1. glycogenolysis & gluconeogenesis
Catabolism of hormones
and other serum proteins
Glucose homeostasis;
glycogenolysis & gluconeogenesis
Chronic Liver Disease
Synthesis:
Albumin
Coagulation factors
Storage:
Glycogen
Iron
Cu, Iron, vitamins
Bile excretion
Katharine Brown

2. Objectives Causes and management of chronic liver disease
Management of an UGI Bleed
Key features of less common types of chronic liver disease

3. 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?

4. Differential Diagnoses
(Decompensated) Alcoholic liver disease
Viral liver disease
Autoimmune liver disease, Wilson’s, HH etc
Hepatocellular Carcinoma
Pancreatic Cancer
Cryptogenic Liver Cirrhosis
What further history would be needed?
What signs would you look for on examination?

5. Signs of CLD

6. 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

7. 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

8. 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

9. 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

10. Acute GI Bleeds ABC Correct clotting abnormalities (vitamin K, FFP)
- 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)

11. CLD Aetiology Surgical Sieve Viral
Autoimmune - Autoimmune hepatitis, PBC, PSC
Genetic - Wilson’s, Haemochromatosis, Alpha 1 antitrypsin deficiency
Toxic / Drugs – alcoholic, paracetamol
Non-alcoholic fatty liver (DM / metabolic syndrome, pregnancy, idiopathic)

12. Hepatitis B & C Hepatitis B Hepatitis C Virus DNA RNA Spread
Blood, sexual
Blood
Presentation
Fever, malaise, anorexia, nausea, arthralgia, jaundice, RUQ pain
Usually asymptomatic early on
Investigation
See below. Biopsy
Anti-HCV, HCV DNA. Biopsy.
% Chronic
5-10%
85%
Treatment
Supportive. Chronic: antivirals (nucleoside analogues). Transplant
Nucleoside analogues, protease inhibitors (anti-retroviral). Liver transplant
HBV DNA = infectious
HBsAg = currently infected
Anti-HBs + Anti-HBc = past infection
Anti-HBs alone = vaccinated

13. 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

14. 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

15. Wilson’s & α1AT Deficiency
Wilson’s 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 α1AT
Serine protease inhibitor produced by liver
Emphysema + liver damage + HCC

16. 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 (Perl’s stain), MRI liver, ECG, Echo
Rx: venesection, low iron diet, treat diabetes, heart failure etc. Genetic screen relatives.

17. 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 Wilson’s 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?