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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-9-10
pubmed:abstractText
Cross-sectional studies reported that hepatitis B core gene mutations are associated with active liver disease and responsiveness to interferon therapy. In view of the heterogeneity in published sequences, it is not possible to tell whether the differences in sequences observed were true mutations that developed during the course of infection. We conducted a longitudinal study to determine the rate of hepatitis B core gene mutations and the timing of these mutations in relation to hepatitis B virus replication, activity of liver disease, hepatitis B virus replication, activity of liver disease, hepatitis B e antigen (HBeAg) seroconversion, and interferon therapy. Serial sera from 55 patients with chronic hepatitis B infection were analyzed by direct sequencing of the hepatitis B precore/core gene to identify the nucleotide and amino acid changes that emerged during during follow-up. Patients who remained HBeAg positive and had normal amino transferase levels (Group I) maintained higher serum hepatitis B virus (HBV) DNA levels but significantly lower rates of both nucleotide and amino acid changes during follow-up compared with patients who remained HBeAg positive but had elevated aminotransferase levels (Groups II) and patients who cleard HBeAg (Group III). The rates of nucleotide and amino acid changes in Groups I, II, III patients were: 0.4 +/- 0.1, 1.9 +/- 0.3, and 2.4 +/- 0.4/nucleotide position/year; and 0.04 +/- 0.02, 0.21 +/- 0.05, and 0.38 +/- 0.07/codon/year, respectively. Most of the amino acid changes in Groups II and III patients occured during or shortly after flares in amino transferase levels, before HBeAg seroconversion. Similar rates of nucleotide and amino acid changes were found in interferon treated versus untreated patients, and in responders versus nonresponders. There was no difference in the location or nature of the hepatitis B core gene mutations between patients with and without HBeAg seroconversion, interferon treated versus untreated patients, and interferon responders versus nonresponders. In summary, changes in the hepatitis B core gene sequence was rarely detected in patients who were still in the immune tolerant phase but very high rates of changes were found during the immune clearance of chronic hepatitis B infection. Interferon therapy did not induce a higher rate or specific pattern of mutations in the hepatitis B core gene. Response to interferon therapy in HBeAg positive patients was unrelated to the number or location of hepatitis B core gene mutations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8707278-Adult, pubmed-meshheading:8707278-Alanine Transaminase, pubmed-meshheading:8707278-Amino Acid Sequence, pubmed-meshheading:8707278-Analysis of Variance, pubmed-meshheading:8707278-Chronic Disease, pubmed-meshheading:8707278-Cross-Sectional Studies, pubmed-meshheading:8707278-DNA, Viral, pubmed-meshheading:8707278-Female, pubmed-meshheading:8707278-Follow-Up Studies, pubmed-meshheading:8707278-Genes, Viral, pubmed-meshheading:8707278-Hepatitis B, pubmed-meshheading:8707278-Hepatitis B Core Antigens, pubmed-meshheading:8707278-Hepatitis B e Antigens, pubmed-meshheading:8707278-Hepatitis B virus, pubmed-meshheading:8707278-Humans, pubmed-meshheading:8707278-Liver, pubmed-meshheading:8707278-Male, pubmed-meshheading:8707278-Point Mutation, pubmed-meshheading:8707278-Polymerase Chain Reaction
pubmed:year
1996
pubmed:articleTitle
High rate of mutations in the hepatitis B core gene during the immune clearance phase of chronic hepatitis B virus infection.
pubmed:affiliation
Section of Gastroenterology and Hepatology, Tulane University, New Orleans, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Randomized Controlled Trial, Research Support, Non-U.S. Gov't