Derivation Derangements
Bilirubin • Organic anion metabolised from haem ↑ due to:
• Conjugated in liver to glucuronic acid • Disorders of bilirubin
• Transported into bile metabolism
• Hepatocellular disease
• Biliary tract obstruction
Albumin Synthesised in liver i.e. marker of • Influenced by nutrition,
synthetic function (10 g/d) catabolism, GI or urinary loss
• Good for prognostication
Total protein Albumin + Ig + carrier proteins
γ-Glutamyl • Canalicular (bile) surface of • Activity can be induced by drugs
transpeptidase hepatocyte e.g. phenytoin and alcohol
(GGT) • Also in pancreas, renal tubules, • Mild ↑ common AND non-specific
intestine • Use in conjunction not isolation

4
LFT components and their derivation:
Component Derivation Derangements
Aspartate • 80% from hepatocyte mitochondria ↑ due to:
aminotransferase • 20% from hepatocyte cytoplasm • Hepatic necrosis
(AST) • Also heart, muscle, kidney, brain • Myocardial infarction, muscle
injury, congestive heart failure
Alkaline Cytosol enzyme more specific to liver ↑ ONLY due to liver disease
aminotransferase
(ALT)
Alkaline • Canalicular (bile) surface of • If GGT is abnormal, hepatic
phosphatase (ALP) hepatocyte origin presumed of ALP
• Also bone, intestine, placenta • ↑ in intrahepatic/extrahepatic
• Origin may be determined by cholestatic disease
electrophoretic separation of • >1000 IU/L in metastatic
isoenzyme or bone-specific mAb hepatic disease and PBC

5
Approach to the jaundiced Bilirubinemia

patient (contd.)
Rules of thumb, rules for life: Conjugated Unconjugated

• Transaminitis (↑ALT, AST) = hepatocellular damage

Congenital
• ALT more liver specific than AST Cholestatic Hepatocellular hyperbilirubine
mias

• AST:ALT = 1 = ischaemic necrosis, hepatitis, CCF

ALP AST Haemolytic
• AST:ALT >2.5 = alcoholic hepatitis, alcohol-induced
deficiency of pyridoxal phosphate
• AST:ALT <1 = ?paracetamol OD, viral/toxic hepatitis, GGT ALT
ischaemic necrosis

6
Approach to the jaundiced
patient (contd.)
Rules of thumb, rules for life:
• If ↑ALP, GGT = cholestatic picture
• ↑ALP = cholestasis, malignant hepatic infiltration
(?bony metastasis)
• ↑GGT = alcohol ingestion, ↑↑↑ with biliary and hepatic
obstruction

7
Summary of LFT changes
Component Pre-hepatic Hepatic Post-hepatic
Total bilirubin ↑ ↑ ↑
Conjugated bilirubin ↔ ↑ ↑
Unconjugated bilirubin ↑ ↑ ↔
Urobilinogen ↑ ↓ Not present
Conjugated bilirubinuria Not present Present Present
Urine colour ↔ Dark Darker
Stool colour Normal Normal/pale Pale
ALP level ↔ ↑ ↑
ALT and AST levels ↑ ↑
Splenomegaly Present Present Absent

8
The Hepatitides
A, B, C, D, E, F..G…?

9
Introduction to
hepatitis
Liver damage may be subclassified
as acute parenchymal damage OR
chronic hepatitis. Acute
parenchymal damage can be
caused by many agents.

Chronic hepatitis = hepatitis > or =

6 months, classified according to
aetiology.

Chronic viral hepatitis is the

principal cause of liver disease,
cirrhosis and hepatocellular
carcinoma worldwide.

10
 1
Introduction
There are 5 known RNA viruses which are
known to infect the human liver: HAV, HCV, to viral
HDV, HEV, GBV-C.
hepatitis
GBV-C = GB virus C formerly HGV, infects
humans BUT not known to cause disease.
?GBV-C may slow HIV replication.

