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Association of NTCP Gene Polymorphisms and Spontaneous Clearance of Hepatitis B Virus in Asia: A Meta-Analysis. HEPATITIS MONTHLY 2019. [DOI: 10.5812/hepatmon.94500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Al-Qahtani A, Khalak HG, Alkuraya FS, Al-hamoudi W, Al-hamoudy W, Alswat K, Al Balwi MA, Al Abdulkareem I, Sanai FM, Abdo AA. Genome-wide association study of chronic hepatitis B virus infection reveals a novel candidate risk allele on 11q22.3. J Med Genet 2013; 50:725-32. [PMID: 24065354 DOI: 10.1136/jmedgenet-2013-101724] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) affects millions of people worldwide. While some people are able to clear the virus following the first encounter, those who develop chronic infection manifest remarkable clinical heterogeneity that ranges from asymptomatic carrier state to cirrhosis and hepatocellular carcinoma. Despite extensive studies, little is known about genetic host factors that influence the outcome of chronic HBV infection. Thus, we conducted this study to investigate the genetic risk of developing active liver disease among chronic carriers of HBV. METHODS In this study, we conducted a genome-wide association study (GWAS) on a cohort of patients with chronic HBV infection. RESULTS One particular SNP that is 16 kb upstream of Ferredoxin 1 was found to have an association with complicated chronic HBV infection (cirrhosis and hepatocellular carcinoma) that reached GWAS significance, and was successfully validated on an independent set of samples. CONCLUSIONS This first GWAS in an Arab population further demonstrates the utility of this approach in elucidating the genetic risk of HBV infection-related complications and highlights the advantage of conducting GWAS in different ethnicities to achieve that goal.
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Affiliation(s)
- Ahmed Al-Qahtani
- Department of Infection and Immunity, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
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Yang Y, Jin L, He YL, Wang K, Ma XH, Wang J, Yan Z, Feng YL, Li YQ, Chen TY, Liu HL, Zhao YR. Hepatitis B virus infection in clustering of infection in families with unfavorable prognoses in northwest China. J Med Virol 2013; 85:1893-9. [PMID: 23934703 DOI: 10.1002/jmv.23649] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2013] [Indexed: 12/22/2022]
Affiliation(s)
- Yuan Yang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Li Jin
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ying-Li He
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ke Wang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Xiao-Hua Ma
- Department of Infectious Disease; the Eighth Hospital; Xi'an Shaanxi China
| | - Jing Wang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Zhi Yan
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Yu-Ling Feng
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Yong-Qin Li
- Department of Infectious Disease; Xi'an Central Hospital; Xi'an Shaanxi China
| | - Tian-Yan Chen
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Hong-Li Liu
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ying-Ren Zhao
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
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Urganci N, Akyildiz BN, Kalyoncu D, Gulec SG. Familial clustering of HBV in families with children who are diagnosed as chronic hepatitis B or inactive carriers of HBV. J Child Health Care 2013; 17:197-203. [PMID: 23455870 DOI: 10.1177/1367493512456115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The aim of this study was to assess and compare the spread of HBV infection in families with children who are diagnosed as chronic hepatitis B or are inactive carriers of HBV. A total of 570 patients aged 2-16 years and 2358 family members were included in the study. Patients were classified as inactive carriers (Group 1, 350 patients) or patients diagnosed as chronic active hepatitis B (Group 2, 220 patients). Demographic features of the families, HBV serological markers and routes of transmission were evaluated. Parental transmission was lower compared to nonparental transmission (34.8% and 65.1%, respectively). HBsAg positivity rate was found to be highest among mothers in both of the groups. HBeAg positivity and anti-HBs positivity were significantly higher in family members of Group 2. Transmission rates were significantly higher in families consisting of five or more members compared to families consisting of less than five members. HBsAg positivity of siblings was lowest when both parents were HbsAg negative and highest when both parents were HBsAg positive in both groups. A high risk of HBV transmission among mothers of HBsAg carriers and patients with chronic hepatitis B was demonstrated.
