Machine-learning-based classification of real-time tissue elastography for hepatic fibrosis in patients with chronic hepatitis B
Introduction
Hepatic fibrosis is the middle stage of hepatitis of various types, of liver cirrhosis and of any late period liver-related diseases. Patients with hepatitis C or B virus who chronically suffer from fibrosis are more vulnerable to hepatocellular carcinoma. Therefore, early detection and prompt intervention are important. It has been reported that more aggravated hepatic fibrosis increases the risk of hepatocellular carcinoma [1]; however, some interferon treatments can slow this process and reduce morbidity from hepatocellular carcinoma [2], which is why the Guide to the Prevention and Treatment for Chronic Hepatitis B considers it essential to evaluate the stage of hepatic fibrosis both for treatment and for monitoring treatment effects.
However, determining the stage of liver fibrosis is still arduous. Although a liver biopsy is widely considered the gold standard for assessing liver fibrosis, the procedure's invasiveness can cause complications such as hemorrhage and pneumothorax. Moreover, limited sample numbers and sizes usually lead to suboptimal accuracy [3], [4], [5]. Another option, serological examination, has some clinical implications; however, it has been reported that its sensitivity and specificity vary greatly. Moreover, serological examination cannot satisfy the requirements for clinical treatments by itself because it is unable to accurately stage liver fibrosis [6], [7]: it can distinguish between hepatic fibrosis and cirrhosis but cannot accurately determine the stage of hepatic fibrosis. In addition, this type of examination is not sufficiently specific because it can be affected by metabolism, extracellular-matrix diseases and late-stage cancers [8]. Therefore, the Asian-Pacific Association for the Study of the Liver recommends elastography instead of serological examination. Many scholars have sought other noninvasive methods to diagnose liver fibrosis, especially physical methods.
One existing noninvasive method is imaging diagnosis, which can completely evaluate the entire organ. Therefore, imaging examination has been widely adopted clinically. Imaging diagnosis can involve ultrasound, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI); of these, CT and MRI are expensive. Ultrasound is the most feasible and inexpensive method. Unlike the others, it is suitable for use on patients with medical metal devices; consequently, ultrasound is widely accepted. Owing to the prevalence of ultrasound contrast and ultrasonic elastography, ultrasound can provide not only information about hepatic morphology and blood dynamics but also information about physical properties such as liver stiffness or elasticity modulus. In view of this capacity, ultrasound may emerge as one of the most important noninvasive methods for evaluating liver fibrosis.
RTE is also increasing in popularity and is considered to be among the most promising methods for staging hepatic fibrosis; however, it is unable to distinguish between intermediate degrees of liver fibrosis [9]. The calculations of both the elastic ratio and fibrosis index of RTE have shown intra-and inter-observer variability [10]. These methods have already been applied to the research of hepatitis C [11], non-alcoholic liver disease [12] and hepatitis B [13]. However, their classification accuracy reaches only approximately 70% for chronic hepatitis B patients, which cannot satisfy clinical demands.
A similar study conducted by Wu et al. [13] obtained predictions of significant fibrosis with the help of a multiple regression statistical analysis. However, multiple regression is a linearly dependent method, while the relationships between the image parameters and stages of hepatitis B are not linear.
As we know, machine-learning (ML) and pattern-recognition methods have been widely studied for early diagnosis of hepatitis diseases, such as in analyses of biochemical indices and clinical figures of hepatic fibrosis [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]. However, because FibroScan has been adopted for assessing the stage of liver fibrosis in recent years [26], [27], [28], studies have seldom been conducted to evaluate the performance of machine learning in real-time ultrasonic tissue elastography. This paper focuses on the analysis of data in patients with chronic hepatitis B via RTE. The data indicate the rigidity of tissue indirectly by the displacement caused by mechanical heart impulses. The RTE software was developed by Hitachi (HI VISION Ascendus; Hitachi Aloka Medical, Tokyo, Japan) and offers 11 parameters to facilitate the quantitative evaluation of liver fibrosis [11], [29]. A total of 513 subjects suffering from chronic viral hepatitis and cirrhosis were studied and enrolled in a multicenter collaborative hospital study. Four classical pattern-recognition methods, which included Naïve Bayes, Random Forest (RF), K-Nearest Neighbor (KNN) and Support Vector Machine (SVM), were applied to build an aided decision-support system to estimate the stage of hepatic fibrosis.
The remainder of the paper is organized as follows. Section 2 presents a brief introduction to the four machine-learning methods used in this study. Section 3 focuses on the study methodology, in which RTE images were acquired to extract features and to perform further data preprocessing. Section 4 presents the experimental results. Finally, Section 5 draws conclusions, discusses the findings, and describes some plans for future work.
