今日の臨床サポート

肝硬変

著者: 元山宏行 大阪市立大学 肝胆膵病態内科学

著者: 河田則文 大阪市立大学 肝胆膵病態内科学

監修: 金子周一 金沢大学大学院

著者校正/監修レビュー済:2021/04/14
参考ガイドライン:
  1. 日本消化器病学会日本肝臓学会:肝硬変診療ガイドライン2020(改訂第3版)
患者向け説明資料

概要・推奨   

  1. 肝硬変の成因として、生活習慣に基づく脂肪性肝炎が増えてきている。また、若年女性での酒量増加が増えてきており、今後注意が必要である。
  1. 肝硬変の診断のゴールドスタンダードは肝生検であるが、侵襲的であるため、肝硬度測定などの非侵襲的検査が勧められる(推奨度2)
  1. 肝生検では、サンプリングエラーが起こり得る。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契 約が必要となります。 閲覧にはご 契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
元山宏行 : 特に申告事項無し[2021年]
河田則文 : 講演料(ギリアド・サイエンシズ株式会社,MSD株式会社,アッヴィ合同会社),研究費・助成金など(ギリアド・サイエンシズ株式会社,武田薬品工業株式会社,中外製薬株式会社,アストラゼネカ株式会社,MSD株式会社),奨学(奨励)寄付など(アッヴィ合同会社,大塚製薬株式会社,エーザイ株式会社)[2021年]
監修:金子周一 : 研究費・助成金など(バイエル薬品株式会社,株式会社キュービクス,アボットジャパン合同会社,日東電工株式会社,株式会社スギ薬局,株式会社サイトパスファインダー),奨学(奨励)寄付など(小野薬品工業株式会社,エーザイ株式会社,株式会社ツムラ,アッヴィ合同会社,大日本住友製薬株式会社,ゼリア新薬工業株式会社,塩野義製薬株式会社,大塚製薬株式会社,アステラス製薬株式会社,田辺三菱製薬株式会社,マイランEPD合同会社,EAファーマ株式会社,大鵬薬品工業株式会社,中外製薬株式会社,協和キリン株式会社,持田製薬株式会社,日本ケミファ株式会社,LifeScan Japan株式会社)[2021年]

改訂のポイント:
  1. 肝硬変診療ガイドラインに基づき、Acute on-chronic liver failureやサルコペニア、肝肺症候群、門脈圧亢進症にともなう肺動脈性肺高血圧症など新たな概念、国際的な診断基準・分類について改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 肝硬変とは、肝臓全体に線維化と線維化に伴う結節形成が解剖学的に認められる状態と定義される。肝発癌リスクが非常に高く、B型肝硬変では年率約3%[1]、C型肝炎では、年率5~8%である[2]
  1. 腹腔鏡での肝全体の観察がゴールドスタンダードであるが、画像検査での形態学的変化や臨床所見にて食道静脈瘤、腹水、脳症の存在や、ほかに血液、凝固、生化学検査を用いて診断されているのが現状である。
  1. わが国での肝硬変患者数は、25~30万人と推測されている。
  1. 最近の肝硬変によるわが国での死亡者数は年間8,000~9,000人である。
  1. 肝硬変の成因別実態2018では、その成因はC型肝炎 49.2%、B型肝炎 11.8%、C型肝炎+B型肝炎 0.8%、アルコール性 19.4%、自己免疫性 2.7%、非アルコール性脂肪肝炎 5.8%となっている[3]
  1. 肝臓の機能として、機能低下による症状を継続的に呈さない時期を代償性肝硬変、症状を呈する時期を非代償性肝硬変と称する。
  1. 肝機能の程度は、Child-Pugh分類を使用する。(表<図表>
  1. 肝硬変診療ガイドライン2020よりAcute on-chronic liver failureやサルコペニア、肝腎症候群、肝肺症候群、門脈圧亢進症にともなう肺動脈性肺高血圧症など新たな病態概念が導入された。
  1. Acute on-chronic liver failureはChild-Pugh score 9点以下の肝硬変患者における肝機能急性増悪であり、何らかの誘因により発症・増悪し、28日以内に急激に肝不全にいたる病態である。
  1. サルコペニアとは、骨格筋量および筋力または身体機能が低下した状態のことである。加齢によるサルコペニアは一次サルコペニア、炎症性疾患や肝疾患などの基礎疾患による骨格筋量および筋力または身体機能が低下した病態は二次性サルコペニアと定義される。
  1. 肝腎症候群は、肝硬変における門脈圧亢進の進行とともに一酸化窒素などの血管拡張物質による腹部内蔵血管床の拡張、全身の血管抵抗の低下、平均動脈圧の低下に対する代償機構として心拍出量が上昇するが、肝硬変では血管抵抗は低下するためレニン・アルドステロン系、交感神経系、バゾプレシンの分泌が亢進する。さらに炎症性サイトカインも循環動態に影響し、腎動脈が収縮し腎皮質の血流低下が起こることで発症する。
  1. 肝肺症候群は、慢性肝疾患においてびまん性あるいは局所性の異常な毛細血管の拡張と肺内動静脈シャントにより低酸素血症を生じる病態である。一方、門脈圧亢進症にともなう肺動脈性肺高血圧症の発生機序は解明されていないが、門脈圧亢進症にともなう心拍出量の増加による肺血管床の血液量増加や炎症性サイトカインなどの肺への流入による血管内皮細胞障害や肺血管の収縮から肺血管抵抗が上昇し、肺高血圧症に至ると考えられている。
問診・診察のポイント  
問診:
  1. 成因について確認する。例:家族歴、飲酒歴、輸血歴、入れ墨の有無、体重の変動、治療歴

