SANDRA LILIANA JIMÉNEZ RESTREPO, M.D. HUGO A. FAJARDO, M.D. ALBA RODRÍGUEZ, M.D. NATIONAL UNIVERSITY OF COLOMBIA BOGOTÁ, COLOMBIA 2013

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1 SANDRA LILIANA JIMÉNEZ RESTREPO, M.D. HUGO A. FAJARDO, M.D. ALBA RODRÍGUEZ, M.D. NATIONAL UNIVERSITY OF COLOMBIA BOGOTÁ, COLOMBIA 213

2 I have no financial relationships to disclose. I will not discuss off-label use and investigational use in my presentation.

3 Analyses of hepatic function tests are one of the most common forms of liver disease studies. The bilirubin and transaminases are the two liver metabolic components, assessed during routine clinical evaluation of pilots seeking annual medical certification. The aeronautics population is exposed continuously to a variety of occupational risk factors that may compromise liver function and therefore health.

4 The level of bilirubin and transaminases is two to three times higher than normal. 1% to 9% of general population in USA without symptoms have elevated liver enzymes ¹. ¹ GEORGE ARAGON, MD, Zobair M. Younossi, MD, MPH When and how to evaluate mildly elevated liver enzymes in apparently healthy patients, Cleveland clinic journal of medicine, volume 77, number 3, march 21.

5 OBJECTIVE Determine the prevalence of abnormal liver function results as obtained from military pilots and their relation to possible causal factors of enzyme elevation. Discard the etiology of Gilbert Syndrome as a cause of elevation of bilirubin.

6 METHODS Descriptive study Total population of aircraft pilots with current medical certificate by as of April in 212 Data was collected from pilots serving to an entity military in Bogotá, during the month of April 212. The last aeromedical examination records for each pilot were evaluated.

7 VARIABLES ANALYZED - Age - Liver function (bilirubin and transaminases) - Lipid profile (total cholesterol, HDL, LDL and triglycerides) - BMI (body mass index) - BP (blood pressure) - History of smoking, alcohol, drugs and pathologies. STATISTICAL ANALYSIS - Data were stored in an MS Exceltm spreadsheet, with further processing and tabulation of results (descriptive statistics). - Version 3.5 programm Epiinfo for linear regression analysis.

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9 RESULTS 87 male airline pilots were identified. 3 pilots were excluded for not presenting laboratory values of bilirubin in their aeromedical certification records. Total final sample was N = 84 (96.5% of the population of pilots). Mean age 32 ± 5.1 years.

10 Clinical Characteristics Characteristics Total group pilots (N=84) Average age, years BMI, kg/m² Total cholesterol, mg/dl HDL cholesterol, mg/dl LDL cholesterol, mg/dl Triglycerides, mg/dl Glycemia, mg/dl Blood Pressure, mmhg Hypercholesterolemia, % Hypertriglyceridemia, % Smoking, % Alcohol, % Diabetes, % Hypertension, % Metabolic Syndrome, % Continuous variables are shown as mean values ± SD and% of pilots. BMI = body mass index 32 ± ± ± ± ± ± ± /

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12 HYPERBILIRUBINEMIA RMV > 2 times above baseline Total bilirubin, mg/dl Indirect bilirubin, mg/dl Direct bilirubin, mg/dl Frecuency % n * Pilots having bilirubin levels twice its RMV (reference maximum value) which value is associated with a possible alteration in liver function.

13 HYPERTRANSAMINASEMIA Reference Frecuency values n Transaminase GPT o ALT Transaminase GOT o AST Both GPT - GOT * HYPERTRANSAMINEMIA RMV > 2 times above baseline Frecuency % % n ALT, U/L AST, U/L * Pilots having bilirubin levels twice its RMV (reference maximum value) which value is associated with a possible alteration in liver function.

