Review articleLiver Biopsy Assessment in Chronic Hepatitis
Introduction
In the nearly 50 years since Menghini popularized the use of percutaneous needle biopsy (1), microscopic evaluation of the liver has remained an important modality in the diagnosis and management of patients with liver disease. For patients suffering from chronic hepatitis, defined as “inflammation of the liver continuing without improvement for 6 months or longer” (2), liver biopsy has been considered the “gold standard” of diagnosis, the most direct way of visualizing the necroinflammatory and architectural status of the liver. Surrogate serum biochemical markers (3) and techniques such as elastography of the liver to measure its stiffness (i.e., fibrosis) 4, 5, 6 are other methodologies currently in use and under investigation as non-invasive tests for inflammation and fibrosis. Nevertheless, experts in the field still rely on liver biopsy, not leastwise for confirmation of their clinical diagnosis, estimation of prognosis and in order to advise (or not) antiviral therapy (7).
Advances in hepatology during the past four decades have delineated the possible causes of chronic hepatitis, which now include hepatitis B and C viruses, autoimmune hepatitis, α-1-antitrypsin deficiency, Wilson disease, and drug hepatotoxicity. Clinical and histopathological criteria for diagnosing these disorders are well established and for the purpose of this review the following discussion will focus on liver biopsy assessment in the evaluation of chronic viral hepatitis B and C.
Section snippets
Chronic Hepatitis: Basic Histopathological Features of the Disease Process
Following acute viral hepatitis, failure of the host immune system to clear the virus during the initial weeks to several months results in ongoing production of infective virions and virus-directed proteins within the liver. Histopathological expression of such ongoing viral infection beyond the 6-month period may vary considerably from case to case but essentially consists of three possible components: 1) inflammation; 2) fibrosis (or cirrhosis); and 3) hepatocellular changes. Features
Periportal (Interface) and Lobular Hepatitis
Immune cells responding to chronic viral infection enter through the portal tracts. The majority of the inflammatory cells are T-lymphocytes, sometimes accompanied by plasma cells and one or two eosinophils. Such infiltrates may be sparse, affecting only some portal tracts, with others appearing relatively normal or may be denser and affect most portal tracts. Periportal hepatocytes may be targeted in the process termed interface hepatitis (formerly “piecemeal necrosis”) (Figure 1) in which the
Fibrosis and Cirrhosis
Over time, particularly with continued interface hepatitis (with potential contributions from the lobular necroinflammatory component) (17) progressive activation of hepatic stellate cells and portal myofibroblasts may result in portal and periportal fibrosis. This may be manifested by rounded, fibrous enlargement of the portal tracts or by formation of stellate periportal scars. Trichrome, reticulin, and picrosirius red staining methods are critical to the assessment of fibrosis. Digital image
Hepatocellular Changes
Hepatocellular changes in chronic hepatitis are principally ballooning degeneration and apoptosis (21). The importance of immune-mediated apoptosis was in fact highlighted over 25 years ago in a seminal publication describing the nature of piecemeal necrosis by Kerr et al. (22). Ballooning and apoptosis vary considerably within a given biopsy sample. Early apoptosis within intact liver-cell plates bordered by closely apposed lymphocytes may be manifested by increased cytoplasmic eosinophilia
Chronic Hepatitis B
The evolution of chronic hepatitis B can be broadly categorized chronologically in three phases: immune tolerance, immune clearance, and replicative quiescence. Each of these phases has specific serological and immunohistochemical connotations, and the necroinflammatory activity varies among the three. Immune tolerance is perhaps best represented by the “carrier” state in which the subject has active viral replication, is seropositive for HBV DNA, hepatitis B e antigen (HBeAg), and hepatitis B
Chronic Hepatitis C
