1. Volume 120, Issue 4, Pages 1009-1022 (March 2001)
Acute flares in chronic hepatitis B: The natural and unnatural history of an immunologically mediated liver disease 
Robert P. Perrillo 
Gastroenterology 
Volume 120, Issue 4, Pages (March 2001)
DOI: /gast
Copyright © 2001 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Photomicrograph of patient with chronic hepatitis B who underwent liver biopsy during an acute flare (hematoxylin-eosin; original magnification 100×). Section reveals marked inflammatory changes in the liver lobule that are most intense around the central veins (arrows) reminiscent of acute viral hepatitis.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Schematic illustration of immunopathogenesis of hepatocyte injury during chronic hepatitis B and the factors that can contribute to acute flares. Cytotoxic T-cell recognition of the viral peptide presented by class I human leukocyte antigens (HLA-I) and binding of tumor necrosis factor (TNF) or Fas ligands (FasL) produced by inflammatory cells all contribute to hepatocyte injury. Up-regulation of T cell responses may represent a reaction to increased levels of wild-type or mutant HBV, a response to withdrawal of immunologically modifying drugs, or the independent effects brought about by infection with other hepatotropic viruses. The originating events that lead to spontaneous flares are not well understood. TNF-R, TNF-receptor; TCR, T cell receptor; ICAM-1, intracellular adhesion molecule-1; lymphocyte function associated antigen, LFA-1.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

4. Fig. 3
HBV reactivation secondary to cyclophosphamide (cytoxan) and prednisone therapy. The patient was a healthy HBsAg carrier who was administered immunosuppressive therapy for glomerulonephropathy. Prednisone had been tapered over the preceding 3 months from an initial dose of 40 to 20 mg daily. Note the sharp decline in serum HBV DNA early in the lamivudine therapy because of the brisk immunologic flare. The patient required liver transplantation despite disappearance of viral replication markers (asterisk 106 Eq/mL).
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

5. Fig. 4
A typical ALT flare that occurs during treatment with interferon (rIFN alfa-2b). Peak ALT was noted after 8 weeks of treatment. This patient had a sustained loss of HBV DNA and HBeAg seroconversion.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Time course of biochemical and virological events in a patient who initially did not respond to prednisone (Pred) followed by interferon (rIFN) alfa-2b. Note that a minor increment in ALT followed the withdrawal of prednisone during the first course. A second course of therapy, using a higher initial dose of prednisone and a shorter treatment cycle, resulted in a marked increase of ALT and loss of HBV DNA and HBeAg.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Pronounced flare in ALT that accompanied emergence of HBV DNA polymerase mutant during lamivudine treatment. This patient had previously received a 6-month course of lamivudine. Wild-type HBV predominated at the time of initiation of a second course of lamivudine (arrow). After a few weeks of treatment, restriction fragment length polymorphism detected a mixed viral species in which substitutions at nucleotides 528 and 552 of the HBV DNA polymerase gene were found in addition to wild-type virus. This occurred in conjunction with a major flare in ALT. HBV DNA levels subsequently increased and ALT declined, at which point only the lamivudine-resistant HBV mutant was detectable.
Gastroenterology  , DOI: ( /gast )
Copyright © 2001 American Gastroenterological Association Terms and Conditions