A MEDED LECTURE Biliary / Liver 2 - PowerPoint Presentation

Slide1

A MEDED LECTURE

Biliary / Liver 2

Gurneet Brar

gkb4317@ic.ac.uk

Slide2

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections – hidden slides

Slide3

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections

Slide4

Anatomy and Physiology

3

2

1

4

Slide5

SBA 1

A neonate presents with N+V, lethargy and jaundice in the hospital. An USS diagnoses biliary atresia whereby there is a failure of development of the biliary system. Which of the following deficiency syndromes would you expect to see?

A. Folate deficiency anaemia

B. Beri

beri

disease

C. Scurvy

D. Iron deficiency anaemia

E. Rickets

Slide6

SBA 1

A neonate presents with N+V, lethargy and jaundice in the hospital. An USS diagnoses biliary atresia whereby there is a failure of development of the biliary system. Which of the following deficiency syndromes would you expect to see as a child?

A. Folate deficiency anaemia

B. Beri

beri

disease

C. Scurvy

D. Iron deficiency anaemia

E. Rickets

Slide7

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections

Slide8

Pancreatic Cancer

Definition and

Aetiology

:

Signs and Symptoms:

Pancreatic Cancer = P

ainless jaundice

, P

alpable gallbladder

(

Courvoiser’s

Law)

75% in head of pancreas,

mostly arising from

exocrine tissue

MEN1 –

pancreatic tumours arising from

endocrine tissue

(much less common)

RFs:

Age >60

,

smoking, obesity, T2DM, chronic pancreatitis,

Poor prognosis as they are often

diagnosed late

Signs are non-specific (hence diagnosed late)

FLAWS

Loss of

exocrine

function



steatorrhoea

Loss of

endocrine

function  diabetes

Painless jaundice

is a late sign

Trossaeu

sign

(migratory thrombophlebitis)

Hepatomegaly

if hepatic

mets

occur

Slide9

Pancreatic Cancer

Investigations:

Management:

Bloods –

CA19-9

USS

High resolution CT scan

–

Ix

of choice if high index of suspicion (more sensitive)

Imaging shows the “double duct” sign

Gold standard

Ix

– biopsy via ERCP or EUS

<20% suitable for surgery due to

mets

– ERCP with stenting

Whipple’s resection + adjuvant chemo –

pancreaticoduodenectomy only if

resectable

S/E:

dumping syndrome and PUD

Slide10

Cholangiocarcinoma

Definition and

Aetiology

:

Signs and Symptoms:

Cancer arising in the

bile ducts

either

intrahepatic

or

extrahepatic

RFs:

advancing age, male, smoking, obesity, chronic inflammation of bile ducts

Abdo exam

Virchow’s Node

Sister Mary Joseph nodule

Vague symptoms (both)

FLAWS

RUQ pain

Sx

and

Sx

of biliary obstruction (extrahepatic only)

Jaundice (painless)

Palpable gallbladder

Pruritus

Pale stool, dark urine

Slide11

Cholangiocarcinoma

Investigations:

Management:

Bloods

– LFTs, clotting studies, CA19-9 and CEA

Imaging –

USS, MRCP

Radiography

-- PTC

Gold standard

– ERCP with biopsy

Patients often present late which limits the scope for surgery

Type of surgery dependent on location:

Removal of bile duct

– small and localised tumour

Partial hepatectomy

– intrahepatic

Whipple’s procedure

-- for distal bile duct tumours

Adjuvant chemotherapy or radiotherapy

can prevent recurrence

Slide12

Hepatocellular carcinoma

Definition and

Aetiology

:

Signs and Symptoms:

Primary malignancy of hepatocytes

Forms 90% of primary liver tumours (cholangiocarcinoma the other 10%)

RFs: Cirrhosis

due to hepatitis, alcohol or drugs, AI hepatitis, haemochromatosis, NAFLD, PBC

Presents late

FLAWS

Signs of chronic liver failure

Hepatosplenomegaly

Pruritus

Jaundice

May present with decompensation

Acute deterioration in liver function

Hepatic encephalopathy

Slide13

Hepatocellular carcinoma

Investigations:

Management:

Screening for high risk groups

Bloods –

aFP

tumour marker

Imaging -

USS

Early disease

Surgical resection – non-cirrhotic

Liver transplantation – cirrhotic

Unsuitable for surgery

Percutaneous ethanol injection for peripheral lesions

Sorafenib –

multikinase

inhibitor

Slide14

SBA 2

An 82 year old man has central abdominal discomfort for the past 3months. It radiates through to the back and is associated with nausea. He has a smaller appetite than usual and has lost 11kg in this time.

