标题: Combined pre-S deletion and core promoter mutations related to hepatocellular ca [打印本页] 作者: StephenW 时间: 2011-1-3 22:34 标题: Combined pre-S deletion and core promoter mutations related to hepatocellular ca
Aim: To investigate the roles of biomedical factors, hepatitis B virus (HBV)
DNA levels, genotypes, and specific viral mutation patterns on the progression
of hepatocellular carcinoma (HCC) in Qidong, China.
Methods: A total of 2387 males (aged 20–65 years) who were seropositive for
the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC,
were recruited to a community-based HCC screening study from August, 1996.
Evaluation of virological parameters at recruitment was determined for 196 HCC
patients during 10 years of follow-up and 323 controls.
Results: After adjustment for age at recruitment, history of cigarette
smoking and alcohol consumption, alanine aminotransferase (ALT) elevation,
alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV
DNA levels ≥4.00 log10 copies/mL, pre-S deletion, T1653 mutation, T1762/A1764
double mutations, and T1766 and/or A1768 mutations were associated with
subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA
levels from less than 2.69 log10 copies/mL to 6.00 log10 copies/mL or greater
was observed. HBV with a complex mutation combination pattern (pre-S deletion,
T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a
single mutation was associated with the development of HCC. The longitudinal
observation demonstrated a gradual combination of pre-S deletion, T1762/A1764
double mutations, and T1766 and/or A1768 mutations during the development of
HCC.
Conclusions: AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and
T1762/A1764 double mutations at recruitment were independent risk factors of
HCC. Combination of pre-S deletion and core promoter mutations increased the
risk of HCC.
病毒原来没有pre-S deletion, and T1762/A1764 double mutations .
The following extract explains some common mutations in HBV:
http://www.medscape.com/viewarticle/512346
The HBV genome contains 4 overlapping open reading frames: the S gene, which codes for the surface proteins (HBsAg); the X gene, which codes for the regulatory gene; the P gene, which codes for DNA polymerase; and the C (core) gene. The latter is divided into the precore region (29 amino acid codons) and the core region (181 codons) by 2 in-frame initiating ATG codons. This results in the transcription of the pregenomic RNA that is essential for HBV replication, and of the nucleocapsid protein or the precore RNA that translates into HBeAg protein that is released into the bloodstream of infected patients.[url=][2][/url] HBeAg is considered to be a marker for viral replication; thus, seroconversion from HBeAg to anti-HBe positivity usually indicates a low level of viral production and low serum HBV DNA levels. This generally correlates with improvement of liver disease.
There is a high error rate associated with the reverse transcription step in HBV replication. As a consequence, HBV has a mutation rate 10-fold higher than that of other DNA viruses. The most potent selective force during the natural course of HBV infection is the host immune response. As a consequence of the development of anti-HBe and the reduction in HBV viremia, "escape" mutants of anti-HBe are selected. Because HBeAg expression is not essential for virus replication, the virus can evade anti-HBe immunity by turning off or reducing HBeAg expression.
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作者: oceanseleven 时间: 2011-1-6 06:07
found the article, but cannot upload as pdf file. 555 作者: StephenW 时间: 2011-1-6 06:50
Characteristics of adefovir resistance in patients with or without
lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year
experience.
What is missing in the summary are the rates of adefovir resistance of patients without previous lamivudine. You may be able to find the article as it is also in the Wiley Online Library. The results should confirm the results posted by Bigben446. From my reading of some of the posts by Dr 王震宇, I understand he is an expert and proponent on the use of lamivudine for the treatment of HBV. He claims to be very confident that he can manage the issues of resistance to lamivudine. As he sees a lot of HBV patients, more than an average liver specialist in the West I presume, his claim must be respected. It is hoped that he can publish his experience with lamivudine. As I mentioned before, here in Australia and America, lamivudine is no longer the antiviral choice for treatment-navie patients. The doctors recommend using drugs with the least resistance profile. You ask me before about mutation. The natural type of the virus is called the "wild" type. Once inside a human body, the virus mutates into types selected by the patient's immune system and drugs used. As drugs for HBV have only been in use for the last 10 years, the long term consequences of anti-viral treatments and resistance are unknown. Hope I am not boring you with all these.