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Abstract
The clinical course of hepatitis B virus (HBV) infection varies from spontaneous recovery to chronic persistent infection leading to severe liver injury. Mounting evidence has recently highlighted the influence of host genotype in the complex interplay between viral and host factors. Studies in adults have suggested the existence of a genetic predisposition to HBV infection secondary to certain defects in the host response. These defects include opsonic deficiency, compromised antigen processing and presentation by human leucocyte antigen variations, attenuated T- and B-cell response, impaired cytokine and chemokine release, and production of receptors for several pertinent factors such as vitamin D and estrogen. By contrast, little is known about the genetic factors involved in the susceptibility to HBV transmission in early childhood. Herein, we review the literature regarding the association between host genetics and susceptibility to primary HBV infection, and we discuss the prospects of investigation in this field. A better understanding of HBV infection immunopathogenesis in the critical period of infancy may allow the development of optimal and innovative prevention and treatment.
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Tong MJ, Nguyen MO, Tong LT, Blatt LM. Development of hepatocellular carcinoma after seroclearance of hepatitis B surface antigen. Clin Gastroenterol Hepatol 2009; 7:889-93. [PMID: 19394445 DOI: 10.1016/j.cgh.2009.04.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2008] [Revised: 02/18/2009] [Accepted: 04/15/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS During the natural course of chronic hepatitis B virus infection, a small proportion of patients experience hepatitis B surface antigen (HBsAg) seroclearance. However, the long-term clinical outcomes of this process are not well established. METHODS Thirty-five patients with chronic hepatitis B, followed between 1976 and 2008 at a community liver clinic, experienced HBsAg seroclearance. Ten patients were Caucasian and 25 were Asian. These patients continued to undergo surveillance for hepatocellular carcinoma that included test for alpha-fetoprotein levels and abdominal ultrasound examinations. The median follow-up time was 185 months (range, 27-400 months). RESULTS During the initial visit to the clinic, the median age of the patients was 41 years (range, 1.5-72 years). Eighteen patients (51.4%) were hepatitis B e antigen (HBeAg) positive 25 (71.4%) were hepatitis B virus DNA positive, and 13 (37.1%) had cirrhosis. At the time of HBsAg loss, the median age was 54 years (range, 13-77 years) and all were hepatitis B e antigen- as well as hepatitis B virus DNA negative. During the long-term follow-up, 4 patients with cirrhosis developed hepatocellular carcinoma (HCC), which was discovered by ultrasound examination. Factors associated with development of HCC were low baseline levels of albumin (P = .04), family histories of HBsAg positivity (P = .01) and HCC (P = .04), and age of less than 50 years at the time of HBsAg clearance (P = .03). CONCLUSIONS HCC can still develop after HBsAg seroclearance. Thus, surveillance should be continued after HBsAg loss in the same manner as for HBsAg positive patients.
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Affiliation(s)
- Myron John Tong
- The Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
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Liu J, Li Y, Chen T, Yang Y, Wang K, He Y, Yang Q, Ye F, Jin Y, Qiu T, Lin S, Liu M, Zhao Y. The distribution of HBV genotypes and clinical significance in familial clustering in an infected population with unfavorable prognosis. Arch Virol 2008; 153:2157-61. [PMID: 18982245 DOI: 10.1007/s00705-008-0239-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2008] [Accepted: 09/29/2008] [Indexed: 01/05/2023]
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Abstract
Genetic epidemiology researches such as twin studies, family-clustering of hepatitis B virus (HBV) infection studies and ethnic difference studies have provided the evidence that host genetic factors play an important role in determining the outcome of HBV infection. The opening questions include which human genes are important in infection and how to find them. Though a number of studies have sought genetic associations between HBV infection/persistence and gene polymorphisms, the candidate gene-based approach is clearly inadequate to fully explain the genetic basis of the disease. With the advent of new genetic markers and automated genotyping, genetic mapping can be conducted extremely rapid. This approach has been successful in some infectious diseases. Linkage analysis can find host genes susceptible to HBV and is of great clinical importance.