Section snippets
Machine-learning-based classification
The existing method, which is intended to determine the fibrosis stage via RTE, is to obtain the LFI as the fibrosis index [13] using a linear regression equation. However, this type of equation has limited functionality, and satisfactory results are often difficult to obtain. In this paper, we employ four classical machine learning methods to predict the stage of hepatic fibrosis based on features extracted from numerous RTE images. Our approach will improve the accuracy of staging hepatic
Acquiring RTE images
The RTE equipment used in this research was a color Doppler ultrasound diagnostic instrument, the Hitachi HI VISION Preirus (Hitachi Aloka Medical Corporation, Tokyo Japan) and a EUP-L52 linear probe (Hitachi Aloka Medical) with a frequency range of 3–7 MHz. This instrument is equipped with real-time elastography software that can analyze tissue dispersion quantitatively, attaining 11 elastography parameters. The equipment is also equipped with a strain histogram measurement data-processing
Data collection
The study protocol was approved by the independent ethics committees of the involved institutions, and the purpose of this research was explained to the patients. Written informed consent was obtained in advance. This prospective, multicenter, cross-sectional study was conducted at the following eight hospitals in China: Third Affiliated Hospital (Sun Yat-sen University), Guangdong General Hospital, Beijing Youan Hospital (Capital Medical University), First Affiliated Hospital (Guangxi Medical
Discussion and conclusions
When applying machine learning to hepatic fibrosis, previous research has focused primarily on the prediction of survival vs. mortality groups [14], [17], [18], [19], [20], [21], [23], [24], [25]; few investigations have been conducted on the four stages of liver fibrosis [15], [26], [27], [28]. Moreover, most of these have focused only on hepatitis C [15], [16], [28]. To our knowledge, no prior studies have applied machine-learning techniques to assess the stage of liver fibrosis in patients
Acknowledgments
The authors thank Zhang Qi for the data collection work, which was a valuable contribution to this study. This study was supported by the 973 Project (2013CB329401), the Natural Science Foundation of China (61573080, 91420105) and the Science and Technology Project of Sichuan Province (2015SZ0141).
References (34)
- et al.
Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection
Am. J. Gastroenterol.
(2002) - et al.
Sampling variability of liver fibrosis in chronic hepatitis C
Hepatology
(2003) - et al.
Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis
J. Hepatol.
(2007) - et al.
Real-time elastography in the assessment of liver fibrosis: a review of qualitative and semi-quantitative methods for elastogram analysis
Ultrasound Med. Biol.
(2014) - et al.
Liver elasticity in NASH patients evaluated with real-time elastography (RTE)
Ultrasound Med. Biol.
(2012) - et al.
A new hybrid method based on local fisher discriminant analysis and support vector machines for hepatitis disease diagnosis
Expert Syst. Appl.
(2011) - et al.
Single stage and multistage classification models for the prediction of liver fibrosis degree in patients with chronic hepatitis C infection
Comput. Meth. programs Biomed.
(2012) - et al.
A new intelligent hepatitis diagnosis system: PCA–LSSVM
Expert Syst. Appl.
(2011) - et al.
A hybrid decision support system based on rough set and extreme learning machine for diagnosis of hepatitis disease
Appl. Soft Comput.
(2013) - et al.
Automatic hepatitis diagnosis system based on linear discriminant analysis and adaptive network based on fuzzy inference system
Expert Syst. Appl.
(2009)
Hepatitis disease diagnosis using a new hybrid system based on feature selection (FS) and artificial immune recognition system with fuzzy resource allocation
Digit. Signal Process.
Hepatitis disease diagnosis using a novel hybrid method based on support vector machine and simulated annealing (SVM-SA)
Comput. Meth. Programs Biomed.
Medical decision support system based on artificial immune recognition immune system (AIRS), fuzzy weighted pre-processing and feature selection
Expert Syst. Appl.
Prediction of hepatitis disease based on principal component analysis and artificial immune recognition system
Appl. Math. Comput.
Intelligent decision-making for liver fibrosis stadialization based on tandem feature selection and evolutionary-driven neural network
Expert Syst. Appl.
Feature selection for a cooperative coevolutionary classifier in liver fibrosis diagnosis
Comput. Biol. Med.
Evolutionary-driven support vector machines for determining the degree of liver fibrosis in chronic hepatitis C
Artif. Intell. Med.
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2022, Computers in Biology and MedicineCitation Excerpt :Although numerous histopathological staging systems have been utilized for liver fibrosis evaluation in current clinical practice, including Knodell, Metavir, Ishak, and Scheuer systems, only manual reviews or semi-quantitative evaluations are conducted by these staging systems, resulting in large inter- and intra-observer variability [3–5]. To reduce such variations, evaluation methods based on artificial intelligence (AI) algorithms, such as random forests, K-nearest neighbors, and support vector machines, have been developed to provide objective diagnostic tools for liver fibrosis staging [6–8]. In contrast to these conventional machine learning methods, deep learning has emerged as a powerful tool for diverse biomedical image processing studies due to its great success across different image modalities [9].