Background:Between January and April 2020, China implemented differentiated prevention and control strategies across the country, based on the severity of the COVID-19 epidemic/pandemic in different regions. These strategies included lockdowns, social distancing, and the closure of public places. These measures may have affected dietary intake to varying degrees. This study aimed to assess variations in food intake and diet quality among pregnant women according to regional severity and related control measures during the most severe period of COVID-19 restrictions in 2020.MethodsA total of 3,678 pregnant women from 19 provinces/municipalities in mainland China were analyzed in this nationwide, multi-center study. Food intake data were obtained and assessed using a validated food frequency questionnaire (FFQ). Diet quality was quantified using the Diet Balance Index for Pregnancy (DBI-P), which included high bound score (HBS, excessive dietary intake), low bound score (LBS, insufficient dietary intake), and diet quality distance (DQD, dietary imbalance). Linear trend tests and multivariable regression analyses were performed to examine the association between food intake, DBI-P and the severity of pandemic.ResultsThe median daily intake of vegetables, fruit, livestock/poultry meat, dairy, and nuts decreased (p < 0.05) according to low, moderate, and high severity of the pandemic, while no significant differences in cereals/potatoes, eggs, and fish/shrimp intake. The median daily intake of cereals/potatoes exceeded the recommended ranges, and the daily intake of eggs and fish/shrimp was below recommended ranges regardless of the pandemic severity (p < 0.05). Regarding diet quality, HBS decreased (lower excessive consumption) (p = 0.047) and LBS increased (greater insufficient consumption) (p = 0.046) with increased severity of the pandemic. On multivariable analyses, moderate and high pandemic severity were related to lower HBS risk (OR = 0.687, OR = 0.537) and higher LBS risk (β = 1.517, β = 3.020) when compared to low pandemic severity.ConclusionsUnder more severe COVID-19 pandemic conditions, pregnant women consumed less quality food, characterized by reduced consumption of vegetables, fruit, livestock/poultry meat, dairy and nuts, while the quality of the foods that pregnant women consumed in excess tended to improve, but the overconsumption of cereals/potatoes was a problem.

Abstract Background The evidence for associations of mental health with COVID-19 pandemic severity is scarce in postpartum women. We aimed to investigate the associations of postpartum depressive symptoms (PDS), perceived social support (PSS) with COVID-19 pandemic severity, respectively, and to explore the associations between PSS and PDS under different pandemic severities. Methods This was a nationwide multicenter study. An online survey was launched from January 23 through February 29, 2020 in mainland China. Participants’ PDS and PSS were measured by Edinburgh Postnatal Depression Scale and Multidimensional Scale of Perceived Social Support, respectively. Results The final sample consisted of 452 participants from 19 hospitals in 19 provinces/municipalities of mainland China. After covariate adjustment, women in Hubei Province experienced higher PDS levels than those in moderate (β coefficient = − 3.883, p = 0.001) and high (β coefficient = − 3.760, p = 0.005) pandemic severity; women in moderate pandemic severity reported higher PSS levels not only than those in high (β coefficient = − 4.947, p = 0.008) pandemic severity and Hubei Province (β coefficient = − 6.480, p = 0.049), but also than low (β coefficient = − 7.428, p = 0.005) pandemic severity. Also, no significant associations were found between PSS and pandemic severity for women with moderate-to-severe PDS (p > 0.05). There were significantly negative associations between PSS and PDS for women under low (OR = 0.837, p = 0.039), moderate (OR = 0.919, p < 0.001), and high (OR = 0.951, p = 0.012) pandemic severity, and no significant association between PSS and PDS was observed in Hubei Province after covariate adjustment (p > 0.05). Conclusion Women in Hubei Province experienced higher PDS levels than those in moderate and high pandemic severity. Women in moderate pandemic severity reported higher PSS levels not only than those in high pandemic severity and Hubei Province, but also than low pandemic severity, and no associations were found between PSS and pandemic severity for women with moderate-to-severe PDS. There were negative associations between PSS and PDS for women in low, moderate and high pandemic severity, but no association between PSS and PDS of women in Hubei Province.

Qidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P < 0.0001) in HBsAg-positive arm compared with HBsAg-negative arm. The relative risk of PLC was 13.25 (95% CI=6.67-26.33, P < 0.0001) and 28.05 (95% CI=13.87-56.73, P < 0.0001) in the HBsAg+/HBeAg- group and the HBsAg+/HBeAg+ group, respectively, as compared to the HBsAg-/HBeAg- group. A series of novel PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

We read with great interest the recent publication by Kim et al 1 showing that patients with untreated immune tolerant (IT) chronic hepatitis B with normal alanine aminotransferase (ALT) levels had significantly higher risks of hepatocellular carcinoma (HCC) and death/transplantation than treated immune active (IA) patients who had elevated ALT levels. These results indicate that ALT is not a sensitive surrogate marker for liver cell damage, and the IT phase of HBV infection cannot be considered fully benign.2 Chu and Liaw3 have challenged this view because they speculated that the IT group in that study might include IA patients who were in remission state after experiencing unrecognised minimal ALT elevations. Apparently, the highly dynamic nature of ALT perturbation makes it inadequate to act as a predictor for HCC. We have developed and validated an easy-to-use scoring system for primary liver cancer (PLC) risk prediction. The development data set was set up in 1996 based on a community-based prospective cohort (qidong hepatitis B infection cohort (QBC)) established in Qidong, China.4 It contained …

Background/Aim: Hepatitis B Virus (HBV) mutations play a role in the development of hepatocellular carcinoma (HCC). However, the association between HBV polymerase gene mutations and HCC has not been reported. In this study, we conducted a multi-stage study to identify HCC-related mutations in the reverse transcriptase (RT) domain of the HBV polymerase gene.Methods: A total of 231 HCCs and 237 non-HCC controls from Qidong, China, were included in this study. The entire sequence of HBV RT was first compared between 29 HCC and 35 non-HCC cases, and candidate mutations were then evaluated in two independent validation sets.Results: There were 15 candidate mutations identified from the discovery set, with A799G and T1055A being consistently associated with HCC across all studies. A pooled analysis of samples revealed that A799G, A987G, and T1055A were independent risk factors for HCC, with adjusted odds ratios of 5.53 [95% confidence interval (CI), 1.69-18.10], 4.20 (95% CI, 1.15-15.35), and 3.78 (95% CI, 1.45-9.86), respectively. A longitudinal study showed that these mutations were detectable 45 years prior to HCC diagnosis.Conclusions: Our study provides evidence the first that HBV RT contains naturally occurring mutations that can be used as predictive markers for HCC.

Objective: To explore the relationship between the mutations in the reverse transcriptase(RT) domain of hepatitis B virus polymerase(HBV-P) gene and the occurrence and development of hepatocellular carcinoma(HCC). Methods: In this case-control study, the serum samples from 202 HCC patients and 202 chronic hepatitis B virus(CHB) carriers matching for age and gender were collected. The sequence of the RT domain of HBV-P gene was determined by direct sequencing following PCR amplifi cation. The relationship between the mutations in the RT domain of HBV-P gene and the occurrence and development of HCC was analyzed. Results: The T895A, A904T and C955T mutations in the RT domain of HBV-P gene were all signif icantly associated with HCC compared to non-HCC controls(P = 0.034, 47.5% vs 37.1%; P = 0.011, 5.4% vs 1.0%; P = 0.030, 5.4% vs 1.5%). Furthermore, the Logistic multivariate analysis showed that T895A was an independent risk factor for HCC [odds ratio(OR) = 2.230, 95% confi dence interval(CI): 1.230-4.044, P = 0.008]. A904T or C955T increased the risk of HCC occurrence either(OR = 6.523, 95% CI: 0.838-50.733; OR = 2.904,95% CI: 0.599-14.093), but it did not reach statistical signifi cance. The mutation rate of combined mutation occurrence either in A904 or C955T was 9.4% in HCC group and 2.5% in non-HCC controls(P = 0.003). The adjusted OR was 4.145(95% CI: 1.170-14.681), demonstrating its signif icant association with HCC(P = 0.028). Conclusion: The mutations in the RT domain of HBV-P gene are associated with the tumorigenesis of HCC.