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文献 

著者: Akihiro Matsumoto, Eiji Tanaka, Akinori Rokuhara, Kendo Kiyosawa, Hiromitsu Kumada, Masao Omata, Kiwamu Okita, Norio Hayashi, Takeshi Okanoue, Shiro Iino, Kyuichi Tanikawa, Inuyama Hepatitis Study Group
雑誌名: Hepatol Res. 2005 Jul;32(3):173-84. doi: 10.1016/j.hepres.2005.02.006. Epub 2005 Jul 18.
Abstract/Text A retrospective survey of Japanese patients histologically diagnosed with chronic hepatitis B was conducted to determine the effectiveness of lamivudine in preventing hepatocellular carcinoma (HCC). Of the 2795 patients who satisfied criteria for analysis after treatment from any of 30 medical institutions, 657 had received lamivudine and the remaining 2138 had not. A Cox regression model with liver biopsy as the starting point revealed seven factors related to HCC: lamivudine therapy, gender, family clustering of hepatitis B, age at liver biopsy, hepatic fibrosis stage, serum albumin level, and platelet count. In a matched case-controlled study, 377 patients in a lamivudine-treated group and 377 matched patients in a non-treated group were selected based on their propensity scores. The mean follow-up period was 2.7 years in the lamivudine group and 5.3 years in the control group. In the lamivudine group, HCC occurred in four patients (1.1%) with an annual incidence rate of 0.4%/(patient/year), whereas in the control group HCC occurred in 50 patients (13.3%) for a rate of 2.5%/(patient/year). A comparison of the cumulative HCC incidence between the two groups by the Kaplan-Meier method showed a significantly lower incidence of HCC in the lamivudine group (p<0.001). These findings suggest that lamivudine effectively reduces the incidence of HCC in patients with chronic hepatitis B.

PMID 16024289  Hepatol Res. 2005 Jul;32(3):173-84. doi: 10.1016/j.hepr・・・
著者: H Yoshida, Y Shiratori, M Moriyama, Y Arakawa, T Ide, M Sata, O Inoue, M Yano, M Tanaka, S Fujiyama, S Nishiguchi, T Kuroki, F Imazeki, O Yokosuka, S Kinoyama, G Yamada, M Omata
雑誌名: Ann Intern Med. 1999 Aug 3;131(3):174-81.
Abstract/Text BACKGROUND: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma.
OBJECTIVE: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis.
DESIGN: Retrospective cohort study.
SETTING: Seven university hospitals and one regional core hospital in Japan.
PATIENTS: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated.
MEASUREMENTS: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression.
RESULTS: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]).
CONCLUSIONS: Interferon therapy significantly reducesthe risk for hepatocellular carcinoma, especially among virologic or biochemical responders.

