Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

Abstract

The proportion of hepatitis B virus (HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation (HBVr) increases with the presence of hepatitis B surface antigen (HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

Hepatitis B Reactivation in Immunosupressed Patients, Prophylaxis and Management

“…Finally, liver damage resolves due to recovery of the immune system strength (spontaneously or as a result of immunosuppressive therapy suspension) or due to administration of antiviral drugs. [2] 3 with HBsAg-negative and HBcAg-positive, hepatitis B virus reactivation is characterized by reappearance of HBsAg with the increase of ALT level in two measurements over a period of 5 days, and increase of hepatitis B virus DNA more than 10 5 copies/mL. 4,5,6 Hepatitis B reactivation has been described as a three-phase event (Figure 1).…”

“…Finally, liver damage resolves due to recovery of the immune system strength (spontaneously or as a result of immunosuppressive therapy suspension) or due to administration of antiviral drugs. [2] Figure 1. Hepatitis B reactivation phases.…”

“…The third phase is determined by resolution, although HBsAg (if reappeared), or elevated HBV DNA, may persist. IS: Immunosuppression; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBsAg: Hepatitis B surface Antigen [2] The causes of hepatitis B virus reactivation are varied, although this could be spontaneous, in most patients who develop viral reactivation, due to imbalance between host immunity and hepatitis B ALT ( UI/L) HBV DNA ( IU/mL) ( The causes of hepatitis B virus reactivation are varied, although this could be spontaneous, in most patients who develop viral reactivation, due to imbalance between host immunity and hepatitis B virus activity. This imbalance may be induced by immunosuppressive agents, cytotoxic chemotherapy, HIV infection, or sudden withdrawal of antiviral therapy.…”

“…That is why it becomes undetectable, until signs and symptoms of chronic liver disease/cirrhosis appear. 2 However, hepatitis B virus reactivation in this population may occur, either spontaneously or upon immunosuppression. Impairment of the host immune system due to treatment with chemotherapeutic or immunosuppressive agents raises the risk of HBV reactivation.…”

“…Roughly 30% of the world's population show serological evidence of current or past infection. 2 Approximately 350-400 millions people live with chronic infection. An estimated 600.000 people die each year due to the acute or chronic consequences of hepatitis B virus infection.…”