Download Chronic Liver Disease

Catabolism of hormones
and other serum proteins
Glucose homeostasis;
glycogenolysis & gluconeogenesis
Chronic Liver
Disease
Synthesis:
- Albumin
- Coagulation factors
Bile excretion
Storage:
- 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, 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?
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 - Wilson’s, 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,
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
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
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
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.
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?