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

Objectives Causes and management of chronic liver disease Management of an UGI Bleed 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 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)

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?