Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline.
There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied. After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post-treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg-negative CHB): 71% vs 5% for HBeAg-positive (P < 0.001) and 60% vs 16% for HBeAg-negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg-positive and HBeAg-negative CHB, respectively). In conclusion, PEG-IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
P
P
Arends
V
V
Rijckborst
P E
PE
Zondervan
E
E
Buster
Y
Y
Cakaloglu
P
P
Ferenci
F
F
Tabak
U S
US
Akarca
K
K
Simon
M J
MJ
Sonneveld
B E
BE
Hansen
H L A
HL
Janssen
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis* / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons; D000410:Alanine Transaminase
chronic hepatitis B; hepatitis B core antigen; hepatitis B surface antigen; immunohistochemistry; intrahepatic staining; peginterferon