| Haimen City, Jiangsu Province, located in the Yangtze River Delta, is the high incidence city of primary hepatocellular carcinoma (HCC). HBV infection, the most important risk factors and promotion condition in younger while living in the same environmental, should be full attention to decision-making in the HCC control.As a DNA virus, there are four overlapping open reading frames (S, C, P and X) in Hepatitis B virus. S gene mutation changes the HBsAg spatial structure and immunogenicity, leading to low levels of antigenicity and protein. C gene mutation, mainly nt 1896 Gâ†'A for termination of HBeAg synthesis, will affect viral load and the process of HCC. The most important and common mutation in Basic core promoter is nt 1762 Aâ†'T, nt 1764 Gâ†'A double mutation,which not only enhanced HBV replication ability, but also reduce HBeAg synthesis as well as increased hepatocyte apoptosis, thereby increasing the patient condition. YMDD mutation (aa M552V or aa M552â… , generate YVDD or YIDD) is the most important mutation in P gene. HBV replication is obviously enhanced due to YMDD mutation with "a" determinant.Currently there are 10 HBV genotypes in the world. The popular genotypes in China are B and C. HBV genotype is connected with prognosis of HBV infection. Compared with genotype B, genotype C is more closely with HCC, and will lead to more severe liver fibrosis. The mixed infection of different genotypes of HBV can cause resurgence.We carried out the hepatitis B serological surveys in the general population of Haimen City with multi-stage random sampling, including general conditions, history of liver diseases, exposure history of hepatitis B virus, and vaccination history for hepatitis B. After HBsAg qualitative detection and semi-quantitative detection of anti-HBs by ELISA, extraction of HBV DNA, Nested PCR amplification of HBV S gene and the LA-PCR amplification of HBV DNA, we grasp the prevalence, the variation and the major genotype of HBV in Haimen.HBsAg positive rate was 6.035% in the totally investigatory population of 5,624. The HBsAg-positive rate between two gender is not statistics different.<30 HBsAg-positive rate in population at aged<30 years was significantly lower than aged≥30 years of age, and HBsAg-positive rate of children under the age of 10 was 0. The higher educational level, HBsAg-positive rate is lower. The lowest rate of HBsAg-positive was in health care workers, but the highest was in peasants. The HBsAg-positive rate in the groups of consanguinities who were hepatitis B patients was significantly higher than the groups of consanguinities without hepatitis B virus. The HBsAg-positive rate in surgery and endoscopy groups was significantly higher than the groups without surgery and endoscopy. The HBsAg positive rate among blood donors is lower than the non-blood donors. The HBsAg-positive rate among the different place of birth was significantly different, as follows: who was born in hospitals above county level< who was born in the township-level hospitals 1OIU/ml population, however, the groups with higher anti-HBs titers is larger than the groups with lower anti-HBs titers. The distribution of anti-HBs titer in HBsAg negative population was same as the general population. In HBsAg-positive population, whose anti-HBs titers<10 IU/ml were accounted for 90.845%; whose anti-HBs titers in (10,160] IU/ml is lower than 1.5%; but whose anti-HBs titers> 160IU/mlwere accounted for 5.282%. The distribution of anti-HBs titer between two genders was similar. In anti-HBs titer<10 IU/ml population, the percentage of younger is gradully lower than elder. In anti-HBs titer> 10 IU/ml population, children below age of 10 whose located in (40,80] IU/ml was accounted for the lowest percentage; the distribution of anti-HBs titer in [10,60) years population was same as the general population; the percentage of different anti-HBs titer in people over the age of 60 was similar. The anti-HBs titer distribution in differently educational and occupational groups was similar to the age groups. Endoscopy done groups had lower anti-HBs titers. The distribution of anti-HBs titer can be impacted by different place of birth (born in or above the county level hospitals> born in township-level hospitals> born at home). Logistic regression analysis showed that endoscopy was the risk factors of anti-HBs protective effects.HBsAg-positive rate of population, especially in those who having done dental in the village doctor or individual clinics, sharing a toothbrush with family members and born in and above township level hospitals, who were born before the era of planned immunization was much higher than after the era of planned immunization, but the average anti-HBs titer was performance of the contrary. Amplified