AIM:To develop a novel non-sequencing method for the detection of hepatitis B virus (HBV) pre-S deletion mutants in HBV carriers. METHODS:The entire region of HBV pre-S1 and pre-S2 was amplified by polymerase chain reaction (PCR). The size of PCR products was subsequently determined by capillary gel electrophoresis (CGE). CGE were carried out in a PACE-MDQ instrument equipped with a UV detector set at 254 nm. The samples were separated in 50 μm ID eCAP Neutral Coated Capillaries using a voltage of 6 kV for 30 min. Data acquisition and analysis were performed using the 32 Karat Software. A total of 114 DNA clones containing different sizes of the HBV pre-S gene were used to determine the accuracy of the CGE method. One hundred and fifty seven hepatocellular carcinoma (HCC) and 160 non-HCC patients were recruited into the study to assess the association between HBV pre-S deletion and HCC by using the newly-established CGE method. Nine HCC cases with HBV pre-S deletion at the diagnosis year were selected to conduct a longitudinal observation using serial serum samples collected 2-9 years prior to HCC diagnosis. RESULTS:CGE allowed the separation of PCR products differing in size > 3 bp and was able to identify 10% of the deleted DNA in a background of wild-type DNA. The accuracy rate of CGE-based analysis was 99.1% compared with the clone sequencing results. Using this assay, pre-S deletion was more frequently found in HCC patients than in non-HCC controls (47.1% vs 28.1%, P < 0.001). Interestingly, the increased risk of HCC was mainly contributed by the short deletion of pre-S. While the deletion ≤ 99 bp was associated with a 2.971-fold increased risk of HCC (95%CI: 1.723-5.122, P < 0.001), large deletion (> 99 bp) did not show any association with HCC (P = 0.918, OR = 0.966, 95%CI: 0.501-1.863). Of the 9 patients who carried pre-S deletions at the stage of HCC, 88.9% (8/9) had deletions 2-5 years prior to HCC, while only 44.4%4 (4/9) contained such deletions 6-9 years prior to HCC. CONCLUSION:CGE is a sensitive approach for HBV pre-S deletion analysis. Pre-S deletion, especially for short DNA fragment deletion, is a useful predictive marker for HCC.

Increasing evidence suggests that a link exists between hepatitis B virus (HBV) serum markers and pancreatic cancer (PC). In this study, HBsAg and HBcAg were expressed in 21.0% (34/162) of PC and 29.0% (47/162) of non-tumor pancreatic tissues, and they were significantly associated with chronic pancreatitis (P = 0.000). The HBV S, C and X genes were identified in 20% (6/30) of PC and 26.9% (7/26) of non-tumor tissues by PCR. A serological survey revealed that the prevalence of HBV DNA and anti-HBc was significantly increased in PC patients compared with healthy controls. Our data suggest that HBV infection in the pancreas may play an etiologic role in PC.

There have been several studies suggesting that cancer stem cells (CSCs) contribute to the high rates of recurrence and resistance to therapies observed in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) has been demonstrated to be a biomarker of CSCs and a potential therapeutic target in HCC. Here, we prepared two anti-EpCAM monoclonal antibodies (1H8 and 2F2) and an anti-EpCAM bispecific T cell engager (BiTE) 1H8/CD3, which was derived from 1H8, and used them to treat HCC in vitro and in vivo. The results demonstrated that all of the developed anti-EpCAM antibodies specifically bound to EpCAM. Neither anti-EpCAM monoclonal antibody had obvious anti-HCC activities in vitro or in vivo. However, anti-EpCAM BiTE 1H8/CD3 induced strong peripheral blood mononuclear cell-dependent cellular cytotoxicity in Huh-7 and Hep3B cells but not EpCAM-negative SK-Hep-1 cells. Notably, 1H8/CD3 completely inhibited the growth of Huh-7 and Hep3B xenografts in vivo. Treatment of the Huh-7 HCC xenografts with 1H8/CD3 significantly suppressed tumor proliferation and reduced the expression of most CSC biomarkers. Intriguingly, galectin-1 (Gal-1) overexpression inhibited 1H8/CD3-induced lymphocytotoxicity in HCCs while knockdown of Gal-1 increased the lymphocytotoxicity. Collectively, these results indicate that anti-EpCAM BiTE 1H8/CD3 is a promising therapeutic agent for HCC treatment. Gal-1 may contribute to the resistance of HCC cells to 1H8/CD3-induced lysis.

