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      Single-nucleotide polymorphism of rs7944135 (macrophage-expressed gene 1) is associated with hepatitis B surface antigen seroclearance in chronic hepatitis B infection : A cohort study

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          Abstract

          Clearance of the hepatitis B surface antigen (HBsAg) is the ultimate aim of treatment for patients with chronic hepatitis B (CHB) infection. Genetic, factor age, and gender were reported to be involved in the clearance of HBsAg. However, the rate of HBsAg seroclearance in CHB patients is still low globally and few of the single-nucleotide polymorphism (SNP) had been identified to associated with HBsAg seroclearance in CHB patients.

          Recently, 3 associated SNPs (rs7944135, rs171941, and rs6462008) were reported in the clearance of HBsAg in the Korean population. However, these SNPs have not been investigated in the CHB Taiwanese population. In present study, these 3 SNPs were genotyped in 2565 Taiwanese CHB patients including 493 CHB patients with HBsAg seroclearance and 2072 without HBsAg seroclearance.

          We observed that SNP rs7944135 was solely associated with HBsAg seroclearance. Subjects with the AA genotype at rs7944135 of macrophage-expressed gene 1 had a higher susceptibility to HBsAg clearance, compared to those with the AG or GG genotype under the genotypic model (odds ratio [OR] = 1.76. 95% confidence interval [CI] = 1.14–2.72, P = .045). Furthermore, we found a 1.74-fold increased risk of acquiring HBsAg seroclearance associated with the AA genotype compared to AG + GG of rs7944135 under the recessive model (OR = 1.74. 95% CI = 1.13–2.66, P = .014). According to the cumulative fraction curve with the log-rank test revealed that patients with the AA genotype of rs7944135 showed higher susceptibility to occur HBsAg seroclearance ( P = .039) and HBV DNA undetectable ( P = .0074) compared to those with the AG or GG genotype.

          This study examined the associations of 3 SNPs (rs7944135, rs171941, and rs6462008) with HBsAg seroclearance, and we identified that rs7944135 is solely associated with HBsAg seroclearance in Taiwanese CHB patients.

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          HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up.

          Chia-Ming Chu, Yun-Fan Liaw (2007)
          Spontaneous hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection has long been suggested as a rare event in high endemic areas. The prevalence of HBsAg in the general population of Taiwan, however, decreased remarkably from 15%-20% before age 40 to 5%-10% after age 60 or 70. This study aimed to reexamine the rates of HBsAg seroclearance by a long-term follow-up of 1965 hepatitis B e antibody-positive asymptomatic adult carriers. Of these, 1076 (55%) were males, the mean (+/-SD) age was 35.6+/-9.2 years and the mean follow-up was 10.8+/-5.4 years. Hepatitis relapsed in 314 patients, 0.5 to 18 (mean+/-SD=5.8+/-4.4) years after the entry. The probability of hepatitis relapse correlated positively with male sex (P<0.0001) and age at entry (P<0.0001). Serum HBsAg cleared in 245 patients at the mean age of 47.8+/-9.6 years. The cumulative probabilities of HBsAg seroclearance were 8.1% after 10 years, but increased disproportionally to 24.9% and 44.7%, respectively, after 20 and 25 years. In multivariate analysis, the probability of HBsAg seroclearance correlated positively with age at entry (P<0.0001) and sustained remission of hepatitis (P<0.0001) and marginally significantly with male sex (P=0.053). Cumulative rate of HBsAg seroclearance in asymptomatic adult carriers from high endemic areas was approximately 40% after 25 years of follow-up. The low HBsAg seroclearance rates in previous studies might be due to the relative short period of follow-up.
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            Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis

            Yee Yeo, Hsiu Ho, Hwai-I Yang … (2019)
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              Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus.

              Josephine Simonetti, Lisa Bulkow, Brian J McMahon … (2010)
              Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1,271 Alaska Native persons with chronic HBV infection followed for an average of 19.6 years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A, B, C, D, and F) found in this population. Participants were followed for an average of 108.9 months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3 years after HBsAg clearance (range, 2.0-15.5 years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5-80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1-264.5; P < 0.001]). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6 years after clearance. HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: December 2019
                Publication date (Electronic): 20 December 2019
                Volume: 98
                Issue: 51
                Electronic Location Identifier: e17936
                Affiliations
                [a ]Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy
                [b ]Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
                [c ]Faculty of Pharmacy, University of Ahmad Dahlan, Yogyakarta, Indonesia
                [d ]Genomics Research Center, Academia Sinica
                [e ]Institute of Clinical Medicine, National Yang-Ming University
                [f ]Integrative Research Center for Critical Care, Wan fang Hospital, Taipei Medical University, Taipei
                [g ]Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
                Author notes
                [∗ ]Correspondence: Wei-Chiao Chang, Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan (e-mail: wcc@ 123456tmu.edu.tw ); Hwai-I Yang, Genomics Research Center, Academia Sinica, Taipei, Taiwan (e-mail: hiyang@ 123456gate.sinica.edu.tw ).
                Article
                Publisher ID: MD-D-19-04438 Accession ID: 17936
                DOI: 10.1097/MD.0000000000017936
                PMC ID: 6940119
                PubMed ID: 31860948
                SO-VID: e053d017-bc4a-4959-b1e8-539980068599
                Copyright © Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                Date received : 04 June 2019
                Date revision received : 04 September 2019
                Date accepted : 14 October 2019
                Categories
                Subject: 4500
                Subject: Research Article
                Subject: Observational Study
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: chb,hbsag seroclearance,hbv,rs7944135,single-nucleotide polymorphism
                Data availability:
                Keywords: chb, hbsag seroclearance, hbv, rs7944135, single-nucleotide polymorphism

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