Liver, Pancreas and Biliary Tract
Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD)

https://doi.org/10.1016/j.dld.2007.10.019Get rights and content

Abstract

Background

Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis.

Aim

We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients.

Study population

A total of 97 nonalcoholic fatty liver disease patients.

Methods

Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain.

Results

The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal–Wallis test p < 0.0001). The areas under the receiver-operating characteristic curves were 0.927 for ≥F1, 0.865 for ≥F2, 0.904 for ≥F3, 0.991 for ≥F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001).

Conclusions

Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver injury in many countries around the world [1], [2]. It represents a spectrum of conditions that are histologically characterized by macrovesicular hepatic steatosis, and the diagnosis is made in patients who have not consumed alcohol in amounts sufficient to be considered to be harmful to the liver. The histological changes range over a wide spectrum, extending from simple steatosis, which is generally non-progressive, to nonalcoholic steatohepatitis (NASH), liver cirrhosis, liver failure, and sometimes even hepatocellular carcinoma [3], [4]. Liver biopsy is recommended as the gold standard method for the diagnosis as well as staging of fibrosis in patients with NASH [1], [4], [5]. This procedure, however, is invasive and associated with a relatively high risk of complications [6]. Several clinical studies have attempted to identify serum markers that might be correlated with the severity of liver fibrosis in these patients. Many clinical variables have been proposed until now as predictors of severe fibrosis in patients with NAFLD, including old age, underlying type 2 diabetes mellitus, obesity, serum transaminase levels, platelet count, etc. [7], [8], [9].

Assessment of the severity of liver fibrosis is important in the evaluation of the prognosis of patients with NAFLD. Transient elastography (Fibroscan, EchoSens, Paris, France) is a new technique that allows rapid and no -invasive measurement of the mean tissue stiffness [10]. Studies have suggested that this technique is useful for the accurate prediction of hepatic fibrosis in patients with chronic hepatitis C [11], [12], [13]. We have previously reported that transient elastography have the possibility of the measurement of the fibrosis in patients with NAFLD [14]. The purpose of this study was to investigate the clinical usefulness of liver stiffness measurement (LSM) with the new medical device called Fibroscan, based on ultrasound transient elastography, relative to that of the histopathological assessment of the stage of fibrosis in liver biopsy samples, which is the gold standard for such assessment in patients with NAFLD.

Section snippets

Patients

We prospectively evaluated the data of 102 NASH patients who underwent liver biopsy at Yokohama City University Hospital and Dokkyo Medical University. The study was conducted with the approval of the Ethics Committee of Yokohama City University Hospital.

A detailed history was obtained from all of the 102 patients, who were also subjected to a thorough physical examination. The histological criteria for the diagnosis of NAFLD are the presence of macrovesicular fatty change in hepatocytes with

Characteristics of the patients

One hundred and two patients met the inclusion criteria, of which five patients were excluded because of unreliable liver stiffness measurement (success rate <60% or IQR >30%). All of the five patients were obese, with a BMI of over 30. Thus 97 patients were finally included for the analysis. Their characteristics are summarized in Table 1. Liver stiffness values ranged from 3.3 to 35.3 kPa (median, 7.8 kPa) and IQR ranged 6.8–26.8% (mean, 17.6%). The histological findings in the liver biopsy

Discussion

In the present study, we demonstrated a significant positive correlation between liver stiffness and the severity of liver fibrosis in patients with NAFLD. This observation is consistent, because the stiffness of a tissue largely depends on the molecular building blocks (collagen) and on the microscopic structural organization of these blocks (septa) [22]. Rapid and noninvasive detection of fibrosis in patients with NAFLD is of major clinical interest, because these patients have been shown to

Conflict of interest statement

None to declare.

Acknowledgements

This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan to A.N., a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KIBAN-B) to A.N., and a grant from the National Institute of Biomedical Innovation to A.N.

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