Factors associated with the effect of interferon‐α sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B

“…One of these markers is the HBV core‐related antigen (HBcrAg), which is measured by an immunoassay that simultaneously detects HBeAg, HBcAg and p22cr. Results from studies in Asian populations, mainly with HBV genotypes B and C infection, suggest that HBcrAg could be a potential marker for predicting a favourable outcome following discontinuation of NAs therapy . Low HBcrAg levels were associated with a lower risk of a biochemical relapse following discontinuation of lamivudine .…”

Section: Predicting Off Na Treatment Responsementioning

confidence: 99%

“…Results from studies in Asian populations, mainly with HBV genotypes B and C infection, suggest that HBcrAg could be a potential marker for predicting a favourable outcome following discontinuation of NAs therapy . Low HBcrAg levels were associated with a lower risk of a biochemical relapse following discontinuation of lamivudine . Guidelines for using HBcrAg levels to estimate the risks following discontinuation of NAs have been proposed and incorporated in the Japan Society of Hepatology (JSH) guidelines for the management of HBV infection .…”

Section: Predicting Off Na Treatment Responsementioning

confidence: 99%

Stopping long‐term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg‐negative chronic hepatitis B

Boemmel

2018

Liver International

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The immune response against the infection is impaired in patients with chronic hepatitis B, and although HBV DNA can effectively be suppressed by nucleos(t)ide analogues (NA), durable immune control is only established in a minority of patients. This especially applies in HBeAg-negative patients who usually must receive lifelong NA treatment. Calculated withdrawal of NA leads to a relapse of HBV DNA in most patients. There is evidence that this sudden exposure of viral antigens can trigger immune control in some patients which may result in HBsAg loss or a form of immune control, then sustained low HBV DNA levels and normal alanine aminotransferase (ALT). In the first prospective randomized trial investigating tenofovir treatment cessation in HBeAg-negative patients, most patients did not need retreatment after NA cessation, although all patients showed a transient relapse in HBV DNA. HBsAg loss was identified in almost 20% nearly 3 years after stopping NA. Further confirmation of these findings is needed in larger randomized trials and patients who are most likely to benefit from finite therapy must be identified to individualize NA stopping strategies.However, these results suggest that in patients without risk factors such as cirrhosis or other severe conditions, NA treatment may be stopped, as long as adequate safety rules for retreatment are followed. K E Y W O R D SHBV, immune control, treatment cessation, withdrawal

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“…Chronic hepatitis B virus (CHB) infection is correlated with high risk of developing liver fibrosis, cirrhosis, and hepatocellular carcinoma . Currently, interferon‐α (IFN‐α) is one of the most commonly used treatment for HBV infection . Antiviral responses to IFN‐α are mediated by many antiviral proteins induced through activation of the JAK‐STAT signaling pathway .…”

Section: Introductionmentioning

confidence: 99%

Induction of interleukin 6 impairs the anti‐HBV efficiency of IFN‐α in human hepatocytes through upregulation of SOCS3

Yang

Guan

Zhang

et al. 2019

Journal of Medical Virology

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Interleukin 6 (IL‐6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells, including hepatocytes. Previous studies have shown that serum IL‐6 levels are increased in hepatitis B patients. However, the role of IL‐6 in modulating the anti‐hepatitis B virus (HBV) activity of interferon‐α (IFN‐α) remains unclear. In this study, we found that both HBV and viral proteins could induce the expression of IL‐6 in hepatocytes (LO2 and HepG2). Exogenous IL‐6 had no effect on HBV replication, whereas knockdown of IL‐6 expression by RNAi inhibited that. Interestingly, IFN‐α markedly induced IL‐6 expression in hepatocytes, especially in HBV replicating hepatocytes. In turn, IL‐6 impaired the anti‐HBV efficiency of IFN‐α by decreases the expression of IFN‐α downstream effectors by upregulation of suppressor of cytokine signaling‐3 (SOCS3). Furthermore, we demonstrated that downregulation of SOCS3 improved IFN antiviral activity to some extent in HBV replicating hepatocytes. These data provided new insights for a better understanding of the mechanism of IFN‐α resistance and may represent a novel therapeutic strategy to efficiently target HBV infection.

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Factors associated with the effect of interferon‐α sequential therapy in order to discontinue nucleoside/nucleotide analog treatment in patients with chronic hepatitis B

Abstract: The combinational use of HBsAg and HBcrAg levels may be useful to predict the 24-month outcome of NUC/IFN-α sequential therapy. Maximal levels of ALT and HBV DNA during post-treatment follow-up may also help monitor responses to IFN-α sequential therapy.

Cited by 22 publications

References 29 publications

Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure

Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure

Stopping long‐term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg‐negative chronic hepatitis B

Induction of interleukin 6 impairs the anti‐HBV efficiency of IFN‐α in human hepatocytes through upregulation of SOCS3

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