PMID 10428733  Ann Intern Med. 1999 Aug 3;131(3):174-81.
著者: Hiroyuki Nakanishi, Masayuki Kurosaki, Kaoru Tsuchiya, Natsuko Nakakuki, Hitomi Takada, Shuya Matsuda, Kouichi Gondo, Yu Asano, Nobuhiro Hattori, Nobuharu Tamaki, Shoko Suzuki, Yutaka Yasui, Takanori Hosokawa, Jun Itakura, Yuka Takahashi, Namiki Izumi
雑誌名: Clin Gastroenterol Hepatol. 2015 Aug;13(8):1540-3. doi: 10.1016/j.cgh.2014.12.005. Epub 2014 Dec 9.
Abstract/Text We performed a prospective study to evaluate the ability of L-carnitine, which is involved in the β-oxidation of fatty acids, to reduce muscle cramps in patients with cirrhosis. Consecutive patients with cirrhosis and muscle cramps were given L-carnitine 300 mg, 3 times/day (900 mg/day, n = 19) or 4 times/day (1200 mg/day, n = 23) for 8 weeks. The frequency of muscle cramps was assessed by questionnaires, and the degree of muscle cramping was assessed by using the visual analogue scale (VAS). Muscle cramping was reduced in 88.1% of all subjects at the end of the 8-week study period and disappeared for 28.6% of patients. Overall VAS scores decreased significantly from 69.9 ± 22.5 at baseline to 26.2 ± 29.1 after 8 weeks (P < .0001). The dose of L-carnitine was significantly associated with percentages of patients with reduced muscle cramps after 8 weeks (43.5% in the 1200 mg/day group vs 10.5% in the 900 mg/day group, P = .037) and VAS scores at 8 weeks (9.9 ± 13.5 in the 1200 mg/day group vs 39.6 ± 31.9 in the 900 mg/day group, P = .003). No adverse events were reported. Therefore, L-carnitine appears to be safe and effective for reducing liver cramps in patients with cirrhosis.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 25496816  Clin Gastroenterol Hepatol. 2015 Aug;13(8):1540-3. doi:・・・
著者: Francoise Degos, Paul Perez, Bruno Roche, Amel Mahmoudi, Julien Asselineau, Hélène Voitot, Pierre Bedossa, FIBROSTIC study group
雑誌名: J Hepatol. 2010 Dec;53(6):1013-21. doi: 10.1016/j.jhep.2010.05.035. Epub 2010 Aug 14.
Abstract/Text BACKGROUND & AIMS: The diagnostic accuracy of non-invasive liver fibrosis tests that may replace liver biopsy in patients with chronic hepatitis remains controversial. We assessed and compared the accuracy of FibroScan® and that of the main biomarkers used for predicting cirrhosis and significant fibrosis (METAVIR ≥ F2) in patients with chronic viral hepatitis.
METHODS: A multicenter prospective cross-sectional diagnostic accuracy study was conducted in the Hepatology departments of 23 French university hospitals. Index tests and reference standard (METAVIR fibrosis score on liver biopsy) were measured on the same day and interpreted blindly. Consecutive patients with chronic viral hepatitis (hepatitis B or C virus, including possible Human Immunodeficiency Virus co-infection) requiring liver biopsy were recruited in the study.
RESULTS: The analysis was first conducted on the total population (1839 patients), and after excluding 532 protocol deviations, on 1307 patients (non-compliant FibroScan® examinations). The overall accuracy of FibroScan® was high (AUROC 0.89 and 0.90, respectively) and significantly higher than that of biomarkers in predicting cirrhosis (AUROC 0.77-0.86). All non-invasive methods had a moderate accuracy in predicting significant fibrosis (AUROC 0.72-0.78). Based on multilevel likelihood ratios, non-invasive tests provided a relevant gain in the likelihood of diagnosis in 0-60% of patients (cirrhosis) and 9-30% of patients (significant fibrosis).
CONCLUSIONS: The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis.

Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID 20850886  J Hepatol. 2010 Dec;53(6):1013-21. doi: 10.1016/j.jhep.・・・
著者: Arie Regev, Mariana Berho, Lennox J Jeffers, Clara Milikowski, Enrique G Molina, Nikolaos T Pyrsopoulos, Zheng-Zhou Feng, K Rajender Reddy, Eugene R Schiff
雑誌名: Am J Gastroenterol. 2002 Oct;97(10):2614-8. doi: 10.1111/j.1572-0241.2002.06038.x.
Abstract/Text OBJECTIVES: Needle liver biopsy has been shown to have a high rate of sampling error in patients with diffuse parenchymal liver diseases. In these cases, the sample of liver tissue does not reflect the true degree of inflammation, fibrosis, or cirrhosis, despite an adequate sample size. The aim of this study was to determine the rate and extent of sampling error in patients with chronic hepatitis C virus infection, and to assess the intraobserver variation with the commonly used scoring system proposed by Scheuer and modified by Batts and Ludwig.
METHODS: A total of 124 patients with chronic hepatitis C virus infection underwent simultaneous laparoscopy-guided biopsies of the right and left hepatic lobes. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin and with trichrome. The slides were blindly coded and randomly divided among two hepatopathologists. Inflammation and fibrosis were scored according to the standard grading (inflammation) and staging (fibrosis) method based on the modified Scheuer system. Following the interpretation, the slides were uncoded to compare the results of the right and left lobes. Fifty of the samples were blindly resubmitted to each of the pathologists to determine the intraobserver variation.
RESULTS: Thirty of 124 patients (24.2%) had a difference of at least one grade, and 41 of 124 patients (33.1%) had a difference of at least one stage between the right and left lobes. In 18 patients (14.5%), interpretation of cirrhosis was given in one lobe, whereas stage 3 fibrosis was given in the other. A difference of two stages or two grades was found in only three (2.4%) and two (1.6%) patients, respectively. Of the 50 samples that were examined twice, the grading by each pathologist on the second examination differed from the first examination in 0% and 4%, and the staging differed in 6% and 10%, respectively. All observed variations were of one grade or one stage.
CONCLUSIONS: Liver biopsy samples taken from the right and left hepatic lobes differed in histological grading and staging in a large proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These differences could not be attributed to intraobserver variation, which appeared to be low.

PMID 12385448  Am J Gastroenterol. 2002 Oct;97(10):2614-8. doi: 10.111・・・
著者: Marie-Christine Rousselet, Sophie Michalak, Florence Dupré, Anne Croué, Pierre Bedossa, Jean-Paul Saint-André, Paul Calès, Hepatitis Network 49
雑誌名: Hepatology. 2005 Feb;41(2):257-64. doi: 10.1002/hep.20535.
Abstract/Text Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis (kappa = 0.59) than for activity (kappa = 0.43) and poor for lobular necrosis (kappa = 0.15). The mean agreement was better for senior (0.60 +/- 0.24) than junior pathologists (0.52 +/- 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 +/- 0.18 vs. 0.58 +/- 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: kappa = 0.48 and 0.77, activity: kappa = 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity (kappa = 0.22-0.25) or fibrosis (kappa = 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading.

