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Conference Paper: Evolutionary changes of hepatitis B virus pre-S mutations prior to development of hepatocellular carcinoma

TitleEvolutionary changes of hepatitis B virus pre-S mutations prior to development of hepatocellular carcinoma
Authors
KeywordsMedical sciences
Gastroenterology
Issue Date2015
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The 50th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress™ 2015), Vienna, Austria, 22-26 April 2015. In Journal of Hepatology, 2015, v. 62 n. suppl. 2, p. S543, abstract no. P0604 How to Cite?
AbstractBACKGROUND AND AIMS: Hepatitis B virus (HBV) pre-S deletions/mutations have been associated with hepatocellular carcinoma (HCC). However, the evolutionary changes of pre-S mutations prior to HCC diagnosis remain unexplored. METHODS: HBV pre-S sequences were determined in 74 chronic hepatitis B (CHB) patients with HCC and 146 CHB patients who have been followed up for >3 years with no HCC (HCC-free). Samples collected at the following time points were studied: 1–3 years, 4–6 years, 7–9 years and ≥10 years prior to HCC development and at the same time points for the HCC-free group from last follow-up. HBV pre-S mutations were assessed by comparison with 54 wild-type reference sequences retrieved from the NCBI Genbank. RESULTS: Pre-S deletions were detected in 31.1%, 25%, 48.5%, and 42.8% of HCC patients at 1–3 years, 4–6 years, 7–9 years, and ≥10 years prior to HCC development, respectively. In the HCC-free group, the frequencies of pre-S deletions at the 4 corresponding time points were lower (9.6%, 7.9%, 8.8%, and 17.6%, respectively; with p values of <0.001, 0.036, <0.001, and 0.096, respectively). At 1–3 years prior to HCC development, higher frequencies of pre-S point mutations at 11 codons (codons 4, 27, 51, 54, 60, 62, 100, 125, 137, 166 and 167) were observed in the HCC patients (range: 14.9–75.7%) than in the HCC-free patients (range: 5.5–26%; all p < 0.05). Ten out of these 11 pre-S mutations (except codon 4, which emerged at 4–6 years before HCC) existed ≥10 years before HCC. Among these 11 codons, the number of mutated codons with differential distribution between HCC and HCC-free patients increased with time prior to HCC: a significantly higher frequency of mutations was detected in the HCC patients in 2/11 codons at ≥10 years, in 9/11 codons at 7–9 years, and in 10/11 codons at 4–6 years prior to HCC. The total number of HCC-associated pre-S point mutations increased with time prior to HCC and correlated with the time to HCC development (r = 0.151, p = 0.042), while no correlation was observed in the HCC-free group (r = 0.073, p = 0.398). Multivariable logistic regression analysis showed that pre-S deletions and point mutations at codons 27, 51 and 167 were independent factors associated with increased HCC risk (all p < 0.05). CONCLUSIONS: High prevalence and cumulative evolution of pre-S mutations preceding HCC development confirmed the carcinogenic role of pre-S mutations. The effect of individual pre-S mutations on HCC development warrants further studies.
DescriptionPoster Presentation: no. P0604
This journal suppl. entitled: Abstracts of The International Liver Congress™ 2015 - 50 Annual meeting of the European Association for the Study of the Liver
Persistent Identifierhttp://hdl.handle.net/10722/214869
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorZhang, A-
dc.contributor.authorWong, DKH-
dc.contributor.authorHuang, FY-
dc.contributor.authorSeto, WK-
dc.contributor.authorFung, J-
dc.contributor.authorLai, CL-
dc.contributor.authorYuen, MF-
dc.date.accessioned2015-08-21T12:00:03Z-
dc.date.available2015-08-21T12:00:03Z-
dc.date.issued2015-
dc.identifier.citationThe 50th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress™ 2015), Vienna, Austria, 22-26 April 2015. In Journal of Hepatology, 2015, v. 62 n. suppl. 2, p. S543, abstract no. P0604-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/214869-
dc.descriptionPoster Presentation: no. P0604-
dc.descriptionThis journal suppl. entitled: Abstracts of The International Liver Congress™ 2015 - 50 Annual meeting of the European Association for the Study of the Liver-
dc.description.abstractBACKGROUND AND AIMS: Hepatitis B virus (HBV) pre-S deletions/mutations have been associated with hepatocellular carcinoma (HCC). However, the evolutionary changes of pre-S mutations prior to HCC diagnosis remain unexplored. METHODS: HBV pre-S sequences were determined in 74 chronic hepatitis B (CHB) patients with HCC and 146 CHB patients who have been followed up for >3 years with no HCC (HCC-free). Samples collected at the following time points were studied: 1–3 years, 4–6 years, 7–9 years and ≥10 years prior to HCC development and at the same time points for the HCC-free group from last follow-up. HBV pre-S mutations were assessed by comparison with 54 wild-type reference sequences retrieved from the NCBI Genbank. RESULTS: Pre-S deletions were detected in 31.1%, 25%, 48.5%, and 42.8% of HCC patients at 1–3 years, 4–6 years, 7–9 years, and ≥10 years prior to HCC development, respectively. In the HCC-free group, the frequencies of pre-S deletions at the 4 corresponding time points were lower (9.6%, 7.9%, 8.8%, and 17.6%, respectively; with p values of <0.001, 0.036, <0.001, and 0.096, respectively). At 1–3 years prior to HCC development, higher frequencies of pre-S point mutations at 11 codons (codons 4, 27, 51, 54, 60, 62, 100, 125, 137, 166 and 167) were observed in the HCC patients (range: 14.9–75.7%) than in the HCC-free patients (range: 5.5–26%; all p < 0.05). Ten out of these 11 pre-S mutations (except codon 4, which emerged at 4–6 years before HCC) existed ≥10 years before HCC. Among these 11 codons, the number of mutated codons with differential distribution between HCC and HCC-free patients increased with time prior to HCC: a significantly higher frequency of mutations was detected in the HCC patients in 2/11 codons at ≥10 years, in 9/11 codons at 7–9 years, and in 10/11 codons at 4–6 years prior to HCC. The total number of HCC-associated pre-S point mutations increased with time prior to HCC and correlated with the time to HCC development (r = 0.151, p = 0.042), while no correlation was observed in the HCC-free group (r = 0.073, p = 0.398). Multivariable logistic regression analysis showed that pre-S deletions and point mutations at codons 27, 51 and 167 were independent factors associated with increased HCC risk (all p < 0.05). CONCLUSIONS: High prevalence and cumulative evolution of pre-S mutations preceding HCC development confirmed the carcinogenic role of pre-S mutations. The effect of individual pre-S mutations on HCC development warrants further studies.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.subjectMedical sciences-
dc.subjectGastroenterology-
dc.titleEvolutionary changes of hepatitis B virus pre-S mutations prior to development of hepatocellular carcinoma-
dc.typeConference_Paper-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailHuang, FY: fungyu@hkucc.hku.hk-
dc.identifier.emailSeto, WK: wkseto@hku.hk-
dc.identifier.emailFung, J: jfung@hkucc.hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hkucc.hku.hk-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authoritySeto, WK=rp01659-
dc.identifier.authorityFung, J=rp00518-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.authorityYuen, MF=rp00479-
dc.identifier.doi10.1016/S0168-8278(15)30810-2-
dc.identifier.hkuros248020-
dc.identifier.volume62-
dc.identifier.issuesuppl. 2-
dc.identifier.spageS543, abstract no. P0604-
dc.identifier.epageS543, abstract no. P0604-
dc.publisher.placeNetherlands-

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