Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma

Tong, Myron J.; Weiner, John M.; Ashcavai, Mary; Vyas, Girish N.

doi:10.1002/1097-0142(197912)44:6<2338::aid-cncr2820440650>3.0.co;2-i

Cited by 26 publications

(15 citation statements)

References 29 publications

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“…Further evidence was provided by familial clustering of patients with HCC who are also chronically infected with HBV (Ohbayashi et al . 1972; Tong et al . 1979).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus and hepatocellular carcinoma

Arbuthnot

Kew

2001

Int J Experimental Path

259

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Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100-fold increased relative risk of developing the tumour. Several mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the genome of hepatocytes occurs commonly, although integration at cellular sites that are important for regulation of hepatocyte proliferation appears to be a rare event. Functions of the HBx protein are also potentially oncogenic. These include transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA. The effects of HBx are mediated by interaction with cellular proteins and activation of cell signalling pathways. Variations in HBV genome sequences may be important in hepatocarcinogenesis, although their significance has not yet been completely elucidated. Necroinflammatory hepatic disease, which often accompanies chronic HBV infection, may contribute indirectly to hepatocyte transformation in a number of ways, including by facilitating HBV DNA integration, predisposing to the acquisition of cellular mutations and generating mutagenic oxygen reactive species. Although HCC is a malignancy with a poor prognosis, the availability of an effective vaccine against HBV infection, and its inclusion in the Expanded Programme of Immunization of many countries, augurs well for the eventual elimination of HBV-associated HCC.

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“…Further evidence was provided by familial clustering of patients with HCC who are also chronically infected with HBV (Ohbayashi et al . 1972; Tong et al . 1979).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus and hepatocellular carcinoma

Arbuthnot

Kew

2001

Int J Experimental Path

259

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“…More than 70% of the mothers of patients with HCC are HBsAg carriers. [7][8][9][10] Maternal HBV status was documented in about half of the study patients, but we were unable to find a significantly higher prevalence of HBeAg in HBsAg carriers who were infected by vertical transmission. It was difficult to analyze this question because we had not observed the patients since birth.…”

Section: Discussionmentioning

confidence: 99%

“…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][7][8][9][10] Since 50% of HBV carriers are infected by vertical transmission in Taiwan, [11][12][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.…”

mentioning

confidence: 99%

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

Tai¹,

Changchien²,

Hung³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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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...

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“…When advanced, it leads to liver cirrhosis (LC). HBV or HCV infection also increases the risk of development of hepatocellular carcinoma (HCC), which is one of the most common human cancers that lead to death [27,28].…”

Section: Introductionmentioning

confidence: 98%