Predictors of elevated transaminase levels in patients with central obesity V. Papastergiou, G. Ntetskas, L. Skorda, F. Lambrianou, K. Roufas, E. Asonitis, M. Stampori, C. Psellas, I. Karagiorgi, S. Karatapanis First Department of Internal Medicine, General Hospital of Rhodes,

Nonalcoholic fatty liver disease Common indolently progressive liver disease Range from simple steatosis, through the more severe nonalcoholic steatohepatitis (NASH), to advanced fibrosis/cirrhosis Strongly related to insulin resistance and obesity hepatic component of the metabolic syndrome Angulo, NEJM, 2002 Marchesini, Hepatology, 2003

ALT Elevated activities may be associated with liver disease Strongly related to obesity, diabetes, dyslipidemia Prevalence elevated ALT: 7.9% in general population, 20% in diabetics, >80% in candidates for bariatric surgery Elevation may act as a surrogate of NAFLD presence Trombetta, APT, 2005 Angulo, NEJM, 2002

ALT More related to fat accumulation than AST Activity in the hepatocytes is 7000 fold greater than in the serum Marker 0f NAFLD in many epidemiological studies Westerbacka, Diabetologia, 2004 Clark, Gastroenterology, 2003

Elevated ALT Predictive of the presence of NAFLD, if two basic criteria are met: Exclusion of alternative liver disease (eg; viral hepatitis, ALD, haemochromatosis) Presence of features of the metabolic syndrome Clark, Am J Gastr, 2003

Abdominal obesity “ upper body” obesity M>F Adiposity in subcutaneous and intra-abdominal compartments (visceral fat) Predictor of adverse metabolic/cardiovascular outcomes irrespective to BMI (reflects general obesity) Waist Circumference (WC) convenient measure of abdominal obesity Included as a criterion for the definition of metabolic syndrome (IDF 2009 revision) ≥ 94 cm in men ≥80 cm in women

Magnitude of elevated liver enzymes (LIFTs) in subjects with increased WC remains limited Few data in the Greek population AIM To estimate the prevalence of elevated liver enzymes among subjects with increased WC and to determine the associated factors

Methods Study population Consecutive adults undergoing abdominal ultrasonography WC: ≥ 94 cm in men, ≥80 cm in women

Exclusion criteria Alcohol consumption (>20 gr/day in women, >30 gr/day in men) Seropositivity for viral hepatitis (HBsAg, anti- HCV) Clinical/biochemical evidence of other liver disease (autoimmune, PBC, haemochromatosis, Wilson)

Recorded variables Demographics WC BMI ALT Alkaline phosphatase Serum triglycerides γ-GT Ultrasonographic features consistent with fatty liver (diffuse increase in liver echogenicity as compared with that of the kidneys) HOMA-IR (IR was considered with HOMA > or =2)

Data analysis Patients were divided in 2 groups: -increased ALT (M: >30 IU/mL, F: >20 IU/mL) -normal ALT Multivariate regression was carried out to identify predictors associated with increased ALT.

Results 211 subjects included 139 (65.9%) males Mean age: 43.8±9.2 years Mean WC: 95.2± (0.9%) normal (BMI<25 Kg/m 2 ) 97 (46%) overweight (BMI 25 to 29.9 Kg/m 2 ) 112 (53.1%) obese (BMI >30 Kg/m 2 )

Abnormal LFTs ALT: 39 (18.5%) AST: 15 (7%) G-GT: 20 (9.5%) ALP: 7 (3.5%) 50 (23.7%) patients had an increase in at least 1 liver enzyme

U/S – “bright” liver 41 (19.4%) patients

Distribution of increased ALT according to Gender and BMI category

Univariate analysis Normal ALT (n=172) Elevated ALT (n=39) P-value Age; years (mean) Male Gender (n,%) 106 (61.6)33 (84.6)< HOMA>2 (n, %)22 (12.8%)18 (46.2%)< BMI; Kg/m 2 (mean) Triglycerides ; mg/dL (mean) < U/S -bright liver (n, %) 20 (11.6)21 (53.8)< g-GT; IU/mL (mean) ALP; IU/mL (mean)

Multivariate analysis VariableOdds ratio (95% CI) Male gender1.8 ( ) HOMA-IR>21.9 ( ) Triglyceride levels2.3 ( )

Conclusions The prevalence of abnormal LFTs in a Greek population with central obesity (assessed by WC) is 23.7% Male gender, presence of insulin resistance and the level of triglycerides, rather than BMI and U/S evidence of fatty liver, are independent predictors of abnormal ALT in patients with central obesity.

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