Histopathological evaluation of recurrent hepatitis C after liver transplantation: a review

Abstract

Although the morphological features of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) have been well established in the last decades, the differential diagnosis still represents a challenge for the pathologist, especially early recurrent hepatitis C vs mild acute cellular rejection. The present review focuses on the role of the pathologist and the pathology laboratory in the management of recipients with recurrent hepatitis C, the usefulness of early and late post-OLT liver biopsies, and the potential role of ancillary techniques (immunohistochemistry and reverse transcription-polymerase chain reaction, RT-PCR). The English literature on the topic is reviewed, focusing on the histopathology, the immunohistochemistry and the use of RT-PCR on HCV-positive post-OLT biopsies. The different histopathological illustrations of early and chronic recurrent hepatitis C are presented, with special focus on the main differential diagnoses and those features with prognostic relevance (cholestasis above all). The usefulness of ancillary techniques are discussed, especially HCV RNA quantitation by RT-PCR. Finally, the usefulness of long-term protocol biopsies is addressed: their usefulness for the study of allograft disease progression is clear, but their meaning in the long term is still debated. The significance of plasma cell infiltrate in HCV-positive allografts, the prognostic weight of graft steatosis, and the impact of donor age in recurrent hepatitis C also represent additional open issues.

Keywords: Hepatitis C virus; Histopathology; Immunohistochemistry; Orthotopic liver transplantation; Polymerase chain reaction; Recurrent hepatitis C.

Figure 1

Typical histopathological appearance of acute recurrent hepatitis C. A: Lobular architectural disarray, lobular necrosis with lymphocytic sinusoidal infiltrate and visible Councilman bodies (black arrow) are evident, as well as a mild portal tract inflammation (arrowhead); hematoxylin-eosin stain, × 20 magnification; B: Detail of the same case at × 40 magnification: note the high number of Councilman bodies in a single field (black arrows), and a minimal amount of macrovesicular steatosis.

Figure 2

Histopathological appearance of fibrosing cholestatic recurrent hepatitis C. Hematoxylin-eosin stain × 10 (A) and × 40 (B) magnification: note the lobular architectural disarray, the portal tract fibrosis and distortion, the lobular necrosis with Councilman bodies and the cholestasis with hepatocellular feathery degeneration and ballooning. The immunohistochemistry for keratin 19 (C) highlights the prominent ductular reaction, while the reticulin stain (D) indicates advanced fibrosis.

Figure 3

Histopathological features with a prognostic significance in recurrent hepatitis C. Steatosis (A) and cholestasis (B) are well shown. Cholestasis can be associated with bile duct proliferation (C) and/or hepatocellular ballooning (D). Hematoxylin-eosin stain, × 10 (A) and × 40 (B-D) magnification.

Figure 4

Histopathological appearance of recurrent hepatitis C (left) and acute cellular rejection (right). Portal inflammation is commonly mild in recurrent hepatitis C (A), with a predominant lympho-monocytic infiltrate and mild bile duct invasion (B), while in acute cellular rejection there is a mixed and more pronounced inflammatory infiltrate (E), with evident bile duct invasion (F). Endothelialitis can be found in both conditions (C, G). Lobular necrosis is more typical of recurrent hepatitis C (D); in acute cellular rejection hemorrhage and sinusoid dilatation are more evident (H).