Objectives: To characterize the mutation pattern of a hepatitis B virus (HBV) core protein (HBcAg) derived from hepatocellular carcinoma (HCC) and adjacent nontumor tissues. Methods: HBV core gene fragments (nt. 1901–2365) were amplified from 98 HBV-related HCC tissues and 33 adjacent nontumor tissues. The deduced amino acids (AAs) of the core gene were aligned with the prototype sequences of HBV genotypes B and C. Results: In total, there were 54 positions that showed polymorphism at the deduced AA level. The mutations were predominantly located in three major (codons 83–87, 95–104 and 130–135) and three minor (codons 21–38, 59–63 and 151–155) mutation-clustering regions (MCRs). The substitution rate in MCRs was significantly higher than in mutation-devoid regions (p < 0.001). The most frequently occurring mutations in rank were codon P130T (38.8%), I97L (37.8%) and S87G (23.5%). In addition, there were 7 patients that showed internal deletions in the middle of HBcAg with sizes ranging from 34 to 59 AAs. Unexpectedly, the core genes isolated from tumor tissues had fewer mutations compared with those isolated from adjacent nontumor tissues from the same patients (p < 0.05). Conclusions: Accumulation of naturally occurring mutations in certain restricted segments of HBcAg may be related to the development of HCC.

Objective: To obtain human papillomavirus(HPV) type 16/18/33/58 major capsid protein L1 with bac ulovirus expression system.Methods: The genes encoding the L1 proteins of HPV 16/18/33/58 serotype were cloned and modified by a variety of strategies to HPV16/18/33/58 mL1.The modified genes were inserted into the pFastBac Dual vector,and the recombinant bacmid was generated after the E.coli DH10Bac competent cell was transformed by the recombinant pFastBac Dual vector,recombinant baculovirus were transfected into insect cell Sf9.Results: Recombinant baculovirus expressing mL1 protein of HPV16/18/33/58 serotypes was obtained.Western blotting and SDS-PAGE analysis showed that the mL1 protein of the HPV strains was expressed when the Sf9 cells were infected by the recombinant baculovirus,and the mL1 proteins were found distributed mainly in the cell.The mL1 was highly expressed by optimized expression time and multiplicity of infection(MOI).Conclusion: Cloning and expression of L1 protein of multiple subtypes of HPV,laid the foundation for the Chinese indepen dent serotype vaccine.

To investigate the roles of mutations in enhancer II (Enh II) and basal core promoter (BCP) of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC), we determined the sequence of Enh II/BCP in 152 HCC and 136 non-HCC patients from a high-incidence area of East China. A longitudinal study was conducted on 21 cases in which serial plasma samples were available before HCC. In total, six point mutations, including T1653, V1753, T1762, A1764, T1766 and A1768, were found to occur more frequently in HCC patients. Multivariate analysis showed that the T1653 [odds ratio (OR), 2.07; 95% confidence interval (CI), 1.114-3.845] and V1753 (OR, 3.099; 95% CI, 1.520-6.317) were independent factors that were associated with HCC. Although a T1762/A1764 double mutation was found in 73.0% of the HCC patients and 66.9% of the non-HCC patients, if the combined pattern with other adjacent mutations was not taken into account, it alone showed a lower frequency in HCC patients compared with non-HCC patients (19.7 versus 34.6%, P = 0.005). Interestingly, while the OR of HCC patients with a double mutation was only 0.393 (95% CI, 0.234-0.660), it increased to 1.861 (95% CI, 1.161-2.984) with a triple mutation and to 4.434 (95% CI, 1.630-12.063) with a quadruple mutation. The longitudinal study demonstrated that the mutations in Enh II/BCP accumulated during the development of HCC. In conclusion, the T1653 and V1753 mutations were independent risk factors for HCC in East China. The T1762/A1764 double mutation was necessary but not sufficient to produce an association between Enh II/BCP mutations and HCC.

