A Study On The Correlation Between Familial Hepatitis B With Primary Hepatocellular Carcinoma And The Polymorphism Of Human Leucocyte Antigen-DRB1 Alleles In Shanxi Province

The primary hepatocellular carcinoma (PHC) was called liver cancer for short, which wasoccurred in the parenchyma of liver cell or the intrahepatic bile duct epithelial cells. It was oneof malignant tumors, which was the commonest and the most dangerous one in our country andeven in the world. The incidence of PHC might be related to the combined effects of manyfactors. Studies had shown that the occurrence of PHC was concerned with hepatitis B virus(HBV) infection and the immune function of the host[1]. HLA as the important gene cluster ofthe immune response had the close relationship with the anti-HBV immune response and theHCC occurrence. The hepatitis B virus infection and the incidence of PHC presented familialaggregation. The hepatitis B gathered the family development to liver cirrhosis, whether did livercancer also present the aggregation? We would carry on the epidemiology investigation to thefamilial hepatitis B crowds in Shanxi; understand HCC morbidity characteristic and the infectionpattern in the hepatitis B crowds. This research would study the host hereditary factors andexplore the relationship between HLA-DRB1 gene polymorphism and the HBV infection in thefamilial hepatitis B crowd.Objective (1) To study the clinical characteristic of the familial hepatitis B with PHC andhepatitis B virus infection pattern in Shanxi. (2) To discusses the association between humanleukocytes antigen (HLA) - the DRB1 polymorphism and the incidence of the familial hepatitisB crowd with PHC, liver cirrhosis, the chronic hepatitis B in Shanxi.Methods (1) The 207 subjects were enrolled from the liver cancer patients related HBVinfection and their immediate family members, according to the hepatitis B family history, whichwas divided into the familial hepatitis B liver cancer group and the non-familial hepatitis B livercancer group. First, to understand clinical epidemiology features of familial hepatitis B byinvestigation the familial hepatitis B in Shanxi. Then, two groups were compared with incidenceage, aggregation of PHC, replication status and infection pattern of HBV. (2) The liver cancerpatients and their lineal consanguinity with familial hepatitis B were divided into chronichepatitis B (CHB) group, hepatitis liver cirrhosis (HC) group, liver cancer (PHC) group and thehealthy control (CON) group. Then the frequencies of HLA- DRB1 were analyzed by PCR-SSOand flow PRATMbeads among the groups and among different replication of HBV.Results 1. (1) Analysis from single-factor Logistic regression showed that the family history ofhepatitis B or liver cancer, positive with HBsAg or HBcAb were risk factors of PHC. (2)There was significant difference in age between familial hepatitis B liver cancer group and thenon-familial hepatitis B liver cancer group patients (uc=5.263,P<0.05). The age of morbidity inthe liver cancer patients with the familial hepatitis B was more common during 30 years old to50 years old, thus which of the non-familial hepatitis B liver cancer patients was during 50 yearsold to 70 years old. (3)The proportion of the PHC with the hepatitis B family history, familyaccumulation was higher than which of the non-familial hepatitis B liver cancer patients. (4) Thepositive rate of HBV-DNA in the liver cancer patients with hepatitis B family history is higherthan which of the non-hepatitis B family history patients, the difference was statisticallysignificant（χ~2=8.96，P＜0.05）. (5) Positive HBsAg, HBeAb and HBcAb were more common inHBV infection pattern of PHC, the proportion is 62.5% (45/72).2. The frequency of HLA-DRB1*0701 allele in the normal control group was 8.5%, whichwas higher than those in CHB group(23.0%), LC group(20.5%) and HCC group (21.3%), and thedifferences were statistical significance(χ~2=6.846, 4.807 and 5.765; P＜0.05, OR=3.200, 2.755and 2.976). The frequency of HLA-DRB1 *0701 allele was higher in the HBV-DNA positivegroup(24.2%) than that in the HBV-DNA negative group(12.6%), the difference had thestatistical significance(χ~2=7.999, P＜0.05). The frequency of HLA-DRB1*0101 allele in familialhepatitis B liver cancer group was 9.6%, which was higher than the normal control group (1.2%,χ~2=4.252, P＜0.05, OR=8.576). The frequencies of HLA-DRB1*1501 allele in familial hepatitisB liver cancer group, liver cirrhosis group were 4.3% and 6.8%, were lower than the normalcontrol group (17.1%,χ~2=7.837 and 4.300, P＜0.05, OR=0.355 and 0.216).Conclusions 1. Hepatitis B virus infection, the history of HBV and familial aggregation ofliver cancer are risk factors of liver cancer .The onset age of PHC patient with the hepatitis Bfamily history was younger which was during 30 years old to 50 years old. The familial hepatitisB patients presented the characteristic of the high incidence and aggregation of PHC. PositiveHBsAg, HBeAb and HBcAb were more common in HBV infection pattern of PHC. It took animportant role HBV-DNA replication in the morbidity of PHC. It showed that anti-virustreatment was important in the familial hepatitis B patients especially in the familial PHC.2. HLA-DRB1*0701 allele is the susceptible gene in the patients of chronic hepatitis B,liver cirrhosis and liver cancer with familial hepatitis B. HLA-DRB1*0701 allele is associatedwith the replication of HBV. HLA-DRB1*0101 allele may be the susceptible gene in the PHCwith the familial hepatitis B. HLA-DRB1*1501 may be the resistance gene in liver cirrhosis andthe liver cancer with hepatitis B family history.