Histologic evidence of active liver injury in chronic hepatitis b patients with normal range or minimally elevated alanine aminotransferase levels

Ke Qin Hu, Eugene R. Schiff, Kris V. Kowdley, Albert D. Min, Mitchell L. Shiffman, William M. Lee, Zachary D. Goodman, Lauren O. Dau, Kenneth J. Peschell, Elizabeth A. Fagan, John F. Flaherty

Research output: Contribution to journalArticle

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Abstract

GOALS: To evaluate the proportion of patients with histologic evidence of active liver disease (HEALD) who have chronic hepatitis B (CHB) and normal/minimally elevated serum alanine aminotransferase (ALT). Sub-analysis was performed to determine whether HEALD based upon liver biopsy better correlates with ALT using modified ALT (30 men/19 women) upper limit of normal (ULN) criteria compared with local conventional laboratory. BACKGROUND: There are limited data on CHB with normal range ALT (NRALT). We designed a study to evaluate histologic damage in this cohort of patients. STUDY: A retrospective, multicenter study evaluated CHB patients with normal/minimally elevated ALT [≤1.2 × ULN (hepatitis B e antigen positive) or ≤1.5 × ULN (hepatitis B e antigen negative)]. Liver biopsy specimens were reviewed by an independent histopathologist. HEALD was defined as Knodell necroinflammatory score greater than 5 and Ishak fibrosis stage greater than 1. RESULTS: Forty-five patients met criteria: median age of 40 years; 51% males; 73% Asian; and 67% hepatitis B e antigen negative. Median hepatitis B virus DNA was 6.04 log10 copies/mL, aspartate aminotransferase (AST) 30 IU/L, and ALT 42 IU/L; and 40% of the patients had ALT greater than ULN. Overall, 20% had HEALD and among patients with NRALT, 4 of 27 (15%) and 0 of 5 (0%) had HEALD through conventional or modified ALT ULN, respectively. CONCLUSIONS: One fifth of patients with CHB and normal/minimally elevated ALT had HEALD. Among the subset of patients with NRALT, 15% (4 of 27) had HEALD when using conventional laboratory compared with 0% (0 of 5) patients by modified ALT ULN criteria. Use of the modified ALT ULN will likely improve accuracy in identifying patients who may have HEALD compared with conventional laboratory ULN.

Original languageEnglish (US)
Pages (from-to)510-516
Number of pages7
JournalJournal of Clinical Gastroenterology
Volume44
Issue number7
DOIs
StatePublished - 2010

Fingerprint

Chronic Hepatitis
Alanine Transaminase
Reference Values
Liver Diseases
Liver
Wounds and Injuries
Chronic Hepatitis B
Hepatitis B e Antigens
Biopsy
Aspartate Aminotransferases
Hepatitis B virus
Alanine
Multicenter Studies
Fibrosis
Retrospective Studies

Keywords

  • alanine aminotransferase
  • ALT
  • chronic hepatitis B

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Histologic evidence of active liver injury in chronic hepatitis b patients with normal range or minimally elevated alanine aminotransferase levels. / Hu, Ke Qin; Schiff, Eugene R.; Kowdley, Kris V.; Min, Albert D.; Shiffman, Mitchell L.; Lee, William M.; Goodman, Zachary D.; Dau, Lauren O.; Peschell, Kenneth J.; Fagan, Elizabeth A.; Flaherty, John F.

In: Journal of Clinical Gastroenterology, Vol. 44, No. 7, 2010, p. 510-516.

Research output: Contribution to journalArticle

Hu, KQ, Schiff, ER, Kowdley, KV, Min, AD, Shiffman, ML, Lee, WM, Goodman, ZD, Dau, LO, Peschell, KJ, Fagan, EA & Flaherty, JF 2010, 'Histologic evidence of active liver injury in chronic hepatitis b patients with normal range or minimally elevated alanine aminotransferase levels', Journal of Clinical Gastroenterology, vol. 44, no. 7, pp. 510-516. https://doi.org/10.1097/MCG.0b013e3181d34c65
Hu, Ke Qin ; Schiff, Eugene R. ; Kowdley, Kris V. ; Min, Albert D. ; Shiffman, Mitchell L. ; Lee, William M. ; Goodman, Zachary D. ; Dau, Lauren O. ; Peschell, Kenneth J. ; Fagan, Elizabeth A. ; Flaherty, John F. / Histologic evidence of active liver injury in chronic hepatitis b patients with normal range or minimally elevated alanine aminotransferase levels. In: Journal of Clinical Gastroenterology. 2010 ; Vol. 44, No. 7. pp. 510-516.
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abstract = "GOALS: To evaluate the proportion of patients with histologic evidence of active liver disease (HEALD) who have chronic hepatitis B (CHB) and normal/minimally elevated serum alanine aminotransferase (ALT). Sub-analysis was performed to determine whether HEALD based upon liver biopsy better correlates with ALT using modified ALT (30 men/19 women) upper limit of normal (ULN) criteria compared with local conventional laboratory. BACKGROUND: There are limited data on CHB with normal range ALT (NRALT). We designed a study to evaluate histologic damage in this cohort of patients. STUDY: A retrospective, multicenter study evaluated CHB patients with normal/minimally elevated ALT [≤1.2 × ULN (hepatitis B e antigen positive) or ≤1.5 × ULN (hepatitis B e antigen negative)]. Liver biopsy specimens were reviewed by an independent histopathologist. HEALD was defined as Knodell necroinflammatory score greater than 5 and Ishak fibrosis stage greater than 1. RESULTS: Forty-five patients met criteria: median age of 40 years; 51{\%} males; 73{\%} Asian; and 67{\%} hepatitis B e antigen negative. Median hepatitis B virus DNA was 6.04 log10 copies/mL, aspartate aminotransferase (AST) 30 IU/L, and ALT 42 IU/L; and 40{\%} of the patients had ALT greater than ULN. Overall, 20{\%} had HEALD and among patients with NRALT, 4 of 27 (15{\%}) and 0 of 5 (0{\%}) had HEALD through conventional or modified ALT ULN, respectively. CONCLUSIONS: One fifth of patients with CHB and normal/minimally elevated ALT had HEALD. Among the subset of patients with NRALT, 15{\%} (4 of 27) had HEALD when using conventional laboratory compared with 0{\%} (0 of 5) patients by modified ALT ULN criteria. Use of the modified ALT ULN will likely improve accuracy in identifying patients who may have HEALD compared with conventional laboratory ULN.",
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T1 - Histologic evidence of active liver injury in chronic hepatitis b patients with normal range or minimally elevated alanine aminotransferase levels