Objective:To explore the correlation between hepatitis B virus e antigen(HBeAg) and hepatocellular carcinoma(HCC) in residents of Qidong — a high-risk area of HCC in Jiangsu Province,China.Methods:This study included 807 hepatitis B virus surface antigen(HBsAg) carriers and 761 age-and gender-matched HBsAg(-) controls enrolled in a prospective cohort in Qidong during 1992.The relationship between the occurrence of HCC and HBsAg was analyzed during the follow-up period from May 1992 to March 2010.Results:A total of 24 715 person-years(PY) was observed.Of 807 cases in HBsAg-positive group,156 cases had developed HCC,and the incidence rate of HCC was 1 288.83/100 000 PY;while in HBsAg-negative group,9 of 761 cases had developed HCC,and the incidence rate of HCC was 71.37/100 000 PY.The relative risks(RRs) of HCC were 13.25(95% confidence interval:6.67-26.33;P0.001) and 28.05(95% confidence interval:13.87-56.73;P0.001) in HBsAg(+) /HBeAg(-) group and HBsAg(+) /HBeAg(+) group,respectively.In the HBsAg(+) group,the RRs for HCC of the four subgroups(HBeAg titer24,1:24-1:27,1:28-1:212,and212) were 2.55(95% confidence interval:1.54-4.22;P0.001),5.02(95% confidence interval:2.89-8.73;P0.001),1.71(95% confidence interval:0.91-3.18;P0.05),and 1.19(95% confidence interval:0.64-2.23;P0.05) folds higher than that of HBeAg(-) subgroup,respectively.Conclusion:HBeAg is an essential predictive factor for the development of HCC.The patients with low titers of HBeAg are at a high-risk of HCC.

OBJECTIVES:To investigate the prevalence of hepatitis B virus (HBV) genotypes and the association with hepatocellular carcinoma (HCC) or basal core promoter (BCP) mutation in Qidong, China.METHODS:The whole genome of HBV or X gene sequences were obtained from serum samples of HBV infected patients by using PCR and direct sequencing methods. Phylogenetic tree was constructed to determine the genotypes or subgenotypes of HBV.RESULTS:According to the phylogenetic tree constructed from full-length sequence of HBV, genotype C2 was predominant in Qidong area. It was prevalent in 44 out of the 48 cases (91.7%), whereas genotype B2 only existed in 4 cases (8.3%). No other genotypes or recombinant types were found in Qidong patients. The result of genotyping based on X gene sequence confirmed the above observation. In a total of 182 samples, 169 (92.9%) showed genotype C2 and 10 (5.5%) showed genotype B2. There were 3 (1.6%) patients showed a coinfection with C2 and B2. The infection rate of genotype C in Qidong was significantly higher than that in neighboring city Shanghai (chi(2) = 12.252, P less than 0.01). There was no significant difference of genotype distribution between HCC and chronic hepatitis groups (P is more than 0.05). The frequency of T1762/A1764 double mutation in genotype C2 (70.3%) was significantly higher than that in genotype B2 (30.8%, P less than 0.05). The other two types of point mutation which also occurred in BCP, i.e. T1766 and A1768, were only seen in genotype C2.CONCLUSION:(1) Genotype C2 is the predominant genotype in Qidong, China. (2) There is no association between genotype C and HCC in Qidong. (3) Genotype C has a higher prevalence of BCP mutation than genotype B.

