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Transcript
The Use of Mortality Data to Improve Risk Assessment CTHOLUA Seminar February, 2011 Robert Stout, Ph.D., President and Director Clinical Reference Laboratory Mortality studies… • National studies of prevalence. – Behaviors – Disease(s) • Clinical studies of markers of risk. • Company studies of insured lives. National population estimates… • National Health and Nutrition Examination Survey (NHANES). • National Cancer Survey (NCI) • Center for Disease Control and Prevention (CDC). – Diseases and Conditions – Travel advice • Others Clinical studies… • Bias in selection of the study group. • Bias in the interpretation of the data. • How does it apply to a healthy population? Industry studies… • Insured lives • What about the ones we rated or declined? Laboratory mortality studies… • All comers, not just insured • Huge data base – Numbers and duration • Information on self reported impairments plus bp, BMI, EKG. • All cause mortality As an example: Liver enzyme elevations are pain in the neck for underwriters, agents and applicants. QUESTIONS... Is there liver disease? What is the severity of the disease? What is the mortality risk? Is there liver disease? • Applicant reported? • Abnormal liver enzyme levels The Underwriter‘s approach to elevated liver enzymes... • Family history: hemochromatosis, familial hyperbilirubinemia, kryptogenic cirrhosis • Country of birth: vertical transmission of hepatitis B in endemic countries • Alcohol ingestion: unreliable, but have regard to lifestyle, weight, lipids • Drug ingestion: liver toxic medications, antiepileptics • History of blood transfusion, organ transplantation or other blood products before 1990: risk of hepatitis C The pattern of liver enzymes elevations is important... HEPATITIC PATTERN CHOLESTATIC PATTERN AST, ALT ↑↑↑ • think Viral hepatitis AST alcohol Autoimmune Drug induced ALP, GGT, Bili ↑↑↑ • think Mechanic cholestasis (tumor, gall stones) If GGT heart disease and alcohol. Causes of liver diseases... Common Non-alcoholic fatty LD Uncommon Drug-induced LD Hepatitis C Alcoholic LD Autoimmune hepatitis Alpha-1-antitrypsin deficiency Wilson’s Disease Hemochromatosis Miscellaneous Hepatitis B QUESTIONS... Is there any liver disease? What is the severity of the liver disease? Prognosis of the liver disease? Serum aminotransferase levels in various liver diseases… Giannini, E. G. et al. CMAJ 2005;172:367-379 Copyright ©2005 Canadian Medical Association or its licensors Markers of liver function... • • • • • • Indirect: platelets (very sensitive!) Prothrombin time or INR Serum Albumin Cholinesterase Serum cholesterol (very late!) Bilirubin ….THESE TELL US MUCH MORE ABOUT LIVER DAMAGE THAN DO SERUM LIVER ENZYMES LEVELS. QUESTIONS... Is there any liver disease? What is the severity of the liver disease? Prognosis (mortality)of the liver disease? What risk can we exclude? Hints towards diagnosis of ALD... • Serum alcohol • GGT = most common elevation, may be isolated – Sensitivity and specificity 50% • AST > ALT, AST: ALT >1 • MCV ↑↑. • Fatty liver on imaging (ultrasound, CT) – 100% , if alcohol consumption >60g/d • Carbohydrate deficient transferrin (CDT) Hepatitis CWhy is it important? • Prevalence in US about 3-4 million cases, about 0.5%. • Chonic disease in -85%, only 15-25% heal spontaneously • 20% cases have normal liver enzymes with a fairly benign course. • Time to cirrhosis varies from 10 to 50 years, largely dependent on at what age the HCV acquired. • Cofactors (alcohol, obesity, hepatotoxic drugs) play an important role. Risk factors for HCV infection… 60% 40% Injection drug use unknown 30% Health care 20% Sexual 50% 10% Pre-screening transfusion 0% HCV infection risk THE MOST LIKELY REASON FOR ELEVATED LFTs – THE WINNER IS…… When to suspect NAFLD? IF ONE OR MORE OF THE FOLLOWING: • • • • • • • Overweight/obesity Diabetes Hyperlipidemia Hypertension Medication (cortisone, amiodarone etc) History of gastro-jejunal bypass surgery History of rapid weight loss ALT GGT ALKPHOS AST AST GGT GGT AK AST AK ALL + Liver enzyme distribution NEGATIVE Liver enzyme distribution… NEG ALT GGT ALKPHOS AST AST GGT GGT AK AST AK ALL + Number 5823589 431667 353436 240727 160849 87066 50848 10428 23776 Fraction of population 0.8108 0.0601 0.0492 0.0335 0.0224 0.0121 0.0071 0.0015 0.0033 1400000 4.50 4.00 1200000 3.50 800000 GGT 3.00 Mortality Ratio 600000 2.00 1000000 2.50 1.50 400000 1.00 200000 0.50 0.00 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 101-110 111-120 121-130 131-140 141-150 151> 0 Frequency MR Liver enzyme mortality… MALE <60 300% 275% GGT AP AST 300% 275% 250% FEMALE <60 GGT AP AST 250% 225% 225% 200% Mortality Ratio Mortality Ratio 200% 175% 175% 150% 150% 125% 125% 100% 100% 75% 75% 50% 50% 25% 25% LFT Group by Percentile of Each Subpopulation Fulk M Stout R Dolan V J Insur Med 2008; 40:191-203 LFT Group by Percentile of Each Subpopulation 0.14 AST AND ALT BY DEATH RATE FOR GGT >45 0.12 0.1 0.08 DEATH RATE ALT 0.06 AST 0.04 0.02 0 5 15 25 35 45 55 65 75 85 95 105 115 CONCENTRATION AST, ALT for female applicants with a GGT>45… Take home messages... Laboratory studies will help define mortality risk and reshape underwriting guidelines. AST, GGT, and AK are important in identification of risk. In the absence of viral hepatitis moderately elevated ALT has little risk, if AST is elevated consider alcohol as a possible factor! In the identification of preffered risk GGT is a better marker than cholesterol.