Acute exacerbation of chronic hepatitis B: the dilemma of differentiation from acute viral hepatitis B

Abstract

Exacerbations of chronic hepatitis B are common in endemic countries. Acute exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver functions may be seen in a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. While reactivation of HBV is usually seen in HBsAg positive patients, it is being increasingly recognized in patients with apparently resolved HBV infection who do not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the serum, especially so in patients on chemotherapy, immunosuppressive therapy or undergoing hematopoietic stem cell transplantation. In an icteric patient who is HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important not only for prognostication but also because management strategies are different. Most cases of AVH-B will resolve on their own, HBsAg clearance is achieved spontaneously in 90-95% of adults and treatment is rarely indicated except in the few with severe/fulminant disease. In contrast, in CHB-AE, the onset of jaundice may lead to decompensation of liver disease and treatment is warranted. The mechanisms of acute exacerbation and the differentiating features between AVH-B and CHB-AE are reviewed.

Keywords: AFP, alfa feto-protein; ALF, acute liver failure; ALT, alanine amino-transferase; AVH-B, acute viral hepatitis B; CHB-AE, chronic hepatitis B with acute exacerbation; HAART, highly active antiretroviral therapy; HBV, hepatitis B virus; HBVDNA; HBsAg; HIV, human immunodeficiency virus; IFNγ, interferon gamma; IL, interleukin; IgM anti-HBc; LSM, liver stiffness measurement; NK, natural killer; NKT, natural killer T; NUC, nucleoside; S/CO, sample to the cut-off value; S/N, signal-to-noise; TNF, tumor necrosis factor; Treg, T regulatory; acute hepatitis B; chronic hepatitis B.

Figure 1

Two forms of acute exacerbation in the natural history of chronic HBV*: (a) Flare of HBV in the immune reactive HBeAg positive patient (b) Reactivation of HBV in the HBeAg negative patient. HBsAg negative patients who have apparently “resolved” HBV infection may undergo reverse seroconversion especially following immunosuppression, cancer chemotherapy or transplantation leading to reactivation. * These phases in the natural history of HBV do not necessarily occur sequentially in all patients.

Figure 2

The phases of HBV reactivation during immunosuppression. The initial phase of increased viral replication during immunosuppression is followed by immune attack on HBV-infected hepatocytes during immune restoration leading to rise in transaminases and hepatitis. The laboratory findings can vary widely between patients with reactivation depending on when the patients are tested. The duration of course of events also vary widely. ALT: Alanine transaminase, HBV: hepatitis B virus.