Catabolism of hormones Glucose homeostasis;

and other serum proteins glycogenolysis & gluconeogenesis

Chronic Liver
Disease
Synthesis:
- Albumin
- Coagulation factors
Storage:
Bile excretion - Glycogen
- Iron
- Cu, Iron, vitamins

Katharine Brown
 Objectives
1. Causes and management of chronic liver disease
2. Management of an UGI Bleed
3. Key features of less common types of chronic liver
disease
 A patient case
54 year old gentleman presents to his GP with increasing swelling of his
abdomen and feet over the last 2 months. He has been increasing
tired over this time and feels nauseous and is off his food. His wife has
commented that his eyes have turned yellow over the last few days.
He works in a warehouse and smokes 10 cigarettes a day. He admits to
drinking 4 cans of lager a night. His wife says he drinks at least 8 cans a
night and a bottle of whisky a week.
On examination he is jaundiced but has no hepatic flap and is
orientated in time, place and person. His abdomen is distended but
soft and non-tender. There is no palpable organomegaly but there is
shifting dullness.

What are your main differential diagnoses for this gentleman?

 Differential Diagnoses
(Decompensated) Alcoholic liver disease
Viral liver disease
Autoimmune liver disease, Wilsons, HH etc
Hepatocellular Carcinoma
Pancreatic Cancer
Cryptogenic Liver Cirrhosis

What further history would be needed?

What signs would you look for on examination?
Signs of CLD
How would you investigate this patient?
Bedside
Observations, BM, fluid balance, weight
Blood tests
LFTs (pre/post) (including albumin), INR
FBC, U&Es, CRP
Liver screen: autoantibodies, alpha-1 antitrypsin, caeruloplasmin,
serum copper, ferritin, viral hepatitis serology
Imaging
US abdomen + portal vein doppler
CXR, CT, MRI, MRCP
Special tests
Ascitic tap, OGD (oesophageal varices), liver biopsy
 What is your management plan?
Conservative
Alcohol abstinence, optimise nutrition, low salt diet, fluid restriction
Medical
Vitamin B supplementation (IV/PO), chlordiazepoxide
Diuretics
Paracentesis (give albumin)
NG feeding
Antibiotics (? SBP)
Steroids + albumin (N.B. avoid NaCl)
Lactulose (in hepatic encephalopathy)
Surgical
TIPSS
Liver transplantation
 Complications of CLD
Portal hypertension: oesophageal varices, ascites
SBP
Hepatic encephalopathy (constipation, GI bleed, infection, renal failure)
Hepatocellular carcinoma
Coagulopathy
Hepato-renal syndrome
Liver failure

5 year survival rate in cirrhotic CLD 50%

Child Pugh Score: bilirubin, INR, albumin, ascites, hepatic
encephalopathy
 Hepatic Encephalopathy

Stage 1: shorted attention span, reversal of sleep-wake cycle,

subtle personality changes (anxiety, irritability)
Stage 2: lethargy, personality change, disorientation. Asterixis.
Stage 3: stupor but responsive, severe confusion and
disorientation, abnormal behaviour, incomprehensible speech
Stage 4: coma
 Acute GI Bleeds
ABC
- Protect airway
- High flow O2
- Haemodynamically stable?
- Bloods (Hb, Urea, Crossmatch 4-6 units), ABG
- Fluid resuscitation anything, blood is best
Correct clotting abnormalities (vitamin K, FFP)
Emergency endoscopy: banding, adrenaline injections
Terlipressin
IV omeprazole, antibiotics
Rockall Risk Score: Age, Co-morbidities, Shock, Diagnosis, evidence
of bleeding (OGD)
 CLD Aetiology
Surgical Sieve
Viral
Autoimmune - Autoimmune hepatitis, PBC, PSC
Genetic - Wilsons, Haemochromatosis, Alpha 1 antitrypsin
deficiency
Toxic / Drugs alcoholic, paracetamol
Non-alcoholic fatty liver (DM / metabolic syndrome, pregnancy,
idiopathic)
 Hepatitis B & C
Hepatitis B Hepatitis C
Virus DNA RNA
Spread Blood, sexual Blood
Presentation Fever, malaise, anorexia, nausea, Usually asymptomatic early on
arthralgia, jaundice, RUQ pain
Investigation See below. Biopsy Anti-HCV, HCV DNA. Biopsy.
% Chronic 5-10% 85%
Treatment Supportive. Chronic: antivirals (nucleoside Nucleoside analogues, protease inhibitors
analogues). Transplant (anti-retroviral). Liver transplant

HBV DNA = infectious

HBsAg = currently infected
Anti-HBs + Anti-HBc = past infection
Anti-HBs alone = vaccinated
 Autoimmune Hepatitis
Autoantibodies against hepatocytes
Young/middle age, mainly women
Presentation: jaundice, RUQ pain, systemic symptoms
May be associated with other autoimmune conditions
Investigations
- Type 1: anti-smooth muscle antibodies (80%), anti-nuclear
antibodies (10%)
- Type 2 (children): anti-liver/kidney microsomal type 1
antibodies
- Liver biopsy
Rx: immunosuppressant's (steroids, azathioprine), transplant
 PBC and PSC
Primary Biliary Cirrhosis
Chronic granulomatous inflammation of interlobular bile ducts
Autoimmune: anti-mitochrondrial antibody (98%)
Associated with other autoimmune conditions
F:M 9:1, 50 y/o

Primary Sclerosing Cholangitis

Inflammation, fibrosis and strictures (beading)
of intra and extra-hepatic bile ducts
? Autoimmune: ANCA (80%)
Associated with IBD
20-30% develop cholangiocarcinoma
 Wilsons & 1AT Deficiency
Wilsons Disease
AR defect in copper transporting ATPase
Copper accumulates in liver + CNS +
Kayser-Fleischer rings
Rx: penicillamine, transplant

Alpha-1 Antitrypsin Deficiency

AR deficiency of 1AT
Serine protease inhibitor produced by liver
Emphysema + liver damage + HCC
 Hereditory Haemochromatosis
Defect in HFE causes increased
intestinal iron absorption
Iron accumulates in liver, joints
(arthralgia), pancreas (bronze
diabetes), heart (dilated
cardiomyopathy), pituitary
(hypogonadism), adrenals, skin
Ix: LFTs, serum ferritin, iron,
transferrin saturation, TIBC, HFE
genotyping, glucose, x-ray joints, liver
biopsy (Perls stain), MRI liver, ECG,
Echo
Rx: venesection, low iron diet, treat
diabetes, heart failure etc. Genetic
screen relatives.
 Summary
Alcoholic liver disease is the most common type of CLD
Treatment of ALD is mostly supportive with treatment of the
complications; optimising nutrition and fluid balance is key.
There are three autoimmune forms of CLD
In Wilsons disease copper accumulates in the liver and CNS
In HH iron accumulates in the liver, skin, joints, pituitary, adrenals,
pancreas, heart etc.
Liver transplant is usually the only cure in chronic liver disease

Any Questions?