The difficulties of managing severe hepatitis B virus reactivation

Abstract

Reactivation of hepatitis B is characterized by a sudden increase in hepatitis B virus (HBV) replication in a patient with prior evidence of resolved or inactive HBV infection. Although HBV reactivation can occur spontaneously, it usually occurs after chemotherapy, immunosuppression (organ transplantation) or an alteration in immune function (therapy for autoimmune disease, human immunodeficiency virus infection). The clinical presentation cases can vary, ranging from a subclinical, asymptomatic course to severe acute hepatitis and even death. Although reactivation of HBV is mainly found in HBsAg-positive patients, it can be observed in serologically recovered anti-hepatitis B core antibody (HBc)-positive, HBsAg-negative patients. Serum HBV DNA typically increases during immune suppression, followed by a disease flare and HBV DNA clearance following immune restoration after immune suppression is stopped. In organ transplant recipients, without immune reconstitution, high HBV DNA levels can lead to fibrosing cholestatic hepatitis related to the direct cytopathic effect of HBV. Several randomized, controlled trials and meta-analyses have shown that reactivation can be prevented by lamivudine prophylaxis. Screening for HBsAg and anti-HBc should be performed before beginning immunosuppressive treatment and routine prophylaxis is recommended in HBsAgpositive patients. The optimal duration of prophylaxis remains to be determined. In anti-HBc-positive patients with or without anti-hepatitis B surface antigen, alanine transaminase and HBV DNA levels should be closely monitored and antiviral therapy should be started when HBV reactivation is confirmed. The use of new more potent nucleos(t)ides analogues with lower resistance rates would seem to be logical; however, experience with these drugs in the prophylaxis and treatment of severe HBV reactivation is limited.

Patients with hematological malignancies and serological signs of prior resolved hepatitis B

“…The Italian guidelines suggest that [18,22,73] all patients with HM scheduled to receive CHT should be screened for HBV infection. Those who are anti-HBc positive should also be analyzed for HBVDNA in order to rule out false OBI [11] .…”

Factors associated with hepatic dysfunction in hepatitis B-positive patients with postgastrectomy adenocarcinoma

“…The most commonly reported types of chemotherapy associated with HBV reactivation are those used for the treatment of hematological malignancies, including acute leukemia, myeloproliferative disorders, lymphoproliferative disorders and plasma cell dyscrasias (17)(18)(19). One of the most frequently studied examples is HBV reactivation in lymphoma treated with rituximab since it is able to specifically induce the apoptosis of B lymphocytes and leads to a marked immunosuppression in patients.…”

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.…”

“…Reactivation is mostly reported with the more potent monoclonal antibodies infliximab or adalimumab rather than etarnacept. 28 Reactivation after organ transplant had been extremely common prior to antiviral prophylaxis. [44][45][46][47] Reactivation after liver transplantation in a recipient without HBV infection can also occur from the donor with anti-HBc without HBsAg.…”