11
 2
Introduction
There is 1 known DNA virus which can
infect the human liver.
to viral
hepatitis
Hepatitis B virus (HBV)

12
 3
Route A B C D E
Faeco-oral Y N N N Y Features of
Sanguineous
Vertical
Rare
N
Y
Y
Y
Rare
Y
Occasional
N
N
viral hepatitis
Saliva Y Y Y ?N ?
Sexual Rare Y Rare Rare N
CLD N Y Y Y N
Cancer N Y Rare Y N
Carrier N Y Y ? N

13
Hepatitis A virus
•RNA picornavirus with faeco-oral transmission
(shellfish!), often in institutions
•Incubation period of 2 to 4 weeks
•Predominantly acute infection
•Most common viral hepatitis occurring worldwide
typically affecting children and young adults
•Usually a benign, self-limiting disease, with a serious
outcome being very rare – NO chronicity/carrier state
•Complications are rare and there is no increased risk of
hepatocellular cancer
•Disease is commonly seen in the autumn

14
 Natural history
and diagnosis of
HAV infection
Diagnosis: (Ig)M anti-HAV antibodies

• Detectable at symptom onset

• Peak during acute/early

convalescent phase

• Remain detectable for 3-6 months

OR persist if relapsing hepatitis

• Serum IgG antibodies appear early

in convalescent phase, remain
detectable for decades, associated
with lifelong protective immunity

• Anti-HAV IgG in absence of anti-

HAV = past infection/immunisation

15

Natural history
and diagnosis of
HAV infection
Phases of HAV infection
• Incubation period
• Prodromal/pre-icteric phase
• Icteric phase
• Convalescent phase
1. Incubation period: 28 days (15 to 50 days)
2. Pre-icteric phase with non-specific symptoms
1. Malaise
2. Anorexia, nausea, vomiting
3. Weight loss of 2-10 lbs
4. Mild-moderate RUQ pain
5. 10 to 15% develop a serum-sickness-like
syndrome with low-grade fever, rash, and
arthralgias
3. Icteric phase (ideally coinciding with diagnosis)
1. Patient: dark bilirubinuria, pale stools
2. Results: Transaminitis +/- prolonged PT
4. Convalescent phase
1. Devolution of symptomology
2. NANB usually diagnosed by exclusion
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Differential
diagnosis of
HAV infection
Hepatitis B, C, D, E

Epstein-Barr and cytomegalovirus

Yellow fever

Herpes simplex virus

Adenovirus

HIV infection

17
Features of
HAV infection
•Flu-like prodrome (2-8 weeks)
followed by icteric phase with
jaundice and splenomegaly
• Fever, malaise, nausea,
arthralgia
• Then jaundice – rare in
children, hepatosplenomegaly
and adenopathy

•Convalescent phase with

resolution
•Most infections are in
childhood – beware the
asymptomatic child with
hepatitic LFTs!
•Distaste for cigarettes

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Rare extrahepatic
manifestations of
HAV infection
•Evanescent rash
•Arthralgias
•Leukocytoclastic vasculitis
•Myocarditis
•Acute kidney injury
•Thrombocytopenia
•Aplastic anaemia
•Red cell aplasia
•Glomerulonephritis
•Optic neuritis
•Transverse myelitis
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 Complications
of HAV
infection
• Known sequelae:
• Cholestatic hepatitis (<5%)
• Relapsing hepatitis (10%)
• Autoimmune hepatitis

• <1% of cases will progress to

fulminant hepatic failure +/-
subsequent death

• BUT NO oncogenicity and NO

chronicity despite relapse

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 Who should be vaccinated?
• Travelers to endemic areas
Management • Patients with chronic liver disease
and prevention • Recipients of blood products such as haemophiliacs
• Homosexual men
of HAV • Australian aboriginals and recognised community-wide HAV epidemics
• Workers in frequent contact with hepatitis cases
infection
1 IM dose of Havrix Monodose® if >16 years old provides antibodies for a
• Management is supportive
year with immunity lasting beyond 10 years. Antibodies persisting for 20 years
• Avoid alcohol possible with a booster dose any time between 6 to 12 months after primary dose.
• Rarely interferon-alpha for
fulminant hepatitis

• Corticosteroids have NO benefit

• Active immunisation via a

formaldehyde-inactivated HAV
vaccine

• Passive immunisation with normal

human IgG if exposure to HAV <2
weeks, also administer HAV
vaccine unless serious febrile
illness

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Hepatitis B virus
•Double-stranded DNA hepadnavirus spread through
exposure to infected blood or body fluids, including
vertical transmission from mother to child
•Incubation period of 6 to 20 weeks
•Can present as an acute or chronic infection
•Extrahepatic manifestations can occur with both acute
and chronic infection
•Risk of hepatocellular carcinoma in HBV increases with
increasing age – likely a surrogate for increasing liver
fibrosis/cirrhosis whereas risk of hepatocellular
carcinoma increases only after cirrhosis develops