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Affiliation(s)
- Ying-Li He
- Department of Infectious Diseases, the First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
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Carrilho FJ, Ono-Nita SK, Cardoso RA, Cancado ELR, Pinho JRR, Alves VAF, Da Silva LC. A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin. Braz J Med Biol Res 2005; 38:1399-408. [PMID: 16138224 DOI: 10.1590/s0100-879x2005000900015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectively. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.
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Affiliation(s)
- F J Carrilho
- Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
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Doganci T, Uysal G, Kir T, Bakirtas A, Kuyucu N, Doganci L. Horizontal transmission of hepatitis B virus in children with chronic hepatitis B. World J Gastroenterol 2005; 11:418-20. [PMID: 15637758 PMCID: PMC4205352 DOI: 10.3748/wjg.v11.i3.418] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the possible routes of intrafamilial transmission pattern in pediatric cases of chronic hepatitis B virus (HBV) infection.
METHODS: In this descriptive retrospective study, 302 children with chronic HBV infection from 251 families and their parents attending the Social Security Children’s Hospital and Doctor Sami Ulus Children’s Hopsital in Ankara between December 1998 and May 2000, were enrolled in. Screenings and diagnosis of chronic HBV infections were established according to the Consensus 2000.
RESULTS: In the studied 302 children with chronic HBV infection, mothers of 38% and fathers of 23% were HBsAg positive. The HBsAg positivity in at least two siblings of the same family was 61% when both parents were HBsAg positive.
CONCLUSION: It is well known that horizontal transmission is quite common in countries where Hepatitis B Virus is moderately endemic. To our best knowledge, this is the largest series observed regarding the horizontal transmission in pediatric chronic HBV infection in Turkey. It is necessary to expand the preventive programs to target not only the newborn period but also all stages of childhood.
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Affiliation(s)
- Tumay Doganci
- Department of Pediatric Gastroenterology, SSK Ankara Children's Hospital, 06018 Ankara, Turkey
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Ono-Nita SK, Carrilho FJ, Cardoso RA, Nita ME, da Silva LC. Searching for chronic hepatitis B patients in a low prevalence area--role of racial origin. BMC FAMILY PRACTICE 2004; 5:7. [PMID: 15084223 PMCID: PMC419702 DOI: 10.1186/1471-2296-5-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/11/2003] [Accepted: 04/13/2004] [Indexed: 01/25/2023]
Abstract
Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B.
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Affiliation(s)
- Suzane Kioko Ono-Nita
- Hepatology Branch, Dept. of Gastroenterology, University of São Paulo School of Medicine, Brazil
| | - Flair José Carrilho
- Hepatology Branch, Dept. of Gastroenterology, University of São Paulo School of Medicine, Brazil
| | - Rita A Cardoso
- Hepatology Branch, Dept. of Gastroenterology, University of São Paulo School of Medicine, Brazil
| | - Marcelo Eidi Nita
- Hepatology Branch, Dept. of Gastroenterology, University of São Paulo School of Medicine, Brazil
| | - Luiz Caetano da Silva
- Hepatology Branch, Dept. of Gastroenterology, University of São Paulo School of Medicine, Brazil
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Lin CC, Ng LT, Hsu FF, Shieh DE, Chiang LC. Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth. Clin Exp Pharmacol Physiol 2004; 31:65-9. [PMID: 14756686 DOI: 10.1111/j.1440-1681.2004.03951.x] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
1. The present study was conducted to evaluate the cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents on hepatoma and leukaemia cells in vitro. 2. Four human liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and four leukaemia cell lines, namely K562, U937, P3H1 and Raji, were used in the present study. 3. Of the two crude drugs, C. chinensis exhibited the strongest activity against SK-Hep1 (IC50 = 7 microg/mL) and Raji (IC50 = 4 microg/mL) cell lines. The IC50 values for C. chinensis on HepG2, Hep3B and PLC/PRF/5 cell lines were 20, 55 and 35 microg/mL, respectively. The IC50 values for C. chinensis on K562, U937 and P3H1 cell lines were 29, 29 and 31 microg/mL, respectively. 4. With the exception of HepG2 and Hep3B, the E. sagittatum extract inhibited the proliferation of all cell lines (SK-Hep1, PLC/PRF/5, K562, U937, P3H1 and Raji), with IC50 values of 15, 57, 74, 221, 40 and 80 microg/mL, respectively. 5. Interestingly, the two major compounds of C. chinensis, berberine and coptisine, showed a strong inhibition on the proliferation of both hepatoma and leukaemia cell lines, with IC50 values varying from 1.4 to 15.2 microg/mL and from 0.6 to 14.1 microg/mL, respectively. However, icariin (the major compound of E. sagittatum) showed no inhibition of either the hepatoma or leukaemia cell lines. 6. The results of the present study suggest that the C. chinensis extract and its major constituents berberine and coptisine possess active antihepatoma and antileukaemia activities.
