Liver biopsy for assessment of chronic liver diseases: a synopsis

Abstract

The world-wide increase in chronic liver disease (CLD) calls for refinement of diagnostic and prognostic measures for early and accurate disease detection and management. Regardless of the aetiology, liver biopsy allows direct visualisation of specimen under the microscope. It facilitates histological evaluation of disease-specific morphological alterations. Thereby, it aids in disease diagnosis, prognosis, and assessment of treatment compliance/response. Indeed, with the advent of non-invasive methods, liver biopsy is used less frequently than before, but it is still considered as a gold standard for staging and grading several CLDs. This short review revisits liver biopsy. It highlights the significance of liver biopsy in evaluating CLDs and explains the commonly used Ishak, METAVIR and Batts-Ludwig scoring systems for grading and staging CLDs. The utility of liver biopsy in examining alcohol-related liver disease and non-alcoholic fatty liver disease (NAFLD) is discussed along with the disease-specific alcoholic hepatitis histology score (AHHS) and non-alcoholic fatty liver disease activity score (NAS). Additionally, the review elaborates on the role of liver biopsy in evaluating viral hepatitis, haemochromatosis, and hepatocellular carcinoma. Contextual explanation on the diagnosis of metabolic dysfunction-associated liver disease (MAFLD) is provided. The significance and clinical indications of repeat biopsy are also explained. Lastly, caveats and limitations associated with liver biopsy are reviewed. Essentially, this review collates the application of liver biopsy in assessing various CLDs and provides succinct explanations of the core scoring systems, all under one roof. It is clinically relevant and provides a useful synopsis to budding scientists and hepato-pathologists.

Keywords: Alcoholic hepatitis histology score (AHHS); Batts-Ludwig; Ishak; Liver biopsy; MAFLD; METAVIR; NAFLD activity score (NAS); Repeat biopsy.

Fig. 1

Batts-Ludwig scoring system. The Batts-Ludwig scoring system is used for staging of fibrosis (a) and grading (b) of histological specimens obtained from the liver of patients with chronic hepatitis. Here, values of both stage (a) and grade (b) range from 0 to 4. (a) Staging is based on the presence of portal/periportal fibrosis and septa formation with/without cirrhosis, which correspond to stage 4, while (b) grading is based on either the portal/periportal activity or lobular activity. Here, whichever activity demonstrates greater severity is affirmed [11, 18] i.e. the overall grade is the one which is present at the greatest degree. The Batts-Ludwig system is also known as the modified Scheuer system. Tables adapted from Rockey et al. [11] and Batts Ludwig [18]

Fig. 2

METAVIR scoring system. The METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) scoring system is used for the assessment of histological samples obtained from a liver biopsy. It assesses fibrosis level (a) and histological activity score (b), reflecting disease stage and grade, respectively. Here, fibrosis level (a) ranges from F0 (no fibrosis) to F4 (cirrhosis) and is primarily based on the presence of fibrosis in the portal tract and the number of septa (fibrous bands of tissue). Level F2 or higher is considered as significant fibrosis, while F3 or higher is considered as advanced fibrosis [9]. The histological activity score (b) is generated by the METAVIR algorithm which constitutes no activity (A0), mild activity (A1), moderate activity (A2) and severe activity (A3). This activity score is generated by combining the degree of piecemeal necrosis (PMN) (interface hepatitis) and lobular necrosis (LN) in the liver specimen [19, 20]. PMN is the necrosis of the periportal zone (as often seen in autoimmune and viral hepatitis) characterised by inflammation that extents from portal tract to periportal zone and damaged periportal hepatocytes [21]. It essentially reflects inflammation and destruction of hepatocytes bordering the portal tracts. PMN 0,1,2 and 3 correspond to none, mild, moderate, and severe, respectively. On the other hand, LN involves necrosis of liver lobule and can range in severity from focal necrosis (group of necrotic hepatocytes with infiltrated inflammatory cells in an area) to bridging necrosis (confluent necrosis that links terminal venules to portal tracts) [22]. LN 0,1 and 2 correspond to none or mild, moderate, and severe, respectively. Tables adapted from Rockey et al. [11], Theise [20], and Bedossa and Poynard [19]

Fig. 3

Ishak scoring system. The Ishak system [23] is also known as the modified Knodell or modified histology activity index (HAI) score. It assesses the level of fibrosis (a) where scores range from 0 (no fibrosis) to 6 (cirrhosis). Here, levels F5 and F6 reflect incomplete and definite cirrhosis, respectively [9]. This system also helps ascertain the levels of necro-inflammatory activity through grading (b). It assesses the level of piecemeal necrosis (score 0–4), confluent necrosis (score 0–6), focal necrosis, apoptosis, and focal inflammation (score 0–4), and portal inflammation (score 0–4). Severity of each parameter is assessed, and the overall score for grading could be given between 0 and 18 [23]. Further details reviewed by Theise [20]. Tables adapted from Ishak et al. [23] and Theise [20]

Fig. 4

Proposed correspondence and comparison between Ishak, METAVIR and Batts-Ludwig scoring systems. The figure proposes a possible correspondence in pathological stages between the three systems. The Ishak staging system provides more descriptive and comprehensive information on fibrosis than the METAVIR and Batt-Ludwig systems. A single METAVIR fibrosis level or Batts-Ludwig stage constitutes multiple Ishak scores and there are several Ishak scores between the METAVIR fibrosis levels and Batts-Ludwig stages. In the METAVIR and Batt-Ludwig systems, cirrhosis is stage 4, unlike the Ishak system where cirrhosis is represented at stages 5 and 6. Although the Ishak score provides more information on fibrosis, due to its complexity, it is less reproducible and not easily applicable in clinical practice

Fig. 5

Alcoholic Hepatitis Histological Score (AHHS). The AHHS individually assessed and scored the level/severity of four histological features associated with ARLD, namely, fibrosis, bilirubinostasis, megamitochondria and polymorphonuclear infiltration. Scores were given for each histological feature, which made the total score range from 0 to 9, and the severity category was determined accordingly. Based on the total score achieved, patients were designated into three categories: mild (scores 0–3), intermediate (scores 4–5) and severe (scores 6–9). This categorisation allowed physicians to predict different risks of death within 90 days for the three different groups [29]

Fig. 6

NAFLD activity score (NAS) and staging of fibrosis in NAFLD. A standardised semiquantitative histological scoring system for NAFLD is used in clinical practice. NAFLD Activity score (NAS) (a) is the sum of steatosis, hepatocyte ballooning and lobular inflammation (other miscellaneous features are included). These are features of active injury. The total score (could be from 0 to 8) is deduced by adding the scores achieved in these three features. In addition to including both NAFL and NASH, NAS offers other advantages such as relative ease in usage and understanding and allowing hepato-pathologists to be able to provide a clear statement that the score is based on the three lesions/features. Also, this system is particularly useful in monitoring disease progression because the features of active injury described under NAS have been found to be reversible with treatment. NAS does not assess fibrosis. Therefore, usage of a separate fibrosis staging system (b) in conjunction with NAS has been proposed to obtain a wider picture of pathology [34]. Information adapted from Kleiner et al. [34]