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发表于 2004-7-21 10:56
The Present Perspective
A more recent approach to the problem of specimen size has been to compare “large” versus “thin” liver biopsies in the diagnosis of diffuse diseases. The rationale behind these studies is that taking biopsies with larger needles can cause more complications. Fine-needle biopsies are easier to perform in outpatients under local anesthesia, and patients are more compliant. Using a finer needle is also an advantage in clinical conditions in which large-needle biopsy is contraindicated.
Rocken et al[73] compared thin and large biopsy samples and concluded that the amount of tissue available correlated strongly with the type of needle, although thin biopsies (20G) yield sufficient material to make a diagnosis of diffuse liver disease of various etiologies. The study, however, did not address the grading and staging of chronic hepatitis.
This was the aim of a more recently published study by the same group,[74] in which large (17G Menghini needle) and thin (20G modified cutting Menghini needle) biopsies from 88 patients with chronic type B or C hepatitis were retrospectively re-evaluated for grading and staging purposes. The study concluded that a thin biopsy is as good as a large one for the grading and staging of chronic viral hepatitis. It is important to note, however, that (1) the thin and large samples came from different patients; (2) there was no clearly defined gold standard for assessing diagnostic accuracy; and (3) because the study was retrospective, patients were not randomized to undergo large or thin biopsy, and patients with thin biopsies were more often found to have low platelet counts and high alanine aminotransferase levels, which introduce a selection bias. It is also worth noting that, in the small subgroup of patients whose clinical diagnosis of cirrhosis was taken as the gold standard, cirrhosis was histologically diagnosed by thin samples in 44% of cases and by large biopsies in 60%, which means that biopsy size becomes relevant when a gold standard is established.
More recently, a study was designed to evaluate the effect of core length and diameter on the grading and staging of chronic types B and C hepatitis.[75] The method was similar to the one used in previous studies[69][70] and consisted of progressively reducing the length and width of the original samples, which were all at least 30 mm long and 1.4 mm wide. The same pathologist reviewed all the slides throughout the various sessions and intraobserver agreement proved to be high. This study provided evidence that both the length and the diameter of the biopsy core affect grading and staging and (as in the previous studies[69][70]) that examining shorter and thinner samples leads to an underestimation of the severity of disease. Disease activity and fibrosis were underestimated in thin biopsies (i.e., 1 mm wide) regardless of the length of the biopsy, suggesting that the main problem lies in the lower number of complete portal tracts in the smaller samples. Portal areas are the elective sites of damage in chronic hepatitis, and they must be intact for disease grading and staging. The study demonstrated that 11 to 15 complete portal tracts was the critical number below which disease grade and stage were significantly underestimated and that a liver biopsy 2 cm long and 1.4 mm wide guaranteed this number of portal tracts in 94% of cases. The study also suggested that the number of complete portal tracts should be mentioned in the histological report to focus the clinicians' attention on the adequacy of their samples and on the limits of histological interpretation.
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CONCLUSIONS
Clinicians having to decide whether to perform a liver biopsy will gain little from reading this article, which is concerned exclusively with what happens after such a decision has been made.
For this article, we tried to answer two questions: (1) Can a random sample reflect damage to the organ as a whole? Sherlock had the answer[3]: “It is surprising that such a small biopsy should so often be representative of changes in the whole liver.” Available data confirm that, in diffuse processes such as acute and chronic hepatitis, a needle biopsy is representative of the liver disease, ensuring an accurate diagnostic classification.[56][69][70] In practice, needle liver biopsy is still indicated to diagnose chronic viral hepatitis when clinical or serological data, or both, produce inconsistent results or when confirmation is required for clinical purposes (e.g., in the liver transplantation setting) or research.
(2) Can the sample size affect the histological assessment of chronic hepatitis in terms of grade and stage? Our earlier analyses showed that most of the available data predated the recent grading and staging system of chronic viral hepatitis. Almost all studies agreed that the more tissue there is, the greater is the diagnostic accuracy-a fact that has to be balanced against the patient's safety (primum non nocere). The traditional assumption that a sample 1.5 mm long or containing four to six portal tracts, or both, is adequate is no longer true for the grading and staging of chronic hepatitis. In fact, none of the studies using this standard length produced consistent results[57][58][64][66][67][68][69][75] and when different-sized samples were compared, the smaller specimens resulted in a diagnosis of less severe disease.[69][70][75] Samples at least 2 cm long can ensure greater diagnostic accuracy.[63][67][69][70] Below this length, grade and stage are significantly underestimated.[75] As for the portal tracts, their number clearly correlates with sample size,[73][74][75] and there is evidence that four to five portal tracts are not enough, not for grading and staging at least; with fewer than 11 to 15 portal tracts, grade and stage are significantly underestimated.[75] The study by Colloredo et al[75] introduced the concept of a “minimum number of complete portal tracts.” The lower number of complete portal tracts may explain the lower diagnostic accuracy obtained with smaller samples.[68][71][73]
Although technological advances are making medical practice progressively less bloody and painful (e.g., with the wider diffusion of mini-invasive surgery and refinement of endoscopic techniques), many medical procedures in daily practice nevertheless remain invasive. Invasiveness is a feature of both therapeutic and diagnostic procedures, including morphological analyses, and liver biopsies are no exception. Their potential harmfulness is often stressed in the current lively debate on whether it is appropriate to take liver biopsies in chronic viral hepatitis. “First, do no harm.”[76] No one would disagree with this ethic, but this is not necessarily the same as saying “Do no biopsy.” Harm can also be done by failing to perform a biopsy[77] or by basing action on the strength of an inadequate sample.
In the current scenario of chronic viral hepatitis, the main goal of liver biopsy is to grade and stage the liver damage for prognosis and treatment. An adequate (although probably still imperfect) sample, pending the availability of reliable noninvasive methods, needs to be at least 2 cm long and to contain no fewer than 11 complete portal tracts.
Procedures for obtaining such an “adequate” biopsy sample are currently available and in routine use at most liver units.
While this article was in press, two additional articles have been published dealing with the same topic. In the first one, Bedossa et al, (Hepatology 2003; 38:1446-57) addressed the problem of sampling variability by using a virtual, computer assisted, analysis. In the second, Brunetti et al (J Hepatol 2004; 40:501-6) evaluated the diagnostic yield of a series of paired, fine and coarse liver blopsies obtained in 149 consecutive patients with chronic hepatitis C. Both these studies further support our conclusions on the characteristics of liver sample to be considered adequate for assessing grading and staging in chronic hepatitis.
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ABBREVIATIONS
CAH chronic active hepatitis
CT computed tomography
HBV hepatitis B virus
HCV hepatitis C virus
US ultrasound
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