Prodromal fever indicates a high risk of liver failure in acute hepatitis B

The role of prodromal fever in the clinical course of acute hepatitis B virus (HBV) infection is still largely unclear. This study was conducted to investigate the factors associated with prodromal fever and its role in the development of acute liver failure (ALF) in patients with acute hepatitis B (AHB).

Inpatients with AHB diagnosed between January 2006 and December 2010 were evaluated and followed. Clinical manifestations, results of laboratory tests, and outcomes were compared between patients with and without prodromal fever. The diagnosis of AHB was based on the discrete onset of symptoms, jaundice, abnormal liver function tests, the detection of high-titer IgM antibody to hepatitis B core antigen (anti-HBc), and a compatible clinical history.

A total of 618 AHB inpatients were identified during the study period, of whom 102 (16.5%) had prodromal fever and 41 (6.6%) developed ALF. Prodromal fever indicated more severe liver injury and was independently associated with hepatitis B e antigen (HBeAg) negativity. The occurrence of ALF was more common in febrile patients than in non-febrile patients (18.6% vs. 4.3%, p<0.001). Multivariate logistic regression showed prodromal fever and temperature >38.0°C to be independently associated with the risk of ALF, with an odds ratio (95% confidence interval) of 3.5 (1.4-8.6) and 7.1 (2.6-19.7), respectively.

AHB patients with prodromal fever, which is associated with a lack of HBeAg due to HBV mutation, are at high risk of ALF. Febrile patients with AHB should be managed with particular care.