AU - Hu, Ke Qin

AU - Schiff, Eugene R.

AU - Kowdley, Kris V.

AU - Min, Albert D.

AU - Shiffman, Mitchell L.

AU - Lee, William M.

AU - Goodman, Zachary D.

AU - Dau, Lauren O.

AU - Peschell, Kenneth J.

AU - Fagan, Elizabeth A.

AU - Flaherty, John F.

PY - 2010

Y1 - 2010

N2 - GOALS: To evaluate the proportion of patients with histologic evidence of active liver disease (HEALD) who have chronic hepatitis B (CHB) and normal/minimally elevated serum alanine aminotransferase (ALT). Sub-analysis was performed to determine whether HEALD based upon liver biopsy better correlates with ALT using modified ALT (30 men/19 women) upper limit of normal (ULN) criteria compared with local conventional laboratory. BACKGROUND: There are limited data on CHB with normal range ALT (NRALT). We designed a study to evaluate histologic damage in this cohort of patients. STUDY: A retrospective, multicenter study evaluated CHB patients with normal/minimally elevated ALT [≤1.2 × ULN (hepatitis B e antigen positive) or ≤1.5 × ULN (hepatitis B e antigen negative)]. Liver biopsy specimens were reviewed by an independent histopathologist. HEALD was defined as Knodell necroinflammatory score greater than 5 and Ishak fibrosis stage greater than 1. RESULTS: Forty-five patients met criteria: median age of 40 years; 51% males; 73% Asian; and 67% hepatitis B e antigen negative. Median hepatitis B virus DNA was 6.04 log10 copies/mL, aspartate aminotransferase (AST) 30 IU/L, and ALT 42 IU/L; and 40% of the patients had ALT greater than ULN. Overall, 20% had HEALD and among patients with NRALT, 4 of 27 (15%) and 0 of 5 (0%) had HEALD through conventional or modified ALT ULN, respectively. CONCLUSIONS: One fifth of patients with CHB and normal/minimally elevated ALT had HEALD. Among the subset of patients with NRALT, 15% (4 of 27) had HEALD when using conventional laboratory compared with 0% (0 of 5) patients by modified ALT ULN criteria. Use of the modified ALT ULN will likely improve accuracy in identifying patients who may have HEALD compared with conventional laboratory ULN.

AB - GOALS: To evaluate the proportion of patients with histologic evidence of active liver disease (HEALD) who have chronic hepatitis B (CHB) and normal/minimally elevated serum alanine aminotransferase (ALT). Sub-analysis was performed to determine whether HEALD based upon liver biopsy better correlates with ALT using modified ALT (30 men/19 women) upper limit of normal (ULN) criteria compared with local conventional laboratory. BACKGROUND: There are limited data on CHB with normal range ALT (NRALT). We designed a study to evaluate histologic damage in this cohort of patients. STUDY: A retrospective, multicenter study evaluated CHB patients with normal/minimally elevated ALT [≤1.2 × ULN (hepatitis B e antigen positive) or ≤1.5 × ULN (hepatitis B e antigen negative)]. Liver biopsy specimens were reviewed by an independent histopathologist. HEALD was defined as Knodell necroinflammatory score greater than 5 and Ishak fibrosis stage greater than 1. RESULTS: Forty-five patients met criteria: median age of 40 years; 51% males; 73% Asian; and 67% hepatitis B e antigen negative. Median hepatitis B virus DNA was 6.04 log10 copies/mL, aspartate aminotransferase (AST) 30 IU/L, and ALT 42 IU/L; and 40% of the patients had ALT greater than ULN. Overall, 20% had HEALD and among patients with NRALT, 4 of 27 (15%) and 0 of 5 (0%) had HEALD through conventional or modified ALT ULN, respectively. CONCLUSIONS: One fifth of patients with CHB and normal/minimally elevated ALT had HEALD. Among the subset of patients with NRALT, 15% (4 of 27) had HEALD when using conventional laboratory compared with 0% (0 of 5) patients by modified ALT ULN criteria. Use of the modified ALT ULN will likely improve accuracy in identifying patients who may have HEALD compared with conventional laboratory ULN.

KW - alanine aminotransferase

KW - ALT

KW - chronic hepatitis B

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