Clinical Significance of Hepatitis B Virus Precore and Core ... : Journal of Clinical Gastroenterology (original) (raw)

LIVER, PANCREAS AND BILIARY TRACT: Original Articles

Clinical Significance of Hepatitis B Virus Precore and Core Promoter Variants in Korean Patients With Chronic Hepatitis B

Yim, Sun Young MD*; Um, Soon Ho MD, PhD*; Young Jung, Jin MD*; Kim, Tae Hyung MD*; Kim, Jin Dong MD, PhD†; Keum, Bora MD, PhD*; Seo, Yeon Seok MD, PhD*; Yim, Hyung Joon MD, PhD*; Jeen, Yoon Tae MD, PhD*; Lee, Hong Sik MD, PhD*; Chun, Hoon Jai MD, PhD*; Kim, Chang Duck MD, PhD*; Ryu, Ho Sang MD, PhD*

*Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University College of Medicine, Seoul

†Department of Internal Medicine, Division of Gastroenterology and Hepatology, Cheju Halla General Hospital, Cheju, Korea

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Supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. (A102065).

The authors declare that they have nothing to disclose.

Reprints: Soon Ho Um, MD, PhD, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea (e-mail: [email protected]).

Received June 25, 2013

Accepted November 11, 2013

Abstract

Background/Aim:

We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients.

Methods:

We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A).

Results:

CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (_P_=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (_P<_0.05) and with CP variants in the HBeAg-positive group (_P_=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (_P_=0.004).

Conclusions:

In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.