Kenji Fujimoto

Noninvasive Evaluation of Hepatic Fibrosis Using Serum Fibrotic Markers, Transient Elastography (FibroScan) and Real-Time Tissue Elastography

Objective: The aim of this study was to investigate the accuracy of noninvasive tests, e.g. serum fibrotic markers, transient elastography and real-time tissue elastography, in the diagnosis of hepatic fibrosis, and to determine whether they can replace liver biopsy. Methods: 119 patients with chronic liver disease were included in this study. Serum fibrotic markers including hyaluronic acid, type IV collagen, type IV collagen 7S domain and type III procollagen-N-peptide were measured. Aspartate aminotransferase (AST) and platelet counts were also measured to calculate the AST to platelet ratio index (APRI). Liver stiffness was measured using FibroScan and real-time tissue elastography. Results: The fibrotic stage, determined by histopathological diagnosis of a liver biopsy sample, did not correlate as well with serum fibrotic markers although it was useful to diagnose liver cirrhosis. However, the stage of hepatic fibrosis correlated well with liver stiffness measured by FibroScan. FibroScan was also a much better predictor of liver cirrhosis than APRI. Furthermore, the levels of liver strain measured by real-time tissue elastography correlated well with liver stiffness (p < 0.05). Conclusion: Serum fibrotic markers and FibroScan are useful for distinguishing liver cirrhosis (F4) from chronic hepatitis (F1–F3). In addition, real-time tissue elastography is a novel and promising method to determine the stage of hepatic fibrosis.

In-Situ Chemically Cleaning Poly-Si Growth at Low Temperature

We report a novel growth method of polysilicon thin films on glass substrates at a low temperature (450°C) by plasma chemical vapor deposition (PCVD) using SiH4/SiF4 mixture gases. In this method, the conventional low-cost glass substrates such as Corning 7059 may be used because of the low deposition temperature. Furthermore, the conventional vacuum chamber with its base pressure of ~1×10-4 Pa, which is usually thought to be inadequate for high-quality Si growth because of its many impurities, can be used since the growing surface of polysilicon is in-situ chemically cleaned by SiF4 plasma. The polysilicon films obtained on glass show strong (100) preferred orientation. A grain size as large as 250 nm is obtained in a film with 700 nm thickness. The field-effect mobility of 44 cm2/Vs has been achieved in a thin-film transistor (TFT) using this polysilicon film.

Non-Invasive Evaluation of Hepatic Fibrosis for Type C Chronic Hepatitis

Objective: The aim of this study was to investigate liver fibrosis using non-invasive Real-time Tissue Elastography® (RTE) and transient elastography (FibroScan®) methods. Methods: RTE, FibroScan and percutaneous liver biopsy were all performed on patients with chronic liver disease, particularly hepatitis C, to investigate liver fibrosis. Results: FibroScan and RTE were compared for fibrous liver staging (F stage), which was pathologically classified using liver biopsy. In FibroScan, significant differences were observed between F1/F3 and F2/F4, but no such differences were observed between F1/F2, F2/F3 and F3/F4. In RTE, significant differences were observed between F1/F2, F2/F3 and F2/F4. But for F3/F4, no significant differences were observed. Conclusion: FibroScan and RTE correlated well with F staging of the liver. In particular RTE was more successful than FibroScan in diagnosing the degree of liver fibrosis.

Composition Dependence of Superconductivity in Y–Ba–(Ag, Co)–O System

High Tc superconductors, YBa2(AgxCu1-x)3O9-y with composition of 0x0.6 were prepared by a ceramic technique, and the compositional change of Tc was examined. Samples with nominal compositions of x<0.4, expecially YBa2(Ag0.1Cu0.9)3O9-y and YBa2(Ag0.2Cu0.8)3O9-y, show sharp superconducting transitions with widths as narrow as about 1 K or less. The superconductivity is discussed in relation to the results of X-ray diffraction study.

Assessment of Liver Fibrosis with Real-Time Tissue Elastography in Chronic Viral Hepatitis

Objective: The aim of this study was to assess prospectively the accuracy of measurement of liver fibrosis with real-time tissue elastography (RTE) in patients with chronic viral hepatitis. Methods: Two hundred and forty-five patients were prospectively enrolled. Nine image features were measured from strain images, and Liver Fibrosis Index (LFI) was calculated from these features. Fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided biopsy. LFI and serological markers were compared with pathological diagnosis, and the diagnostic performance of RTE was compared. Results: LFI in stages F0-F1, F2, F3 and F4 was 1.58, 2.03, 2.40 and 2.86, respectively, demonstrating a stepwise increase with increasing severity of liver fibrosis (p < 0.001). LFI in F2 did not significantly differ from that in F3, whereas for all other combinations of stages, there were significant differences. The area under the receiver operating characteristic curve of the LFI, platelet count, aspartate/alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio, and FibroIndex for predicting F3 stage or higher (F0-F2 vs. F3-F4) was 0.865, 0.824, 0.708, 0.789 and 0.828, respectively. Conclusions: RTE is useful for diagnosis of liver fibrosis, regardless of stage, in patients with chronic viral hepatitis.

