Replication of hepatitis B virus in first-degree relatives of patients with hepatocellular carcinoma.

Abstract

Abstract. Hepatocellular carcinoma (HCC) may occur in family clusters. No genetic mechanism has been identified as responsible for this familial tendency. We suspected that a longer hepatitis B virus (HBV) replication phase might be the reason for a higher risk of HCC in families with this disease. We performed liver biochemical tests, test for viral hepatitis markers and hepatitis B e antigen (HBeAg), and liver ultrasonography in relatives of patients with HCC. A total of 1,885 first-degree relatives from 688 families participated in this study. Seven hundred fiftytwo relatives were found to be carriers of hepatitis B surface antigen (HBsAg) and 675 of them were tested for HBeAg. The prevalence of HBeAg was 27.4% in relatives of those with HCC and 20% in asymptomatic HBsAg carriers. The HBeAg prevalence rate was higher in relatives of those with HCC Ն 40 years old than in asymptomatic HBsAg carriers. Moreover, HBeAg was more likely to persist in men than in women Ն 40 years old. We conclude that families with HCC showed a prolonged HBV replication phase that may be one of the cofactors for a familial tendency for HCC.A familial tendency is one of the risk factors for hepatocellular carcinoma (HCC). 1-5 Between 6% and 20% of patients with HCC have more than 1 case of HCC in their family. Among the known factors involved in hepatocarcinogenesis, genetic mechanisms may be responsible for familial HCC. However, this has not been confirmed. 3 Families with HCC are usually clustered with carriers of hepatitis B surface antigen (HBsAg), and their infections with hepatitis B virus (HBV) have usually been acquired through vertical transmission. 6-10 Since 50% of HBV carriers are infected by vertical transmission in Taiwan, 11-13 vertical transmission alone does not explain the familial tendency of HCC. It had been postulated that damage to genomic DNA by prolonged hepatic inflammation and regeneration may be the main reason for replication of HBV. 14-16 A familial tendency of prolonged HBV replication could be a possible mechanism for familial HCC.Both serum HBV DNA and hepatitis B e antigen (HBeAg) are good indicators of HBV replication. Testing for HBeAg in serum is the less expensive than testing for HBV DNA and has a clear end point that makes interpretation of results and comparisons easier. 13,17,18 Therefore, we studied HBeAg in the HBsAg-positive relatives of families with HCC. PATIENTS AND METHODSOver a 5-year period, we performed a survey in families with HCC. First-degree relatives Ͼ 15 years old were included in this survey. The study was reviewed and approved by the Department of Health, Republic of China and Chang Gung Memorial Hospital. The families with an index case of HCC that was diagnosed in our hospital were encouraged to participate in this study. The relatives of those families with an index case of HCC diagnosed at other hospitals were also accepted into this study if they presented certification from the original hospital. They entered this study as a result of our announcements at an outpatient...

Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with hepatocellular carcinoma

“…Logistic regression analysis identified maternal HBV DNA as a strong independent predictor of persistent HBV infection. Because families with HCC have a long HBV replication period [10], their offsprings receive a larger dose of HBV DNA and thus develop stronger tolerance to HBV [20]. Third, observation of the HCC relatives participating in this study showed that hepatitis B e antigen and HBV DNA frequently clear earlier in younger siblings than in older siblings [27].…”

“…The high prevalence of HBsAg among the offspring indicates a high maternal viral load [17]. Moreover, the high infectivity could result from prolonged viral replication phase [10], more virulent HBV strain [28], or younger maternal age [27,29].…”

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

“…This result has confirmed the prior statement that HBV infection plays a dominant role in the familial aggregation of HCC. (9,24) To better access the genetic factor involving the HCC susceptibility in the case family population, two proteomic approaches were combined for the analyses here. Different from those published proteomic studies that mainly concentrated on the comparison of the protein data for HCC patients and healthy controls, (18,25,26) our study was performed for the healthy family members of the HCC case family and the control family by detecting the molecular differences.…”

Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection—association between TGF-β1 polymorphisms and hepatocellular carcinoma

“…However, the host genetic factors that affect the HCC association remain unclear. A strong genetic component determining the outcome of HBV infection has been suggested in family studies [4]. Cytokines, as the product of host responses to inflammation, play an important role in the defense against viral infections and carcinogenesis [5].…”