by nested PCR, test positive percentage for HBV S gene was 45.8%. B genotype was accounted for 10.8%, C genotype was accounted for 86.9%, and B/ C mixed genotype was accounted for 2.3%. The variability of genotype C HBV S gene, particularly in the hydrophilic region (nt 245-nt 391), was generally higher than genotype B. HBV S gene among different disease patients with the same genotype was no significant separation, and genotype B HBV S gene was higher homology. All that may lead to HBV antigens and immune response changes, accounting for 5.38%, were genotype C, which average age was 46.71±1.17 years and anti-HBs titer was less than 10 Ul/1. All Haimen's HBV samples were mainly adrq+ HBsAg serotypes (accounted for 82.3%), followed by adw2 serotypes (accounted for 16.2%).Amplified by LA-PCR, test positive percentage for HBV DNA was 15.4%, and the nt 1814-nt 2452 region is relatively conservative.4 cases of pre-C gene occurred nt 1896 Gâ†'A single base substitutions. BCP double mutations did not occur (nt1762Aâ†'T and nt1764Gâ†'A) in genotype B; in genotype C, however, BCP double mutations (ntl762Aâ†'T and ntl764Gâ†'A) was accounted for 47.06%, where as only ntl762Aâ†'T mutation and only nt1764Gâ†'A mutation was accounted for 5.88% and 11.76%, respectively. The average evolutionary distance of HBV DNA among Haimen, Shanghai and Heilongjiang was the smallest gap, followed by Beijing, Anhui, Qidong, Taiwan and Tibet, which is mainly due to different genotype distribution.On the genotype C HBV DNA, the evolutionary distance among Haimen strains was relatively large, even much greater than the distance between Haimen and some areas'strains. The distance on the pre-C/C gene, C gene and X gene, in the opposite of P gene, in Haimen strains and between Haimen and other areas' strains were lower than the HBV DNA among the same areas' strains. Compared with other regions, the pre-S1/pre-S2 gene in Haimen strains had grester variation. Despite of the high HCC incidence in Haimen, the evolutionary distance on HBV DNA between Haimen strains from the general population and other areas' strains from HCC patients is larger than those between Haimen and Beijing strains from HB patiants.After nearly two decades of hepatitis B vaccine program immunization, HBV prevention in Haimen City is effective and HBV infection has been significantly decreased. HBV infection rate of young people is increased with growing up; and in the local adult, HBV hepatitis B patients is likely to be removed with aging, or false negative HBsAg caused by HBV S gene mutation. There is HBV infection within the family or family gathering in Haimen, which may be the combined result of vertical transmission, genetic factors and horizontal transmission. But there is non-significant difference of clinical types between familial and non-familial aggregation in virology. Places of birth can influence on HBV infection, indicating that the level of medical received at birth can imapct on HBV infection. For the low education and income families, Hepatitis B vaccine immunization is the main way to prevent HBV infection. HBV is spread through not only some ways of social transmission, such as the endoscope and dental in and below township-level hospitals, but the ways of family transmission by sharing a toothbrush as well. In summary, the main factors of HBV infection in the general Haimen population include:age, educational level, consanguinities who were hepatitis B patients, endoscopy, place of birth and hepatitis B vaccine immunization. Age, educational level and place of birth mainly effect hepatitis B vaccine immunization, and Haimen HBV infection is mainly from vertical transmission and horizontal transmission by endoscopy, dental and sharing a toothbrush in family. Hepatitis B vaccine in the right time is the best way to prevent the spread of HBV in Haimen.The variation of HBV S gene in Haimen, which can changes in antigenicity and immunogenicity, should be closely watched to prevent hepatitis B vaccine failure. As the high-incidence HCC area, the distance of HBV DNA, as well as X gene, was not significant between Haimen and other low-incidence HCC areas, regardless whether from HCC patients, which suggesting that variation of HBV is not the direct cause of high-incidence HCC, but maybe the simulating factor to other direct factors in Haimen, although the viral load of serum HBV is independent expected factors and genetic changes during chronic hepatitis B inflammatory response is the most important factor in HCC occurred.Limited by the experimental conditions, this study did not measure HBV load in HBsAg positive samples, which need to be carried out taking a step forward in follow-up studies. |
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