橋本 千樹

Transient elastgraphy, acoustic radiation force impulse and real-time elastography are the methods with very good or excellent diagnostic accuracy for the assessment of liver fibrosis stage. They do not provide the information on inflammatory activity, steatosis, iron deposition or other findings derived from liver biopsy. Even on account of fibrosis stage, these non-invasive methods do not give us the estimation completely corresponding to that of liver biopsy. However they provide us useful clinical information that liver biopsy has been providing us, such as appropriate time to start antiviral therapy, prediction of response to antiviral therapy, evaluation of effects of antiviral therapy, assessment of natural course of hepatitis and estimation of prognosis of hepatitis. Recently non-invasive methods for assessment of inflammatory activity, steatosis and iron deposition in the liver have been developed. Thus in the near future, non-invasive methods will replace liver biopsy.

Background Liver stiffness (LS) has been reported to correlate with fibrosis stage (F). The correlation between LS and fibrosis stage and the reduction of LS by antiviral therapy were examined in patients with hepatitis B infection. Methods LS was measured by FibroScan in 212 patients infected with hepatitis B virus. Liver biopsies were done in 51 patients. Changes of LS were assessed in 29 patients treated with nucleotide or nucleoside analogs and 52 patients without antiviral therapy. Results LS was significantly correlated with fibrosis stage (rho = 0.686, P < 0.0001). The optimal cut-off values of LS were 7.1 kPa for F >= 2, 10.7 kPa for F >= 3, and 16.0 kPa for F4. LS was significantly reduced by antiviral therapy, from 12.9 (range 6.2-17.9) kPa to 6.6 (4.4-10.3) kPa measured at an interval of 512 (range 366-728) days (P < 0.0001). Eleven of 19 (58%) patients with baseline fibrosis stages of F3-4 deduced from LS had 2-point or greater reductions of deduced stage at the last LS measurement. The change ratio of hyaluronic acid (P = 0.0390) was associated with a 2-point or greater reduction of deduced fibrosis stage. Without antiviral therapy, LS tended to increase, increasing from 6.1 (range 3.9-8.5) kPa to 6.3 (range 4.4-9.7) kPa at an interval of 422 (range 358-709) days (P = 0.0682). Conclusions LS was significantly correlated with fibrosis stage in patients with chronic hepatitis B. The reduction of LS by antiviral therapy was significantly correlated with the reduction of hyaluronic acid. Thus, we conclude that LS can be useful to assess the progression and regression of liver fibrosis stage noninvasively.

Aim: Transient elastography is a non-invasive tool to measure liver stiffness (LS), which has been reported to correlate with stage of liver fibrosis. Extrahepatic cholestasis was reported to cause elevated LS, which is considered to be attributed to the increased hydrostatic pressure in the liver. In the present study, the correlation of LS with laboratory data was investigated in extrahepatic cholestasis. The change of LS after biliary drainage was also assessed. Methods: LS was measured in 29 patients with extrahepatic cholestasis due to carcinomas in 12 and non-neoplastic diseases of biliary tract or pancreas in 17. Results: In 15 patients, LS was 11.4 kPa or higher which suggested liver cirrhosis in chronic infection of hepatitis C virus. LS significantly correlated positively with serum bilirubin levels (r = 0.726, P < 0.0001) and negatively with serum aspartate aminotransferase (AST) levels (r = -0.481, P = 0.0082) and alanine aminotransferase (ALT) levels (r = -0.631, P = 0.0002). Biliary drainage led to a reduction of bilirubin by 13.5 to 0.9 mg/dL which was significantly correlated with a reduction of LS by 14.3 to 0.5 kPa (r = 0.524, P = 0.0257). Conclusion: In extrahepatic cholestasis, the elevation of LS which is probably attributed to the increased hydrostatic pressure in the liver, correlates positively with the accumulation of bilirubin but negatively with damage of hepatocytes indicated by ALT levels. Further studies on the mechanism underlying the elevation of LS should be helpful to elucidate the pathogenesis of extrahepatic cholestasis.