PMID 15660389  Hepatology. 2005 Feb;41(2):257-64. doi: 10.1002/hep.205・・・
著者: Kojiro Michitaka, Shuhei Nishiguchi, Yutaka Aoyagi, Yoichi Hiasa, Yoshio Tokumoto, Morikazu Onji, Japan Etiology of Liver Cirrhosis Study Group
雑誌名: J Gastroenterol. 2010;45(1):86-94. doi: 10.1007/s00535-009-0128-5. Epub 2009 Sep 30.
Abstract/Text BACKGROUND: Little is understood about worldwide changes in the epidemiological distribution of the etiology of liver cirrhosis (LC). The present study examines the etiology of liver cirrhosis in Japan using a nationwide survey.
METHODS: We analyzed data from 33,379 patients with LC at 58 hospitals and presented the findings in a poster symposium regarding the etiology and clinical features of LC in Japan that was included in the program of the 44th Annual Meeting of the Japan Society of Hepatology. We identified the distribution of the etiology of LC and compared the present with previous Japanese findings to estimate the future of etiological changes in LC.
RESULTS: The etiological agents were as follows: hepatitis B virus (HBV) 13.9%, hepatitis C virus (HCV) 60.9%, alcohol 13.6%, primary biliary cirrhosis (PBC) 2.4% and autoimmune hepatitis (AIH) 1.9%. Cirrhosis was considered to be related to nonalcoholic steatohepatitis (NASH) in 2.1% of the patients. The ratio of HCV-related LC was significantly higher among patients with hepatocellular carcinoma (HCC) (P < 0.0001) compared to those without, whereas the ratios of alcohol, PBC, AIH were lower. HCC was evident in 31.5% of NASH-related LC.
CONCLUSIONS: The major etiology of liver cirrhosis in Japan remains HCV. Our survey revealed the prevalence of NASH-related LC in Japan and the frequency of HCC. Future changes in etiology must be considered in establishing preventive or educational strategies, as well as in developing new treatment strategies.

PMID 19789837  J Gastroenterol. 2010;45(1):86-94. doi: 10.1007/s00535-・・・
著者: M Malinchoc, P S Kamath, F D Gordon, C J Peine, J Rank, P C ter Borg
雑誌名: Hepatology. 2000 Apr;31(4):864-71. doi: 10.1053/he.2000.5852.
Abstract/Text Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R > 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.

PMID 10733541  Hepatology. 2000 Apr;31(4):864-71. doi: 10.1053/he.2000・・・
著者: P S Kamath, R H Wiesner, M Malinchoc, W Kremers, T M Therneau, C L Kosberg, G D'Amico, E R Dickson, W R Kim
雑誌名: Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.2001.22172.
Abstract/Text A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as "hospitalized" patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as "historical" patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c-statistic: <.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01-0.03). The MELD scale is a reliable measure of mortality risk in patients with end-stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities.

PMID 11172350  Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.20・・・
著者: Atsushi Hiraoka, Takashi Kumada, Masatoshi Kudo, Masashi Hirooka, Kunihiko Tsuji, Ei Itobayashi, Kazuya Kariyama, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Toshifumi Tada, Hidenori Toyoda, Kazuhiro Nouso, Kouji Joko, Hideki Kawasaki, Yoichi Hiasa, Kojiro Michitaka, Real-Life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics)
雑誌名: Liver Cancer. 2017 Jun;6(3):204-215. doi: 10.1159/000452846. Epub 2017 Mar 9.
Abstract/Text AIM/BACKGROUND: The purpose of this study was to evaluate the validity of 3 classifications for assessing liver function, the liver damage and Child-Pugh classifications and the newly proposed albumin-bilirubin (ALBI) grade, in order to examine the feasibility of evaluating hepatic function using ALBI grade with the hepatocellular carcinoma (HCC) treatment algorithm used in Japan.
METHODS: We analyzed the medical records of 3,495 Japanese HCC patients admitted from 2000 to 2015, which were comprised of 1,580 patients hospitalized in the Ehime Prefecture area and used as a training cohort (Ehime group), and 1,915 others who were used for validation (validation group). ALBI score used for grading (≤-2.60 = grade 1, greater than -2.60 to ≤-1.39 = grade 2, greater than -1.39 = grade 3) as well as clinical features and prognosis (Japan Integrated Staging [JIS], modified JIS, ALBI-TNM [ALBI-T] score) were retrospectively investigated.
RESULTS: For prediction of liver damage A, the values for sensitivity and specificity, positive predictive and negative predictive values, and positive and negative likelihood ratios of ALBI-1 and Child-Pugh A were similar among the 2 groups. Akaike information criterion results showed that prognosis based on ALBI grade/ALBI-T score was better than that based on liver damage/modified JIS score and Child-Pugh/JIS score (22,291.8/21,989.4, 22,379.6/22,076.0, 22,392.1/22,075.1, respectively). The cutoff values for ALBI score for indocyanine green retention rate at 15 min (ICG-R15) <10, <20, and <30% were -2.623 (area under the curve [AUC]: 0.798), -2.470 (AUC: 0.791), and -2.222 (AUC: 0.843), respectively. The distribution of ICG-R15 (<10%, 10 to <20%, 20 to <30%, and ≥30%) for ALBI grade 1 was similar to that for liver damage A. There were only small differences with regard to therapeutic selection with the Japanese HCC treatment algorithm between liver damage and ALBI grade.
CONCLUSION: ALBI grade is a useful and easy classification system for assessment of hepatic function for therapeutic decision making.

