肝穿是检验肝脏组织的金指标. 目前的血清检查纤维化不是非常准确. 然而很多时候医生需要肝穿的结构来决定是否治疗, 或用要选择, 比较效益等. 所以肝穿多年来一直还是没有任何东西可以取代的.
可是肝穿也有不理想的一面. 最重要的是肝穿非常昂贵, 比如在美国一个肝穿大约要$2200美金, 而且患者在接受上, 紧张焦虑上都有很大顾虑. 此外, 最近的研究显示, 肝穿在纤维化分级上仅仅有80%的准确度, 甚至可能会错过高达于30%严重的纤维或硬化病人, 影响肝穿不准确的因素有穿刺的局部性. 穿刺的部分大小和整个肝脏大小相比差距太大. 要克服这个因素, 肝穿需要索取长达35毫米的样品才能有效显示肝脏. 这是病理学上的有名的指标, 而目前临床上的肝脏医生和技术, 加上错做个人, 患者, 往往只有20%的肝穿能够取得这样的目的, 达到这样长度.
基于这些何不精确的血清检查, 人们一直在寻找其它求证肝脏组织学的途径.
最近, 有科学家和研究人员发现, 利用肝脏的僵硬程度来判断肝脏纤维化/硬化的分级. 这个仪器目前起名位"FibroScan", 是利用穿过一个2-5厘米大小的肝脏的部分, 50 mHZ(赫兹)波的剪切流速(shear velocity), 之后将结果转换成千帕 (kPA)压力值. 监测的结构和生化纤维化差不多, 但是对于硬化的检验比生化检验要准确的多(AUC 高达 0.95). 这样结合生化和FibroScan的结果可以评估出纤维化/硬化的级别. 这种机器已经投产, 任何时候都可以大量生产, 但是目前仍然在FDA手中检查审核.
所以未来可能是这样. 如果检查弄不清楚, 则需要肝穿. 其它用药/排除硬化则可以用生化+FibroScan(僵硬化扫描)来进行评估. 虽然它不能马上取代目前的肝穿, 但是是运用其它途径取得相同结果所做的开始.
Staging Liver Fibrosis: Time to Abandon Liver Biopsy?
Nezam H. Afdhal, MD[br]Chief of Hepatology[br]Beth Israel Deaconess Medical Center[br]Associate Professor of Medicine[br]Harvard Medical School[br]http://clinicaloptions.com/hep/ev/2005-6.asp
[br]The established gold standard for the evaluation of liver disease has traditionally been a percutaneous liver biopsy. Liver biopsy is used predominantly for the diagnosis, prognosis, and staging of liver disease. Despite improvements in serologic diagnostic tests for liver disease, a biopsy is often still indicated to make the diagnosis of many forms of liver disease. Biopsy is also useful for determining prognosis, usually by[br]confirming the presence or absence of cirrhosis. More recently, biopsy has been used for staging fibrosis in viral hepatitis and for decision analysis as to the need for treatment. Many treatment algorithms recommend treatment for patients with septal fibrosis or greater (¡Ý METAVIR stage 2). Improvement in either tolerability or efficacy of therapy could easily alter this current treatment paradigm, increasing physician and patient acceptability of therapy and reducing the need for liver biopsy.
Liver biopsy is rarely associated with severe complications in this era of ultrasound guidance or marking, and bleeding is rare (1:10,000 biopsies).[1] The major issues with biopsy are cost (approximately $2200) and patient acceptability and anxiety. In addition, recent studies have suggested that biopsy is only about 80% accurate in the staging of liver fibrosis and may even miss advanced fibrosis or cirrhosis in 30% of patients. The factors associated with the inaccuracy of biopsy include the heterogeneous nature of liver disease, the relatively small size of a biopsy compared to the size of the liver, and the experience of the pathologist. This has led to the[br]concept that a liver biopsy should be at least 25 mm in length to reduce the sampling error.[2] Although this is a noble aim pathologically, it remains a clinical rarity, with only 20% of liver biopsies even approaching this length.
These limitations of biopsy have led clinical investigators to study alternative methods to stage liver disease. Noninvasive serum biomarkers are the most widely used alternative to liver biopsy and have recently been reviewed.[3] There are 2 major types of biomarker tests, those that use clinical variables to stage fibrosis and those that use extracellular matrix (ECM) markers.[4,5] There are advocates of specific tests, but overall the performance characteristics of all these tests are relatively similar.
The accuracy of a test is often given as the area under the curve (AUC) of the receiver operator characteristic (ROC). A perfect test with a 100% sensitivity and specificity would have an AUC of 1.0. The majority of proposed biomarker tests¡ªand in particular, those available for use in clinical practice¡ªhave an AUC of between 0.80-0.85, not for staging disease, but for differentiating mild from (F0/F1) from significant fibrosis[br](F2-F4). Since the biomarker is validated against the biopsy, and the accuracy of the biopsy is only 80%, it is probably statistically impossible for a biomarker to perform any better for staging fibrosis. Interestingly, the performance of biomarkers is superior at the extremes of disease; the indeterminate results occur when patients have F1/2 disease. This is not surprising, since these stages are relatively artificial separations of a spectrum of a dynamic disease process.
An alternative method for staging liver disease is to measure liver stiffness or elasticity using a FibroScan.[6] The principle is relatively simple and involves measuring the shear velocity of a 50 mHZ wave propagated through a 2-5 cm segment of the liver, and converting this into a stiffness value in kilopascals (kPA). The diagnostic accuracy of the test is similar overall to that reported for biomarkers, but it is probably better in[br]diagnosing cirrhosis, with an AUC of 0.95. The test is simple and the results readily available, but the machine is still investigational in the United States and relatively expensive. Combining a FibroScan measurement with biomarkers may increase the accuracy of both tests.[7]
What can we recommend at the present time? Certainly, when the diagnosis is[br]in doubt, a liver biopsy remains the gold standard (just make sure it is an adequate biopsy!) However, when the issue is staging of fibrosis for either treatment decision or exclusion of cirrhosis, biomarkers and noninvasive tests represent a valid initial alternative. If the biomarkers are clearly indicative of mild or advanced disease, no further evaluation is necessary, and where they are equivocal, a biopsy can subsequently be performed. Eventually one could even anticipate following patients on an annual basis with biomarkers and stiffness scans to follow the progression or regression of disease. It is not yet time to abandon liver biopsy for disease staging,[br]but the lifeboats are out and the sharks are circling.
References
1. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495-500.
2. Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38:1449-1457.
3. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review. Am J Gastroenterol. 2004;99:1160-1174.
4. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T.[br]Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069-1075.
5. Patel K, Gordon SC, Jacobson I, Hezode C, Oh E, Smith KM, Pawlotsky JM,[br]McHutchison JG. Evaluation of a panel of non-invasive serum markers to[br]differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients. J Hepatol. 2004;41:935-942.
6. Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705-1713.
7. Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Ledinghen V. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-350.[br]
发表于 2005-8-8 19:24