症例は76歳男性で、健診にて胆嚢結石を指摘された既往があり、近医にてC型肝炎と多発肝細胞癌(HCC)を指摘され紹介受診した。肝両葉の多発HCCにCDDP肝動注併用カテーテル的動脈下顎塞栓術計3回で腫瘍マーカーは正常化した。その後発熱と倦怠感で入院し、CTで脾周囲の低吸収域と脾実質の圧排所見、胆嚢・総胆管末端に小結石を認めた。超音波ガイド下の経皮的ドレナージで胆汁様液が穿刺され、脾周囲biloma(胆汁性嚢胞)疑いで内視鏡的逆行性胆管膵管造影(ERCP)を行った。総胆管結石と肝内胆管末梢より脾臓周囲への造影剤漏出・貯留を認め、bilomaの診断で内視鏡的胆道ドレナージチューブを挿入留置した。Biloma穿刺液からKlebsiella pneumoniaeが検出され、抗生剤投与で陰性化した。Bilomaは縮小し、内視鏡的乳頭切開術と総胆管の採石を行い、ERCPにて胆汁漏出の消失を認めた。

AIM: To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver fibrosis. METHODS: A new fibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS, platelet count and prothrombin time. The values of the Fibro-Stiffness index differed significantly between neighboring fibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F >= 2 (0.90), F >= 3 (0.90) and F = 4 (0.92) in the estimation group and those for F >= 3 (0.93) and F = 4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F >= 2, F >= 3 and F = 4 in both the estimation and validation groups. The diagnostic performance for F = 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F >= 2, 3 and 4. (C) 2010 Baishideng. All rights reserved.

Aim: To assess the regression of liver fibrosis after interferon (IFN) treatment in patients with chronic hepatitis C, liver stiffness (LS) was measured repeatedly and the factors associated with reduction of LS were assessed. Methods: LS was measured by transient elastography before treatment, at end of treatment (EOT), and 1 year and 2 years after EOT in 145 patients with chronic hepatitis C treated by IFN with or without ribavirin. Results: In the patients with sustained virological response (SVR) (n = 93) and relapsers (n = 28), LS significantly decreased at EOT (median, 5.4 [interquartile range, 4.0-8.6] kilopascals [kPa], P < 0.0001 and 6.8 [4.5-8.9] kPa, P = 0.0023) and 1 year after EOT (5.3 [4.2-7.0] kPa, P < 0.0001 and 6.8 [4.5-9.3] kPa, P = 0.0204) compared with baseline (8.0 [5.0-11.9] kPa and 10.6 [7.0-16.6] kPa). In SVR patients, LS significantly decreased 2 years after EOT (5.3 [4.1-6.3] kPa) compared with baseline (P < 0.0001) and LS at EOT (P = 0.0034). Two points or greater reduction of deduced stage at last LS measurement was observed in 78% of SVR patients, 59% of relapsers and 15% of patients with non-virological response whose pretreatment deduced stages were F3-F4. Fibrosis stage, hyaluronic acid levels, duration of treatment, response to treatment and alanine aminotransferase levels were associated with a 2-point or greater decrease of deduced fibrosis stage. Conclusion: IFN treatment reduced LS in SVR patients and relapsers. Significant reduction of LS is associated with milder fibrosis stage, lower hyaluronic acid levels, longer IFN treatment, virological response of SVR or relapse and higher alanine aminotransferase levels.

要旨: 今回我々は，超音波内視鏡下穿刺吸引術（endoscopic ultrasound-guided fine-needle aspiration: EUS-FNA）が診断に有用であった結核性リンパ節炎による閉塞性黄疸の1例を経験したので報告する．<br> 症例は32歳，男性．約1年前に肺結核にて治療歴があった．上腹部痛にて近医を受診したところ，閉塞性黄疸と診断され当院紹介となった．腹部造影CTにて，肝門部付近に辺縁が造影される低濃度の腫瘤を認め，それを原因とした閉塞性黄疸と考えられた．減黄&middot;原因精査目的にてPTBDを施行したところ，上部胆管に左方からの圧排による平滑な狭窄を認め，腫大した肝門部リンパ節による圧排が疑われた．減黄後，腫大したリンパ節に対しEUS-FNA施行した．生検組織に乾酪壊死を伴う類上皮性肉芽腫を認め，結核菌PCR検査が陽性であったため，肝門部の結核性リンパ節炎と診断した．肝機能正常化後，抗結核薬投与を開始した．以後，リンパ節は徐々に縮小傾向を認めている．<br>

