Friday, December 17, 2010

Hepatitis B; Predictors of postoperative survival in hepatocellular carcinoma

Predictors of postoperative survival in hepatocellular carcinoma

Hepatitis B virus–DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma, reports December's issue of Hepatology.

Hepatitis B virus is a major etiological factor of hepatocellular carcinoma.

However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has never been investigated.

Dr Chau-Ting Yeh and colleagues from Taiwan obtained 185 liver samples from the noncancerous part of surgically removed Hepatitis B virus-associated hepatocellular carcinoma tissues.

The samples were subjected to virological analysis.
Short stretch pre-S deletions were associated with poorer survival
Hepatology

Assayed factors included the amount of Hepatitis B-DNA in the liver tissues, genotype, and the presence of the Hepatitis B virus precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre-S deletions/stop codon mutation.

All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival.

The researchers found that Hepatitis B-DNA levels more than 3 × 107 copies/g of liver tissue, and the presence of the basal core promoter mutation independently predicted disease-free, and overall survival.

The research team observed that in-frame, short stretch pre-S deletions, but not large fragment pre-S deletions, were significantly associated with poorer disease-free, and overall survival.

A hot deletion region located between codons 107 and 141 of the pre-S sequence was identified for the short stretch pre-S deletion mutants.

Dr Yeh's team commented, "The amount of Hepatitis B virus-DNA in liver tissue and the presence of the basal core promoter mutation were 2 independent predictors for postoperative survival in hepatocellular carcinoma."

"A short stretch pre-S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis."

Hepatitis B virus–DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma
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Chau-Ting Yeh1,4,*,, Mary So5, Jennifer Ng5, Han-Wen Yang1, Ming-Ling Chang1,
Ming-Wei Lai6, Tse-Ching Chen2, Chun-Yen Lin1, Ta-Sen Yeh3, Wei-Chen Lee3
Article first published online: 2 SEP 2010
DOI: 10.1002/hep.23898
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Abstract
Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has never been investigated. To address this issue, 185 liver samples obtained from the noncancerous part of surgically removed HBV-associated HCC tissues were subjected to virological analysis.
Assayed factors included the amount of HBV-DNA in the liver tissues; genotype; and the presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre-S deletions/stop codon mutation.
All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival.
It was found that an HBV-DNA level more then 3.0 × 107 copies/g of liver tissue and the presence of the basal core promoter mutation independently predicted disease-free (adjusted hazard ratio 1.641 [95% confidence interval (CI) 1.010-2.667] and 2.075 [95% CI 1.203-3.579], respectively) and overall (adjusted hazard ratio 2.807 [95% CI 1.000-7.880] and 5.697 [95% CI 1.678-19.342], respectively) survival. Kaplan-Meier survival analysis indicated that in-frame, short stretch (less then 100 bp) pre-S deletions, but not large fragment (>100 bp) pre-S deletions, were significantly associated with poorer disease-free (P = 0.005) and overall (P = 0.020) survival. A hot deletion region located between codons 107 and 141 of the pre-S sequence was identified for the short stretch pre-S deletion mutants.
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Conclusion: The amount of HBV-DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. A short stretch pre-S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis. (Hepatology 2010)

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