PMID 28626732  Liver Cancer. 2017 Jun;6(3):204-215. doi: 10.1159/00045・・・
著者: K Kubota, M Makuuchi, K Kusaka, T Kobayashi, K Miki, K Hasegawa, Y Harihara, T Takayama
雑誌名: Hepatology. 1997 Nov;26(5):1176-81. doi: 10.1053/jhep.1997.v26.pm0009362359.
Abstract/Text The respective volumes of hepatic tumors and nontumorous parenchyma of 50 patients requiring hepatectomy of more than one segment of Healey for tumor removal were measured using computed tomography (Vol-CT). The volume estimated by Vol-CT was found to correlate with the real weight resected (P < .0001) with a mean absolute error of 64.9 mL. The ratio of the nontumorous parenchymal volume of the resected liver to that of the whole liver (R2) in 15 patients who underwent right or extended right hepatic lobectomy was 43% +/- 15%. Eight of 15 patients with R2s < 60% underwent the procedures without right portal vein embolization (PE). The other seven with R2s exceeding 60% or an indocyanine green retention rate after 15 minutes (ICG15) of 10% to 20% underwent PE: in six of seven, the nontumorous parenchyma of the right hepatic lobe became atrophic and in all seven, the volume of the remaining left hepatic lobe increased with a decrease in the mean R2 from 62% +/- 14% to 55% +/- 8% (P = .0006). In the remaining 35 who underwent other hepatectomy procedures, R2s also remained <60%. Overall, at surgery, in 27 with normal liver function (ICG15 < 10%), R2s exceeded 60% in one, remained at 50% to 60% in five, and <50% in 21, whereas 23 patients except for one with an ICG15 exceeding 10%, had R2s of <50%. The postoperative serum total bilirubin levels in 84% of the patients remained within the normal range and there was no surgery-related mortality. In conclusion, 1) Vol-CT can accurately assess the extent of liver resection, 2) individuals with normal liver function can undergo resection of up to 60% of the nontumorous parenchyma without the need for PE, and 3) PE can be used to reduce the size of the resected tissue and increase the volume of the remnant liver to approximate the target limits in individuals with large tumors or minimally abnormal liver function.

PMID 9362359  Hepatology. 1997 Nov;26(5):1176-81. doi: 10.1053/jhep.1・・・
著者: Jean-Pierre Zarski, Nathalie Sturm, Jérôme Guechot, Adeline Paris, Elie-Serge Zafrani, Tarik Asselah, Renée-Claude Boisson, Jean-Luc Bosson, Dominique Guyader, Jean-Charles Renversez, Jean-Pierre Bronowicki, Marie-Christine Gelineau, Albert Tran, Candice Trocme, Victor De Ledinghen, Elisabeth Lasnier, Armelle Poujol-Robert, Frédéric Ziegler, Marc Bourliere, Hélène Voitot, Dominique Larrey, Maria Alessandra Rosenthal-Allieri, Isabelle Fouchard Hubert, François Bailly, Michel Vaubourdolle, ANRS HCEP 23 Fibrostar Group
雑誌名: J Hepatol. 2012 Jan;56(1):55-62. doi: 10.1016/j.jhep.2011.05.024. Epub 2011 Jul 23.
Abstract/Text BACKGROUND & AIMS: Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC).
METHODS: This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method.
RESULTS: Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis.
CONCLUSIONS: Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis.

Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID 21781944  J Hepatol. 2012 Jan;56(1):55-62. doi: 10.1016/j.jhep.20・・・
著者: Christophe Cassinotto, Bruno Lapuyade, Amaury Mouries, Jean-Baptiste Hiriart, Julien Vergniol, Delphine Gaye, Claire Castain, Brigitte Le Bail, Faiza Chermak, Juliette Foucher, François Laurent, Michel Montaudon, Victor De Ledinghen
雑誌名: J Hepatol. 2014 Sep;61(3):550-7. doi: 10.1016/j.jhep.2014.04.044. Epub 2014 May 9.
Abstract/Text BACKGROUND & AIMS: Non-invasive assessment of liver fibrosis by elastography is a rapidly developing field with frequent technological innovations. The aim of this study was to assess the diagnostic performances of Supersonic Shear Imaging (SSI) for the diagnosis of liver fibrosis in chronic liver disease.
METHODS: A total of 349 consecutive patients with chronic liver diseases who underwent liver biopsy from November 2011 to October 2013 were prospectively enrolled. For each patient, liver stiffness was assessed by SSI, ARFI, FibroScan® (M probe for patients with BMI <30 kg/m(2), and XL probe for patients with BMI ⩾30 kg/m(2)), performed within two weeks of liver biopsy. Areas under the receiver operating curves (AUROCs) were performed and compared for each degree of liver fibrosis.
RESULTS: SSI, FibroScan®, and ARFI correlated significantly with histological fibrosis score (r=0.79, p<0.00001; r=0.70, p<0.00001; r=0.64, p<0.00001, respectively). AUROCs of SSI, FibroScan®, and ARFI were 0.89, 0.86, and 0.84 for the diagnosis of mild fibrosis; 0.88, 0.84, and 0.81 for the diagnosis of significant fibrosis; 0.93, 0.87, and 0.89, for the diagnosis of severe fibrosis; 0.93, 0.90, and 0.90 for the diagnosis of cirrhosis, respectively. SSI had a higher accuracy than FibroScan® for the diagnosis of severe fibrosis (⩾F3) (p=0.0016), and a higher accuracy than ARFI for the diagnosis of significant fibrosis (⩾F2) (p=0.0003). No significant difference was observed for the diagnosis of mild fibrosis and cirrhosis.
CONCLUSIONS: SSI is an efficient method for the assessment of liver fibrosis in chronic liver diseases, comparing favourably to FibroScan® and ARFI.

Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID 24815876  J Hepatol. 2014 Sep;61(3):550-7. doi: 10.1016/j.jhep.20・・・
著者: European Association for Study of Liver, Asociacion Latinoamericana para el Estudio del Higado
雑誌名: J Hepatol. 2015 Jul;63(1):237-64. doi: 10.1016/j.jhep.2015.04.006. Epub 2015 Apr 21.
Abstract/Text
PMID 25911335  J Hepatol. 2015 Jul;63(1):237-64. doi: 10.1016/j.jhep.2・・・
著者: Robert M Merion, Douglas E Schaubel, Dawn M Dykstra, Richard B Freeman, Friedrich K Port, Robert A Wolfe
雑誌名: Am J Transplant. 2005 Feb;5(2):307-13. doi: 10.1111/j.1600-6143.2004.00703.x.
Abstract/Text Demand for liver transplantation continues to exceed donor organ supply. Comparing recipient survival to that of comparable candidates without a transplant can improve understanding of transplant survival benefit. Waiting list and post-transplant mortality was studied among a cohort of 12 996 adult patients placed on the waiting list between 2001 and 2003. Time-dependent Cox regression models were fitted to determine relative mortality rates for candidates and recipients. Overall, deceased donor transplant recipients had a 79% lower mortality risk than candidates (HR = 0.21; p < 0.001). At Model for End-stage Liver Disease (MELD) 18-20, mortality risk was 38% lower (p < 0.01) among recipients compared to candidates. Survival benefit increased with increasing MELD score; at the maximum score of 40, recipient mortality risk was 96% lower than that for candidates (p < 0.001). In contrast, at lower MELD scores, recipient mortality risk during the first post-transplant year was much higher than for candidates (HR = 3.64 at MELD 6-11, HR = 2.35 at MELD 12-14; both p < 0.001). Liver transplant survival benefit at 1 year is concentrated among patients at higher risk of pre-transplant death. Futile transplants among severely ill patients are not identified under current practice. With 1 year post-transplant follow-up, patients at lower risk of pre-transplant death do not have a demonstrable survival benefit from liver transplant.

PMID 15643990  Am J Transplant. 2005 Feb;5(2):307-13. doi: 10.1111/j.1・・・
著者: Yasutoshi Muto, Shunichi Sato, Akiharu Watanabe, Hisataka Moriwaki, Kazuyuki Suzuki, Akinobu Kato, Masahiko Kato, Teiji Nakamura, Kiyohiro Higuchi, Shuhei Nishiguchi, Hiromitsu Kumada, Long-Term Survival Study Group
雑誌名: Clin Gastroenterol Hepatol. 2005 Jul;3(7):705-13.
Abstract/Text BACKGROUND & AIMS: Nutritional intervention with branched-chain amino acid (BCAA) is reported to increase serum albumin concentration in patients with decompensated cirrhosis. However, a definite conclusion on whether it can improve patients' survival has not yet been reached. The present study aimed to test possibilities of improving survival of patients with decompensated cirrhosis by using a BCAA preparation that is suitable for long-term oral administration.
METHODS: A multicenter, randomized, and nutrient intake-controlled trial on the comparative effects of BCAA orally administered at 12 g/day for 2 years versus diet therapy with defined daily food intake (1.0-1.4 g protein kg(-1) day(-1) including BCAA preparation and 25-35 kcal kg(-1) day(-1)) was conducted in 646 patients with decompensated cirrhosis. The primary end point was a composite of death by any cause, development of liver cancer, rupture of esophageal varices, or progress of hepatic failure (event-free survival). The secondary end points were serum albumin concentration and health-related quality of life (QOL) measured by Short Form-36 questionnaire.
RESULTS: The incidence of events comprising the primary end point significantly decreased in the BCAA group as compared with the diet group (hazard ratio, 0.67; 95% confidence interval, 0.49-0.93; P = .015; median observation period, 445 days). Serum albumin concentration increased significantly in the BCAA group as compared with the diet group (P = .018). The "general health perception" domain in Short Form-36 measures was also improved (P = .003). Patients' adherence to the prescription was favorable.
CONCLUSIONS: Oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival, serum albumin concentration, and QOL in patients with decompensated cirrhosis with an adequate daily food intake.

