今日の臨床サポート

肝機能異常(胆汁うっ滞)

著者: 山本和秀 岡山済生会総合病院 名誉院長

監修: 金子周一 金沢大学大学院

著者校正/監修レビュー済:2021/06/30
患者向け説明資料

概要・推奨   

  1. 肝細胞障害を示す肝機能異常では、B型肝炎・C型肝炎感染を検索する(推奨度1)。
  1. 肝機能異常を示す症例では、腹部超音波検査を施行する(推奨度2)。
  1. 閉塞性黄疸を疑う症例では、MRCPを考慮する(推奨度2)。
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:
山本和秀 : 特に申告事項無し[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. 定期レビューを行い、図表とフローチャート、語句の変更を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 肝機能検査は検診や通常の診療でよく測定される検査である。
  1. 肝機能検査のなかで、肝逸脱酵素と胆道系酵素がよく用いられる。
  1. 肝逸脱酵素(AST、ALT)は肝細胞障害により上昇する。胆道系酵素(ALP、LAP、γ-GTP)は胆汁うっ滞により上昇する。
  1. 健常者のAST、ALTは30 IU/mL以下であり、一般に用いられている正常上限値より低い[1][2]
  1. メタボリック症候群や肥満症を伴う肝機能異常では高率に脂肪性肝疾患を合併する[3]
  1. 肝機能異常を認めた場合には、原因について精査・鑑別が重要である。
問診・診察のポイント  
問診:
  1. 以下の項目を確認する。

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文献 

著者: A Piton, T Poynard, F Imbert-Bismut, L Khalil, J Delattre, E Pelissier, N Sansonetti, P Opolon
雑誌名: Hepatology. 1998 May;27(5):1213-9. doi: 10.1002/hep.510270505.
Abstract/Text In clinical research, the definition of the upper limit of normal (ULN) alanine transaminase (ALT) is never detailed. However, such a definition can vary and may have practical consequences. Our aim was to assess factors associated with serum ALT activity in apparently healthy subjects and then to apply seven different definitions of ULN in three different populations so as to assess the prevalence of subjects with normal ALT among blood donors and among hepatitis C patients before (normal ALT hepatitis C patients) and after treatment (interferon [IFN] responders). ALT measurements were performed in the same laboratory using the same technique; 1,033 donors were prospectively investigated, 186 patients with hepatitis C never treated and 40 patients treated with 3 MU three times per week of IFN-alpha for at least 6 months. The seven definitions (D) of ULN were: D1: 95th percentile of ALT; D2: 95th percentile after separating males and females; D3: males and females separately, ULN=10 (mean of log10 ALT + 1.96 SD); D4: ULN=45 IU/L given by the manufacturer; D5: mean + 1 SD after exclusion of the 5% extreme values; D6: 95th percentile after separating subjects with body mass index (BMI) under or equal to the median (23); and D7: 95th percentile after separating subjects according to BMI and sex. BMI and male sex were independently associated (P < .0001; logistic regression) with ALT, without an association with alcohol. The range of ULN varied from 26 IU/L in females (D5) to 66 IU/L in males with BMI >23 (D7). Depending on the definition, the prevalence of blood donors with normal ALT varied from 82% to 96%, i.e., a range of 14%; that of hepatitis C patients with normal ALT varied from 16% to 27%, i.e., a range of 11%; the prevalence of IFN responders varied from 25% to 42%, i.e., a range of 17%. Definitions of normal ALT values should be adjusted for sex and BMI to reduce artificial heterogeneity in blood donor selection and in hepatitis C clinical studies.