Aim: Liver stiffness (LS) measured by transient elastography (TE) has been reported to correlate with liver fibrosis, which is usually semiquantitatively assessed. In the present study, the fibrosis area was measured by image analysis software in liver biopsy specimens and its correlation with LS was assessed. Methods: LS was measured by TE in all 165 patients with chronic hepatitis C virus (HCV) infection who underwent liver biopsy consecutively in Fujita Health University Hospital from July 2004 to September 2007. Results: Fibrosis area was significantly correlated with fibrosis stage as assessed by the Metavir score (rho = 0.733, P &lt; 0.0001). The optimal cut-off value of fibrosis area was 1.6% for F &gt; or = 2, 3.1% for F &gt; or = 3, and 3.8-6.4% for F4. LS was significantly correlated with fibrosis stage (rho = 0.734, P &lt; 0.0001). The optimal cut-off value of LS was 7.1 kPa for F &gt; or = 2, 9.6 kPa for F &gt; or = 3 and 11.6-16.9 kPa for F4. Multiple linear regression analysis selected fibrosis area (P = 0.0002), alanine aminotransferase (ALT) (P = 0.0237), gamma-glutamyltransferase (gamma-GTP) (P = 0.0114), prothrombin time (P = 0.0114) and hyaluronic acid (P &lt; 0.0001) as factors correlating with LS. Conclusion: The correlation between LS and liver fibrosis was confirmed by the objective measurement of fibrosis area. ALT was significantly correlated with LS, suggesting that inflammatory activity also affects LS values. Despite some limitation, LS measurement is a useful method for the diagnosis of liver fibrosis.

Background The aim of this study was to investigate the correlation between precore (PC)/basal core promoter (BCP) mutations and the viral loads or activity of hepatitis in patients with chronic hepatitis B virus (HBV) infection. Methods HBV genotypes, PC mutations, BCP mutations, HBV DNA levels, and serological markers of HBV were analyzed in all the patients with chronic HBV infection seen in Fujita Health University Hospital from June 2004 to November 2008 (n = 215). Results HBV genotype was C in 169 patients, B in 16, A in 3, F in 1, and unclassifiable in 5. Among the patients with genotype C, the prevalence of PC wild type was significantly lower in hepatitis B envelope antigen (HBeAg)(-) patients than in HBeAg(?) patients (9.5% versus 49.0%, P\0.0001). Among HBeAg(-) patients, the patients with PC wild type had significantly lower serum viral loads and alanine aminotransferase (ALT) levels compared with those with PC mutant (P\0.001). Among HBeAg(-) patients, the patients with genotype B had lower serum viral loads compared with those with genotype C (3.6 +/- 0.9 versus 4.6 +/- 1.6, P &lt; 0.05), and the prevalence of BCP wild type was significantly higher in those with genotype B than in those with genotype C (58.3% versus 10.8%, P &lt; 0.05). Conclusions Among HBeAg(-) patients with genotype C, the patients with PC wild type had significantly lower viral loads and ALT levels than those with PC mutant. This suggests that the patients with PC wild type may have better prognosis than those with PC mutant among HBeAg(-) patients with genotype C.

三次元体外式超音波 (3DUS) の原理, 装置および胆膵領域における有用性について述べる. 3DUSを利用することで胆嚢の容積を正確に測定でき, 胆嚢の正確な機能評価が可能である. またUS-virtual endoscopy像を作成することにより, 二次元の超音波断層像より, 病変の立体的形態, 表面性状などが把握しやすくなり, 客観的で説得力のある画像が得られる. 3DUSは将来, 胆膵領域における超音波診断能の向上に寄与するようになると期待する.