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C

Abstract: A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-α2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Novel Image Analysis Method Using Ultrasound Elastography for Noninvasive Evaluation of Hepatic Fibrosis in Patients with Chronic Hepatitis C

It has been established that the long-term infection of chronic hepatitis C leads to the increased risk of hepatic fibrosis and hepatocellular carcinoma. Currently, histological diagnosis by invasive and painful liver biopsy is the gold standard for evaluating the hepatic fibrosis stage. Because of a side effect or patient inability to cope with the pain, it is difficult to assess the fibrosis stage frequently using liver biopsy. Recently, instead of liver biopsy, many articles have been published showing the usefulness of ultrasound elastography to evaluate the stage of hepatic fibrosis. We also reported the usefulness of real-time tissue elastography (RTE) for liver fibrosis staging in 2007. However, in our previous report, fibrosis classification was performed manually and the number of patients involved was also small. In the current study, the fibrosis staging is performed automatically using software by characterizing the elastography images. We have also increased the number of patients from 64 to 310. Thus, the aim of this study is to increase objectivity by using a newly developed automatic analysis method. We obtain the Liver Fibrosis Index (LFI), which is calculated from image features of RTE images, using multiple regression analysis performed on clinical data of 310 cases as the training data set. The correlation coefficient obtained between the LFI and the stage of hepatic fibrosis was r = 0.68, and significant differences exist between all stages of fibrosis (p < 0.001). Our new method seems promising since it has the ability to diagnose fibrosis even in the presence of inflammation.

JSUM ultrasound elastography practice guidelines: liver

In diffuse liver disease, it is extremely important to make an accurate diagnosis of liver fibrosis prior to determining indications for therapy or predicting treatment outcome and malignant potential. Although liver biopsy has long been the gold standard in the diagnosis of liver fibrosis, it is still an invasive method. In addition, the sampling error is an intrinsic problem of liver biopsy. Non-invasive serological methods for the diagnosis of liver fibrosis can be affected by factors unrelated to the liver. Recently, after the introduction of FibroScan, it became possible to measure liver fibrosis directly and non-invasively by elastography, which has attracted attention as a non-invasive imaging diagnostic tool for liver fibrosis. In addition, real-time tissue elastography is currently being used to conduct clinical trials at many institutions. Moreover, virtual touch quantification enables the observation of liver stiffness at any location by simply observing B-mode images. Furthermore, the recently developed ShearWave elastography visualizes liver stiffness on a color map. Elastography is thought to be useful for all types of diffuse liver diseases. Because of its association with portal hypertension and liver carcinogenesis, elastography is expected to function as a novel prognostic tool for liver disease. Although various elastographic devices have been developed by multiple companies, each device has its own measurement principle, method, and outcome, creating confusion in clinical settings. Therefore, it is extremely important to understand the characteristics of each device in advance. The objective of this guideline, which describes the characteristics of each device based on the latest knowledge, is for all users to be able to make the correct diagnosis of hepatic fibrosis by ultrasound elastography.

Mechanical Model Analysis for Quantitative Evaluation of Liver Fibrosis Based on Ultrasound Tissue Elasticity Imaging

Precise evaluation of the stage of chronic hepatitis C with respect to fibrosis has become an important issue to prevent the occurrence of cirrhosis and to initiate appropriate therapeutic intervention such as viral eradication using interferon. Ultrasound tissue elasticity imaging, i.e., elastography can visualize tissue hardness/softness, and its clinical usefulness has been studied to detect and evaluate tumors. We have recently reported that the texture of elasticity image changes as fibrosis progresses. To evaluate fibrosis progression quantitatively on the basis of ultrasound tissue elasticity imaging, we introduced a mechanical model of fibrosis progression and simulated the process by which hepatic fibrosis affects elasticity images and compared the results with those clinical data analysis. As a result, it was confirmed that even in diffuse diseases like chronic hepatitis, the patterns of elasticity images are related to fibrous structural changes caused by hepatic disease and can be used to derive features for quantitative evaluation of fibrosis stage.

Direct ethanol injection for skull metastasis from hepatocellular carcinoma. The techniques and consequences of a therapeutic trial

The frequency of skull metastasis from hepatocellular carcinoma (HCC) is increasing together with the recent progress in the management of the primary lesion. Cases are often complicated with poor general conditions or metastasis to the other organs, and not readily indicated for surgery. A direct injection of ethanol to the lesion could be one of the therapeutic options to cope with this complicated situation. To evaluate the feasibility of this technique, we planned a therapeutic trial in a patient with HCC associated with lumbar and skull metastasis, the latter metastasis repeated twice during the past one year. A total of 10 ml of ethanol was injected into the skull metastasis percutaneously under ultrasound (US) guidance. US guidance was very useful in determining the sites of injections and the distribution of ethanol as well as monitoring the blood flow within the tumor vessels. The patient transiently complained of local pain at the injection sites, but there were no other adverse effects. Four days after the injection, the lesion was resected by surgery, which confirmed the pathologic diagnosis as well as the nearly-total necrosis of the tumor. This technique is simple, safe and repeatable with low cost. The technical details and the histologic effects are described.