PMID 9581673  Hepatology. 1998 May;27(5):1213-9. doi: 10.1002/hep.510・・・
著者: Jae Keun Lee, Ju Hyun Shim, Han Chu Lee, Sae Hwan Lee, Kang Mo Kim, Young-Suk Lim, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh
雑誌名: Hepatology. 2010 May;51(5):1577-83. doi: 10.1002/hep.23505.
Abstract/Text UNLABELLED: A recent study in young Italian subjects suggested that the healthy thresholds for serum alanine aminotransferase (ALT) levels should be adjusted to 30 IU/L for men and 19 IU/L for women when assessing risk factors for nonalcoholic fatty liver disease. Our aim was to assess serum ALT concentrations in healthy Korean individuals and to determine the factors affecting ALT levels in these populations. We included 1,105 potential liver donors (643 men and 462 women) with biopsy-proven normal livers. Median ages were 25 years in men and 30 years in women, with a median body mass index (BMI) of 22.3 kg/m(2) in men and 21.4 kg/m(2) in women. The calculated thresholds for ALT values in these subjects were 35 IU/L for men and 26 IU/L for women. Age and BMI were independently correlated with ALT levels in both sexes, whereas serum total cholesterol concentration was significant only in men and blood glucose level only in women (P < 0.05). When we chose a subgroup of 665 individuals (346 men and 319 women) using Prati criteria, modified by the BMI cutoff points for Asians (<23 kg/m(2)), we found that the healthy ALT values were 33 IU/L for men and 25 IU/L for women. The mean ALT concentrations for subjects within the Prati criteria were significantly lower than for those outside the criteria (16.7 versus 19.5 IU/L for men, 12.8 versus 14.9 IU/L for women; P < 0.001).
CONCLUSION: The healthy ALT thresholds in biopsy-proven normal Asians were clearly lower than the previously accepted thresholds, as has also been noted in Europeans. Age, BMI, and/or other metabolic parameters significantly affect ALT levels, even in subjects with normal livers.

PMID 20162730  Hepatology. 2010 May;51(5):1577-83. doi: 10.1002/hep.23・・・
著者: Yuichiro Eguchi, Hideyuki Hyogo, Masafumi Ono, Toshihiko Mizuta, Naofumi Ono, Kazuma Fujimoto, Kazuaki Chayama, Toshiji Saibara, JSG-NAFLD
雑誌名: J Gastroenterol. 2012 May;47(5):586-95. doi: 10.1007/s00535-012-0533-z. Epub 2012 Feb 11.
Abstract/Text BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. This study aimed to assess the recent prevalence of NAFLD and to predict the prevalence of nonalcoholic steatohepatitis (NASH) with liver fibrosis using established scoring systems in the general population.
METHODS: A cross-sectional study was conducted among 8352 subjects who received health checkups from 2009 to 2010 in three health centers in Japan. Subjects with an intake over 20 g of alcohol/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. The probability of NASH with advanced fibrosis was calculated according to the body mass index, age, ALT, and triglyceride (BAAT) and FIB-4 (based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet counts) indices.
RESULTS: A total of 5075 subjects were enrolled. The overall prevalence of NAFLD was 29.7%. There was a significant threefold difference in the mean prevalence between males (41.0%) and females (17.7%). This prevalence showed a linear increase with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even without obesity. The estimated prevalence of NASH according to the BAAT index ≥3 was 2.7%, and according to the FIB-4 index it was 1.9%.
CONCLUSIONS: The prevalence of NAFLD has increased in the general population, especially in males. There is a linear relationship between the prevalence of NAFLD and various metabolic parameters, even in nonobese subjects. The prevalence of NASH with advanced fibrosis is estimated to be considerably high in subjects with NAFLD.

PMID 22328022  J Gastroenterol. 2012 May;47(5):586-95. doi: 10.1007/s0・・・
著者: Junko Tanaka, Junko Kumagai, Keiko Katayama, Yutaka Komiya, Masaaki Mizui, Retsuji Yamanaka, Kou Suzuki, Yuzo Miyakawa, Hiroshi Yoshizawa
雑誌名: Intervirology. 2004;47(1):32-40. doi: 10.1159/000076640.
Abstract/Text OBJECTIVE: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were estimated on a national basis.
METHODS: Sera from the first-time blood donors aged 16-64 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995-2000 were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Viremia with HCV was estimated to be present in 70% of donors with anti-HCV.
RESULTS: HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of 1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010 (0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier rate by the population registered in the Census 2000, the total HBV carriers aged 15-65 years were estimated at 967,753 (95% confidence interval 806,760-1,128,745), of whom 571,210 (479,267-663,152) were men and 396,543 (327,494-465,593) were women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence interval 725,082-1,044,826), of whom 464,363 (377,927-550,799) were men and 420,591 (347,156-494,027) were women.
CONCLUSION: Estimated numbers of HBV and HCV carriers would help plan to prevent the development of hepatocellular carcinoma in Japan.