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 1 2
Immune tolerance
(replicative)
In patients with perinatally
acquired HBV infection
where there are high levels of
HBV replication/serum
HBV-DNA/HBeAg positive
but no evidence of acute liver
disease.
Immune clearance
(replicative)
HBeAg seroconversion,
characterized by progressive
disease without treatment and
increasing liver fibrosis. Likely
to benefit from treatment.
3 4
Immune control (non-
replicative)/inactive carrier
/ state
HBeAg -ve and anti-HBe
+ve, ALT/AST normal due
to lack of immune-mediated
liver damage afforded by
immune control. Risk of
reactivation to phase 2.
Immune escape: HBeAg-
negative chronic hepatitis
Moderate levels of HBV
replication and active liver
disease BUT HBeAg –ve
because wild-type virus or
HBV variants with precore or
core mutations.

Natural history of chronic HBV infection

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Course of
chronic HBV
infection
The course of chronic HBV
infection is considered to consist
of four phases: immune tolerance,
immune clearance (HBeAg-positive
chronic hepatitis), inactive carrier,
and reactivation (HBeAg-negative
chronic hepatitis), although not all
patients go through every phase.

Key:
HBeAg, hepatitis B e antigen;
anti-HBe, antibody to HBeAg;
HBV, hepatitis B virus;
ALT, alanine aminotransferase.

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 Features of
HBV infection
Acute hepatitis:
 Subclinical or anicteric hepatitis
(70%)
 Icteric hepatitis (30%)
 Fulminant hepatic failure (<0.5%)
 Prodromal period +/- serum-
sickness like syndrome followed by
constitutional symptoms and
resolution within 3 months

Chronic hepatitis:
 Asymptomatic unless
decompensated/extrahepatic
manifestations
 Non-specific symptoms or symptoms
of hepatic failure

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 Extrahepatic
manifestations
of HBV
infection
• Occur in 10 to 20% of patients with
chronic hepatitis B infection

• Two major extrahepatic

complications of chronic HBV:
• Polyarteritis nodosa
• Glomerular disease

• Common manifestation of
glomerular disease is membranous
nephropathy

• Less often, membranoproliferative

glomerulonephritis may be
encountered

• Associations: aplastic anaemia

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Serology in HBV infection
Disease HBsAg Anti-HBs HBeAg Anti-Hbe Anti-HBc Liver enzymes
Acute HBV + - + - IgM
Chronic HBV e-Ag +ve + - + - IgG ↑ALT, AST
Chronic HBV e-Ag -ve + - - + IgG ↔ALT, AST
Resolved infection - +/- - +/- IgG
Immunisation - + - - -

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 Complications
of HBV
infection
• Chronic hepatitis (5 to 10%)

• Fulminant liver failure (1%)

• Hepatocellular carcinoma

• Glomerulonephritis

• Polyarteritis nodosa

• Cryglobulinaemia

Graph: Cumulative probability of developing hepatocellular carcinoma in

patients with compensated cirrhosis related to HBV infection.

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 Complications
of HBV
infection
• Majority recover
• Fulminant hepatitis is a rare
outcome
• 5 to 10% progress to carrier state
• 4% progress to chronic hepatitis
• 20 to 30% progress to cirrhosis
• Risk of HCC is 0.02% per annum for
chronic hepatitis B
• Risk of HCC is 2.5% per annum when
cirrhosis develops

• High rate of malignancy in Asia and

Pacific Rim due to high endemic
burden of chronic hepatitis B

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 Management and
prevention of
HBV infection
• Rx acute hepatitis
• Mainly symptomatic
• Entecavir/Tenofovir for persistent
HbeAg beyond 12 weeks

• Chronic hepatitis
• Entecavir/Tenofovir
• OR peginterferon alpha-2a

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Hepatitis C virus
•Single-stranded RNA flavivirus that typically presents as
chronic liver disease (80 to 85% of cases)
•Only 20% of patients develop an acute infection, and
only 15 to 20% of these patients will clear the virus after
an acute infection and hence the majority will develop
chronic hepatitis C
•Transmission of HCV:
• 2% risk with needle stick injury
• 6% vertical transmission, higher if co-existent HIV
• Breast feeding is not contraindicated
• <5% transmission risk with sexual intercourse

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01 02 03
<20% develop 15 to 20% of 80 to 85% progress
acute infection patients will clear to chronic HCV
post HCV the virus after an infection.
exposure. acute infection.

