How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. Time for an individualised approach?

Abstract

Chronic hepatitis B virus (HBV) infection remains a global problem. Several HBV genotypes exist with different biology and geographical prevalence. Whilst the future aim of HBV treatment remains viral eradication, current treatment strategies aim to suppress the virus and prevent the progression of liver disease. Current strategies also involve identification of patients for treatment, namely those at risk of progressive liver disease. Identification of HBV genotype, HBV mutants and other predictive factors allow for tailoured treatments, and risk-surveillance pathways, such as hepatocellular cancer screening. In the future, these factors may enable stratification not only of treatment decisions, but also of patients at risk of higher relapse rates when current therapies are discontinued. Newer technologies, such as next-generation sequencing, to assess drug-resistant or immune escape variants and quasi-species heterogeneity in patients, may allow for more information-based treatment decisions between the clinician and the patient. This article serves to discuss how HBV genotypes and genetic variants impact not only upon the disease course and outcomes, but also current treatment strategies. Adopting a personalised genotypic approach may play a role in future strategies to combat the disease. Herein, we discuss new technologies that may allow more informed decision-making for response guided therapy in the battle against HBV.

Impact of HBV genotype and mutations on HBV DNA and qHBsAg levels in patients with HBeAg‐negative chronic HBV infection

“…In our study, 465 patients with HBeAg‐negative chronic HBV were analysed including a high percentage of HBV genotype A and D infected patients, but also a significant number of patients with HBV genotype B, C and E. Mutations in PC, BCP and preS were found in a genotype‐dependent pattern, which has been described for BCP and PC mutations among genotypes A‐D and for preS mutations among genotypes B and C, respectively . As no data are published regarding the prevalence of these mutations in HBV genotype E, we found that the vast majority of GTE‐infected patients harboured the BCP double mutation. While preS mutations were also commonly found, mutations in precore were detected only infrequently in this genotype.…”

Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients

“…However, the major limitation is that the heterogeneity of the patient characteristics is inevitable in this multi‐centre study, although HBV DNA, HBV serological markers and noninvasive markers (PIIINP, MMP‐1, Hp, HA, sCD163 and α2‐MG) were measured at the central laboratory, and liver histological examination was performed by special hepatopathologists, and the upper limit of normal (ULN) of ALT and AST was determined according to the detection method used in each institute. In addition, HBV genotype, which influences disease course and treatment outcomes of CHB, 54 was not investigated in our cohort. Studies have confirmed no statistically significant differences between HBV genotype and virological responses to nucleos(t)ide analogue therapies 54 .…”

“…In addition, HBV genotype, which influences disease course and treatment outcomes of CHB, 54 was not investigated in our cohort. Studies have confirmed no statistically significant differences between HBV genotype and virological responses to nucleos(t)ide analogue therapies 54 . Given the fact that the complex interaction mechanism between HBV and host immunity has not been thoroughly studied, the current research results are limited to Asians.…”

“…Quantitative HBsAg and anti-HBc were identified as predictors of SF and AF by univariate analysis, but multivariate analysis did not show a significant relationship between these two markers and liver fibrosis. In addition, HBV genotype, which influences disease course and treatment outcomes of CHB, 54 was not investigated in our cohort. Studies have confirmed no statistically significant differences between HBV genotype and virological responses to nucleos(t)ide analogue therapies.…”

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

“…This has been exemplified by the management of hepatitis C virus infection (5), and a similar approach for HBV is starting to emerge, with recent EASL guidelines for HBV treatment suggesting different stopping points for treatment non-response in genotypes A-D (6). Evidence increasingly supports a role for HBV genotype in influencing disease progression including risk of developing chronic infection, e-antigen seroconversion, transmission mode, and the development of hepatocellular carcinoma (7,8). Studies often refer to ‘wild-type’ virus (8,9), but ‘wild-type’ for one genotype may not reflect consensus for other genotypes (10,11).…”