Histopathology and pathobiology of hepatotropic virus‐induced liver injury

Abstract

The present report concerns current knowledge regarding immunopathogenesis that can be applied in the interpretation of histopathological changes in acute and chronic viral hepatitis. The histopathological features of viral hepatitis have not been changed and light microscopic examination remains essential for making a diagnosis and classification of chronic hepatitis and for the provision of objective parameters on grading and staging. However, new understanding and knowledge of viral pathogenesis, host immune responses, the biological behaviour of the causative viral agents and, in particular, viral interference in multiple hepatotropic viral infections must be taken into consideration in the interpretation of histopathological and immunopathological findings of liver tissues. This report also presents some histopathological analyses on multiple hepatotropic viral infections. It can be concluded that the diagnostic histological criteria for acute hepatitis remain applicable in such settings. However, the cause of acute flare up in chronic hepatitis could not be determined without clinical, virological and serological information. Routine histopathology cannot distinguish a new infection from an acute exacerbation due to a high level of viral replication or mutant virus. A repertoire of immunocytochemical stainings for viral antigens is helpful, but caution must be exercised in suggesting a specific viral aetiology due to the fact that suppression of pre-existing viral antigens can be pronounced when the new or concurrent infection is hepatitis C virus related.

Activation of nuclear factor ?B in hepatitis C virus infection: Implications for pathogenesis and hepatocarcinogenesis

“…This can be relevant to the findings that NF-B stainings are more prominent in HCV-infected livers, and consistent with the histopathologic observation that a relatively lower number of hepatocytes show apoptosis in terms of acidophil body formation in chronic hepatitis C, as compared with hepatitis B. [38][39][40] The activation of NF-B by HCV core has been reported by several groups. 9,41,42 Our data were consistent with these reports and with those of Ray et al that HCV core-transfected cells are resistant to TNF-␣-mediated apoptosis.…”

What is expected from the pathologist in the diagnosis of viral hepatitis?

“…Patients infected with precore mutant virus express nuclear/cytoplasmic HBcAg and HBeAg, show high viral DNA serum levels and "active" chronic hepatitis, whereas in patients infected with a mixture of wild type and mutant viruses, low activity was observed with weaker expression of nuclear HBcAg, no cytoplasmic HBcAg or HBeAg, and low viremia [34,36]. The point mutation at position 1896 (G to A substitution) of the precore region creates a stop codon inhibiting the translation of HBeAg [9,32,34,36]. Since translation from the second start codon in the core region is still possible, HBcAg can arise and virus replication is maintained.…”

“…Portal inflammation with lymphocyte predominance is the most characteristic lesion in chronic hepatitis. The inflammatory infiltrate, predominantly consisting of T lymphocytes with admixed plasma cells, histiocytes and macrophages, may involve all or only some portal tracts [7,9]. In less active disease, inflammation is largely restricted to normal-sized or expanded portal tracts (i.e., portal hepatitis), but with increasing activity, the necroinflammatory process attacks the periportal (periseptal) hepatocytes of the limiting plate.…”

“…Portal-portal and portalcentral bridging necrosis differed in their clinical significance; 29% of patients with portal-central bridging developed cirrhosis in contrast to 10% of patients with portalportal bridging [38,39]. Exacerbation or relapse of necroinflammation in chronic hepatitis B may occur spontaneously, upon interferon therapy, withdrawal of immunosuppresive therapy or HAV, HDV, or HIV superinfection [7,9,26]. Exacerbation in chronic hepatitis B is characterized by lobular hepatitis, eventually with BHN combined with signs of chronicity [40].…”

“…Ballooning degeneration can progress to lytic necrosis. The pathogenesis of cell swelling is multifactorial: excess influx or retention of electrolytes and water due to failure of membrane transport pumps are major causes [9]. Leaky membranes account for the elevation of serum aminotransferases.…”