橋本 千樹

慢性肝障害患者における治療の選択には肝線維化をはじめとした肝障害ステージを把握し行われている。現在、肝障害ステージを確認するには肝生検が重要であるが、肝生検にはリスクが多い。このため簡便かつ信頼性の高い線維化診断が可能な検査として超音波による肝硬度測定が注目され、肝硬度測定においてARFIによる評価は重要な検査となりつつある。(著者抄録)

AIM: To evaluate the changes of shear-wave velocity (Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C.METHODS: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon (IFN) plus ribavirin (RBV). Vs value (m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment (EOT), 1 year after EOT, and 2 years after EOT.RESULTS: In patients with a sustained virological response (SVR) (n = 41), Vs significantly decreased at EOT [1.19 (1.07-1.37), P = 0.0004], 1 year after EOT [1.10 (1.00-1.22), P = 0.0001], and 2 years after EOT [1.05 (0.95-1.16), P < 0.0001] compared with baseline [1.27 (1.11-1.49)]. In patients with a relapse (n = 26), Vs did not significantly decrease at EOT [1.23 (1.12-1.55)], 1 year after EOT [1.20 (1.12-1.80)], and 2 years after EOT [1.41 (1.08-2.01)] compared with baseline [1.39 (1.15-1.57)]. In patients with a nonvirological response (n = 20), Vs did not significantly decrease at EOT [1.64 (1.43-2.06)], 1 year after EOT [1.66 (1.30-1.95)], and 2 years after EOT [1.61 (1.36-2.37)] compared with baseline [1.80 (1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28 (1.04-1.40)] than in non-SVR patients [1.56 (1.20-1.83)] (P = 0.0142).CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.

Background/Aims: To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. Materials and Methods: A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. Results: Serum albumin levels significantly decreased from 6 months before baseline (3.14+/-0.47 g/dL) to baseline (2.83+/-0.46 g/dL), despite the treatment with BCAA granules (p&lt;0.001), and tended to increase from baseline to 6 months after baseline (2.95+/-0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93+/-0.38 g/dL) to 6 months after baseline (3.15+/-0.34 g/dL) (p=0.014). Conclusion: Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

Endoscopic ultrasonography (EUS) has high spatial and contrast resolution, and is thought to be one of the most reliable and efficient diagnostic modalities for pancreatobiliary diseases. Recent progress in EUS, especially in the development of the electronic scanning method, has enabled the application of several utilities and software of a high-end transabdominal ultrasound apparatus as an image-enhanced EUS. Tissue harmonic imaging (THI) is a novel US acquisition method that provides better US images by using second harmonic signals. The potential advantages of THI are improved lateral resolution, reduced side lobe artifact and an increased signal-to-noise ratio. EUS-elastography is another novel technique that provides information about the distributed pattern of tissue hardness. Clinical benefits of EUS-elastography for the differential diagnosis of pancreatic tumors and the evaluation of pancreatic fibrosis have been reported. It is necessary to develop a unified and objective method of imaging and analysis to increase the use of EUS-elastography in the future.

Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of liver disease worldwide. To detect early stages of NAFLD and start treatment or to monitor the changes in trials of new drugs, non-invasive diagnostic methods are needed, such as biochemical markers or liver stiffness measurement (LSM). LSM with transient elastography (TE) and acoustic radiation force impulse (ARFI) has been shown to be useful in NAFLD, although the cut-off values have varied among reports. Magnetic resonance elastography and real-time tissue elastography also can be useful for the diagnosis of NAFLD, although the number of studies is limited. Fibrosis is absent in 8-40% of patients with non-alcoholic steatohepatitis (NASH), making it difficult to diagnose NASH by LSM because LSM is usually associated with fibrotic stage. The presence of inflammation or hepatocyte ballooning may affect LSM and aid the diagnosis of NASH without fibrosis. However, obesity significantly increases the failure of LSM and its interference is more conspicuous in TE than in ARFI. The newly implemented XL probe of TE has overcome the difficulty to some degree. Nonetheless, the effects of obesity, hepatocyte ballooning, steatosis and inflammation on LSM values have not yet been adequately investigated, although they are likely to affect LSM values. Further studies are needed to establish the clinical utility of LSM in NAFLD.