Natural history of HCV infection

32
Natural history of HCV infection
33
 Features of
HCV infection
• Most infections are asymptomatic
• 10% have a mild flu-like illness
• Jaundice
• Rise in serum
aminotransferases

• Most patients will only be

diagnosed years later with chronic
liver disease or evidence of
abnormal transaminase values
• Alcoholism can make changes
more rapid
• 2% progress to hepatocellular
carcinoma

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Diagnosis of
HCV infection
•Frequently by exclusion in
a high-risk individual with
NANB hepatitis
•HCV RNA can be detected
from 1 to 8 weeks after
infection
•Anti-HCV tests are
positive 8 weeks from
infection

35
 Management of
HCV infection
• Assessment: extent of liver
disease, viral genotype
• Alcohol cessation and
counselling on illicit drug use
• Treatment depends on genotype
• Pegylated interferon + Ribavirin
+ Protease inhibitor e.g.
boceprevir, simprevir, telaprevir
• Cure rates now approaching
90%, the aim of treatment is
sustained virological response
(SVR)
• Serum HCV RNA 6 months after
the end of therapy

36
Alcoholic liver disease
(ALD)
A P RIME R ON E T OH M E TABOLI S M A N D N A DH /NAD RAT I OS

37
Introduction to alcoholic liver
disease
•Spectrum of liver disease associated with alcohol excess
• Alcoholic fatty liver disease +/- steatohepatitis
• Alcoholic hepatitis
• Alcoholic cirrhosis

•Ethanol undergoes hepatic metabolisation via two

pathways resulting in an increase in the NADH/NAD
ratio which then increases hepatic fatty acid
synthesis with decreased fatty acid oxidation
leading to hepatic accumulation of fatty acid that
is then esterified to glycerides
•TNF-alpha released from Kupffer cells leads to the
release of ROS causing tissue injury and fibrosis

38
 Investigating
ALD
• Consider a diagnosis in a patient
with transaminitis, suggestions of
fatty liver on imaging, steatosis on
biopsy
• Investigative panel
• Bloodwork – elevated MCV
• LFT – elevated transaminases
• AST:ALT > 2:1
• High GGT
• Imaging with ultrasound/CT will
demonstrate fatty infiltration
• Liver histology will also reveal
steatosis
• Elastography to estimate the degree
of fibrosis

39
 Management
of ALD
• General measures
• Alcohol cessation
• Diazepam for delirium tremens
• IV thiamine for Wernicke-Korsakoff
encephalopathy

• Alcoholic hepatitis
• Enteral feeding and vitamin
supplementation
• Steroid therapy and/or acetylcysteine may
improve short-term outcomes

• Other measures:
• Metadoxine (pyridoxine + pyrrolidine)
• Calorie-rich diet to encourage hepatic
regeneration

• Liver transplantation

40
Non-alcoholic fatty liver
disease (NAFLD)
BAFFLED BY NAFLD

41
Introduction to non-alcoholic
fatty liver disease (NAFLD)
•Non-alcoholic fatty liver disease refers to the presence of
hepatic steatosis when no other causes for secondary
hepatic fat accumulation are present
•NAFLD may progress to cirrhosis and is likely an important
cause of cryptogenic cirrhosis
•NAFLD is further subdivided into:
• Non-alcoholic fatty liver (NAFL)
• Hepatis steatosis
• NO evidence of inflammation
• Non-alcoholic steatohepatitis (NASH)
• Hepatic steatosis
• Associated with hepatic inflammation
• Inflammation histologically indistinguishable from
alcoholic steatohepatitis
•Dr Google: “The accumulation of liver fat in people who
drink little or no alcohol.”

