**7. Further research**

**6. Pathological considerations**

14 Liver Biopsy - Indications, Procedures, Results

liver changes may be unevenly distributed.

at least 11 CPTs [48].

cellaneous factors) [78].

adopted rapidly as optimal standards.

Even though LB gives significant diagnostic and prognostic information and helps define treatment plans, it must be recognized that sampling variability and intra observer variabili‐ ty may restrain the diagnostic value of LB. The quality of LB is usually determined by

Sample size can affect the diagnostic accuracy of LB specimens [33]. s almost always means that size of the needle biopsy specimen should be of large enough size to accurately assess the degree of liver injury. Considering that a biopsy sample taken from an adult corre‐ sponds to a fraction of just 1/50,000th of the whole liver, a biopsy specimen would seem to be inadequate in the case of diffuse diseases, such as a chronic viral hepatitis, in which the

Several studies demonstrated that cirrhosis can be missed on a single blind percutaneous LB in 10%-30% of cases [69-71]. In a detailed study, Colloredo et al. [72] carefully evaluated the impact of sample size on correct stadiation of liver fibrosis in patients with chronic hepatitis C. By reducing progressively the dimensions of the same LB, they reported that the smaller the sample analyzed, the milder the diagnosis made by the pathologist with respect to the stage of fibrosis. The reduction in length (<2 cm) led to a significant decrease in number of complete portal tracts and underestimation of grading and staging. The study by Colloredo et al also introduced the concept of a ''minimum number of CPTs.'' Since the number of por‐ tal tracts is proportional to biopsy size [73], there was evidence that with fewer than 11 to 15 CPTs grade and stage are significantly underestimated [72]. The lower number of complete portal tracts may explain the lower diagnostic accuracy obtained with smaller samples [73,74]. Guido and Rugge have suggested that a biopsy sample ≥20 mm containing at least 11 CPTs should be considered reliable for adequate staging [75]. Other authors have recom‐ mended even bigger samples, up to 25 mm in length [76]. Scheuer suggested that ''bigger is better'' [77]. Very recently, the American Association for the Study of Liver Diseases (AASLD) has recommended a biopsy sample of at least 20–30 mm in length, and containing

In summary, an adequate (although probably still imperfect) sample needs to be at least 2 cm long (1.4 mm width, 16G) and to contain no fewer than 11 CPTs. These criteria have been

Of equal importance to adequate specimen size is the necessity that a pathologist experi‐ enced in liver disease interprets the biopsy, ideally in partnership with the clinician who performed the biopsy and/or whom is caring for the patient. Rousselet et al. reported that the degree of experience of the pathologist (specialization, duration, and location of practice) may have a significant impact on the diagnostic interpretation of LB, even high‐ er than that related to characteristics of the specimen (length, fibrosis class number, mis‐

Assessment of disease severity with liver histology is supported by a wide body of liter‐ ature [79]. Complex scoring systems, such as the Knodell scoring system [80] and its re‐

length, width, fragmentation and complete portal tracts (CPTs) [33].

Until a few years ago, LB was the only tool for the diagnosis of liver disease. However, the indications for performing a LB have undergone changes in the last decade. Given the inva‐ sive nature of LB, several simple and non-invasive methods (radiologic, immunologic, bio‐ chemical, genetic markers) have been studied and proposed as surrogates of liver histology. The main advantages of serum biomarkers vs. LB include being less invasive and the possi‐ bility to be easily repeated to monitor the status of liver disease. However, at this time, they are primarily useful for detecting advanced fibrosis or for excluding minimal or no fibrosis. They are not sufficiently accurate for assessing disease progression or the effect of therapy. Due to inadequate diagnostic accuracy or to lack of sufficient validation, current guidelines do not recommend serum biomarkers a substitute for LB that is still considered the refer‐ ence standard. Notably, non-invasive serum biomarkers, when combined, may reduce by 50%-80% the number of liver biopsies needed for correctly classifying hepatic fibrosis. Se‐ rum biomarkers for liver fibrosis are particularly useful for the initial assessment as well as for long-term monitoring of particular subsets of patients (ie, chronic hepatitis C). In this view, combination algorithms of the most validated non-invasive methods for liver fibrosis and LB represent a rational approach to the diagnosis of liver fibrosis in chronic liver diseas‐ es. Novel imaging techniques, such as measuring the elasticity of the liver using transient elastography (Fibroscan) [84], may assess fibrosis more directly. However, the use of such techniques in routine clinical practice has not been well defined and require further investi‐ gation. LB cannot be avoided completely, but should be used in those cases in which noninvasive methods show poor accuracy. Nevertheless, large scale, prospective, independent studies are needed in other aetiologies of CLDs. Many questions about LB remain and they require much more research. For instance, it is not clear which biopsy devices or techniques are best. In addition, few if any studies have assessed the biopsy's long-term effects. Because the liver is cut and bleeds during procedure, there will be some subsequent scarring.
