一31岁的妇女因腹痛住进地区医院

一例急性肝损伤病人血浆对乙酰氨基酚浓度持续升高。

为何？香港玛利亚医院一31岁的妇女因腹痛住进地区医院，食欲减退，心神不安，表情困惑，茶色尿。

检查显示为急性肝损伤，可见肝功能明显下降，氨基酸转移酶、胆红素、PT时间（INR值）明显升高。

没有任何肝病史、中草药摄入、药物过量摄入情况。

2天后，患者情况恶化，转入我院进行进一步治疗，欲进行肝移植。

物理检查显示：黄疸、脸色苍白、右上腹柔软无抵抗，下腹柔软无抵抗。

一天后患者进入昏迷状态。

刚入院时常规抽血化验结果显示：检测项目：结果参考区间BIL：1210 μmol/L(7–19 μmol/L)ALT：5080 U/L (12–28 U/L)ALP：150 U/L (34–104 U/L)血氨：171 μmol/L(0–33 μmol/L)LDH：6830 U/L ( 200–360 U/L)INR： 3.3对乙酰氨基酚：121μmol/L (<100 μmol/L)其他结果不太显著。

血清学检测：否定甲肝、乙肝的可能。

怀疑临床药物过量引起的血浆对乙酰氨基酚浓度升高，但是患者否定使用过相关药物，此后，后续的几天一直监测患者的肝脏酶谱、PT/INR、对乙酰氨基酚浓度，患者大体情况和肝功能逐步好转，但是血浆对乙酰氨基酚浓度适中保持在100 μmol/L以上，怀疑肝代谢此药物失败。

问题：1、引起急性肝损伤的原因有哪些？2、对乙酰氨基酚摄入人体之后代谢形式，使用该药物过量是怎样损伤肝脏的？3、有没有其他方法检测对乙酰氨基酚的浓度？4、影响对乙酰氨基酚测量的因素？摘自：American Association for Clinical Chemistry DOI: 10.1373/clinchem.2010.144527网址：/resourcecenters/casestudies/2011/Documents/January2011_CCS.p dfCommentaryRoger 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. Fax904-244-4290; e-mail roger.bertholf@.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 Rumack–Matthew 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 12–24h 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 physiologically—free,mono- and diconjugated, and albumin-bound—so 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.FootnotesAuthor Contributions:All authors confirmed they have contributed to the intellectual content of this paper and have met the following3 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. References1.Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R.Improvement by acetylcysteine of hemodynamics and oxygen transport infulminant hepatic failure. N Engl J Med 1991; 324: 1852–7.[Web ofScience][Medline][Order article via Infotrieve]2.Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R. Improvedoutcome of paracetamol-induced fulminant hepatic failure by lateadministration of acetylcysteine. Lancet 1990; 335:1572–3.[CrossRef][Web of Science][Medline][Order article viaInfotrieve]Related articles in Clinical Chemistry:Persistently Increased Acetaminophen Concentrations in a Patient with Acute Liver FailureBonnie 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-mailwilliam.lee@.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 27of 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 <10mg/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).FootnotesAuthor Contributions:All authors confirmed they have contributed to the intellectual content of this paper and have met the following3 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,OraSureTechnologies, 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. Referencesrson AM, Fontana RJ, Davern TJ, Polson J, Lalani EK, Hynan LS, et al.,theAcute Liver Failure Study Group. Acetaminophen-induced acute liverfailure: results of a United States multicenter, prospective study.Hepatology 2005; 42: 1364–72.[CrossRef][Web of Science][Medline][Order article via Infotrieve]2.Polson J, Wians FH, Jr, Orsulak P, Fuller D, Murray NG, Koff JM, et al.,theAcute Liver Failure Study Group. False positive acetaminophenconcentrations in patients with liver injury. Clin Chim Acta 2008; 391:24–30.[CrossRef][Web of Science][Medline][Order article via Infotrieve]3.Khandelwal N, James LP, Sanders C, Larson AM, Lee WM.Unrecognized acetaminophen toxicity as a cause of ‘indeterminate’acute liver failure. Hepatology. 2010 11 4. Accepted version online.Related articles in Clinical Chemistry:Persistently Increased Acetaminophen Concentrations in a Patient with Acute Liver FailureBonnie Mei-wah Fong, Tak Shing Siu, and Sidney T amClinical Chemistry 2011 57: 9-11. [Extract][Full Text]。