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 Management of
NAFLD
• Weight loss and exercise
• Avoid alcohol consumption
• Hepatitis vaccination for patients
without serological evidence of
immunity
• Liver transplantation for patients
with decompensated cirrhosis
• Strict control of:
• Hypertension
• Diabetes
• Lipid levels

• Experimental therapies:
• Thiazolidinediones may show
histological improvement
• 400 IU vitamin E for patients with
advanced fibrosis AND no DM/CAD
• Liraglutide, Orlistat, UDCA

43
Autoimmune hepatitis
Wilson’s disease
Hereditary haemochromatosis
Budd-Chiari syndrome
1 S L ID E S UMMA RI ES OF S E M I - I M P ORTANT M AT RI X C ON D I TI ONS

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Autoimmune hepatitis (AIH)
Type 1 (classic AIH)
◦ Typically women aged 40 to 50 years
◦ Marked hyperglobulinaemia
◦ Anti-smooth muscle antibody (ASMA),
ANA, anti-soluble liver/liver pancreas
antigen (anti-SLA/LP)
Clinical features
◦ Fluctuating clinical picture from
asymptomatic to acute liver failure
◦ Extrahepatic and associations: arthralgia,
haemolytic anaemia, ITP, T1DM, thyroiditis,
coeliac disease, UC

Type 2 Investigations
◦ Usually female children ◦ Deranged LFTs
◦ More common in Mediterranean ◦ Raised AST and ALT
populations Treatment
◦ Liver/kidney microsomal antibody (LKM-1) ◦ Prednisolone
◦ Azathioprine

45
Wilson’s disease
Pathogenesis Investigations
◦ Autosomal recessive 1/30,000 ◦ Low serum caeruloplasmin
◦ Mutation in ATP7B gene on chromosome 13 ◦ High urinary copper
◦ Decreased caeruloplasmin Management
◦ Defective excretion of copper in the bile ◦ Low copper diet
◦ Copper accumulation in tissue, especially liver, ◦ Penicillamine (↑ urinary excretion)
brain, eyes
◦ Zinc (↓ copper absorption)
Clinical features ◦ Pyridoxine (peripheral neuropathy)
◦ Micronodular cirrhosis and jaundice ◦ Liver transplant
◦ Dyskinesia, dementia, chorea, secondary
Parkinsonism
◦ Kayser-Fleischer rings

46
Hereditary haemochromatosis
Pathogenesis
◦ Autosomal recessive gene except type 4
ferroportin which is dominantly transmitted
◦ Excess iron deposition in various organs leading
to eventual fibrosis and functional organ failure
Subtypes
◦ Type 1 HFE: commonest, chromosome 6
◦ Type 2A Juvenile HJV gene mutation
◦ Type 2B Juvenile HAMP gene mutation
◦ Type 3 TfR2 gene mutation
◦ Type 4 ferroportin SLC40A1 gene mutation
Clinical features
◦ Fatigue, bronze or slate-grey hyperpigmentation
◦ Hepatomegaly, deranged LFTs, micronodular
cirrhosis, HCC (45% of deaths)
◦ T2DM – pancreatic copper deposition
◦ Arthropathy, pseudo-osteoarthritis, CPPD
◦ Heart disease, hypopituitarism
Diagnosis and management
◦ Increased ferritin, hypointense liver on MRI, Perl’s
Prussian blue stain for iron overload in hepatocytes
◦ Dietary changes (low-iron foods), venesection of
500 ml blood per week until serum ferritin <50
μg/L, limiting alcohol consumption
47
Budd-Chiari syndrome
Pathogenesis
◦ Obstruction of venous outflow (hepatic vein)
◦ Risk factors: hypercoagulable states, posterior
abdominal wall sarcomas, renal/adrenal tumours,
hepatocellular carcinoma, hepatic infections
Clinical features
◦ Tender hepatomegaly with ascites
◦ Acutely – abdominal pain, nausea, vomiting
◦ Chronic – enlargement of liver, particularly
caudate lobe, negative hepatojugular reflux,
splenomegaly with portal hypertension
Investigations
◦ High protein content of ascetic fluid
◦ Centrizonal congestion, haemorrhage, fibrosis,
cirrhosis on liver histology
◦ USS/CT/MRI – hepatic vein occlusion with
diffuse abnormal parenchyma on contrast
enhancement
◦ Thrombophilia screening is mandatory
Management
◦ Thrombolytic therapy in the acute setting
◦ Transjugular intrahepatic portosystemic shunt
(TIPS) is first treatment of choice
◦ Liver transplantation and lifelong anticoagulation
48
Acute liver disease
FULMINARE, THUNDER AND LIGHTNING

