A simple index of lipid overaccumulation is a good marker of liver steatosis

BackgroundLiver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI). The lipid accumulation product (LAP) is an index formulated in a representative sample of the US population to identify cardiometabolic disorders. Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population from the Northern Italian town where FLI was initially developed.MethodsWe studied 588 individuals (59% males) aged 21 to 79 years. Liver steatosis was detected by ultrasonography and coded ordinally as none, intermediate and severe. 44% of the individuals had liver steatosis. Using proportional-odds ordinal logistic regression, we evaluated the ability of log-transformed LAP (lnLAP) to identify liver steatosis. We considered the benefits to our model of including terms for sex, age, suspected liver disease and ethanol intake. We calculated the 3-level probability of liver steatosis according to lnLAP and sex, providing tables and nomograms for risk assessment.ResultsAn ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe vs. less severe steatosis increased for increasing values of lnLAP (odds ratio [OR] = 4.28, 95%CI 3.28 to 5.58 for each log-unit increment) and was more likely among males (OR = 1.88, 95%CI 1.31 to 2.69).ConclusionIn a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. A more thorough assessment of LAP's potential for identifying liver steatosis will require its cross-evaluation in external populations.

[1]  G. Bedogni,et al.  Natural Course of Chronic HCV and HBV Infection and Role of Alcohol in the General Population: The Dionysos Study , 2008, The American Journal of Gastroenterology.

[2]  B. Hoogwerf,et al.  The Lipid Accumulation Product and All‐cause Mortality in Patients at High Cardiovascular Risk: A PreCIS Database Study , 2010, Obesity.

[3]  E. Ravussin,et al.  Metabolic Changes Following a 1-Year Diet and Exercise Intervention in Patients With Type 2 Diabetes , 2009, Diabetes.

[4]  C. Tiribelli,et al.  Prevalence of chronic liver disease in the general population of northern Italy: The dionysos study , 1994, Hepatology.

[5]  H. Kahn,et al.  The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison , 2005, BMC cardiovascular disorders.

[6]  G. Bedogni,et al.  Fatty liver: how frequent is it and why? , 2004, Annals of hepatology.

[7]  Douglas G Altman,et al.  Dichotomizing continuous predictors in multiple regression: a bad idea , 2006, Statistics in medicine.

[8]  S. Caldwell,et al.  Epidemiology and natural history of non-alcoholic steatohepatitis. , 2009, Clinics in liver disease.

[9]  R. Ross,et al.  Does the relationship between waist circumference, morbidity and mortality depend on measurement protocol for waist circumference? , 2008, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[10]  G. Marchesini,et al.  Diabetes and liver disease: an ominous association. , 2007, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[11]  Steven B Heymsfield,et al.  Comparisons of waist circumferences measured at 4 sites. , 2003, The American journal of clinical nutrition.

[12]  G. Bedogni,et al.  Incidence and natural course of fatty liver in the general population: The Dionysos study , 2007, Hepatology.

[13]  H. Kahn.  The lipid accumulation product is better than BMI for identifying diabetes: a population-based comparison. , 2006, Diabetes care.

[14]  N. Barzilai,et al.  Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies. , 2007, American journal of physiology. Endocrinology and metabolism.

[15]  G. Bedogni,et al.  Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study , 2005, Hepatology.

[16]  A. Raftery.  Bayesian Model Selection in Social Research , 1995 .

[17]  J. Everhart,et al.  Fatty liver: Think globally , 2010, Hepatology.

[18]  F. Thompson,et al.  Dietary assessment resource manual. , 1994, The Journal of nutrition.

[19]  Anna Castiglione,et al.  The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population , 2006, BMC gastroenterology.

[20]  R. Dalle Grave,et al.  Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach , 2007, Hepatology.

[21]  Beverley Balkau,et al.  Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population , 2009, Hepatology.

[22]  T. Lohman,et al.  Anthropometric Standardization Reference Manual , 1988 .

[23]  Jeanne M Clark,et al.  The epidemiology of nonalcoholic fatty liver disease: a global perspective. , 2008, Seminars in liver disease.

[24]  A. Gasbarrini,et al.  Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. , 2010, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[25]  J. S. Long,et al.  Regression models for categorical dependent variables using Stata, 2nd Edition , 2005 .

[26]  Beverley Balkau,et al.  articleNine-year incident diabetes is predicted by fatty liver indices : the French D . E . S . I . R . study , 2015 .

[27]  D. Kleinbaum,et al.  Regression models for ordinal responses: a review of methods and applications. , 1997, International journal of epidemiology.

[28]  Margaret Pepe,et al.  Measures to Summarize and Compare the Predictive Capacity of Markers , 2009, The international journal of biostatistics.

[29]  D G Altman,et al.  What do we mean by validating a prognostic model? , 2000, Statistics in medicine.

[30]  G. Marchesini,et al.  Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? , 2008, Diabetologia.

[31]  A. Lonardo,et al.  Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis. , 2008, Clinical science.

[32]  R. Bender,et al.  Ordinal Logistic Regression in Medical Research , 1997, Journal of the Royal College of Physicians of London.

[33]  H. Kahn,et al.  Longitudinal changes in BMI and in an index estimating excess lipids among white and black adults in the United States , 2008, International Journal of Obesity.

[34]  G. Perseghin.  Viewpoints on the Way to a Consensus Session , 2009, Diabetes Care.

[35]  S. Siegel,et al.  Nonparametric Statistics for the Behavioral Sciences , 2022, The SAGE Encyclopedia of Research Design.

[36]  G. Targher,et al.  Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. , 2007, Atherosclerosis.

[37]  K. Cusi.  Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis. , 2009, Clinics in liver disease.

[38]  Yuichi Harano,et al.  The Severity of Ultrasonographic Findings in Nonalcoholic Fatty Liver Disease Reflects the Metabolic Syndrome and Visceral Fat Accumulation , 2007, The American Journal of Gastroenterology.

[39]  S. Klein,et al.  Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications , 2010, Hepatology.

[40]  G. Bedogni,et al.  The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease , 2009, BMC medicine.