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Affiliation(s)
- Chun-Ching Lin
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
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Lin LT, Liu LT, Chiang LC, Lin CC. In vitro anti-hepatoma activity of fifteen natural medicines from Canada. Phytother Res 2002; 16:440-4. [PMID: 12203264 DOI: 10.1002/ptr.937] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae), Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae), Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent. (Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L. (Malvaceae), which have been used as folk medicine in Canada, were evaluated for their anti-hepatoma activity on five human liver-cancer cell lines, i.e. HepG2/C3A, SK-HEP-1, HA22T/VGH, Hep3B and PLC/PRF/5. The samples were examined by in vitro evaluation for their cytotoxicity. The results showed that the effects of crude drugs on hepatitis B virus genome-containing cell lines were different from those against non hepatitis B virus genome-containing cell lines. C. groenlandica was observed to be the most effective against the growth of all five cell lines and its chemotherapeutic values will be of interest for further studies.
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Affiliation(s)
- Liang-Tzung Lin
- Department of Microbiology and Immunology, McGill University, Canada
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Thomson AB, Mahachai V, Bailey RJ, Kirdeikis P, Zuk L, Marriage B, Simpson I, Jamali F. Twice daily nizatidine or ranitidine is superior to once daily dosing in elevating 24 h intragastric pH in patients with duodenal ulcer disease. J Gastroenterol Hepatol 1996. [PMID: 9034938 DOI: 10.1111/j.1440-1746.1996.tb00279.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00-08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00-22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2 vs N1) or ranitidine (R2 vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2-receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2-receptor antagonists; doubling the dose of the H2-receptor antagonist (R2 vs R1 and N2 vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six-fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.
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Affiliation(s)
- A B Thomson
- Department of Medicine, University of Alberta, Edmonton, Canada
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Alberts SR, Lanier AP, McMahon BJ, Harpster A, Bulkow LR, Heyward WL, Murray C. Clustering of hepatocellular carcinoma in Alaska Native families. Genet Epidemiol 1991; 8:127-39. [PMID: 1655562 DOI: 10.1002/gepi.1370080206] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Alaska Natives have a high incidence of hepatocellular carcinoma (HCC), with regional, ethnic, village, and familial clustering. During 1969-1988, 15 of the 45 incident cases of HCC in Alaska Natives occurred in 5 families. This report presents epidemiologic, virologic, and immunogenetic data on these 5 families. The results of hepatitis B virus (HBV) serologic testing indicates that HBV infection was an important factor in 4 of the 5 families. Human lymphocyte antigen (HLA) testing was performed in 3 families. The HLA results are reviewed in relationship to the familial clustering of HCC.
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Affiliation(s)
- S R Alberts
- Arctic Investigations Program, Centers for Disease Control, Anchorage, Alaska 99501
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Ramia S. Intrafamilial clustering of hepatitis B virus (HBV) infection: study of 10 Saudi families. ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 1990; 84:623-7. [PMID: 2076040 DOI: 10.1080/00034983.1990.11812518] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In order to evaluate the extent of intrafamilial clustering of hepatitis B virus (HBV) infection, serological tests for evidence of HBV infection were performed on family members of 10 Saudi children who were found to be HBs Ag-positive. The overall prevalences of carriers (HBs Ag-positive) and exposure (presence of any HBV marker) in the 89 siblings were 17.9 and 34.8%, respectively. In siblings of families where the mother was a carrier, exposure to HBV (51.6%) was higher (chi 2 = 1.99, P = 0.15) than in siblings of families where only the father was a carrier (31.4%) and significantly higher (chi 2 = 5.24, P = 0.02) than in siblings of families where neither of the parents was a carrier but both had previous exposure to HBV infection (17.4%). Our data indicate that mainly horizontal and perhaps perinatal transmission could account for this relatively high level of intrafamilial clustering of HBV infection in Saudi families. These results are important for the development of a strategy for controlling HBV infection in Saudi Arabia and perhaps in similar HBV endemic areas.
