Katharine Brown

Chronic LiverDisease

Synthesis:- Albumin- Coagulation factors

Glucose homeostasis;glycogenolysis & gluconeogenesis

Storage:- Glycogen- Iron- Cu, Iron, vitamins

Catabolism of hormonesand other serum proteins

Bile excretion

ObjectivesObjectivesObjectivesObjectives

1. Causes and management of chronic liver disease2. Management of an UGI Bleed3. Key features of less common types of chronic liver

disease

A patient case…A patient case…A patient case…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 DiagnosesDifferential DiagnosesDifferential DiagnosesDifferential 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 CLDSigns of CLDSigns of CLDSigns of CLD

How would you investigate this patient?How would you investigate this patient?How would you investigate this patient?How would you investigate this patient?

Bedside• Observations, BM, fluid balance, weightBlood tests• LFTs (pre/post) (including albumin), INR• FBC, U&Es, CRP• Liver screen: autoantibodies, alpha-1 antitrypsin, caeruloplasmin,

serum copper, ferritin, viral hepatitis serologyImaging• US abdomen + portal vein doppler• CXR, CT, MRI, MRCPSpecial tests• Ascitic tap, OGD (oesophageal varices), liver biopsy

What is your management plan?What is your management plan?What is your management plan?What is your management plan?Conservative• Alcohol abstinence, optimise nutrition, low salt diet, fluid restrictionMedical• 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 CLDComplications of CLDComplications of CLDComplications 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 EncephalopathyHepatic EncephalopathyHepatic EncephalopathyHepatic 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 BleedsAcute GI BleedsAcute GI BleedsAcute 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, antibioticsRockall Risk Score: Age, Co-morbidities, Shock, Diagnosis, evidence

of bleeding (OGD)

CLD AetiologyCLD AetiologyCLD AetiologyCLD 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 & CHepatitis B & CHepatitis B & CHepatitis B & C

HBV DNA = infectiousHBsAg = currently infectedAnti-HBs + Anti-HBc = past infectionAnti-HBs alone = vaccinated

Hepatitis B Hepatitis CVirus 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

Autoimmune HepatitisAutoimmune HepatitisAutoimmune HepatitisAutoimmune 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 PSCPBC and PSCPBC and PSCPBC 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 DeficiencyWilson’s & α1AT DeficiencyWilson’s & α1AT DeficiencyWilson’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 HaemochromatosisHereditory HaemochromatosisHereditory HaemochromatosisHereditory 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.

SummarySummarySummarySummary• 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?