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Causes of acute exacerbations of chronic hepatitis B
11st Internal Clinic of 3rd Medical Faculty of Charles University, Prague, Czech Republic.
Insights
Acute exacerbations in chronic hepatitis B patients were analyzed. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation, particularly after glucocorticoid treatment withdrawal, emerged as significant factors contributing to disease worsening.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B (CHB) exacerbations are a significant clinical concern.
- Glucocorticoid therapy is sometimes used in CHB management.
- The role of other viral infections in CHB exacerbations requires further elucidation.
Purpose of the Study:
- To investigate the causes of acute exacerbations in chronic hepatitis B patients.
- To assess the impact of viral reactivation, specifically Epstein-Barr virus (EBV) and cytomegalovirus (CMV), on CHB flares.
- To evaluate the influence of prior glucocorticoid treatment on these exacerbations.
Main Methods:
- Analysis of 24 chronic hepatitis B carriers experiencing 38 exacerbations.
- Testing for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis delta virus (HDV), EBV, and CMV antigens and antibodies.
- Correlation of exacerbations with HBeAg status and glucocorticoid treatment history.
Main Results:
- Epstein-Barr virus (EBV) reactivation or superinfection was observed in 29% of exacerbations.
- Cytomegalovirus (CMV) reactivation or superinfection occurred in 8% of exacerbations.
- Eight patients showed EBV reactivation after glucocorticoid withdrawal, with delays ranging from 3 to 48 months.
Conclusions:
- Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation are significant contributors to acute exacerbations of chronic hepatitis B.
- Previous glucocorticoid treatment may predispose patients to EBV and CMV reactivation, leading to hepatitis flares.
- These findings highlight the importance of considering EBV and CMV in the differential diagnosis of CHB exacerbations, especially in patients with a history of glucocorticoid use.
Abstract:
The authors analyzed acute exacerbations of chronic hepatitis B in 24 chronic HBsAg carriers (20 with positive HBeAg, 4 with anti-HBe), more than half of whom were treated with glucocorticoids, by examining specific antigens and antibodies of the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis delta virus (HDV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Of 38 observed exacerbations of the disease they found in 7 (18%) deterioration after discontinuation of glucocorticoids, in 7 (18%) seroconversion of HBeAg to anti-HBe, in 9 (24%) spontaneous exacerbation of chronic hepatitis B, in 11 (29%) chronic activation, reactivation of EBV superinfection, in 3 (8%) CMV reactivation or superinfection and in one (3%) HDV superinfection. In no instance HAV superinfection was observed. Exacerbations were found five times more frequently in subjects in the stage of active viral replication (in HBeAg+ subjects) than in subjects with anti-HBe. In eight patients EBV reactivation was found after glucocorticoids withdrawal: in five patients after an average period of 5 months (range 3-7) and in three patients after an average period of 33 months (range 22-48). The results provide evidence that in addition to already known causes of acute exacerbations of chronic hepatitis B in our geographical area probably an important cause of deterioration of hepatitis is reactivation or superinfection with EBV and CMV in some patients in conjunction with previous glucocorticoid treatment.