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How big a problem is non-alcoholic fatty liver disease?

BMJ 2011; 343 doi: (Published 18 July 2011) Cite this as: BMJ 2011;343:d3897

Non-invasive estimation of fatty liver in populations or primary care settings

Dear Editor,

We appreciate the article by Anstee and colleagues (BMJ online, 18
July 2011) on the uncertainties and challenges surrounding non-alcoholic
fatty liver disease (NAFLD). Not only could we reduce the outcomes of
advanced liver disease with a better understanding of NAFLD, but we might
also address the heavier burdens associated with cardiometabolic

NAFLD is an independent predictor of incident diabetes (1, 2) and
perhaps also of incident cardiovascular disease (3-5). Despite potential
disagreements about how to define its threshold, NAFLD exists somewhere on
a continuum describing the liver's accumulation of lipid content. The
continuous "fatty liver index" (FLI) we have developed was intended mainly
to simplify the recognition of persons at increased risk of hepatic
steatosis in the general population (6). The FLI is obtained from the
body mass index (weight/squared height), waist circumference,
triglycerides and gamma-glutamyltransferase; it has been independently
shown to be associated with insulin resistance (3), incident diabetes
mellitus (1) and mortality (7). More recently, we have verified that the
"lipid accumulation product" (LAP), a continuous index associated with
cardiovascular risk factors (8) and prevalent diabetes (9), could also be
used to recognize hepatic steatosis (10). The LAP is simpler to employ
than FLI for screening or monitoring because it employs only 2 of its 4
parameters, namely waist circumference and triglycerides.

Our hope is that non-invasive, inexpensive tools like the FLI or LAP
will facilitate our understanding of fatty liver's natural history in the
general population. Although the FLI and LAP need cross-validation and
possibly recalibration in external populations, they may be promising and
handy tools for researchers, clinicians, and epidemiologists.

1. Balkau B, Lange C, Vol S, Fumeron F, Bonnet F, Group Study
D.E.S.I.R. Nine-year incident diabetes is predicted by fatty liver
indices: the French D.E.S.I.R. study. BMC Gastroenterol 2010;10:56.

2. Sung KC, Kim SH. Interrelationship between fatty liver and insulin
resistance in the development of type 2 diabetes. J Clin Endocrinol Metab

3. Gastaldelli A, Kozakova M, Hojlund K, Flyvbjerg A, Favuzzi A,
Mitrakou A, et al. Fatty liver is associated with insulin resistance, risk
of coronary heart disease, and early atherosclerosis in a large European
population. Hepatology 2009;49:1537-44.

4. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in
patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363:1341

5. Ghouri N, Preiss D, Sattar N. Liver enzymes, nonalcoholic fatty
liver disease, and incident cardiovascular disease: A narrative review and
clinical perspective of prospective data. Hepatology 2010;52:1156-61.

6. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M,
Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate
predictor of hepatic steatosis in the general population. BMC
Gastroenterol 2006;6:33.

7. Calori G, Lattuada G, Ragogna F, Garancini MP, Crosignani P, Villa
M, et al. Fatty liver index and mortality: The Cremona study in the 15th
year of follow-up. Hepatology 2011;54:145-52.

8. Kahn HS. The "lipid accumulation product" performs better than the
body mass index for recognizing cardiovascular risk: a population-based
comparison. BMC Cardiovasc Disord 2005;5:26.

9. Kahn HS. The lipid accumulation product is better than BMI for
identifying diabetes: a population-based comparison. Diabetes Care

10. Bedogni G, Kahn HS, Bellentani S, Tiribelli C. A simple index of
lipid overaccumulation is a good marker of liver steatosis. BMC
Gastroenterol 2010;10:98.

Competing interests: GB, SB and CT are involved in the Fatty Liver Inhibition Project (FLIP) sponsored by the EU FP7 framework. The findings and conclusions in this article are those of the authors and do not necessarily reflect the position of the Centers for Disease Control and Prevention.

28 July 2011
Giorgio Bedogni
Senior Researcher (1)
Henry S. Kahn, Medical Epidemiologist (2), Stefano Bellentani, Consultant Gastroenterologist (3), Claudio Tiribelli, Director (1)
(1) Liver Research Center, Trieste, Italy; (2) Centers for Disease Control and Prevention, Atlanta,