AIM: To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. METHODS: Two hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment. RESULTS: PNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03-1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03-1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97-4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13-9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07-1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15-5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90-3.71); p = 0.0936) as the factors independently associated with HCC. CONCLUSION: PNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common debilitating condition in many industrialized countries that increases the risk of cardiovascular disease. The aim of this study was to derive a simple and accurate screening tool for the prediction of NAFLD in the Japanese population. METHODS: A total of 945 participants, 279 men and 666 women living in Hokkaido, Japan, were enrolled among residents who attended a health check-up program from 2010 to 2014. Participants with an alcohol consumption > 20 g/day and/or a chronic liver disease, such as chronic hepatitis B, chronic hepatitis C or autoimmune hepatitis, were excluded from this study. Clinical and laboratory data were examined to identify predictive markers of NAFLD. RESULTS: A new predictive index for NAFLD, the NAFLD index, was constructed for men and for women. The NAFLD index for men = -15.5693+0.3264 [BMI] +0.0134 [triglycerides (mg/dl)], and for women = -31.4686+0.3683 [BMI] +2.5699 [albumin (g/dl)] +4.6740[ALT/AST] -0.0379 [HDL cholesterol (mg/dl)]. The AUROC of the NAFLD index for men and for women was 0.87(95% CI 0.88-1.60) and 0.90 (95% CI 0.66-1.02), respectively. The cut-off point of -5.28 for men predicted NAFLD with an accuracy of 82.8%. For women, the cut-off point of -7.65 predicted NAFLD with an accuracy of 87.7%. CONCLUSION: A new index for the non-invasive prediction of NAFLD, the NAFLD index, was constructed using available clinical and laboratory data. This index is a simple screening tool to predict the presence of NAFLD.

黄色肉芽腫性胆嚢炎(XGC)における超音波像および胆嚢動脈波形分析について検討した。超音波検査を施行し、さらに病理組織診断が得られているXGC 30例を対象とした。対照としてXGCと鑑別が困難となる胆嚢癌32例を検討に加えた。B-mode超音波を施行した30例中、胆石は27例に観察した。Power Doppler法を施行した27例中全例の壁肥厚部に胆嚢動脈と思われる血流表示を観察した。胆嚢癌では全例に線状の豊富な血流表示を認め、XGCの血流表示は胆嚢癌と比較するとやや乏しい傾向であった。限局性壁肥厚であった2例を除く28例中27例にて、胆嚢動脈の波形分析を施行可能であった。いずれもXGCは胆嚢癌に比べ有意に低値を示した。PI1.44以上、かつVmax46cm/s以上の場合が胆嚢癌と診断可能となった。PI1.44未満、かつVmax40cm/s未満であれば、XGCと診断可能となった。

症例は70歳女性、C型肝硬変にて近医通院中に肝腫瘍を認め、肝細胞癌(HCC)が疑われ当科紹介となった。US上、肝S8、S3、S7に境界不明瞭な低エコー結節を認め、ソナゾイド造影USでは同部位が早期に染影され後血管相でdefect像を示した。CTでは肝S8に約5cm、S3に約3cm、S6に約2.5cm大の境界不明瞭な淡い低吸収域を認め、動脈相で淡く濃染され平衡相でやや低吸収域を示した。EOB-MRIではこれらの病変を含め、肝両葉に早期相で染影され肝細胞相で淡い低信号域を示す多発性の腫瘤性病変を認めた。S3の腫瘍内には門脈の腫瘍内貫通像を認めた。PET-CTでは、肝両葉に多数の異常集積を認めた。HCCとしては非典型的であり、IL-2Rの上昇もみられたため肝腫瘍生検を施行。病理所見にてMALTリンパ腫と診断され、化学療法が導入された。肝MALTリンパ腫は稀な疾患であり、C型肝硬変を背景とした肝内多発病変である点、治療前に組織診断を行い化学療法導入が可能になった点で貴重な症例と考え報告する。(著者抄録)