Blood results show: raised bilirubin, ALP and GGT. ALT and AST are in range.

What is the single most appropriate next step?

A. CT abdomen

B. ERCP

C. MRCP

D. USS liver

E. USS abdomen

Slide15

SBA 2

An 82 year old man has central abdominal discomfort for the past 3months. It radiates through to the back and is associated with nausea. He has a smaller appetite than usual and has lost 11kg in this time.

Blood results show: raised bilirubin, ALP and GGT. ALT and AST are in range.

What is the single most appropriate next step?

A. CT abdomen

B. ERCP

C. MRCP

D. USS liver

E. USS abdomen

Slide16

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections

Slide17

Primary Biliary Cirrhosis

Definition and

Aetiology

:

Signs and Symptoms:

AI condition

associated with granuloma formation in the bile ducts

Inflammatory disorder causing destruction of interlobular bile ducts

RFs:

Middle aged female, PMHx of other AI conditions

Later stages may progress to liver failure

Pruritus

Cholestatic jaundice

RUQ pain

Xanthelasma and xanthomata

Clubbing

Hepatosplenomegaly

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Primary Biliary Cirrhosis

Bloods – AMA M2 antibodies,

SMA, raised serum IgM

Cholestyramine

for pruritus

Vitamin A,D,E,K supplements

Ursodeoxycholic

acid

Liver transplant

if BR >100

Investigations:

Management:

Slide19

Primary Sclerosing Cholangitis

Definition and

Aetiology

:

Signs and Symptoms:

Biliary inflammation

of unknown aetiology

Characterised by

inflammation and fibrosis

of

intra and extra hepatic ducts

M>F

Pruritus

Cholestatic jaundice

RUQ pain

Fatigue

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Primary Sclerosing Cholangitis

Bloods –

pANCA

+ve

ERCP / MRCP

– bead on a string appearance

Biopsy –

“onion skin” fibrosis and obliteration of ducts

Investigations:

Management:

Screening for risk of cholangiocarcinoma

At diagnosis: Ca 19-9 and USS / MRCP

F/U: LFTs and tumours markers checked every 6months. Imaging every 12 months

Proceed to ERCP and biopsies of any suspicious lesions

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SBA 3

A 43-year-old man with a history of mild ulcerative colitis is noted to have markedly elevated serum alkaline phosphatase, slightly elevated aminotransferases, and normal bilirubin on routine laboratory testing. He complains of fatigue and upper abdominal pain.

Which investigative finding fits the likely diagnosis?

Presence of antimitochondrial antibodies

Presence of anti-smooth muscle antibodies

Beads on a string appearance on MRCP

Raised CA19-9 tumour marker

Presence of

antihepatitis

B surface antigen antibody (anti-HBsAg)

Slide22

SBA 3

A 43-year-old man with a history of mild ulcerative colitis is noted to have markedly elevated serum alkaline phosphatase, slightly elevated aminotransferases, and normal bilirubin on routine laboratory testing. He complains of fatigue and upper abdominal pain.

Which investigative finding fits the likely diagnosis?

Presence of antimitochondrial antibodies

Presence of anti-smooth muscle antibodies

Beads on a string appearance on MRCP

Raised CA19-9 tumour marker

Presence of

antihepatitis

B surface antigen antibody (anti-HBsAg)

Slide23

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections

Slide24

Wilson’s

Definition and

Aetiology

:

Signs and Symptoms:

An AR disorder

characterised by excessive copper deposition in tissues

Implicated gene

(ATP7B) is on Chr13

Increased copper

absorption

from SI and decreased

hepatic excretion

of copper

Onset

between 10-25 years

Features arise due to copper deposition which is toxic to tissues

Main organs involved:

brain, liver and cornea

Neuro:

basal ganglia degeneration

 Parkinsonism

,

behavioural, psychiatric and speech disturbances

Eyes:

Kayser-Fleischer rings

Liver:

hepatitis and cirrhosis

Slide25

Wilson’s

Investigations:

Management:

Slit lamp examination

of the eye

Bloods:

LFTs, reduced serum

caeruloplasmin,

raised

free copper

Urinalysis:

increased

24hr urinary copper excretion

Genetic testing / liver biopsy

Copper chelation

with penicillamine (1

st

line)

Other options for chelation:

trientine

hydrochloride,

tetrathiomolybdate

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Haemochromatosis

Definition and

Aetiology

:

A disorder characterised by

abnormal iron deposition

in certain organs, leading to oxidative damage

Primary:

(AR inherited) due to mutation of HFE gene on

Chr

6

Secondary

to: frequent blood transfusions, iron supplementation or diseases of erythropoiesis