PMID 16206505  Clin Gastroenterol Hepatol. 2005 Jul;3(7):705-13.
著者: Yasutoshi Muto, Shunichi Sato, Akiharu Watanabe, Hisataka Moriwaki, Kazuyuki Suzuki, Akinobu Kato, Masahiko Kato, Teiji Nakamura, Kiyohiro Higuchi, Shuhei Nishiguchi, Hiromitsu Kumada, Yasuo Ohashi, Long-Term Survival Study (LOTUS) Group
雑誌名: Hepatol Res. 2006 Jul;35(3):204-14. doi: 10.1016/j.hepres.2006.04.007. Epub 2006 Jun 5.
Abstract/Text We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors.

PMID 16737844  Hepatol Res. 2006 Jul;35(3):204-14. doi: 10.1016/j.hepr・・・
著者: Hiroki Nishikawa, Makoto Shiraki, Akira Hiramatsu, Kyoji Moriya, Keisuke Hino, Shuhei Nishiguchi
雑誌名: Hepatol Res. 2016 Sep;46(10):951-63. doi: 10.1111/hepr.12774.
Abstract/Text Sarcopenia is defined by muscle loss and muscle dysfunction. Sarcopenia is classified into primary and secondary types, based on the cause. Primary sarcopenia is mainly aging-related sarcopenia, whereas secondary sarcopenia is the reduced muscle mass and strength that accompanies an underlying disease. Given the essential role of the liver in metabolism, secondary sarcopenia due to nutritional disorders or other factors can frequently occur in liver disease. In 2015, the Japan Society of Hepatology (JSH) decided to establish its own assessment criteria for sarcopenia in liver disease because the number of liver disease patients with sarcopenia is expected to increase and there is cumulative evidence to indicate sarcopenic patients have poor clinical outcomes. A working group to create assessment criteria for sarcopenia has thus been established by the JSH. In this article, we summarize the current knowledge with regard to sarcopenia and present the assessment criteria for sarcopenia in liver disease proposed by the JSH (1st edition). To the best of our knowledge, this is globally the first proposed assessment criteria for sarcopenia specializing in liver disease.

© 2016 The Japan Society of Hepatology.
PMID 27481650  Hepatol Res. 2016 Sep;46(10):951-63. doi: 10.1111/hepr.・・・
著者: Iñigo Les, Eduardo Doval, Rita García-Martínez, Mercè Planas, Guillermo Cárdenas, Pilar Gómez, Montse Flavià, Carlos Jacas, Beatriz Mínguez, Mercedes Vergara, Germán Soriano, Carmen Vila, Rafael Esteban, Juan Córdoba
雑誌名: Am J Gastroenterol. 2011 Jun;106(6):1081-8. doi: 10.1038/ajg.2011.9. Epub 2011 Feb 15.
Abstract/Text OBJECTIVES: Protein intake impacts on nutritional status and may determine the recurrence of hepatic encephalopathy (HE). A low-protein diet has been considered the standard treatment after an episode of HE, while branched-chain amino acids (BCAA) have been shown to improve minimal HE. We performed a study to investigate the long-term effects of supplementing a protein-controlled diet with BCAA.
METHODS: A randomized, double-blind, multicenter study that included 116 patients with cirrhosis and a previous episode of HE was conducted in four tertiary care hospitals. All patients received a standard diet of 35 kcal/kg per day and 0.7 g of proteins/kg per day and a supplement of 30 g of BCAA (BCAA group) or maltodextrin (MDX group) during 56 weeks.
RESULTS: The actuarial risk of remaining free of HE did not differ between groups (BCAA=47%, MDX=34%, P=0.274), but patients in the BCAA group exhibited a better outcome on two neuropsychological tests and an increase in the mid-arm muscle circumference. Recurrence was associated with low plasma albumin at baseline and a decrease in sodium and an increase in creatinine during follow-up. Patients with recurrence of HE exhibited a lack of improvement in global cognitive function.
CONCLUSIONS: Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE. However, supplementation with BCAA improves minimal HE and muscle mass. Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE.

