Diagnostic accuracy of adipose insulin resistance index and visceral adiposity index for progressive liver histology and cardiovascular risk in nonalcoholic fatty liver disease

Authors


  • Funded in part by the Piedmont Region Funds Comitato Interministeriale per la Programmazione Economica 2008.

    Potential conflict of interest: Nothing to report.

Diagnostic Accuracy of Adipose Insulin Resistance Index and Visceral Adiposity Index for Progressive Liver Histology and Cardiovascular Risk in Nonalcoholic Fatty Liver Disease

To the Editor:

We read with interest the article by Lomonaco et al.1 reporting on the association of adipose tissue insulin resistance index (adipo-IR) with liver histology and metabolic profile in nonalcoholic fatty liver disease (NAFLD). Recently, another simple index of visceral fat function, visceral adiposity index (VAI) (see Table 1), predicted cardiometabolic risk in the general population and liver histology in chronic hepatitis C.2, 3 We assessed whether these indexes could be used for diagnostic purposes to noninvasively screen NAFLD patients at risk of progressive liver disease (i.e., nonalcoholic steatohepatitis [NASH] or advanced fibrosis) and of cardiovascular disease (CVD).

Table 1. Diagnostic Accuracy of Adipose Tissue Insulin Resistance Index (Adipo-IR), Visceral Adiposity Index (VAI) and Other Validated Noninvasive Scores for Predicting NASH, Advanced (Stage 3-4) Fibrosis, and Elevated Markers of Endothelial Dysfunction
 Cut-offSensitivity (95% CI)Specificity (95% CI)AUROC (95% CI)
  • AUROC: area under the receiver-operator curve: CK-18: ELISA-detected cytokeratin-18 fragments; ICAM-1: intercellular adhesion molecule-1; adipo-IR (adipose tissue insulin resistance index) was computed as fasting plasma free fatty acids [FFA] × insulin [FPI] concentration. VAI (visceral adiposity index) was computed as follows: males: [waist/39,68+ (1,88 x BMI)] x (Tg/1,03) x (1,31/HDL)

  • females: [waist/36,58+ (1,89 x BMI)] x (Tg/0,81) x (1,52/HDL). NAFLD fibrosis score was computed as follows: –1.675+ 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × impaired glucose tolerance/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio – 0.013 × platelets (x 109/L) – 0.66 × albumin (g/dl). FIB-4 index was computed as follows: [age (years) x AST (U/L)] / [platelet (109) x radq ALT (U/L)].

  • *

    P < 0.05 versus VAI for NASH detection (AUROCs comparison made by nonparametric DeLong method).

  • P < 0.05 versus CK-18, NAFLD fibrosis score and FIB-4 index for detecting highest

  • E-selectin quartile.

  • P < 0.05 versus CK-18, NAFLD fibrosis score and FIB-4 index for detecting highest

  • ICAM-1 quartile.