14 During the study it was decided to analyze the relationship between the values of AST / ALT, looking for possible causes for their respective etiologies elevation, among which are: Non-alcoholic fatty liver disease, alcoholic steatohepatitis, possible hepatocellular damage and Wilson's disease ². Transaminases Pathologies associated relationship AST / ALT < 1 Frecuency % n Non-alcoholic fatty liver disease Hepatocellular damage (viral) AST / ALT > 2 Alcoholic steatohepatitis 5 6 AST / ALT > 4 Wilson disease ² PAUL T. GIBONEY, M.D., Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient, American Family Physician March 15, 25 Volume 71, Number 6.

15 Transaminases Frecuency relationship n % AST / ALT < AST / ALT < 1 + BMI 25 29, AST / ALT < 1 + BMI AST / ALT < 1 + Glycemia > AST / ALT < 1 + Triglycerides > AST / ALT < 1 + HDL Cholesterol < AST / ALT < 1 + Metabolic Syndrome This relationship was analyzed with respect to variables such as overweight and obesity, hyperglycemia, hypertriglyceridemia, HDL cholesterol, and metabolic syndrome considering diagnostic criteria according to the Adult Treatment Panel III (ATP III) ³. ³ BARRERA MP, Pinilla AE, Cortés E, et al. Síndrome metabólico: una mirada interdisciplinaria. Revista Colombiana de Cardiología Mayo/Junio 28 Vol. 15 No. 3.

16 VARIABLE Cholesterol Diastolic Glycemia HDL Triglycerides LDL ALT Coeficient R² AST Coeficient R² BILIR Coeficient Total R².2.2 BILIR Coeficient Indirect R².1.1.4

17 Frequency The diseases most commonly found in the medical records of the pilots were leishmaniasis n= 7 (8.3%) and malaria in n= 8 (9.5%), which represent the nature of their missions (forest area). All pilots had negative results from its hepatic serology HBsAg (surface antigen Hepatitis B).

18 There was a very low population of pilots with significant elevation of bilirubin (2 y 8%) and transaminases (2 y 5%), with no apparent clinical manifestations reported and without other diagnostic studies on the etiology of this situation. A high percentage of asymptomatic pilots (67%) had an AST / ALT ratio <1 the suspects the possibility of having a non-alcoholic fatty liver disease (sensitivity 87% and especificity 84%)⁴, and most of these had characteristics of overweight, dyslipidemia and metabolic Syndrome. ⁴ PAUL T. GIBONEY, M.D., Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient, American Family Physician March 15, 25 Volume 71, Number 6.

19 The predictors of cardiovascular risk factors such as smoking, overweight, obesity, hypercholesterolemia, low HDL and hypertriglyceridemia it found high. Of these factors, overweight prevalence was higher compared to the general population in Colombia (58% vs. 32%)⁵. ⁵ BARRERA MP, Pinilla AE, Cortés E, et al. Síndrome metabólico: una mirada interdisciplinaria. Revista Colombiana de Cardiología Mayo/Junio 28 Vol. 15 No. 3.

20 Although the percentage of the population of pilots with elevated bilirubin and transaminases is of 18 and 22%, the blood levels were not significant neither had commitment from the clinical standpoint or pathological that could affect the health of the aviator. The presence of risk factors for metabolic Syndrome mentioned in the study, could be considered predisposing to the presence of nonalcoholic fatty liver disease and secondary elevations especially transaminases. Still the etiology of this elevation is unknown and if this rise is only temporary, leading to proposed new research studies in this population characteristic.

21 Presence of partial information in both the medical history and/or laboratory as recorded in each of the medical certification of airline pilots. The statistical analysis in the study corresponds to laboratory results from a single blood sample. The cases with significant elevation, no progress was made in the diagnostic investigation of the etiology.

22 Mitigate risk factors from the cardiovascular standpoint under occupational health programs. Follow up more short-term health of pilots who are overweight and concomitantly elevated liver enzyme levels, since the probability of occurrence of diseases such as nonalcoholic fatty liver disease is higher. Conduct further research to explain the elevated liver enzymes found in this study.

23 One could suggest the possibility of omitting the requirement of liver profile within the annual medical certification process of pilots.

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