Catabolism of hormones and other serum proteins Glucose

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 Na. Cl) • 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 O 2 - 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 HBs. Ag = 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 & α 1 AT 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 α 1 AT • 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?