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Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study.

ABSTRACT: HBV is a hepatotropic virus with multiple genotypes. It is uncertain if specific genotype(s) influence virological measures and/or liver markers over time. It is unclear whether nucleos(t)ide analogue therapy response is influenced by genotype. In this retrospective longitudinal study, we utilized data from The Ottawa Hospital Viral Hepatitis Program (TOHVHP) to evaluate the role of HBV genotype on viral load, liver enzymatic levels, fibrosis progression, and parenchymal inflammation and steatosis over time. HBV DNA, ALT, and AST levels, as well as transient elastography scores for fibrosis (E) and inflammation/steatosis (CAP), were modeled using mixed-effects linear regression. Interaction terms between HBV genotype and time were included to investigate if there was a difference in trends between genotypes. A total of 393 HBV patients infected with genotypes A-E were included. The mean age was 44.4 years, and 56% were male. Asian (50.5%), Black (29.1%), and White (6.4%) patients were well-represented. By multivariate analysis, we found no evidence that the trajectories of these commonly measured viral or liver measures varied over time by HBV genotype in those receiving HBV nucleos(t)ides and in those not on antiviral therapy.

SUBMITTER: Keeshan A

PROVIDER: S-EPMC10649073 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study.

Keeshan Alexa A da Silva Carolina Fernandes CF Vachon Alicia A Giles Elizabeth E Osiowy Carla C Coffin Carla C Cooper Curtis L CL

Journal of clinical medicine 20231027 21

HBV is a hepatotropic virus with multiple genotypes. It is uncertain if specific genotype(s) influence virological measures and/or liver markers over time. It is unclear whether nucleos(t)ide analogue therapy response is influenced by genotype. In this retrospective longitudinal study, we utilized data from The Ottawa Hospital Viral Hepatitis Program (TOHVHP) to evaluate the role of HBV genotype on viral load, liver enzymatic levels, fibrosis progression, and parenchymal inflammation and steatos ...[more]

PMID: 37959272

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Project description:AimTo elucidate the influence of quasispecies on virological response and disease severity in patients with chronic hepatitis C.MethodsForty seven patients with hepatitis C [32 with chronic active hepatitis (CAH), 9 with cirrhosis, and 6 with hepatocellular carcinoma (HCC)] were screened for the presence of quasispecies by single stranded conformational polymorphism (SSCP) analysis in the hypervariable region (HVR) and non-structural 5B (NS5B) viral genes of hepatitis C virus. The 41 patients excluding those with HCC were on therapy and followed up for a year with the determination of virological response and disease severity. Virus isolated from twenty three randomly selected patients (11 non-responders and 12 showing a sustained virological response) was sequenced for the assessment of mutations.ResultsThe occurrence of quasispecies was proportionately higher in patients with HCC and cirrhosis than in those with CAH, revealing a significant correlation between the molecular evolution of quasispecies and the severity of disease in patients with hepatitis C. The occurrence of complex quasispecies has a significant association (P < 0.05) with the non-responders, and leads to persistence of infection. Significant differences (P < 0.05) in viral load (log10 IU/mL) were observed among patients infected with complex quasispecies (CQS), those infected with simple quasispecies (SQS) and those with no quasispecies (NQS), after 12 wk (CQS-5.2 +/- 2.3, SQS-3.2 +/- 1.9, NQS-2.8 +/- 2.4) and 24 wk (CQS-3.9 +/- 2.2, SQS-3.0 +/- 2.2, NQS-2.1 +/- 2.3) in the HVR region. However, a statistically significant difference (P < 0.05) was observed between the viral loads of patients infected with CQS and those infected with NQS in NS5B viral gene after 24 wk (CQS-3.9 +/- 2.2, SQS-3.0 +/- 2.2, and NQS-2.1 +/- 2.3) and 48 wk (CQS-3.1 +/- 2.7, SQS-2.3 +/- 2.4, NQS-2.0 +/- 2.3) of therapy. Disease severity was significantly associated with viral load during therapy. The strains isolated from non-responders showed close pairing on phylogeny based on the NS5B gene, but dissimilar HVR regions. This revealed the possibility of the selection of resistant strains during the evolution of quasispecies in NS5B.ConclusionViral quasispecies may be an important predictor of virological responses to combination therapy in patients with chronic hepatitis C. Complex quasispecies and resistant strains may lead to high viral loads during therapy, with a concerted effect on disease severity.

Dataset Information

Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study.

Publications

Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study.

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