一31歲的婦女因腹痛住進(jìn)地區(qū)醫(yī)院.doc

一例急性肝損傷病人血漿對(duì)乙酰氨基酚濃度持續(xù)升高。為何？香港瑪利亞醫(yī)院一31歲的婦女因腹痛住進(jìn)地區(qū)醫(yī)院，食欲減退，心神不安，表情困惑，茶色尿。檢查顯示為急性肝損傷，可見(jiàn)肝功能明顯下降，氨基酸轉(zhuǎn)移酶、膽紅素、PT時(shí)間（INR值）明顯升高。沒(méi)有任何肝病史、中草藥攝入、藥物過(guò)量攝入情況。2天后，患者情況惡化，轉(zhuǎn)入我院進(jìn)行進(jìn)一步治療，欲進(jìn)行肝移植。物理檢查顯示：黃疸、臉色蒼白、右上腹柔軟無(wú)抵抗，下腹柔軟無(wú)抵抗。一天后患者進(jìn)入昏迷狀態(tài)。剛?cè)朐簳r(shí)常規(guī)抽血化驗(yàn)結(jié)果顯示：檢測(cè)項(xiàng)目： 結(jié)果 參考區(qū)間BIL： 1210 mol/L (719 mol/L)ALT： 5080 U/L (1228 U/L)ALP： 150 U/L (34104 U/L)血氨： 171 mol/L (033 mol/L)LDH： 6830 U/L ( 200360 U/L)INR： 3.3對(duì)乙酰氨基酚： 121mol/L (100 mol/L)其他結(jié)果不太顯著。血清學(xué)檢測(cè)：否定甲肝、乙肝 的可能。懷疑臨床藥物過(guò)量引起的血漿對(duì)乙酰氨基酚濃度升高，但是患者否定使用過(guò)相關(guān)藥物，此后，后續(xù)的幾天一直監(jiān)測(cè)患者的肝臟酶譜、PT/INR、對(duì)乙酰氨基酚濃度，患者大體情況和肝功能逐步好轉(zhuǎn)，但是血漿對(duì)乙酰氨基酚濃度適中保持在100 mol/L以上，懷疑肝代謝此藥物失敗。問(wèn)題：1、 引起急性肝損傷的原因有哪些？2、 對(duì)乙酰氨基酚攝入人體之后代謝形式，使用該藥物過(guò)量是怎樣損傷肝臟的？3、 有沒(méi)有其他方法檢測(cè)對(duì)乙酰氨基酚的濃度？4、 影響對(duì)乙酰氨基酚測(cè)量的因素？摘自：American Association for Clinical Chemistry DOI: 10.1373/clinchem.2010.144527網(wǎng)址：/resourcecenters/casestudies/2011/Documents/January2011_CCS.pdfCommentaryRoger L. Bertholf* Department of Pathology, University of Florida Health Science Center/Jax, Jacksonville, FL. * Address correspondence to the author at: University of Florida Health Science Center/Jax, Department of Pathology, 655 W. 8th St., Jacksonville, FL 32209. Fax 904-244-4290; e-mail . Fulminant hepatic failure is a life-threatening condition with a poor prognosis, and clinical assessment typically focuses on the 3 most common causes: viral hepatitis, alcoholic liver disease, and drug toxicity. Less frequent causes include biliary obstruction and several chemical and biological toxins. Drug-induced liver failure is most often due to acetaminophen (paracetamol) overdose. Measurement of plasma acetaminophen concentrations, in combination with the RumackMatthew nomogram, is helpful for predicting the extent of toxic injury to the liver (with ingestion of a single, large amount of the drug) and the probability that treatment with N-acetylcysteine will be effective. N-Acetylcysteine treatment was formerly thought to be ineffective beyond 1224 h after the peak plasma acetaminophen concentration, but more-recent evidence suggests that treatment is beneficial regardless of the time since ingestion or the plasma concentrations of the drug. The benefit is thought to occur via a mechanism that purportedly involves enhanced oxygen delivery to the tissues (1, 2). The aromaticity of the linear tetrapyrrole bilirubin structure confers broad absorptivity in the ultraviolet and visible spectra, but this product of heme metabolism also is a highly reactive chemical species, a property that may contribute to its toxicity in biological systems. Interference from bilirubin in analytical methods is not necessarily limited to its spectral properties; it also may arise from its chemical reactivity with reagents. Moreover, bilirubin exists in multiple forms physiologicallyfree, mono- and diconjugated, and albumin-boundso assessment of bilirubin interference by the addition of pure bilirubin may produce misleading results, compared with those for endogenously hyperbilirubinemic samples. Chemical and spectral interference from bilirubin is a troublesome analytical variable in many clinical laboratory methods, and this case report provides a cogent example. Fortunately, unnecessary treatment with N- acetylcysteine carries little medical risk, but falsely increased acetaminophen measurements may divert attention from the true cause of hepatic failure and delay more appropriate interventions. Footnotes Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest. Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript. Received for publication August 16, 2010. Accepted for publication September 1, 2010. References 1. Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324: 18527.Web of ScienceMedline Order article via Infotrieve 2. Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet 1990; 335: 15723.CrossRefWeb of ScienceMedline Order article via InfotrieveRelated articles in Clinical Chemistry: Persistently Increased Acetaminophen Concentrations in a Patient with Acute Liver Failure Bonnie Mei-wah Fong, Tak Shing Siu, and Sidney TamClinical Chemistry 2011 57: 9-11. Extract Full Text CommentariesCommentaryWilliam M. Lee* Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX. * Address correspondence to the author at: Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX. E-mail . Acetaminophen overdoses leading to severe liver injury or acute liver failure are extremely common and have been studied extensively (1). Measuring plasma acetaminophen concentrations would seem to be quite straightforward, but in fact it is not. Acetaminophen assays are used for determining the amount ingested and to detect the presence of any amount of the parent compound, because patients may fail to report its use, for a variety of reasons. These assays are subject to false-positive results, as the authors have shown. Suspicion of a false positive arises when the acetaminophen concentration does not change from the initial value to subsequent values or when the patient denies acetaminophen use and the value suggests a toxic ingestion. Interfering substances can be problematic in any assay. The authors point this out nicely in regard to acetaminophen by their use of a column to remove bilirubin. Because many substances were undoubtedly removed besides bilirubin, it is still not proved that bilirubin itself was the offending agent (although it is the most likely). After we observed 2 cases similar to the described case, we sought to test different assays to determine what the problem was (2). We obtained results similar to those reported: Colorimetric assays will give false-positive results, particularly with very high bilirubin concentrations. Six different assay platforms were used to test replicate samples from 36 patients with acute liver failure not due to acetaminophen. These 6 assays were the standard assays used in local hospital laboratories. Four of 6 assays demonstrated false-positive results for 5 to 27 of the 36 samples. One immunoassay had a few false-positive samples, whereas 1 colorimetric assay performed perfectly! The Vitros assay was the most affected in our hands. High serum bilirubin concentrations did appear to be the culprit, with no effect observed when the bilirubin concentration was 10 mg/dL. Of note, patients admitted with acetaminophen-caused liver injury are known for their very high aminotransferase concentrations and relatively low bilirubin concentrations (median, 4.2 mg/dL in one series), so the presence of a very high bilirubin value would be very atypical of an acetaminophen overdose in any case and should lead to consideration of other diagnoses (3). Footnotes Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: W.M. Lee, Eli Lilly, Novartis, GlaxoSmithKline, Pfizer, and Forest Laboratories. Stock Ownership: None declared. Honoraria: None declared. Research Funding: W.M. Lee, Bristol-Myers Squibb, Gilead Sciences, Merck/Schering-Plough, Roche, Aegerion Pharmaceuticals, Globeimmune, OraSure Technologies, and Siemens. Expert Testimony: None declared. Role of Sponsor: The funding organizations played a direct role in the final approval of the manuscript. Received for publication October 4, 2010. Accepted for publication October 11, 2010. References 1. Larson AM, Fontana RJ,