Objective:To explore the relationship between mutations at 1-90 amino acid(AA) in N terminal of hepatitis B virus X protein(HBx) and the occurrence of hepatocellular carcinoma(HCC).Methods:The HBV X gene sequences were analyzed by using PCR direct sequencing method in 48 HCC tissues and serum samples of 159 HCC patients and 144 chronic hepatitis patients.A case-control study was used to analyze the relationship between HBx mutation and tumorigenesis of HCC.Results:The N terminal mutation of HBx isolated from HCC tissues was located at 1-49 AA,while 50-90 AA were conserved regions.The average mutation rates in hypervariable and conserved regions were 4.1% and 0.46%,respectively.The serum detection results showed that frequency of HBx N terminal mutation was higher in HCC patients than in non-HCC control patients(2.2% vs 1.8%,P0.05).A mutation of Ala/Thr/Pro to Ser at codon 36 was significantly increased in HCC patients compared with hepatitis patients [10.1% vs 2.1%,P0.01;odds ratio(OR)=5.259,95% confidence interval of 1.499-18.444].A/T/P36S mutation occurred only in type C virus.Conclusion:Accumulation of the N terminal mutations in HBx was related with tumorigenesis of hepatocellular carcinoma.HBx A/T/P36S mutation increased the risk of developing HCC in patients infected with type C HBV.

Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623–30. ©2010 AACR.

Downloa kground: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver e. The aim of this study was to identify new viral variations associated with hepatocellular oma (HCC). thods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and n-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV ces in a consecutive series of plasma samples from four HCC cases before and after the occurrence C. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to in an independent set of 103 HCC cases and 103 sexand age-matched non-HCC controls. ults: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the tion study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate is. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. dds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for C and G2203W. clusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Con Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623–30. ©2010 AACR.

Background/Aims: To investigate the mutations in hepatitis B virus (HBV) that might be related to hepatocellular carcinoma (HCC) in the high-risk area Qidong, China.Methods: DNA sequences of HBV basal core promoter (BCP) and the overlapping X gene were determined in 58 HCC and 71 chronic hepatitis (CH) patients. In addition, a consecutive series of plasma samples from 15 HCC cases were employed to compare the CP/X sequences before and after the occurrence of HCC.Results: T1762/A1764 double mutation was frequently found in Qidong patients, regardless of clinical status (65.5% in HCC and 73.2% in CH, P > 0.05). Unexpectedly, the adjacent T1766/A1768 mutation significantly increased the risk of HCC (P < 0.05). Moreover, the prevalence of triple mutations in BCP was significantly higher in patients with HCC than those with CH (P < 0.05). The longitudinal study demonstrated that the mutations in BCP were gradually accumulated during the development of HCC. Colony formation assay showed while A1764 mutation alone did not alter the colony-inhibitory activity of HBx, double or triple mutations largely abrogated this effect.Conclusions: The complex mutation involving T1766/A1768 was closely related to HCC. The enhanced risk of HCC caused by BCP variants could be attributable partially to the aberrant activity of HBx. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

We investigated the frequency and the clinical relevance of hepatitis B virus (HBV) pre-S mutations in Qidong, China. The results showed HBV pre-S mutants were detected in 48.4% (47/97) of patients with HBV infection. Both pre-S deletion and pre-S2 start codon mutations were more frequently found in HCC than in CH patients (51.1% vs. 18.0%, P < 0.01 and 21.2% vs. 8.0%, P = 0.06). In most cases, pre-S mutants coexisted with the wild-type HBV strain. Longitudinal observation clearly revealed that in four of five cases, HBV deletion mutants emerged during the course of HBV infection and eventually became the predominant or exclusive viral population at the stage of HCC. Thus, it was concluded that HBV pre-S mutations were highly prevalent and closely related to HCC in Qidong. Our results also provided direct evidence that pre-S deletion mutants were not acquired from the beginning of infection but arose de novo during the progression of liver disease.