Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels.
OBJECTIVE
Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (≥2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens.


METHODS
HBeAg-negative CHB patients with PNALT (≤40 IU/l) and high serum HBV DNA (≥2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage ≥2 and/or HAI ≥6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy.


RESULTS
A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123680±494500 IU/ml; the HBV DNA load was 2000-20000 IU/ml in 68 patients (56.6%) and ≥20000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI ≥6). Forty-three patients (35.9%) had a fibrosis stage ≥2. Forty-eight patients (40%) had a fibrosis stage ≥2 and/or HAI ≥6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage ≥2 and/or HAI ≥6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20000 IU/ml were more likely to require treatment compared to those with a viral load ≥20000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years.


CONCLUSIONS
Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Aslı
A
Ormeci
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Yucel
Y
Aydın
Medipol University, Department of Nephrology, Istanbul, Turkey.
Abdullah
A
Sumnu
Department of Gastroenterology, Koç University Hospital, Istanbul, Turkey.
Bulent
B
Baran
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Ozlem Mutluay
OM
Soyer
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Binnur
B
Pınarbasi
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Suut
S
Gokturk
Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Mine
M
Gulluoglu
Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Derya
D
Onel
Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Selim
S
Badur
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Filiz
F
Akyuz
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Cetin
C
Karaca
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Kadir
K
Demir
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey.
Fatih
F
Besisik
Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, 34390, Istanbul, Turkey. Electronic address: kaymakoglus@hotmail.com.
Sabahattin
S
Kaymakoglu
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase
Chronic hepatitis B; HBeAg-negative; Persistently normal ALT