More common in

middle aged

males

Females present later

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Haemochromatosis

Signs and Symptoms:

Commonly affected organs:

liver, pancreas, skin, pituitary, heart and joints

Classic triad:

cirrhosis, diabetes and bronze pigmentation – RARE buzzwords for SBAs

Commonly

Non-specific symptoms: lethargy, impotence and arthralgia

Relating to organ dysfunction: deranged LFTs, diabetes mellitus

Slide28

Haemochromatosis

Investigations:

Management:

Bloods:

Serum ferritin

raised

Transferrin sat

>45%

LFTs

raised AST and ALT

FBC

normal

Genetic testing

C282Y mutation of HFE gene

Liver biopsy

Further

Ix

guided by the PC

Guided by:

serum transferrin saturation

ferritin

clinical symptoms

Advise on

avoiding exogenous iron and vitamin C supplements, limiting alcohol intake

Further management is based on staging

Slide29

Haemochromatosis

Management:

Stage

Criteria

Management

0

Normal iron labs with no clinical symptoms

Monitoring iron labs and symptoms every 3 years

1

Transferrin

sats

>45%, normal ferritin, no symptoms

Monitoring iron labs and symptoms every 1 year

2-4

Transferrin

sats

>45%, raised ferritin +/- clinical symptoms

Venesection / iron chelation therapy

End stage liver disease

Features of chronic liver failure and cirrhosis

Liver transplantation

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But before we move on,

PLEASE FILL IN THE FEEDBACK FORM!

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SBA 4

A

19-year-old girl presents with a 2-week history of increasing unsteadiness on her feet with a pill-rolling tremor and repeatedly dropping objects from her hands.

In the last two days she has become increasingly drowsy and jaundiced.

O/E: Brown ring around the iris seen, palpable liver

Bloods: low. Hb, raised BR and ALP.

Which single investigation is likely to support the diagnosis?

Anti-mitochondrial antibodies

Serum ferritin levels

Serum ammonia levels

Serum copper levels

Serum ethanol levels

Slide32

SBA 4

A

19-year-old girl presents with a 2-week history of increasing unsteadiness on her feet with a pill-rolling tremor and repeatedly dropping objects from her hands.

In the last two days she has become increasingly drowsy and jaundiced.

O/E: Brown ring around the iris seen, palpable liver

Bloods: low. Hb, raised BR and ALT/AST. ALP is normal.

Which single investigation is likely to support the diagnosis?

Anti-mitochondrial antibodies

Serum ferritin levels

Serum ammonia levels

Free serum copper levels

Serum ethanol levels

Slide33

Session Overview

Overview of the liver and biliary system

Cancers of the liver and biliary system

Inflammatory disorders

Genetic disorders

Infections – hidden slides

Slide34

Liver Abscess / Cyst

Definition and

Aetiology

:

Signs and Symptoms:

Collections of thick fluid (cyst) or pus (abscess) containing

dead cells, pathogens +/- blood

More common in patients with diabetes

4 types to know about

Pyogenic abscess

Amoebic abscess

Hydatid Cyst

PCLD

Fever

Malaise

Weight loss / loss of appetite

RUQ pain

Jaundice

Tender hepatomegaly

Dullness to percuss (ascites)

Hx of foreign travel

Slide35

Liver Abscess / Cyst

Investigations:

Management:

Bloods:

FBC, CRP, LFTs,

Stool cultures

Aspiration and culture

of lesion

Imaging:

Liver USS, CT or MRI

Bacterial

source – drainage plus long course antibiotics (amoxicillin + ciprofloxacin + metronidazole)

Amoebic abscess

– antibiotics targeting anaerobes i.e. metronidazole

Hydatid abscess

–sterilisation with anti-

fungals

i.e. mebendazole then surgical resection. Percutaneous aspiration contraindicated

Slide36

SBA 5

A 21 year old male from rural Iraq presents with a 3 month history of malaise, weight loss and RUQ pain. Over the last 2 days he reports profuse bloody diarrhoea.

O/E he appears tender in the RUQ and USS reveals a fluid filled mass with poorly defined borders

Given the likely cause of this man’s cyst, what would you expect on aspiration?

Odourless clear fluid with an anchovy paste like texture

Blood stained fluid

Thick white discharge

Clear fluid with a strong odour

No fluid on aspiration

Slide37

SBA 5

A 21 year old male from rural Iraq presents with a 3 month history of malaise, weight loss and RUQ pain. Over the last 2 days he reports profuse bloody diarrhoea.

O/E he appears tender in the RUQ and USS reveals a fluid filled mass with poorly defined borders

Given the likely cause of this man’s cyst, what would you expect on aspiration?

