Faculty Disclosure. Objectives. Cirrhosis Management for the Family Physician 18/11/2014
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1 Cirrhosis Management for the Family Physician Mang Ma, MD, FRCP Professor University of Alberta Faculty: Mang Ma Faculty Disclosure Relationships with commercial interests: Advisory Board: Merck, Gilead Objectives Assessment of significant hepatic fibrosis in patients with chronic liver diseases Understand the natural history of cirrhosis and complication development Develop a management routine for your patients with cirrhosis 1
2 Natural History of Chronic Liver Disease Chronic injury Fibrosis progression Cirrhosis Portal hypertension and HCC Complications from portal hypertension Liver failure Natural History of Chronic Liver Disease Chronic injury Fibrosis progression Cirrhosis Can be asymptomatic Portal hypertension and HCC Complications from portal hypertension Liver failure Clinical Assessment of Fibrosis/Cirrhosis Biopsy F1 F2 F3 F4 Decompensation Non invasive tests Clinical symptoms None/min. Fatigue Varices EVH/Ascites/HE Blood tests Imaging studies Abn Cirrhosis MELD 2
3 Liver Biopsy Confirming diagnosis Staging of liver Assessing for coexisting liver diseases Liver Biopsy Invasive procedure with a small risk of morbidity and mortality (1/500 to 1/1000) Hemorrhage Sampling error Examine 1/50,000 portion of liver Variable levels of fibrosis throughout the liver (discordance rate ~30%) Inadequate sample can be misleading Indirect Methods to Assess Liver Fibrosis Blood tests Planel of blood tests (routine and special blood tests) A special calculator to determine the fibrosis score Variable sensitivity, specificity, positive predictive value and negative predictive value Transient elastography Measuring liver stiffness 3
4 Indirect Tests for Liver Fibrosis AST/ALT ratio greater than 1 AST to Platelet ratio index (APRI) Fibrotest (alpha 2 macroglobulin, haptoglobin, gamma globulin, apolipoprotein A1, GGT and bilirubin) PGA Index (PT, GGT and apolipoprotein A1) FibroIndex (AST, Plt, GGT) FIB 4 Index (Plt, ALT, AST) Fibrometer (Plt, PT, AST, alfa 2 macroglobulin, hyaluronate, urea and age) Hepascore (bilirubin, GGT, hyaluronic acid, alpha 2 macroglobulin, age, gender) ActiTest (Fibrotest, ALT) The AST-to-Platelet Ratio Index (APRI) (AST/ULN)/platelets x or less - no fibrosis or just a little 1.5 or above - probably have cirrhosis APRI scores between 0.5 and 1.5 are related to progressive fibrosis (Metavir F1-to-F4) Fibrotest Alpha 2 Macroglobulin Haptoglobin GGT Age Bilirubin Apo A1 Gender FibroTest tests and derivatives are patented since 2001 by APHP (Assistance publique - Hôpitaux de Paris), the Parisian public hospital system. In the US, FibroTest is marketed as FibroSure (a LabCorp trademark). BioPredictive is the company licensed by APHP to promote and operate the tests. 4
5 Fibrotest FibroTest METAVIR Knodell Ishak F4 F4 F F3-F4 F3-F4 F F3 F3 F F2 F1-F3 F F1-F2 F1-F3 F2-F F1 F1 F F0-F1 F0-F1 F F0 F0 F0 Transient Elastography US - Acoustic Radiation Force Impulse Imaging (ARFI) Fibroscan MR Elastography No risk Reducing sampling error by examining a larger mass of liver tissue Can be repeated as frequently as one wishes Cirrhosis AST tends to be higher than ALT Ferritin is elevated, iron saturation index continues to rise Patients would have high IgG and MCV More severe portal hypertension WBC and Plt count will be low. 5
6 Assessment of Fibrosis Liver biopsy Non-invasive tests Complementary Information Transient Elastography Complications of Cirrhosis Ascites Variceal Hemorrhage Hepatorenal Syndrome Hepatic Encephalopathy Nutrition deficiency Hepatoma Cardiopulmonary complications Management of Ascites Dietary Na restriction (<88mmol/day) Diuretic therapy (always use combination ~ furosemide and spironolactone) Large volume paracentesis Avoid renal dysfunction Watch out for SBP TIPS Liver transplantation 6
7 AGA ESOPHAGEAL VARICEAL HEMORRHAGE Varices Gastroscopy is recommended when the diagnosis of cirrhosis is made Nonselective blockers should be used for the prevention of first variceal hemorrhage Patients with cirrhosis who survive an episode of active variceal hemorrhage should receive therapy to prevent recurrence of variceal hemorrhage (secondary prophylaxis) Combination of nonselective blockers plus EVL is the best option for secondary prophylaxis of variceal hemorrhage 7
8 NH 3 Treatment of Encephalopathy Look for cause(s) Avoid precipitants Lactulose Antibiotics Rifaximin Precipitants of Encephalopathy AGA 8
9 HCC It tends to be asymptomatic until the tumour is in an advanced stage. Early detection of HCC is essential in improving the prognosis. 80% of patients with HCC have underlying cirrhosis Surveillance = repeated application of screening tests (imaging study every 6 months ~ US/MRI) The goal of surveillance is to decrease the HCC mortality. Approach for Patients with Cirrhosis Identify liver disease and cirrhosis early Treat the underlying liver disease to reverse cirrhosis or prevent progression if possible If disease cannot be controlled, monitor and treat cirrhotic complications Survey for liver cancer every 6 months Identify patients for liver transplantation early (Child Pugh B and MELD > 15) 9
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