Histopathological features attributable to chronic HCV infection have been well characterized (23). A signature finding is the portal lymphoid aggregate (Figure 5), a rounded collection of lymphocytes within the portal connective tissue frequently lying near or surrounding bile ducts. Lymphoid follicles with germinal centers may also be present, though less commonly. Both types of lymphoid structures may also be present in chronic hepatitis B or autoimmune chronic hepatitis, but much less
Historical Perspective on Classification Systems for Chronic Hepatitis
Landmarks in chronic hepatitis classifications are shown in Table 1 and have previously been reviewed by Brunt (38). The simplicity of such a listing should in no way belie the considerable work involved in arriving at each method, translating into countless hours spent over the microscope and in discussion by each group of investigators. The first publication to classify chronic hepatitis was that of De Groote et al. (39) from 1968, a citation classic, which described two types, chronic
Use of Current Scoring Systems
If liver biopsy is to be used to assess the grade and stage of inflammatory disease activity and fibrosis, respectively, the method of communicating the histopathological results should serve specific needs. For routine diagnosis, clear and concise conveyance of such information in biopsy reports should serve patient care first and foremost. To that end, the method chosen for use by the pathologist should be easily practiced (and not consume untenable amounts of time) and should be understood
Problems of Sampling Error, Observer Variation, and Biopsy Technique
A fairly extensive literature has arisen based upon the problems inherent in histological grading and staging systems and this topic was recently comprehensively reviewed (46). Sampling error constitutes a recognized drawback because the needle liver biopsy, regardless of the length or width of the core, is only a finite portion of a very large organ with potential variability in the expression of disease. An example of potential sampling error is shown in Figure 9, which demonstrates how
Conclusions
Liver biopsy assessment continues to offer substantial contributions to the diagnostic and therapeutic management of patients with chronic hepatitis. In addition to providing a grade of necroinflammation and stage of fibrosis, the biopsy may highlight other problems including iron storage, fatty liver disease and metabolic syndrome or previously undiagnosed conditions such as α-1-antitrypsin deficiency. The biopsy sample also can be used for diverse pathobiological studies such as determination
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2019, CellCitation Excerpt :Only regenerative or cirrhotic nodules and no dysplastic nodules were identified in the UT Southwestern samples based on WHO criteria (Table S1). We used histologic scoring systems developed to grade inflammation and stage fibrosis (Guido et al., 2011; Lefkowitch, 2007). The determinants of inflammatory activity were lymphocytic piecemeal necrosis, lobular necroinflammation, and portal inflammation, which were graded 0 to 4.
Distribution of Connective Tissue in the Male and Female Porcine Liver: Histological Mapping and Recommendations for Sampling
2018, Journal of Comparative PathologyCitation Excerpt :Six specific foci of liver fibrogenesis have been proposed for scoring, namely portal, pericellular (i.e. perisinusoidal), pericentral (i.e. perivenular), centrilobular, ductal (i.e. periductal) and ductular (Batts and Ludwig, 1995; Gohlke et al., 1996; Brunt et al., 1999; Sakhuja, 2014; Takahashi and Fukusato, 2014). During chronic hepatitis, fibrosis starts and spreads from portal regions, forming stellate periportal scars or enlarging the portal tracts (Lefkowitch, 2007). Steatofibrosis in alcoholic liver disease begins in the pericentral region and extends in a perisinusoidal pattern, where it is more pronounced than in hepatitis C infection (Zaitoun et al., 2001).
Hepatitis C
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2017, Chemico-Biological InteractionsCitation Excerpt :Fibrosis was graded using Metavir, Batts & Ludwig, Laennec and Ishak systems. Inflammation was graded using Scheuer, Ishak, Knodell, Batts & Ludwig and Metavir systems which assessed lobular activity, focal lytic necrosis, confluent necrosis, periseptal or periportal interface hepatitis, focal and apoptosis inflammation, portal inflammation and parenchymal injury [25]. Cholestasis was scored using the scoring system proffered by Ref. [11] and steatosis was graded using the Kleiner-Brunt scores [5].