Validation of P2/MS and Other Noninvasive Fibrosis Scoring Systems in the Korean Population with Nonalcoholic Fatty Liver Disease

Su Jong Yu; Donghee Kim; Jeong-Hoon Lee; Goh Eun Chung; Jeong Yoon Yim; Min Jung Park; Yoon Jun Kim; Jung-Hwan Yoon; Ja-June Jang; Hyo-Suk Lee

doi:10.4166/kjg.2011.57.1.19

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Yu, Kim, Lee, Chung, Yim, Park, Kim, Yoon, Jang, and Lee: Validation of P2/MS and Other Noninvasive Fibrosis Scoring Systems in the Korean Population with Nonalcoholic Fatty Liver Disease

Original Article

Korean J Gastroenterol 2011;57(1):19-27.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.57.1.19

Validation of P2/MS and Other Noninvasive Fibrosis Scoring Systems in the Korean Population with Nonalcoholic Fatty Liver Disease

Su Jong Yu¹, Donghee Kim², Jeong-Hoon Lee¹, Goh Eun Chung², Jeong Yoon Yim², Min Jung Park², Yoon Jun Kim¹, Jung-Hwan Yoon¹, Ja-June Jang³, Hyo-Suk Lee¹

¹Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

²Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital, Healthcare System Gangnam Center, Seoul, Korea

³Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Donghee Kim, Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital, Healthcare System Gangnam Center, 39th FL Gangnam Finance Center, 737 Yeoksam-dong, Gangnam-gu, Seoul 135-984, Korea. Tel: +82-2-2112-5574, Fax: +82-2-2112-5635, E-mail: messmd@chol.com

Received 25 November 2010 Revised 22 December 2010 Accepted 23 December 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

P2/MS is a noninvasive marker for detecting hepatic fibrosis in patients with viral hepatitis. However, the applicability of P2/MS in patients with nonalcoholic fatty liver disease (NAFLD) has not yet been validated. This study aimed to validate P2/MS and compare it to other noninvasive fibrosis scoring systems in Korean patients with NAFLD.

Methods

Consecutive patients who underwent liver biopsy between January 2002 and December 2009 at Seoul National University Hospital, Seoul, Korea were enrolled in this study. Fibrosis stage was determined using the METAVIR scoring system.

Results

A total of 235 patients were included in the study: advanced fibrosis (METAVIR F3-F4) was present in 7 patients. No patient was over-staged among 162 patients with a P2/MS score above the high cut-off (95), resulting in a high negative predictive value (NPV) of 100% (95% confidence interval, 97.1–100). There was no significant difference between the area under the receiver-operating characteristic curve (AUROC) of the FIB-4 (0.964) and the AUROC of the NAFLD fibrosis score (0.964) or P2/MS (0.940) for detecting advanced fibrosis. If P2/MS was implemented in the Korean patients with NAFLD, 68.9% of liver biopsies might be avoided.

Conclusions

P2/MS has a high NPV for excluding advanced fibrosis in Korean patients with NAFLD, and can reduce the burden of liver biopsy in the majority of cases. Since there were few patients with advanced fibrosis, further studies are warranted in a cohort including more patients with advanced fibrosis to validate the low cut-off value.

Keywords: Fatty liver, Nonalcoholic fatty liver disease, Liver fibrosis

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Fig. 1.

Comparisons of the ROC of P2/MS and other noninvasive fibrosis scoring systems for the diagnosis of advanced fibrosis (defined as METAVIR F3-F4). (A) P2/MS versus FIB-4 and (B) P2/MS versus NAFLD fibrosis score.

Fig. 2.

Scatter plot of noninvasive fibrosis scoring systems versus pathologically determined fibrosis stage. Fibrosis stage was determined using the METAVIR scoring system.²⁵ Circles represent the values of each noninvasive fibrosis scoring systems. The solid line represents a trend-line. (A) P2/MS values showed a significant inverse correlation with the METAVIR fibrosis stage (Spearman's correlation coefficient=−0.127, p＜0.001), (B) FIB-4 scores showed a significant inverse correlation with the METAVIR fibrosis stage (Spearman's correlation coefficient=0.235, p＜0.001), (C) NAFLD fibrosis score values showed a significant inverse correlation with the METAVIR fibrosis stage (Spearman's correlation coefficient= 0.263, p＜0.001).

Table 1.