49
 Introduction to acute
liver disease (ALD)
• Acute liver failure refers to the development of severe acute liver injury
with encephalopathy and impaired synthetic function (INR ≥1.5) in a
paient without cirrhosis or pre-existing liver disease
• Commonly used cutoff in illness duration that differentiates acute liver
failure from chronic liver failure is <26 weeks
• Hyperacute (<7 days)
• Acute (7 to 21 days)
• Subacute (21 days to 26 weeks)
• ABCs of acute liver failure
• Acetaminophen, hepatitis A, autoimmune hepatitis, Amanita
phalloides, adenovirus
• Hepatitis B, Budd-Chiari syndrome
• Cryptogenic, hepatitis C, CMV
• Hepatitis D, drugs and toxins
• Hepatitis E, EBV
• Fatty infiltration – acute fatty liver of pregnancy, Reye’s syndrome
• Genetic – Wilson’s disease
• Hypoperfusion (ischaemic hepatitis, SOS, sepsis), HELLP syndrome,
HSV, heat stroke, hepatectomy, haemophagocytic lymphohistiocytosis
• Infiltration by tumour

50
Complications
of ALD
•Hepatic encephalopathy
•Cerebral oedema
•Coagulopathy
•Hypotension
•Acute kidney injury

51
 Management
of ALD
• ICU admission

• NG tube

• Intubation

• 20 degree tilt to prevent cerebral

oedema

• Treat reversible causes e.g.

acetaminophen overdose with N-
acetylcysteine

• Monitor neurology

• Stratify for transplant

52
Chronic liver disease
(CLD)
ALL CANALICULI LEAD TO CLD

53
 Introduction to chronic liver
disease (CLD)
• Fibrosis and conversion of normal liver architecture to
structurally abnormal nodules known as regenerative nodules,
causing cirrhosis
• ABCD of most common causes:
• Alcohol
• Hepatitis B infection
• Hepatitis C infection
• Diabetes (NASH)

• Less common causes: hemochromatosis, autoimmune hepatitis,

PBC, PSC, Wilson’s disease, A1AT deficiency, coeliac disease,
Budd-Chiari syndrome, cystic fibrosis, glycogen storage diseases
• Patterns of cirrhosis
• Macronodular (>3 mm) with hepatitis B/C/D,
haemochromatosis, Wilson’s disease, A1AT
• Micronodular (<3 mm) with alcoholic liver disease, NASH,
biliary cirrhosis

54
On examination – the
(p)mortally hypertensive
patient
•Non-specific: weight loss, loss appetite, fatigue
•Muscle cramps and wasting (breakdown to release
energy)
•Portal HT – splenomgelay, rectal varices, caput medusa,
ascites
•Hyperestrogenic state – palmar erythema, spider naevi,
gynaecomastia, hypogonadism, menstrual anomalies
•Hyperbilirubinaemia – intrahepatic jaundice, pruritus
•Coagulopathy – easy bruising, petechiae, ecchymoses
•Hypoalbuminaemia – peripheral oedema, ascites,
Muehrcke’s lines, leukonychia
•Encephalopathy – asterixis, hepatic fetor, altered mental
state

55
 Complications
of cirrhosis

• Variceal haemorrhage

• Ascites

• Spontaneous bacterial peritonitis

• Hepatic encephalopathy

• Hepatocellular carcinoma

• Hepatorenal syndrome

• Hepatopulmonary syndrome

56
Management of the cirrhotic
patient – general principles
•Alcohol cessation and avoidance of hepatotoxins,
nephrotoxins
•Antiviral treatment for hepatitits
•Vaccination against viral hepatitis and annual influenza
vaccine
•Endoscopic screening for oesophageal varices and
prophylaxis with non-selective beta blocker or ligation
•6-monthly ultrasonographic surveillance for hepatocellular
carcinoma
•Diuresis/Bactrim to reduce risk of spontaneous bacterial
peritonitis
•Evaluation for and removing precipitants for hepatic
encephalopathy
•Enoxaparin for the prevention of portal vein thrombosis