Prediction of NASH
 Adipo-IR64480 (mmol/L/pmol/L)0.81 (0.75-0.88)0.86 (0.80-0.92)0.84 (0.76-94)*
 VAI1.90.75 (0.68-0.84)0.72 (0.64-0.80)0.69 (0.63-0.77)
 CK-18246 (I.U./L)0.78 (0.71-0.85)0.88 (0.82-0.95)0.83 (0.80-0.90)*
Prediction of advanced (stage 3-4) fibrosis
 Adipo-IR71485 (mmol/L/pmol/L)99 (0.94-1.00)78 (0.72-0.86)0.85 (0.79-0.92)
 VAI2.70.90 (0.85-0.95)76 (0.71-0.82)0.84 (0.80-0.89)
 NAFLD fibrosis score−1.4550.90 (0.85-0.96)0.61 (0.55-0.67)0.85 (0.80-0.92)
0.6760.64 (0.59-0.70)0.97 (0.92-1.00)
 FIB-4 index1.300.76 (0.70-0.83)70 (0.65-0.76)0.83 (0.77-0.89)
2.670.46 (0.40-0.53)0.98 (0.92-1.00)
Prediction of highest E-selectin quartile
 Adipo-IR66127 (mmol/L/pmol/L)0.83 (0.77-0.90)0.87 (0.82-0.92)0.88 (0.82-0.95)
 VAI2.60.80 (0.74-0.87)0.82 (0.74-0.89)0.85 (0.79-0.92)
 CK-18228 (I.U./L)0.70 (0.61-0.78)0.58 (0.50-0.65)0.63 (0.57-0.69)
 NAFLD fibrosis score−1.4550.80 (0.73-0.86)0.54 (0.47-0.62)0.78 (0.70-0.86)
0.6760.60 (0.55-0.69)0.87 (0.82-0.94)
 FIB-4 index1.300.56 (0.50-0.63)0.68 (0.62-0.75)0.63 (0.57-0.69)
2.670.40 (0.35-0.49)0.81 (0.72-0.88)
Prediction of highest ICAM-1 quartile
 Adipo-IR66131 (mmol/L/pmol/L)0.82 (0.76-0.89)0.85 (0.80-0.91)0.86 (0.81-0.92)
 VAI2.80.81 (0.75-0.86)0.83 (0.76-0.89)0.85 (0.79-0.93)
 CK-18241 (I.U./L)0.60 (0.51-0.68)0.55 (0.49-0.62)0.62 (0.55-0.70)
 NAFLD fibrosis score−1.4550.81 (0.74-0.87)0.55 (0.49-0.61)0.78 (0.72-0.85)
0.6760.61 (0.54-0.68)0.85 (0.79-0.91)
 FIB-4 index1.300.41 (0.33-0.49)0.69 (0.62-0.76)0.61 (0.54-0.70)
2.670.35 (0.29-0.42)0.71 (0.62-0.78)

Forty-one unselected otherwise healthy biopsy-proven NAFLD patients (mean ± SE age, 50 ± 3; 60% males; body mass index [BMI] 27 ± 3 kg/m2), 48% with NASH (diagnosed by Brunt criteria), 19% with advanced fibrosis), and 82 healthy controls were evaluated: besides clinically routine variables, extensively validated noninvasive markers/scores for predicting NASH (cytokeratin-18 fragments) and advanced fibrosis (NAFLD fibrosis score, FIB-4 index) were determined.4 Furthermore, circulating markers of endothelial dysfunction (E-selectin and intercellular adhesion molecule-1, ICAM-1) were measured as markers of early cardiovascular risk.5

Compared with patients with simple steatosis, NASH patients had higher adipo-IR (82,437 ± 10,158 versus 48,540 ± 6,243 mmol/L/pmol/L, P = 0.001) and VAI (2.28 ± 0.14 versus 1.54 ± 0.20, P = 0.009), and higher circulating E-selectin (45.9 ± 2.8 versus 25.3 ± 2.4 ng/mL, P = 0.008) and ICAM-1 (279.1 ± 9.3 versus 239.4 ± 8.2 ng/mL, P = 0.029).

The diagnostic accuracy of adipo-IR, VAI, and other noninvasive scores is reported in Table 1.

The area under receiver operating characteristics curve (AUROC) of adipo-IR for predicting NASH and advanced fibrosis was comparable to that of more extensively validated scores/markers, as was the accuracy VAI for advanced fibrosis. Both adipo-IR and VAI were superior to validated scores for predicting endothelial dysfunction.

In conclusion, adipo-IR and VAI accurately predicted progressive liver histology at least as accurately as other validated noninvasive scores and, additionally, they accurately individuated NAFLD patients at increased CVD risk.

Altogether, the findings by Lomonaco et al. and by our group confirm the pathogenic connections between visceral fat dysfunction and liver and cardiometabolic risk in NAFLD and prompt further independent prospective evaluation of adipose tissue dysfunction indexes for individuating NAFLD patients at increased risk of liver-related and cardiovascular complications, the major health burden of these subjects.

Giovanni Musso MD*, Maurizio Cassader PhD†, Roberto Gambino PhD†, * Gradenigo Hospital, Turin, Italy, † Department of Internal Medicine, University of Turin, Turin, Italy.

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