Formulae of Noninvasive Fibrosis Scoring Systems

Formula	Equation
AST to ALT ratio	AST/ALT
AST to platelet ratio	(AST/platelet count [10⁹/L])×100
APRI	([AST/upper limit of normal]/platelet count [10⁹/L])×100
Simple panel for distinguishing moderate fibrosis	1.224+0.01×age (years)+0.105×BMI+1.946×diabetes/IFG (yes=1, no=0)−1.786×AST/ALT ratio−0.01×platelet count [10⁹/L]−0.04×albumin (g/dL)
BARD score: Scale 0–4	BMI≥28 kg/m²=1 point
	AST to ALT ratio≥0.8=2 points
	Diabetes mellitus=1 point
GUCI	(AST/upper limit of normal)×INR×100/(platelet count [10⁹/L])
Cirrhosis discriminant score:	1) Platelet count	2) AST/ALT ratio	3) INR
Score is the sum of three (0–11)	＞340=0	＞1.7=0	＜1.1=0
	280−339=1	1.2−1.7=1	1.1−1.4=1
	220−279=2	0.6−1.19=2	＞1.4=2
	160−219=3	＜0.6=3
	100−159=4
	40−99=5
	＜40=6
NAFLD fibrosis score	−1.675+0.037×age (years)+0.094×BMI (kg/m²)+1.13×IFG/diabetes (yes=1, no=0)+0.99×AST/ALT ratio−0.013×platelet (10⁹/L)−0.66×albumin (g/dL)
FIB-4	(Age [years]×AST [U/L])/(platelet [10⁹/L]×(ALT [U/L])^1/2)
P2/MS	[Platelet count (10⁹/L)]²/[monocyte fraction (%)×segmented neutrophil fraction (%)]

AST, aspartate transaminase; ALT, alanine transaminase; APRI, AST to platelet ratio index; BMI, body mass index; IFG, impaired fasting glucose; INR, international normalization ratio; GUCI, Goteborg University Cirrhosis Index; NALFD, nonalcoholic fatty liver disease.

Table 2.

Baseline Characteristics of All Patients

Variables	F0-F2 (n=228)	F3-F4 (n=7)	p-value
Age (years)	40.6±8.1	60.4±15.3	0.001 ^a
Male, n (%)	124 (54.4)	1 (14.3)	0.037 ^b
BMI (kg/m²)	24.1±3.1	30.2±6.3	0.004 ^a
Waist circumference (cm)	81.7±7.7	90.7±11.0	0.026 ^a
Diabetes, n (%)	30 (13.2)	1 (14.3)	1.000 ^b
IFG, n (%)	57 (25)	2 (28.6)	1.000 ^b
Platelet count (10⁹/L)	238.4±71.1	115.0±38.9	＜0.001 ^a
Total bilirubin (mg/dL)	1.5±2.8	1.2±0.4	0.337 ^a
Albumin (g/dL)	3.9±0.6	3.4±0.7	0.071 ^a
AST (IU/L)	53.5±57.5	60.0±35.0	0.167 ^a
ALT (IU/L)	66.0±77.9	46.3±32.3	0.944 ^a
Prothrombin time (INR)	1.02±0.07	1.25±0.10	＜0.001 ^a
Fasting glucose (mg/dL)	110.6±32.0	120.7±50.8	0.622 ^a
HbA1c (%)	5.57±0.53	6.95±1.91	0.170 ^a
Total cholesterol (mg/dL)	159.4±45.8	142.0±35.1	0.336 ^a
HDL-cholesterol	50.3±13.1	40.7±6.47	0.049 ^a
LDL-cholesterol	85.2±42.0	64.4±54.3	0.211 ^a
Triglycerides	133.1±274.0	181.5±100.5	0.020 ^a

Values are expressed as mean±SD.

BMI, body mass index; IFG, impaired fasting glucose; AST, aspartate transaminase; ALT, alanine transaminase; INR, international normalization ratio; HbA1c, hemoglobin A1c; HDL, high density lipoproteins; LDL, low density lipoproteins.

^a Mann-Whitney test.

^b Two-sided Fisher's exact test.

Table 3.

AUROC of Noninvasive Fibrosis Scoring Systems for Predicting Advanced Fibrosis (METAVIR F3-F4)

Noninvasive fibrosis scoring systems	AUROC (95% CI)	p-value ^a
P2/MS	0.940 (0.841–1.000)	−
FIB-4	0.964 (0.935–0.992)	0.764
NAFLD fibrosis score	0.964 (0.917–1.000)	0.764
Cirrhosis discriminant score: Score is the sum of three (0–11)	0.936 (0.859–1.000)	0.964
Goteborg University Cirrhosis Index	0.860 (0.780–0.940)	0.465
AST to platelet ratio index	0.825 (0.737–0.914)	0.320
AST to platelet ratio	0.825 (0.737–0.914)	0.320
AST to ALT ratio	0.787 (0.687–0.888)	0.206
BARD score: Scale 0–4	0.691 (0.542–0.841)	0.054
Simple panel for distinguishing moderate fibrosis	0.691 (0.464–0.919)	0.054

AUROC, area under the receiver operating characteristic curve; CI, confidence interval; NAFLD, nonalcoholic fatty liver disease

P2/MS, [Platelet count (10⁹/l)]²/[monocyte fraction (%)×segmented neutrophil fraction (%)].

^a Compared to AUROC of P2/MS.

Table 4.

Predictive Values of P2/MS for Advanced Fibrosis (METAVIR F3-F4)

	Low (＜49)	Intermediate	High (＞95)	Total
Total	23	50	162	235
No advanced fibrosis	18	48	162	228
Advanced fibrosis	5	2	0	7
Sensitivity	71.4%		100%
Specificity	92.1%		71.1%
PPV	21.7%		9.60%
NPV	99.1%		100%
PLR	9.05		3.45
NLR	0.31		0

PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio.

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