57
Hepatocellular
carcinoma (HCC)
STRATIFY AND RESECT

58
 Introduction to hepatocellular
carcinoma (HCC)
• Primary hepatocyte neoplasia accounts for 90% of all primary liver
cancers and is the third most common cause of cancer worldwide
• Common in Africa and China (40% of cancer)
• Main risk factor for developing HCC is liver cirrhosis
• HBV infection is the leading cause with 90% of HCC cases in HBV prevalent
areas being positive for HBV (integration of HBV DNA into host genome)
• HCV infection – higher risk of developing HCC than HBV infection
• Autoimmune hepatitis
• Cirrhosis secondary to alcohol, haemochromatosis, PBC
• Non-alcoholic fatty liver
• Aflatoxin – a metabolite of a fungus found in groundnuts
• Anabolic (androgenic) steroids
• Clonorchis sinensis
• Weak association with contraceptive pill

• Tumour occurs as single or multiple nodules and histologically

resembles hepatocytes
• Metastasis via hepatic/portal veins to lymph nodes, bones, and
lungs
59
Features of HCC
•Non-specific: weight loss, anorexia, fever
•Jaundice, haemobilia in advanced disease
•Ache in the right hypochondrium
•Ascites +/- hepatic bruits
•Enlarged, irregular, tender liver
•Paraneoplastic syndromes: hypoglycaemia, erythrocytosis,
hypercalcaemia, diarrhoea
•Investigations:
• Markers - serum alpha-fetoprotein (normal in 1/3 cases),
des-gamma carboxyprothrombin
• USS filling defects in 90% of cases
• 4-phase CT – delayed portal vein wash-out and
hypervascularity of nodule
• MRI – good for delineating lesions and helpful to
differentiate small HCCs from regenerative dysplastic
nodules in the setting of cirrhosis

60
 Management
of HCC
• Surgical resection of isolated
lesions <5 cm in diameter or up to
three lesions <3 cm in diameter is
associated with a median survival
of 5 years
• Liver transplant gives a 5 years
survival rate of 70%
• Percutaneus ablation
• Transarterial chemoembolization
(TACE) – causes fever and
abdominal pain in 50%
• Antiangiogenic compounds e.g.
sorafenib prolongs survival to 10
months in patients with non-
resectable tumours

61
Benign hepatic tumours
A SINGLE-SLIDE BUZZWORD SUMMARY

62
Benign hepatic tumours
Hepatic haemangioma
◦ Also known as hepatic venous malformations
◦ Benign non-neoplastic hypervascular liver lesions
◦ Usually small and single but can be large and
multiple
◦ Usually found incidentally on USS, CT, MRI
◦ Female to male ratio = 5:1
◦ Well-defined hyperechoic lesions on USS
◦ Well-defined hypointense lesion on T1 MRI
Hepatic adenomas
◦ Strongly associated with oral contraceptives
◦ May present with abdominal pain or intraperitoneal
bleeding
◦ Women of child-bearing age who have used oral
contraceptive pills
◦ Rx is surgical resection for tumours >5 cm in
diameter or in those whom discontinuation of
OCP does not result in tumour regression
63
Biliary tract disease
1 PAGE SUMMARIES TO GET YOU BUZZED

64
Primary biliary cirrhosis/sclerosing cholangitis
Primary biliary cirrhosis
◦ Autoimmune hepatobiliary disease characterised by
slow progressive destruction of small and medium-
sized intralobular bile ducts of the liver
◦ Extra-hepatic ducts are not affected
◦ Middle-aged white woman (95), smoker
◦ Pruritus, jaundice, xanthomata, bilateral xanthalesma,
fatigue, RUQ discomfort, hepatosplenomegaly
◦ Associations: Sjogren’s syndrome, autoimmune
thyroiditis, systemic sclerosis, rheumatoid arthritis,
renal tubular acidosis
◦ Anti-mitochondrial antibody (AMA) with a
macroscopically green-stained liver
◦ Rx: ursodeoxycholic acid (UDCA), liver transplant
Primary sclerosing cholangitis
◦ Diffuse segmental inflammation of entire biliary tree,
bile duct proliferation, ductopenia, fibrous cholangitis
◦ Middle-aged men with fatigue, pruritus, jaundice,
abdominal pain
◦ Associations: strong with UC, HLA-A1; B8; DR3,
AIH, malignancy risk including cholangiocarcinoma as
sequela (10%), pancreatic cancer, colorectal cancer
◦ p-ANCA, anti-smooth muscle, elevated IgM, MRI –
‘beading of hepatic ducts’
◦ Rx: liver transplant, screening for UC,
cholecystectomy for gallbladder polyps, UDCA may
protect against colon cancer and improve LFT,
cholestyramine for pruritus, antibiotics for bacterial
cholangitis
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Buzzword central
Buzzword/phrase Buzz-diagnosis
Anti-mitochondrial (AMA) Primary biliary cirrhosis (PBC)
Beading of the hepatic ducts Primary sclerosing cholangitis (PSC)
p-ANCA Primary sclerosing cholangitis (PSC)
Anti-smooth muscle antibody (ASMA) Autoimmune hepatitis (AIH)
Tender hepatomegaly + ascites Budd-Chiari syndrome
Travel to Asia + street food + high fever and Hepatitis A
jaundice on return
Psychosis and hepatomegaly in a young patient Wilson’s disease
Kayser Fleischer rings Wilson’s disease
OCP + liver mass Liver adenoma
Well demarcated hypodense mass with Hepatic haemangioma
peripheral lightening

