Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy — pathogenesis and management

Abstract

In an endemic area for chronic hepatitis B infection, reactivation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. Careful prospective serological testing has shown that hepatitis B virus reactivation is a two-staged process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterised by enhanced viral replication, as reflected by increases in the serum levels of hepatitis B virus DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of naïve hepatocytes with hepatitis B virus. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure and even death. The occurrence and severity of hepatitis B virus reactivation after various cytotoxic or immunosuppressive therapy is unpredictable and treatment has been disappointing, largely due to the late administration of therapy. Recently, pre-emptive treatment of chronic hepatitis B patients undergoing cytotoxic or immunosuppressive therapy, with potent nucleoside analogues has shown some promising results. Further controlled studies are needed to define the incidence and risk factors of hepatitis B reactivation so that pre-emptive treatment with nucleoside analogues could be administered to those patients at high risk of disease.

Viral Hepatitis: Manifestations and Management Strategy

“…7 It is best defined by the occurrence of hepatitis during or after cytotoxic chemotherapy accompanied by an increase/detection of HBV replication from a low to a high virus level (≥ 10-fold increase) in patients with chronic or past HBV infection. 16 The mechanism by which this reactivation occurs is poorly characterized but likely involves a two-stage process. 16 There is an initial stage of activated or enhanced viral replication during the cytotoxic or immunosuppressive therapy.…”

Effectiveness of Prophylactic Anti-HBV Therapy in Allogeneic Hematopoietic Stem Cell Transplantation with HBsAg Positive Donors

“…In addition, there were emerging data on the safety and effectiveness of "early" rather than "deferred" pre-emptive lamivudine in decreasing HBV-related hepatitis after HSCT or cytotoxic therapy at the conception of this treatment strategy (26). Furthermore, as mortality can still occur when lamivudine is only started after the occurrence of cytotoxic chemotherapy induced HBV-related hepatitis, we decided to start lamivudine pre-emptively before HSCT (27).…”

Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

“…27 Hepatitis due to HBV reactivation following immunosuppression is characterized by the initial phase of enhanced viral replication during the immune suppression followed by immune mediated destruction of HBVinfected hepatocytes, resulting in hepatitis when immunosuppression is withdrawn. 28,29 This is depicted in Figure 2. In the initial phase of increased viral replication, there is a rise of HBVDNA; HBeAg may reappear in patients who were initially HBeAg negative; and reverse seroconversion may occur in HBsAg negative patients with the reappearance of HBsAg in the serum.…”