Contradictory immune response in post liver transplantation hepatitis B and C

Abstract

Hepatitis B and C often progress to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). After OLT, hepatitis B recurrence is clinically controlled with a combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using a HBV envelope antigen vaccine. Patients who had not been HBV carriers such as acutely infected liver failure or who received liver from HBV self-limited donor are good candidate. For chronic HBV carrier patients, a successful response can only be achieved in selected patients such as those treated with experimentally reduced immunosuppression protocols or received an anti-HBV adaptive memory carrying donor liver. Hepatitis C virus (HCV) reinfects transplanted livers at a rate of >90%. HCV reinfected patients show different severities of hepatitis, from mild and slowly progressing to severe and rapidly progressing, possibly resulting from different adaptive immune responses. More than half the patients require interferon treatment, although the success rate is low and carries risks for leukocytopenia and rejection. Managing the immune response has an important role in controlling recurrent hepatitis C. This study aimed to review the adaptive immune response in post-OLT hepatitis B and C.

Figure 1

Immune status in chronic hepatitis C and postorthotopic liver transplantation (OLT) hepatitis C. (a) NK cells are the first immunological defense system from hepatitis C virus (HCV). The phenotype defined with the activation or inhibitory receptor gene polymorphism affects the chronic hepatitis C activity and the post-OLT hepatitis activity. The interferon producing function is decreased by HCV proteins. (b) Kupffer cells or dendritic cells (DCs) have important roles in bridging innate and adaptive immune responses. These cells show proinflammatory and anti-inflammatory functions when infected with HCV. These cytokines' balance is well controlled for viral persistence and chronic inflammatory state by viral antigens. After OLT, regulatory T cells might affect to reduce antiviral defence but not to reduce inflammatory cytokines resulting in severer chronic hepatitis. The type 1 regulatory T cells (Tr1) may induce severe hepatitis, while a lower frequency of Tr1 is correlated with hepatitis control with HCV positive status. NK: natural killer cell, OLT: orthotopic liver transplantation, HCV: hepatitis C virus, MHC: major histocompatibility complex, IFN: interferon, Treg: regulatory T cell, and Tr1: type 1 regulatory T cell.