General Principles of Biopsy Assessment

Introduction

Liver biopsy is one of many diagnostic tools used in the evaluation and management of patients with liver disease. It continues to play an important role because the concepts and classifications of liver disease are rooted in morphology. Moreover, looking at a liver biopsy specimen through the microscope is a very direct way of visualising the morphological changes that affect the liver in disease. The pathologist’s interpretation (rather than mere enumeration) of these changes is used to answer important clinical questions such as disease causation and activity, and is important in therapeutic decision making. A thorough and informed interpretation of liver biopsy findings therefore stands to have substantial impact on patient care. It bears emphasising that the evidence base for much of liver biopsy interpretation rests on the large body of important observations reported in the pathology literature during the past 60 years since Menghini in 1958 first introduced the technique of percutaneous needle biopsy. Questions of a more basic pathobiological nature can also be addressed by applying contemporary techniques of molecular and genomic medicine to liver biopsy material.

There are many reasons for performing liver biopsy ( Box 1.1 ), as will be apparent from the contents of this book. In many instances in both adult and paediatric patients, the diagnosis is uncertain from clinical and radiological data, and liver biopsy provides the direct answer. Establishing a tissue diagnosis of neoplastic disease, evaluation of jaundice of uncertain cause and assessment of pyrexia of unknown aetiology are other important diagnostic problems. In the present era of emerging personalised and precision medicine, liver biopsy for tumour diagnosis (especially for hepatocellular carcinoma) optimises the possibility of genetic and molecular analysis for targeting therapy. Pathologists are well familiar with the need for formal grading and staging of chronic hepatitis (covered in Ch. 9 ), although the availability of direct-acting antiviral therapy for hepatitis C virus has greatly reduced the volume of such biopsies. The ubiquitous ‘elevated liver function tests’ inscribed on biopsy requisitions are now very often explained by steatosis, steatohepatitis or related conditions ( Ch. 7 ) stemming from the wide prevalence of obesity, diabetes, hyperlipidaemia and metabolic syndrome. Indeed, in evaluating abnormal liver function tests in patients with negative serological studies, liver biopsy is rarely normal. Even when normal or ‘near-normal’, later follow-up biopsy and/or clinical data may well provide a diagnosis of autoimmune hepatitis, primary biliary cholangitis, non-alcoholic fatty liver disease or another liver disease in a significant number of these individuals. The workup of liver dysfunction following liver, kidney or haematopoietic cell transplantation is also reliant on information from liver biopsies, which must be reported promptly and with due consideration that the pathological changes in these patients may reflect more than one aetiological factor.

In contemporary hepatology, there are various non-invasive methods for assessing hepatic fibrosis and necroinflammatory activity which potentially might obviate the need for liver biopsy, but these methods also have recognised pitfalls.