Browsing by Author "Coffin, Carla S"

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    Burden of Chronic Hepatitis B in Alberta, Canada
    (2023-10-12) Kochaksaraei, Golasa Samadi; Shaheen, Abdel-Aziz; Coffin, Carla S; Barkema, Herman; Seow, Cynthia
    Limited recent data exist on chronic hepatitis B (CHB) burden in the North American general population, especially among women of childbearing age (WoCBA). Despite evidence supporting peripartum tenofovir disoproxil fumarate (TDF) prophylaxis in reducing mother-to-child transmission (MTCT), long-term outcomes of untreated and TDF-treated CHB pregnant women are understudied. We aimed to identify the CHB burden in Alberta, Canada, among all ages and WoCBA (18-49 years) and assess clinical outcomes in a multiethnic cohort of CHB patients during pregnancy and postpartum. We retrospectively searched Alberta Analytics administrative databases to describe CHB epidemiology and natural history in all ages and WoCBA between fiscal years 2012-2020. We also examined care linkage among hepatitis B surface antigen (HBsAg)-positive pregnant women during the same period. Furthermore, we collected real-world clinical data during pregnancy and postpartum in women with CHB between 2011-2019. From 2015-2020, the CHB incidence declined to 13.4/100,000 (from 36.4/100,000) for all ages and 18.2/100,000 (from 52.6/100,000) for WoCBA. However, prevalence increased to 210.3/100,000 (from 98.9/100,000) for all ages and 248.6/100,000 (from 131.7/100,000) for WoCBA. CHB patients had lower survival rates than age/sex-matched Canadians (standardized mortality ratios of 3.9 and 5.7 for all ages and WoCBA, respectively). Among 1,927 women (2,436 HBsAg-positive pregnancies) between 2012-2020, 27.6% had recommended hepatitis B-directed assessment during pregnancy and 66.4% of those eligible for antiviral prophylaxis received treatment. In 341 women (446 pregnancies) followed for a median of 33 months postpartum, 19% received TDF (64/341, 53/64 for MTCT prevention). In HBeAg-positive patients (65/341), alanine aminotransferase (ALT) flares were more common, especially in those who stopped TDF postpartum. HBsAg clearance occurred in 2.6% (9/341, 2/9 TDF treated) at a median of 30 months, and 37% (24/65) of hepatitis B e antigen (HBeAg)-positive patients had HBeAg loss at a median of 17 months postpartum. In conclusion, CHB incidence decreased in Alberta among all ages and WoCBA. Our study demonstrates frequent ALT flares, particularly after TDF withdrawal, HBeAg clearance in 37%, and HBsAg loss in 2.9% of patients during long-term postpartum follow-up. The lower survival and suboptimal management of CHB during pregnancy emphasize addressing barriers to guideline recommended HBV care in WoCBA.
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    Chronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants
    (2017-10-24) Gao, Shan; Joshi, Shivali S; Osiowy, Carla; Chen, Y.; Coffin, Carla S; Duan, Z-P.
    Abstract Background The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. Methods Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. Results Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p < 0.0001). Conclusion In our study, ACLF was not associated with a specific genomic mutation. However, higher frequency of IE mutations along with various mutations clustering in the HBV S region could contribute to or be an outcome of ACLF in CHB infection. (words 226).
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    Clinical associations and potential novel antigenic targets of autoantibodies directed against rods and rings in chronic hepatitis C infection
    (BioMed Central, 2013-03-19) Stinton, Laura M; Myers, Robert P; Coffin, Carla S; Fritzler, Marvin J
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    Compartmental Hepatitis B Virus (HBV) Evolution, Replication and Infectivity in vivo and ex vivo
    (2017) Gao, Shan; Coffin, Carla S; Lee, Samuel S.; Duan, Zhongping; Van Marle, Guido; van der Meer, Frank
    Hepatitis B Virus (HBV) is classically considered a hepatotropic virus, however, the presence of different HBV genomic molecules in lymphoid cells and tissues support its lymphotropic nature. Our previous studies showed that HBV evolved in a compartment- and disease phase-specific fashion. However, the effect of nucleos/tide analogue (NA) therapy on HBV evolution and replication in different compartments (i.e., liver, plasma and peripheral blood mononuclear cell (PBMC)) is unknown, as well as the replicative competence and infectious capacity of PBMC-derived HBV. We hypothesize that HBV replicating in lymphoid cells is infectious, and the HBV evolves in PBMC and/or plasma in chronic hepatitis B (CHB) patients under the influence of NA therapy or host immune pressure (i.e., fulminant hepatitis B). The study on HBV replication and genetic evolution in PBMC, liver and plasma of CHB patients under NA therapy revealed the HBV evolution varied between three compartments both before and after treatment. NA had little effect on HBV cccDNA level and persistence of mRNA in PBMC. The study on HBV genetic features in CHB carriers with acute-on-chronic liver failure (ACLF) revealed the frequent immune escape mutations with clusters of surface gene variants possibly associated with development of fulminant hepatitis B. Mitogen stimulation in PBMC of CHB patients revealed presence of replicating HBV, which can be upregulated in PBMC and exhibited infectious capacity to HepaRG cells in vitro. In summary, our data suggests potent NAs have little effect on HBV cccDNA in liver and PBMC, which highlights the need for continued suppressive antiviral therapy. The HBV evolution varied between different compartments in CHB patients under NA therapy. Distinct variants in HBV surface gene were found to be associated with HBV fulminant hepatitis. Moreover, HBV residing in lymphoid cells is increased after mitogen stimulation of PBMC and infectious to a hepatocyte cell line. The study furthers our understanding of HBV lymphotropism, role on viral persistence and the pathogenesis of chronic hepatitis B.
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    Treatment Outcomes with Telaprevir-Based Therapy for HIV/Hepatitis C Coinfected Patients are Comparable with Hepatitis C Monoinfected Patients
    (2015-01-01) O’Neil, Conar R; Pang, Jack XQ; Lee, Samuel S; Swain, Mark G; Burak, Kelly W; Klein, Patricia; Myers, Robert P; Kapler, Jeff; Gill, Michael J; Labrie, Martin; Coffin, Carla S