Non-alcoholic fatty liver disease: the pathologist's perspective

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

Keywords: Biopsy; Diagnosis; Histology; Non-alcoholic fatty liver disease; Prognosis.

Figure 1.

Steatosis. A combination of large and small droplet macrovesicular steatosis is seen in this example of non-alcoholic steatohepatitis. In large droplet macrovesicular steatosis, the fat droplet occupies more than half of the hepatocyte cytoplasm and pushes the nucleus to the edge of the cell (black arrows). Smaller droplets are also seen. A small patch of microvesicular steatosis is noted on the right (black star), characterized by innumerable tiny fat droplets in the hepatocyte cytoplasm. A few ballooned hepatocytes are also noted (white arrows) (H&E, original magnification ×200).

Figure 2.

The many faces of ballooned hepatocytes (A–C: H&E, original magnification x400). (A) A cluster of classical ballooned cells. (B) Occasionally the cytoplasmic keratins aggregate to form tighter and more eosinophilic clumps, also known as Mallory-Denk bodies (black arrowhead). (C) A lonely non-classical ballooned cell (black arrow) which is similar in size to the adjacent non-ballooned hepatocytes.

Figure 3.

Lobular necroinflammation. Foci of lobular spotty necrosis are seen in this example of non-alcoholic steatohepatitis (yellow circles). The inflammatory cell infiltrations are mainly composed of mononuclear cells (H&E, original magnification ×200).

Figure 4.

Stages of fibrosis and the utility of histochemical stains in accentuating the histological appearance. (A1, A2) The classical ‘chickenwire’ appearance of pericellular fibrosis is accentuated with a Sirius Red histochemical stain, which reveals the collagen fibers in red. (B1, B2) Stage 2 fibrosis is the co-presence of pericellular fibrosis and also portal fibrosis. Masson Trichrome stain shows the blue pericellular collagen fibers on the left and the portal fibrosis on the right. (C1, C2) The fibrosis extends across the hepatic lobules and forms bridging fibrosis. (D1, D2) The presence of hepatocytic nodules heralds cirrhosis, with Masson Trichrome stain confirming the broad fibrous bands. Original magnification ×200 (A1, A2), ×40 (B1–D2); H&E (A1, B1, C1, D1), Sirius Red (A2), Masson Trichrome (B2, C2, D2).

Figure 5.

An example of a case of non-alcoholic fatty liver disease -cirrhosis seen by second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) (SHG/TPEF microscopy, scanning power).