Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications.
BACKGROUND
The modified histology activity index (HAI) score has been extensively used as an additional primary or secondary end point in most phase III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in modified HAI after antiviral therapy has usually been defined as a 2-point reduction in modified HAI score.


OBJECTIVE
We studied whether a 2-point change in modified HAI score after antiviral therapy for chronic hepatitis B is associated with progression to liver complications (decompensated cirrhosis or hepatocellular carcinoma).


METHODS
Eighty-nine patients treated with interferon-alpha with liver biopsy before and at 6 to 12 months after the end of therapy were followed-up for a median 119.4 months.


RESULTS
At the time of analysis, 11 patients (12.4%) had liver complications. Liver complications were higher in patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%) vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On Cox regression analysis, a 2-point increase in modified HAI score was associated with increased liver complications (relative risk 5.564, P=0.036).


CONCLUSIONS
A 2-point increase in modified HAI score after antiviral therapy is associated with increased progression to liver complications.
Hui
Chee-Kin
CK
Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China. ckhui23@gmail.com
Leung
Nancy
N
Shek
Wai-Hung
WH
Zhang
Hai-Ying
HY
Luk
John M
JM
Poon
Ronnie T P
RT
Lo
Chung-Mau
CM
Fan
Sheung-Tat
ST
Lau
George K K
GK
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D013997:Time Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens