Comparative ultrastructural analysis of PBMCs isolated from patients with chronic hepatitis C and B: insights into the clinical outcome

ABSTRACT

Differences between chronic hepatitis C virus [HCV] and hepatitis B virus [HBV] infections have been established in incidence percentage and course of development of chronic liver disease as well as lymphoproliferative disorders. Lymphotropism has been regarded as one factor underlying persistence and chronicity of both diseases. However, this could not explain the variation in their clinical outcome which could be elucidated by a comparative study of the differential morphological behaviour of the peripheral blood mononuclear cells [PBMCs] harbouring the virus. An ultrastructural analysis by transmission electron microscopy [TEM] was hence performed on PBMCs isolated from patients with chronic HCV and HBV infections and from healthy subjects as controls. In this work, a morphological difference at the ultrastructural level was demonstrated in the PBMCs isolated from HCV and HBV- infected patients. Whereas minimal nuclear and cytoplasmic alterations and few intact forms of the virus were seen in hepatitis C patients, more aggressive degenerative and apoptotic features as well as more viral particles were viewed in cells of hepatitis B patients. These findings imply latency and quiescence of HCV in PBMCs leading to a state of chronic infection in most of the cases but with a very insidious course of progression towards cirrhosis or hepatocellular carcinoma [HCC]. In addition, stimulation and expansion of B cells could lead to various lymphoproliferative disorders. In the case of HBV infections, there is an earlier and more destructive effect of the virus on the infected cells which helps their rapid eradication with less propensity to persistence in the majority of cases. However in those patients where infection persists [possibly with lower immune response], chronicity could develop with rapid progression to cirrhosis due to the release of many viral particles from the uneliminated damaged PBMCs