Liver Biopsy Sampling in Chronic Viral Hepatitis
Liver Biopsy Sampling in Chronic Viral Hepatitis
In chronic viral hepatitis, liver biopsy is performed to grade and stage liver damage. Liver biopsy samples are usually taken with a needle using a percutaneous procedure. This method produces a core of tissue representing approximately 1/50,000th of the liver mass, which raises concern about how representative a needle biopsy can be. A critical review of the literature reveals methodological limits unacceptable in this era of evidence-based medicine. Integrating earlier experience with more recently produced data indicates that a biopsy sample 2 cm or more in length containing at least 11 complete portal tracts should be reliable for grading and staging chronic viral hepatitis.
In the past 20 years, pathologists have radically changed the way they generate their reports. In the fields of neoplastic and inflammatory diseases, increasingly sophisticated information, such as the results of molecular studies, is needed for diagnosis and treatment. The introduction of new methods for analyzing tissues has prompted an ever-closer interaction between clinician and pathologist to ensure the most appropriate sampling in a given clinical context. This is also true of liver diseases, particularly in chronic viral hepatitis, which means taking a new look at the old liver biopsy procedure.
Liver biopsy was introduced by Paul Ehrlich more than 100 years ago and has since been widely used, enabling substantial progress in our understanding of liver histology, pathophysiology, and pathology. The diffusion of the use of liver biopsy was mainly because of the Menghini "one-second liver biopsy" technique, which provided samples suitable for various morphological studies, including the histochemical, immunohistochemical, ultrastructural and, more recently, molecular biology studies. Low mortality and relatively low morbidity rates have facilitated the widespread use of liver biopsy procedures.
Because of advances in imaging techniques and the development of reliable serological and virological tests, the indications for liver biopsy have changed dramatically, and the technical biopsy procedures have also been refined. Different methods for obtaining liver biopsy samples are available, and the choice of technique is dictated by the clinical setting (e.g., associated coagulation disorders, presence or absence of ascites, results of prior ultrasound examination), the operator's preference and experience, and the nature of the disease prompting the histological investigation.
The purpose of this article is not to review the topic of "liver biopsy," which includes many relevant (and still debated) issues, such as clinical indications and contraindications, complications, costs, and benefits. Our aim is to focus on the problem of "sampling errors" and when a sample can be considered to be "adequate" if a liver biopsy is needed to evaluate the severity of chronic hepatitis, especially in cases due to the most frequent hepatotropic viruses, in other words, hepatitis B virus (HBV) and hepatitis C virus (HCV).
As we have learned from epidemiological studies, sampling errors occur when the samples considered fail to represent the target population (e.g., tissue in our setting) from which it is derived. Considering that a biopsy sample taken from an adult corresponds to a fraction of just 1/50,000th to 1/100,000th of the whole liver, a biopsy specimen would seem to be inadequate in the case of nonfocal diseases, such as a chronic viral hepatitis, in which the liver changes may be unevenly distributed.
There are several facets to the problem, but, from a practical point of view, it can be brought down to two partially overlapping questions: (1) could a random sample reflect damage to the organ as a whole and (2) would the sample size affect the histological assessment of chronic hepatitis in terms of grade and stage?
In chronic viral hepatitis, liver biopsy is performed to grade and stage liver damage. Liver biopsy samples are usually taken with a needle using a percutaneous procedure. This method produces a core of tissue representing approximately 1/50,000th of the liver mass, which raises concern about how representative a needle biopsy can be. A critical review of the literature reveals methodological limits unacceptable in this era of evidence-based medicine. Integrating earlier experience with more recently produced data indicates that a biopsy sample 2 cm or more in length containing at least 11 complete portal tracts should be reliable for grading and staging chronic viral hepatitis.
In the past 20 years, pathologists have radically changed the way they generate their reports. In the fields of neoplastic and inflammatory diseases, increasingly sophisticated information, such as the results of molecular studies, is needed for diagnosis and treatment. The introduction of new methods for analyzing tissues has prompted an ever-closer interaction between clinician and pathologist to ensure the most appropriate sampling in a given clinical context. This is also true of liver diseases, particularly in chronic viral hepatitis, which means taking a new look at the old liver biopsy procedure.
Liver biopsy was introduced by Paul Ehrlich more than 100 years ago and has since been widely used, enabling substantial progress in our understanding of liver histology, pathophysiology, and pathology. The diffusion of the use of liver biopsy was mainly because of the Menghini "one-second liver biopsy" technique, which provided samples suitable for various morphological studies, including the histochemical, immunohistochemical, ultrastructural and, more recently, molecular biology studies. Low mortality and relatively low morbidity rates have facilitated the widespread use of liver biopsy procedures.
Because of advances in imaging techniques and the development of reliable serological and virological tests, the indications for liver biopsy have changed dramatically, and the technical biopsy procedures have also been refined. Different methods for obtaining liver biopsy samples are available, and the choice of technique is dictated by the clinical setting (e.g., associated coagulation disorders, presence or absence of ascites, results of prior ultrasound examination), the operator's preference and experience, and the nature of the disease prompting the histological investigation.
The purpose of this article is not to review the topic of "liver biopsy," which includes many relevant (and still debated) issues, such as clinical indications and contraindications, complications, costs, and benefits. Our aim is to focus on the problem of "sampling errors" and when a sample can be considered to be "adequate" if a liver biopsy is needed to evaluate the severity of chronic hepatitis, especially in cases due to the most frequent hepatotropic viruses, in other words, hepatitis B virus (HBV) and hepatitis C virus (HCV).
As we have learned from epidemiological studies, sampling errors occur when the samples considered fail to represent the target population (e.g., tissue in our setting) from which it is derived. Considering that a biopsy sample taken from an adult corresponds to a fraction of just 1/50,000th to 1/100,000th of the whole liver, a biopsy specimen would seem to be inadequate in the case of nonfocal diseases, such as a chronic viral hepatitis, in which the liver changes may be unevenly distributed.
There are several facets to the problem, but, from a practical point of view, it can be brought down to two partially overlapping questions: (1) could a random sample reflect damage to the organ as a whole and (2) would the sample size affect the histological assessment of chronic hepatitis in terms of grade and stage?
Source...