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Exam-style questions
NOW YOU SEE THEM, ON DROPBOX YOU WON’T!

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K
E
H
D

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A
J
L
M

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B
J
E
H

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Question 7
A 27-year-old man presents with generalised A. Perinuclear anti-neutrophil
pruritus, RUQ pain, and jaundice for the past
month. He has a history of recurrent bloody cytoplasmic antibodies (p-ANCA)
bowel movements and painful defecation, and is
now being treated with sulfasalazine. His B. Antinuclear antibodies (ANA)
previous colonoscopy has shown superficial
mucosal ulceration and inflammation with many C. Anti-smooth muscle antibody
pseudopolyps involving the distal rectum up to (ASMA)
the middle third of the transverse colon. On
abdominal examination, the liver is slightly D. Anti-Saccharomyces cerevisiae
enlarged and tender. Total bilirubin is 102.6 antibody (ASCA)
micromole/L and indirect bilirubin is 47.9
micromole/L. ALP and GGT concentrations are E. Anti-dsDNA antibody
moderately increased. ALT and AST are mildly
elevated. Which of the following autoantibodies
is most likely to be positive in this patient?

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Question 7
A 27-year-old man presents with generalised A. Perinuclear anti-neutrophil
pruritus, RUQ pain, and jaundice for the past
month. He has a history of recurrent bloody cytoplasmic antibodies (p-
bowel movements and painful defecation, and is ANCA)
now being treated with sulfasalazine. His
previous colonoscopy has shown superficial B. Antinuclear antibodies (ANA)
mucosal ulceration and inflammation with many
pseudopolyps involving the distal rectum up to C. Anti-smooth muscle antibody
the middle third of the transverse colon. On (ASMA)
abdominal examination, the liver is slightly
enlarged and tender. Total bilirubin is 102.6 D. Anti-Saccharomyces cerevisiae
micromole/L and indirect bilirubin is 47.9 antibody (ASCA)
micromole/L. ALP and GGT concentrations are
moderately increased. ALT and AST are mildly
elevated. Which of the following autoantibodies E. Anti-dsDNA antibody
is most likely to be positive in this patient?

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Question 8
A 36-year-old woman was admitted to ED with A. Wilson’s disease
confusion. She has previously been diagnosed
with manic illness. There is no history of alcohol B. Haemochromatosis
or drug abuse. On examination, she appears
mildly jaundiced and has signs of chronic liver C. Alcohol-related cirrhosis
disease, including spider naevi and palmar
erythema. Also noticeable is a brownish ring D. Viral hepatitis
discoloration at the limbus of the cornea.
E. Primary sclerosing cholangitis
Investigations: bilirubin 130 micromole/L, ALT
85 IU/L, ferritin 100 micrograms/L.
Which diagnosis first best with this clinical
picture?

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Question 8
A 36-year-old woman was admitted to ED with A. Wilson’s disease
confusion. She has previously been diagnosed
with manic illness. There is no history of alcohol B. Haemochromatosis
or drug abuse. On examination, she appears
mildly jaundiced and has signs of chronic liver C. Alcohol-related cirrhosis
disease, including spider naevi and palmar
erythema. Also noticeable is a brownish ring D. Viral hepatitis
discoloration at the limbus of the cornea.
E. Primary sclerosing cholangitis
Investigations: bilirubin 130 micromole/L, ALT
85 IU/L, ferritin 100 micrograms/L.
Which diagnosis first best with this clinical
picture?

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rteka1@student.monash.edu

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