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Affiliation(s)
- S Ramia
- Department of Pathology, College of Medicine King Khalid University Hospital, Riyadh, Saudi Arabia
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Taylor R, Montaville B, Levy S, Gust I, Moreau JP, Dimitrakakis M, Bach F, Brethes B, Laille M, DeRoeck D. Hepatitis B infection in Vanuatu: age of acquisition of infection and possible routes of transmission. Asia Pac J Public Health 1989; 3:205-12. [PMID: 2620021 DOI: 10.1177/101053958900300306] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Seroepidemiological studies of hepatitis B were carried out on diverse groups of children (477) and adults (629) from the Pacific Island country of Vanuatu. In children under 14 years, prevalences of HBsAg and of all markers were 6% and 53.3% respectively; in adults greater than or equal to 20 years the prevalences were 15% and 70%. Age specific prevalence of hepatitis B infection (all markers) was low in infancy (less than 1 year) but rose sharply afterwards, suggesting that the main mechanism of transmission was horizontal spread. This finding is consistent with other developing country studies from the Pacific Islands and elsewhere. In view of the main ages and mechanisms of transmission of hepatitis B in children in developing countries and the need for simple and inexpensive immunisation strategies in this context, it is recommended that mass vaccination of all infants with hepatitis B vaccine be undertaken in hyperendemic areas.
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Arya SC. Re: Epidemiological aspects of acute viral hepatitis in Portugal. Infection 1987; 15:265-7. [PMID: 3666971 DOI: 10.1007/bf01644134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Wu TC, Tong MJ, Hwang B, Lee SD, Hu MM. Primary hepatocellular carcinoma and hepatitis B infection during childhood. Hepatology 1987; 7:46-8. [PMID: 2433204 DOI: 10.1002/hep.1840070111] [Citation(s) in RCA: 70] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Twenty pediatric patients with primary hepatocellular carcinoma in Taiwan were tested for HBsAg, and all were found to be positive. The youngest case was 8 months of age, five cases occurred between 9 and 10 years of age, and 14 cases occurred between 11 and 16 years of age. The serum alpha-fetoprotein was elevated in all 20 primary hepatocellular carcinoma patients, and the average survival of these cases after diagnosis was 4.7 months. Seventy per cent of the mothers of the pediatric primary hepatocellular carcinoma cases and 52.9% of their siblings who were tested also were positive for HBsAg. In addition, two families had clustering of primary hepatocellular carcinoma cases. The occurrence of primary hepatoceullar carcinoma in the pediatric age group suggests the need for close follow-up of young HBsAg-positive carriers. Also, prevention of perinatal transmission of hepatitis B virus by immunoprophylaxis will significantly decrease both the hepatitis B virus carrier rate and the incidence of primary hepatocellular carcinoma in the asian population.
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Kashiwagi S, Hayashi J, Nomura H, Ikematsu H, Kajiyama W. Large-scale survey of hepatitis B virus infection in families. Microbiol Immunol 1985; 29:951-8. [PMID: 4079845 DOI: 10.1111/j.1348-0421.1985.tb02959.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
To investigate HBV transmission in families on three islands in Okinawa, Japan, prevalence of HBV markers in two groups of inhabitants was determined. One group consisted of members of families in which there was at least one HBsAg carrier (carrier families); the other group consisted of members of families in which there were no HBsAg carriers (non-carrier families). A total of 3,261 serum samples were collected from subjects on Iriomote Island, Hateruma Island, and Yonaguni Island. These samples were tested for HBsAg by reversed passive hemagglutination (RPHA) and for antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay. Overall prevalences of HBsAg and anti-HBc were 8.2 and 65.8 per cent respectively. The prevalence of anti-HBC among members of carrier families (80.8%) was significantly higher than that among members of non-carrier families (61.6%) (P less than 0.001). The prevalence of anti-HBc among members of carrier families was higher in all age groups, and was particularly so in children. Within carrier families, the prevalence of anti-HBc was significantly higher in families in which there was at least one HBsAg carrier with HBeAg (94.5%) than in families with no HBeAg-positive carriers (76.1%). This difference was especially marked in young children. These data suggest that in families with HBsAg carrier(s), the risk of transmitting HBV to members, particularly to young children, is higher than in families without carriers, and that the risk is further increased in families with HBeAg-positive carrier(s).
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Ben-Porath E, Wands JR, Marciniak RA, Wong MA, Hornstein L, Ryder R, Canlas M, Lingao A, Isselbacher KJ. Structural analysis of hepatitis B surface antigen by monoclonal antibodies. J Clin Invest 1985; 76:1338-47. [PMID: 2414317 PMCID: PMC424071 DOI: 10.1172/jci112108] [Citation(s) in RCA: 31] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
A method has been developed for the analysis of hepatitis B surface antigen (HBsAg) antigenic structure at the molecular level that creates "fingerprints" or "signatures" of various hepatitis B viral (HBV) strains. This technique employs high affinity IgM and IgG monoclonal antibodies (anti-HBs) directed against distinct and separate determinants on HBsAg. In performing this antigenic structural analysis, separate binding curves for different monoclonal anti-HBs are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum by radioimmunoassay. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples are aligned by an iterative least-squares procedure to generate the numerical signature characteristic of the viral strain. The numerical signatures are then displayed on a computer-graphic plot. The signature profiles of HBsAg subtypes are a true reflection of their antigenic structure, and in vertical and horizontal transmission studies the molecular characteristics of the viral epitopes are conserved. By signature analysis we found substantial antigenic heterogeneity among the ayw3 strain both in the U.S. and France, as well as in populations of the Far East and Africa. Populations in Ethiopia, Gambia, and the Philippines were infected with two antigenically distinct HBV strains. In some newly identified HBV strains, it was found that epitopes identified by some monoclonal antibodies were absent or substantially reduced, which suggested that a genetic mutation may have occurred. Thus this study suggests that there is far more antigenic heterogeneity in HBV than previously recognized. These variants are antigenically distinct from each other at the epitope level, and were heretofore unrecognized by polyvalent anti-HBsAg antibodies.
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Goh KT, Ding JL, Monteiro EH, Oon CJ. Hepatitis B infection in households of acute cases. J Epidemiol Community Health 1985; 39:123-8. [PMID: 4009096 PMCID: PMC1052419 DOI: 10.1136/jech.39.2.123] [Citation(s) in RCA: 33] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Seroepidemiological studies conducted in 369 household contacts of 80 acute cases of hepatitis B in Singapore showed that asymptomatic chronic carriers of hepatitis B surface antigen (HBs Ag) are the main source of acute hepatitis B infection. The HBs Ag prevalence rate in asymptomatic household members was 20% compared with a 6% prevalence for the general population. The majority of the household carriers (60%) were highly infectious with positive hepatitis e antigen (HBe Ag). The overall prevalence of HBV infection (with at least one HBV marker) of the household contacts was 40.7%. Spouses and parents of acute cases had a significantly higher prevalence of HBV infection than other members of the families. HBV prevalence rate showed no association with the household size. Factors associated with the risk of transmission of HBV infection included sharing of various personal and household articles, such as toothbrush, towel, handkerchief, clothing, razor, comb, bed and bedding. Sleeping in the same bedroom, eating together at meals, and sharing of eating and drinking utensils were not associated with an increased risk of transmission of infection. Follow-up studies six months later showed that 30% of the acute cases became chronic HBs Ag carriers (with 46% HBe Ag positive), thus providing an additional source of infection in the families, while 8% of the susceptible household members acquired asymptomatic HBV infection. Health education on the prevention of HBV transmission in the homes of acute cases should be based on sound epidemiological information. Household contacts of acute cases of hepatitis B should be routinely screened and the susceptible vaccinated against the disease as soon as possible.
