Occult HBV Infection Reactivation in Non-Hodgkin’s Lymphoma: An Update on Prevalence and Management

Occult hepatitis B virus infection (OBI) is characterised by the persistence of hepatitis B virus (HBV) genome in the liver, without any evidence of overt infection: without HBV surface antigen (HBsAg) and HBV DNA detectable in the serum, or fugacious spots of very low levels of viraemia. OBI, a possible phase in the natural history of chronic hepatitis B, is mainly due to the strong suppression of viral replication by host’s immunity. Although every condition inducing a strong immunosuppression may cause an OBI reactivation, onco-haematological patients, particularly those affected by non-Hodgkin’s lymphoma (NHL), are at the highest risk of this occurrence. This is mostly due to the primary involvement of the immune system that characterises these diseases, and the strong immunosuppressive treatments used for their cure. OBI reactivation represents a life-threatening risk, because of the possible development of an overt acute hepatitis that may lead to hepatic failure. Prophylaxis with lamivudine can prevent OBI reactivation and, when it occurs, the prompt administration of an antiviral therapy with nucleos(t)ide analogues can stop it. Currently, no valid serological tests for occult HBV detection are available, in this way every  HBsAg-negative patient undergoing treatment for NHL is to be considered at risk of a ‘probable OBI reactivation’. The estimation of the real extent of this occurrence in a NHL setting is a difficult challenge,  mostly due to the difficulty of obtaining a definitive diagnosis (which involves the availability of a liver  biopsy performed before its development) and the high variability of the literature reports on this issue. In  fact, the data concerning this prevalence range from 2.3-27.7% among the different papers, according to  different study designs, different diagnostic criteria, different study populations, and different geographical  areas of origin of the patients. The aim of this review is to browse the available knowledge about occult HBV infection amongst NHL patients, focusing on the prevalence of OBI reactivations, their identification,  and their management.