Odourless clear fluid with an anchovy paste like texture

Blood stained fluid

Thick white discharge

Clear fluid with a strong odour

No fluid on aspiration

Slide38

Aetiology

:

Investigations:

Pancreatic Cancer: SUMMARY SLIDE

History:

FLAWS

Loss of pancreatic function

Trosseau

sign

Differentials:

Cholecystitis / Cholangitis

Cholangiocarcinoma

Tumour

of pancreatic cells – exocrine most common

Age >60

Smoking

Obesity

T2DM

Chronic pancreatitis

USS

Management:

Bloods:

CA-19,9

High resolution CT

Surgical:

Whipple’s resection + adjuvant chemo

Late stage:

ERCP with stenting

Complications:

Hepatic

mets

Poor prognosis

Biopsy

Complications of surgery

Slide39

Aetiology

:

Investigations:

Cholangiocarcinoma: SUMMARY SLIDE

History:

FLAWS

Lymphadenopathy

Obstructive jaundice

Differentials:

Cholangitis / Cholecystitis

Cancer in the bile ducts

Age

Male

Lifestyle (obesity, smoking)

Chronic duct inflammation

Biliary strictures

USS, MRCP

Management:

Bloods:

LFTs, clotting studies, CA-19-9 and CEA

Percutaenous

Transhepatic Cholangiography

Surgical:

Removal of bile duct / partial hepatectomy / Whipple’s

Adjuvant

chemotherapy or radiotherapy

Complications:

Biliary sepsis

Surgical risks

ERCP with biopsy

Slide40

Aetiology

:

Investigations:

HCC: SUMMARY SLIDE

History:

FLAWS

Chronic Liver Failure

Acute decompensation

Differentials:

Cholangiocarci-noma

Secondary

mets

Primary malignancy of hepatocytes

Hepatitis

Alcohol abuse

NAFLD

PBC

Haemochromatosis

Bloods:

aFP

Management:

Screening for high-risk groups

USS, CT and MRI

Early disease:

Surgical resection / transplant

Later stage:

PC ethanol injection / immunomodulatory therapy

Complications:

Liver failure

Secondary

mets

Death

Biopsy

Slide41

PBC vs PSC: SUMMARY SLIDE

PBC

PSC

Epidemiology

F>M

Middle aged

M>F

20-40s

Site

Intrahepatic

Intra and extrahepatic

Cause

Granulomatous inflammation

Fibrotic destruction of bile ducts

Clinical features

Fatigue and pruritus

Progressive obstructive jaundice

Diagnostic features

AMA antibodies

Beaded appearance of bile ducts on MRCP

“Onion skin fibrosis”

Associations

Other AI disorders

UC

Treatment

Symptomatic management

Screening for risk of cholangiocarcinoma every 6/12m

Complications

Cirrhosis

Cirrhosis, Cholangiocarcinoma

Slide42

Wilson’s and Haemochromatosis: SUMMARY SLIDE

Wilson’s

Haemochromatosis

Aetiology

AR genetic mutation of ATP7B gene on Chr13

Primary = AR genetic mutation of HFE gene on

Chr

6

Secondary = repeated transfusions / iron supplements / erythropoietic dysfunction

Clinical features

Basal ganglia degeneration

Kayser-Fleischer rings

Hepatitis / Cirrhosis

Cirrhosis, diabetes , bronzed skin

Impotence

Lethargy, arthralgia

Investigations

Slit lamp examination

Serum caeruloplasmin + free copper

Urinalysis

Genetic testing / liver biopsy

Serum ferritin, transferrin

sats

, LFTs, FBC

Genetic testing

Liver biopsy

Treatment

Copper chelation

Lifestyle advice

Active monitoring / venesection / liver transplantation

Slide43

Liver abscess/cyst: SUMMARY SLIDE

Pyogenic abscess

S. Aureus (kids), E. Coli (adults)

60% related to biliary disease e.g., gallstones, strictures

USS

shows fluid filled cavity with

hyperechoic

walls

Drainage plus long course of antibiotics

Amoebic abscess

Entamoeba histolytica

Amoebic dysentery

(profuse bloody diarrhoea)

USS

shows fluid fille

d structure with poorly defined boundaries

Aspiration

= sterile, odourless fluid with pasty consistency

Anaerobic antibiotics

Hydatid cyst

Tapeworm

Echinococcus granulosis

infection

Can be massive.

Sheep-rearing

countries

Associated with

eosinophilia

and

abnormal LFTs

Antifungals and surgical resection

Polycystic liver disease

Usually in association with PCKD

AD disorder

Slide44

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PLEASE FILL IN THE FEEDBACK FORM!