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.

Keywords: Acute liver failure; Anti-tumor necrosis factor-α drugs; Biologic therapy; Hepatitis B; Immunosuppressive therapy.

Figure 1

Hepatitis B reactivation phases. In the initial phase, there is an increase in HBV DNA levels, usually with an asymptomatic evolution. In the second phase, both ALT and HBV DNA are elevated; symptoms are frequently present, and they may be severe. The third phase is determined by resolution, although HBsAg (if reappeared), or elevated HBV DNA, may persist[3,17,55]. IS: Immunosuppression; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBsAg: Hepatitis B surface antigen.

Figure 2

Immunosuppressing agents and related risk of hepatitis B reactivation. HCC: Hepatocellular carcinoma; TNF-α: Tumor necrosis factor-α; HBVr: Hepatitis B virus reactivation.

Figure 3

Risk factors for hepatitis B reactivation in patients with current/past hepatitis B infection. ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; IS: Immunosuppression[2,4,27,56,57].