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Chadwick RG, Hall AJ, Davidson I, Bull FG, Wright R. Hepatitis B among Indochinese refugees in Great Britain. Postgrad Med J 1982; 58:676-9. [PMID: 7170264 PMCID: PMC2426574 DOI: 10.1136/pgmj.58.685.676] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Six hundred and thirty-two blood samples from 879 consecutive admissions to one resettlement camp for Indochinese refugees in Great Britain were screened for markers of hepatitis B (HB) virus infection. The overall prevalence of HB surface antigen (HBsAg) was 15%, being 16% in those aged 40 years or less, and falling to 8% in those older than 40 (P less than 0.05). No significant difference in prevalence was found between males and females. HBe antigen was detected in 56% of those with HBsAg and was demonstrable in 55-76% of those under 30 years of age. HBe antibody was found in 21% of HBsAg-positive refugees. In those under 40 years old, HB core (HBc) antibody was commoner in males (P less than 0.01). HBc antibody prevalence increased significantly with age in females (P less than 0.01) but not in males. There was no definite evidence that vertical transmission of hepatitis B was present in the group studied.
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Bastiaans MJ, Nath N, Dodd RY, Barker LF. Hepatitis-associated markers in the American Red Cross volunteer blood donor population. IV. A comparison of HBV-associated serologic markers in HBsAg-positive first-time and repeat blood donors. Vox Sang 1982; 42:203-10. [PMID: 7090335 DOI: 10.1111/j.1423-0410.1982.tb01096.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The present study was undertaken to determine whether there were any differences in the distribution of hepatitis B virus-(HBV) associated serologic markers among hepatitis B surface antigen-(HBsAg) positive first-time and repeat blood donors. The markers examined in samples from 412 newly identified HBsAg-positive donors (254 first-time and 158 repeat) included HBsAg titer and subtype, HBeAg/anti-HBe, and anti-HBc. Repeat donors were more frequently HBeAg-positive (25.9%) than were first-time donors (17.7%). Anti-HBc and anti-HBe were observed more often among first-time (99.6 and 76%) than repeat (91.8 and 60.8%) donors. No differences were found in the mean HBsAg titer nor in the subtype distribution in the two populations. The frequency of HBeAg positivity and the mean HBsAg titer in blood were significantly lower among first-time donors aged 30 or older as compared to those younger than 30. Such age-related tendencies did not occur among the repeat donors. The profiles of HBV makers suggest that the HBsAg-positive first-time donor group consists predominantly of long-term HBsAg carriers who may have acquired HBV at an early age, while the HBsAg-positive repeat donors have newly acquired infections.
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Skinhøj P, Aldershvile J, Black F, Kjersem H, Kryger P, Mathiesen L. Viral hepatitis in southeast Asian refugees. J Med Virol 1981; 7:149-55. [PMID: 6267189 DOI: 10.1002/jmv.1890070209] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Five hundred sixty-four Vietnam refugees were studied for past or present infection with hepatitis A and B virus (HAV and HBV) by sensitive serological assays for hepatitis B surface and e-antigen and antibodies to HBsAg, HBeAg, HBcAg, and HAV. Fifteen percent of the men and 6% of the women were HBsAg-positive. Of these 66% were also positive for HBeAg. Serum transaminase values did not effectively differentiate between the infectious HBeAg carriers and the less infectious anti-HBe carriers. The HBsAg carrier rate did not increase by age after infancy, and among children, carriers clustered around HBsAg carrier mothers only. In contrast, the distribution of antibodies to the three HBV-associated antigens suggested continuous exposure throughout childhood, and a 90% prevalence rate was found at the age of 20 years. Screening for HBeAg in this new population group is necessary if appropriate precautions are to be taken, and if medical management of these patients is to be optimal. The prevalence of antibody to hepatitis A increases with age to 90% at 15 years. Among anti-HAV-positive children and adults IgM- anti-HAV was found in 8% of the children and none of the adults, indicating that only a few children may be in an infectious stage at the time of study, and therefore no specific prophylactic precautions are necessary.
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