PMID 21326220  Am J Gastroenterol. 2011 Jun;106(6):1081-8. doi: 10.103・・・
著者: Tatsunori Hanai, Makoto Shiraki, Kayoko Nishimura, Sachiyo Ohnishi, Kenji Imai, Atsushi Suetsugu, Koji Takai, Masahito Shimizu, Hisataka Moriwaki
雑誌名: Nutrition. 2015 Jan;31(1):193-9. doi: 10.1016/j.nut.2014.07.005. Epub 2014 Jul 30.
Abstract/Text OBJECTIVE: Sarcopenia is characterized by the loss of skeletal muscle mass, and is reported to appear in patients with liver cirrhosis (LC). The aim of this study was to investigate the prevalence of sarcopenia in patients with LC, and to test the association between sarcopenia and patient outcomes. We also analyzed the effect of branched-chain amino acid (BCAA) supplementation on sarcopenic LC.
METHODS: Clinical and blood biochemical data of 130 patients with LC who underwent abdominal computed tomography scan were analyzed in this retrospective study. The cross-sectional area of skeletal muscles was measured at the level of the third lumbar vertebra on the scan. The skeletal muscle index was calculated to identify sarcopenia. Cirrhotic patients who were treated with BCAA supplementation of 12 g/d for ≥ 1 y were defined as the BCAA group, and the effect of BCAA on sarcopenic LC was evaluated.
RESULTS: Sixty-eight percent of all patients (82% of men and 50% of women) were diagnosed with sarcopenia. Male sex (P = 0.01) and body mass index (P < 0.0001) were predictors of sarcopenia. The multivariate Cox proportional hazards model found BCAA supplementation (hazard ratio [HR], 0.38; P = 0.01), sarcopenia (HR, 3.03; P < 0.01), and Child-Pugh classes B (HR, 2.39; P = 0.03) and C (HR, 5.49; P < 0.001) to be independently associated with mortality. The mortality of sarcopenic LC was significantly higher than that of non-sarcopenic LC (P = 0.01). Moreover, BCAA supplementation improved the survival of sarcopenic patients in subgroup analysis (P < 0.01).
CONCLUSIONS: Sarcopenia is significantly associated with mortality in patients with LC. BCAA supplementation might be associated with improved survival of such patients.

Copyright © 2015 Elsevier Inc. All rights reserved.
PMID 25441595  Nutrition. 2015 Jan;31(1):193-9. doi: 10.1016/j.nut.201・・・
著者: Masahiro Tajika, Masahiko Kato, Hiromi Mohri, Yoshiyuki Miwa, Tomohiro Kato, Hiroo Ohnishi, Hisataka Moriwaki
雑誌名: Nutrition. 2002 Mar;18(3):229-34.
Abstract/Text The effect of energy malnutrition on survival in patients with non-alcoholic viral liver cirrhosis has not been well defined. We characterized energy metabolism at study entrance and prospectively analyzed its effect on subsequent survival in cirrhotics. One hundred nine consecutive patients with viral liver cirrhosis and 22 healthy control subjects participated in the study. By indirect calorimetry after overnight bedrest and fasting, resting energy expenditure (REE) was measured and non-protein respiratory quotient (npRQ) was calculated. Survival of cirrhotics were followed for up to 8 y. Survival rate was estimated with the Kaplan-Meier method. REE at entrance was significantly higher than the predicted basal metabolic rate (BMR) in cirrhotics (P < 0.001). NpRQ was significantly lower in cirrhotics than in controls (P < 0.001). Survival rate was significantly lower in patients with low npRQ ( < 0.85) than in patients with scores above 0.85 (P < 0.01) and was significantly higher in normal metabolic patients (0.9 < REE/BMR < 1.1) than in hypometabolic (REE/BMR < 0.9) or hypermetabolic (1.1 < REE/BMR) patients (P < 0.05). The proportional hazards model showed that npRQ (relative risk = 0.0003, 95% confidence interval = 0.0000-0.0970), REE/BMR (0.0199, 0.0007-0.5652), prothrombin time, and ammonia were independent significant factors determining survival. Thus evaluation of energy metabolism can be used to predict survival in patients with viral liver cirrhosis.

PMID 11882395  Nutrition. 2002 Mar;18(3):229-34.
著者: David Bihari
雑誌名: JPEN J Parenter Enteral Nutr. 2002 Jan-Feb;26(1):67-9.
Abstract/Text
PMID 11833755  JPEN J Parenter Enteral Nutr. 2002 Jan-Feb;26(1):67-9.
著者: Yutaka Nakaya, Kiwamu Okita, Kazuyuki Suzuki, Hisataka Moriwaki, Akinobu Kato, Yoshiyuki Miwa, Koichi Shiraishi, Hiroaki Okuda, Morikazu Onji, Hidenori Kanazawa, Hirohito Tsubouchi, Shinzo Kato, Masahiko Kaito, Akiharu Watanabe, Daiki Habu, Susumu Ito, Tomohisa Ishikawa, Naohiro Kawamura, Yasuyuki Arakawa, Hepatic Nutritional Therapy (HNT) Study Group
雑誌名: Nutrition. 2007 Feb;23(2):113-20. doi: 10.1016/j.nut.2006.10.008.
Abstract/Text OBJECTIVE: A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis.
METHODS: In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study.
RESULTS: Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group.
CONCLUSION: Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

PMID 17234504  Nutrition. 2007 Feb;23(2):113-20. doi: 10.1016/j.nut.20・・・
著者: Hashem B El-Serag, Fasiha Kanwal, Peter Richardson, Jennifer Kramer
雑誌名: Hepatology. 2016 Jul;64(1):130-7. doi: 10.1002/hep.28535. Epub 2016 Apr 19.
Abstract/Text UNLABELLED: The long-term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow-up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Cox's proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post-SVR. We identified 33,005 HCV-infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow-up of 30,562 person-years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21-2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96-2.734) were significantly more likely to develop HCC.
CONCLUSIONS: Risk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post-SVR HCC. (Hepatology 2016;64:130-137).

© 2016 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PMID 26946190  Hepatology. 2016 Jul;64(1):130-7. doi: 10.1002/hep.2853・・・

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