Copyright 2004 S. Karger AG, Basel
PMID 15044834  Intervirology. 2004;47(1):32-40. doi: 10.1159/000076640・・・
著者: Laurent Castera
雑誌名: Gastroenterology. 2012 May;142(6):1293-1302.e4. doi: 10.1053/j.gastro.2012.02.017.
Abstract/Text The prognosis and management of patients with chronic viral hepatitis B and C depend on the amount and progression of liver fibrosis and the risk for cirrhosis. Liver biopsy, traditionally considered to be the reference standard for staging of fibrosis, has been challenged over the past decade by the development of noninvasive methodologies. These methods rely on distinct but complementary approaches: a biologic approach, which quantifies serum levels of biomarkers of fibrosis, and a physical approach, which measures liver stiffness by ultrasound or magnetic resonance elastography. Noninvasive methods were initially studied and validated in patients with chronic hepatitis C but are now used increasingly for patients with hepatitis B, reducing the need for liver biopsy analysis. We review the advantages and limitations of the noninvasive methods used to manage patients with chronic viral hepatitis B or C infection.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 22537436  Gastroenterology. 2012 May;142(6):1293-1302.e4. doi: 10・・・
著者: R E Hintze, A Adler, W Veltzke, H Abou-Rebyeh, R Hammerstingl, T Vogl, R Felix
雑誌名: Endoscopy. 1997 Mar;29(3):182-7. doi: 10.1055/s-2007-1004160.
Abstract/Text BACKGROUND AND STUDY AIMS: The clinical importance of magnetic resonance cholangiopancreatography (MRCP) as a noninvasive diagnostic modality for investigation of the biliary tree and pancreatic duct system is under debate. Using endoscopic retrograde cholangiopancreatography (ERCP) as the gold standard, this study determined in a prospective, blinded fashion the sensitivity and further statistic values of MRCP findings for evaluation of the biliary and pancreatic tract.
PATIENTS AND METHODS: Seventy-eight patients referred for ERCP were studied prospectively with MRCP and ERCP during a 12-month period. All images were interpreted on a blinded basis by two radiologists. Any dilations, strictures, and intraductal abnormalities were recorded and correlated with the clinical diagnoses.
RESULTS: MRCP images of diagnostic quality were obtained in 76 of the 78 patients (97%). Magnetic resonance cholangiography (MRC) showed sensitivities (and positive predictive values) of 71% (62%) for recognition of normal bile ducts, 83% (91%) for recognition of dilation, 85% (100%) for recognition of strictures, 77% (91%) for correct stricture location, and 80% (100%) for diagnosing bile duct calculi. In addition, the sensitivity of MRC in classifying benign and malignant strictures was 50% and 80%, respectively. The statistical values (sensitivity and positive predictive value) for magnetic resonance pancreatography findings were determined for the recognition of normal pancreatic ducts (33% and 50%), recognition of dilation (62% and 100%), recognition of strictures (76% and 87%) and correct location (66% and 100%), diagnosis of benign strictures (87% and 87%) and malignant strictures (60% and 75%), and for diagnosing pancreatic duct stones (60% and 100%).
CONCLUSIONS: MRCP is capable of providing diagnostic information equivalent to ERCP in many patients, and should be applied whenever established techniques provide no results, or inadequate results.

PMID 9201467  Endoscopy. 1997 Mar;29(3):182-7. doi: 10.1055/s-2007-10・・・
著者: Changhua Liang, Huajie Mao, Qinghua Wang, Dongming Han, Li Li Yuxia, Junyan Yue, Hongkai Cui, Fengxia Sun, Ruimin Yang
雑誌名: Cell Biochem Biophys. 2011 Nov;61(2):383-8. doi: 10.1007/s12013-011-9195-3.
Abstract/Text Malignant obstructive jaundice is caused by tumors arising from the head of the pancreas and biliary tree, or seen due to secondary metastases in the porta hepatis lymph nodes. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive diagnostic technique that can be used for imaging the entire biliary tree and pancreatic duct system. The objective of this study was to evaluate the accuracy of MRCP in the diagnosis of malignant obstructive jaundice. The methods used involved comparative review of the images obtained by using magnetic resonance imaging and MRCP as well as comparison between MRCP- and pathology-based diagnoses. The accuracy of MRCP-based diagnosis of malignant obstructive jaundice was analyzed. Our data show that the positive rate of anatomical diagnosis and the detection rate of bile ducts on the proximal side of obstruction are 100%. The diagnostic accuracy of malignant obstruction was 82.9%. MRCP was found to have high diagnostic specificity for determining the location and extent of obstruction. We, therefore, concluded that MRCP had significance for clinical diagnosis of malignant obstructive jaundice. The positive rate of localization diagnosis was 100%. Distinguishing the quality of obstruction was also important. The diagnostic accuracy of MRCP for malignant obstructive jaundice was remarkably higher.

PMID 21567133  Cell Biochem Biophys. 2011 Nov;61(2):383-8. doi: 10.100・・・

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