In patients who have previously achieved immune control of HBV, immunosuppressive therapy may allow viral replication to escape, resulting in spread of infection within the liver and an increase in circulating HBV DNA. Following completion of immunosuppressive therapy, restoration of the host’s immune response may lead to an immune clearance-like response that results in widespread cytotoxic T cell-mediated lysis of infected hepatocytes and severe liver injury. This syndrome

of so-called ‘Hepatitis B reactivation following chemotherapy’ has been recognized for over thirty years5,6 and has been reported following treatment of a wide range of hematological malignancies and solid tumors. Reactivation largely occurs in patients with chronic hepatitis B (CHB) who are positive for hepatitis B surface antigen (HBsAg), but it can also affect

previously infected patients who have apparently cleared the Tamoxifen supplier virus. These patients can be identified serologically by the presence of hepatitis B core antibody (HBcAb) in the absence of HBsAg. Although reactivation of hepatitis B occurs most commonly in the setting of cancer chemotherapy, mTOR inhibitor it may also follow the use of immunomodulatory therapy for non-malignant conditions. These include solid organ transplantation, infliximab therapy for inflammatory bowel disease and treatment of rheumatological diseases with corticosteroids, methotrexate,7–9 infliximab alone10,11 or in combination with other therapies.12,13 Early studies of hepatitis B reactivation were hindered by a lack of uniformity in case definition and the relative insensitivity of previous methods used

to measure viral replication. The current generally accepted definition of HBV reactivation, or a flare following chemotherapy, is the development of hepatitis with a serum ALT greater than three times the upper limit of normal, or an absolute increase of 100 IU/L, associated with a demonstrable increase in HBV DNA by at least a 10-fold, or an absolute increase to > 108 IU/mL.14–16 The clinical presentation of HBV reactivation can range from asymptomatic anicteric elevation of hepatic enzymes to fulminant hepatitis. Icteric hepatitis is said to occur if the serum see more bilirubin is greater than twice the upper limit of the normal bilirubin concentration (< 15 µmol/L). Typically, there is an increase in HBV DNA during or shortly after a cycle of chemotherapy which precedes any elevation of ALT by up to 3 weeks. Subsequently HBV DNA titers decrease, so at the time of clinical hepatitis, HBV DNA may be undetectable.4 As a result, in the absence of serial monitoring of HBV DNA, the preceding increase in viral replication may be missed. In order to make the diagnosis, other causes of hepatitis need to be excluded. These include chemotherapy-induced hepatic injury, tumor infiltration of the liver and concurrent infection with other viruses such as hepatitis A, Epstein-Barr virus (EBV), and cytomegalovirus (CMV).