Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage

I. Chin Wu, Ching Lung Lai, Steven Huy Bui Han, Kwang Hyup Han, Stuart C. Gordon, You Chen Chao, Chee Kiat Tan, William Sievert, Tawesak Tanwandee, Dong Xu, Boon Leong Neo, Ting Tsung Chang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2×ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2×ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 × ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT>2×ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement,HBVDNAless than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2×ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negativeCHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 × ULN.

Original languageEnglish
Pages (from-to)1185-1189
Number of pages5
JournalHepatology
Volume51
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1

Fingerprint

Chronic Hepatitis
Alanine Transaminase
Hepatitis B e Antigens
Biopsy
Fibrosis
Chronic Hepatitis B
Hepatitis B virus
entecavir
Therapeutics
Phase III Clinical Trials
Lamivudine
DNA
Nucleosides
Liver Diseases
Guidelines

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Wu, I. Chin ; Lai, Ching Lung ; Bui Han, Steven Huy ; Han, Kwang Hyup ; Gordon, Stuart C. ; Chao, You Chen ; Tan, Chee Kiat ; Sievert, William ; Tanwandee, Tawesak ; Xu, Dong ; Neo, Boon Leong ; Chang, Ting Tsung. / Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage. In: Hepatology. 2010 ; Vol. 51, No. 4. pp. 1185-1189.
@article{2dd902ae16f9404fa9ceb16fe0d3da28,
title = "Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage",
abstract = "Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2×ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-na{\"i}ve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2×ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25{\%} of the total study population, had screening and baseline ALT 1.3 to 2 × ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60{\%} and 72{\%} of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8{\%} and 15{\%} of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT>2×ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement,HBVDNAless than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2×ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negativeCHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 × ULN.",
author = "Wu, {I. Chin} and Lai, {Ching Lung} and {Bui Han}, {Steven Huy} and Han, {Kwang Hyup} and Gordon, {Stuart C.} and Chao, {You Chen} and Tan, {Chee Kiat} and William Sievert and Tawesak Tanwandee and Dong Xu and Neo, {Boon Leong} and Chang, {Ting Tsung}",
year = "2010",
month = "4",
day = "1",
doi = "10.1002/hep.23424",
language = "English",
volume = "51",
pages = "1185--1189",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

Wu, IC, Lai, CL, Bui Han, SH, Han, KH, Gordon, SC, Chao, YC, Tan, CK, Sievert, W, Tanwandee, T, Xu, D, Neo, BL & Chang, TT 2010, 'Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage', Hepatology, vol. 51, no. 4, pp. 1185-1189. https://doi.org/10.1002/hep.23424

Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage. / Wu, I. Chin; Lai, Ching Lung; Bui Han, Steven Huy; Han, Kwang Hyup; Gordon, Stuart C.; Chao, You Chen; Tan, Chee Kiat; Sievert, William; Tanwandee, Tawesak; Xu, Dong; Neo, Boon Leong; Chang, Ting Tsung.

In: Hepatology, Vol. 51, No. 4, 01.04.2010, p. 1185-1189.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy of entecavir in chronic hepatitis b patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage

AU - Wu, I. Chin

AU - Lai, Ching Lung

AU - Bui Han, Steven Huy

AU - Han, Kwang Hyup

AU - Gordon, Stuart C.

AU - Chao, You Chen

AU - Tan, Chee Kiat

AU - Sievert, William

AU - Tanwandee, Tawesak

AU - Xu, Dong

AU - Neo, Boon Leong

AU - Chang, Ting Tsung

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2×ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2×ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 × ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT>2×ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement,HBVDNAless than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2×ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negativeCHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 × ULN.

AB - Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2×ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2×ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 × ULN. Clinically significant necroinflammation (Knodell necroinflammation score >7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAgnegative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT>2×ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement,HBVDNAless than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2×ULN. Conclusion: This retrospective analysis demonstrated that HBeAg-negativeCHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 × ULN.

UR - http://www.scopus.com/inward/record.url?scp=77950609092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950609092&partnerID=8YFLogxK

U2 - 10.1002/hep.23424

DO - 10.1002/hep.23424

M3 - Article

C2 - 20044806

AN - SCOPUS:77950609092

VL - 51

SP - 1185

EP - 1189

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -