Accuracy of noninvasive scoring systems to assess advanced liver fibrosis in Thai patients with nonalcoholic fatty liver disease

All patients included provided their written informed consent to participate in the present study. We prospectively included 139 consecutive patients with liver biopsy-proven NAFLD patients in King Chulalongkorn Memorial Hospital (KCMH) from January 2009 to October 2012. The inclusion criteria included patients at least 18 years old with NAFLD was diagnosed by liver biopsy with standard criteria. Exclusion criteria were incomplete data needed for the 4 noninvasive scoring system calculations. Patients who met the inclusion criteria were admitted for liver biopsy using standard procedures with ultrasonography guidance. Data of all patients were recorded, including demographic data, anthropometric data and biochemical tests on the day of liver biopsy or within 2 weeks of the procedure. All patients were followed-up with the results of liver histological findings within the following 2 weeks. We used the histological findings of liver fibrosis as the criterion standard or index diagnosis.

The diagnosis of NAFLD was based on the following criteria: (1) liver biopsy showing steatosis in at least 5% of hepatocytes, or (2) fatty infiltration of the liver confirmed on imaging studies (ultrasound, computed tomography, or magnetic resonance imaging), and (3) exclusion of liver disease from other etiologies including alcohol-induced (history of excessive alcohol consumption defined as >20 gm/ day), drug-induced liver disease, autoimmune or viral hepatitis, and cholestatic or metabolic/genetic liver disease [17]. The staging of liver inflammation and fibrosis in patients with NAFLD was based on that proposed by Kleiner et al. [18]. The presence of metabolic syndrome (Mets) was defined by using the 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria and the new definition, which required the presence of at least 3 of the 5 features [19], BMI was calculated as weight divided by height squared (kg/m²). Because waist circumference (WC) measurements were not taken from the majority of patients, we defined obesity using BMI >30 kg/m² in accordance with the World Health Organization (WHO) definition of insulin resistance syndrome [20, 21]. The histological liver fibrosis stages 1–2 (F1–F2) were classified as “mild liver fibrosis” and those with histological fibrosis stages 3–4 (F3–F4) were classified as “advanced liver fibrosis” according to standard criteria [18]. Baseline NAFLD Fibrosis Scores, BARD, and FIB-4 calculations were used to distinguish NAFLD patients with and without advanced liver fibrosis, for which the cutoff NFS at >–1.455 (web-based calculation; http://gihep.com/calculators/hepatology/nafld-fibrosis-score/), BARD score with the cutoff >2 (web-based calculation; http://gihep.com/calculators/hepatology/bard/), and FIB-4 with the cutoff >1.3 (web-based calculation; http://gihep.com/calculators/hepatology/fibrosis-4-score/) predict the advanced liver fibrosis or F3–F4.

Thai NAFLD patients were categorized by the severity or staging of liver fibrosis into 2 groups of the mild and advanced liver fibrosis based on histological diagnosis. Continuous outcomes are presented as mean (standard deviation, SD) and categorical data are presented as numbers (percentage). Differences between groups were tested by independent t tests for continuous variables, and were tested by χ² tests for proportions. Differences with P < 0.05 were considered significant. The overall accuracy of the NAFLD Fibrosis Score in identifying the mild or advanced stage of liver fibrosis was analyzed using the area under the receiver operating characteristic (ROC) curves. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

The analyses in this study were performed using SPSS for Windows (version 15.0.1.1; SPSS Inc, Chicago, IL, USA).

We included 139 Thai patients with liver biopsy-proven NAFLD with mean age of 40.95 (13.3) years, and 47% were male. There were 75 (54%) patients with impaired fasting glucose or diabetes mellitus and 73% of Thai NAFLD patients had a BMI >28 kg/m². Baseline characteristics are shown in Table 1.

Table 1

Baseline characteristics of 139 Thai patients with nonalcoholic fatty liver disease

Advanced fibrosis (F3–F4) was found histologically in 9 patients (6%). Using the baseline AST/ALT ratio with a cutoff >0.8, NFS with a cutoff ≥–1.455, BARD with a cutoff ≥2, and FIB-4 calculation with a cutoff >1.3, the prevalence of patients with a high risk of advanced liver fibrosis were 36%, 54.5%, 61.2%, and 19.1%, respectively.

The sensitivity, specificity, positive-predictive values (PPV), and negative-predictive values (NPV) of the 4 noninvasive scoring systems were calculated. NFS with a cutoff ≥ –1.455 was found to be the best scoring system with highest sensitivity for identifying patients with advanced fibrosis, followed by BARD score ≥2, FIB-4 >1.45, and AST/ALT ratio >0.8, respectively (Table 2).

Table 2

Comparison of the 4 noninvasive scoring systems for the diagnosis of advanced fibrosis in 139 Thai patients with nonalcoholic fatty liver disease

Patients with advanced fibrosis were significantly older and had higher blood glucose level than those with mild liver fibrosis. Using the area under the ROC curve of four noninvasive scoring systems at baseline, FIB–4 and NFS showed the highest AUROC in Thai NAFLD patients for predicting the advance liver fibrosis (Figure 1). By using these 4 noninvasive scoring systems, liver biopsy could potentially be avoided in at least 38% of patients with BARD score, 45% with NFS, 64% with AST/ALT ratio, and 80% with FIB–4.

Figure 1