Systematic review with meta‐analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

Qiu, Kui; Liu, B.; Li, S.‐Y.; Li, H.; Chen, Z.‐W.; Luo, Aoran; Peng, Mingli; Ren, Hong; Hu, Peng

doi:10.1111/apt.14629

Cited by 53 publications

(44 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, there is some discrepancy between whether combination therapy is really more efficacious than IFN monotherapy. The discrepancy between our findings and those of Qiu et al 8 is due to the differences in selection of studies. We only selected RCTs that compared combination therapy to NA monotherapy while Qiu et al selected combination therapy without any requirement for a control group.…”

Section: Discussioncontrasting

confidence: 99%

“…In an era where there is increasing interest in functional cure defined as HBsAg loss, accurate estimates of the relative efficacy of current therapies are much needed. In a recent meta‐analyses, Qiu et al 8 examined combination therapies based on pegylated IFN and its impact on HBsAg clearance. The authors found that the de novo peginterferon and NA strategy led to HBsAg loss of 9%(95% CI 6%, 10%), add‐on strategy 8% (95% CI 5%, 13%) and switch strategy 14% (95% CI 9%, 20%).…”

Section: Discussionmentioning

confidence: 99%

“…With the increasing interest in new agents to treat CHB, it is timely to examine systematically the efficacy of existing therapy. Published meta‐analysis of HBsAg seroclearance with existing therapy either compared efficacy between combination therapy (immunomodulator and nucleoside analogues) and nucleoside analogue monotherapy 5‐7 or using different combinations (immunomodulator and nucleoside analogues)of therapy 8 . However, no meta‐analysis has examined all three treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Fonseca¹,

Ling

Al‐Siyabi

et al. 2020

Journal of Viral Hepatitis

View full text Add to dashboard Cite

Current therapies for chronic hepatitis B (CHB) include nucleos(t)ide analogues (NAs) and interferon (IFN), but their relative efficacy as monotherapy or in combination has not been examined systematically for HBsAg loss (functional cure). Hence, we systematically reviewed the evidence for HBsAg loss in CHB patients treated with IFN, NA or the combination. We searched PubMed, EMBASE and abstracts from EASL, Asia Pacific Association for study of the Liver and American Association for the Study of Liver Disease for randomized controlled trials of CHB patients, comparing NA, IFN or the combination. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by NA genetic barrier, cirrhosis, type of combination therapy, HBeAg, treatment naivety, IFN dosage/duration and outcome duration. Sensitivity analysis was performed for selected strata, and HBsAg loss was measured at the end‐of‐study (EOS), end‐of‐treatment (EOT) or end‐of‐follow‐up (EOF). Effects were reported as risk differences (RD) with 95% confidence intervals (CI) using a random‐effects model. Forty‐five studies were included, all with low risk of bias. For HBsAg loss at EOS, when comparing combination vs IFN, RD = 1%, 95%CI‐1%, 2%; combination vs NA, RD = 5%, 95%CI 3%,7%; IFN vs NA, RD = 3%, 95%CI 2%,5%. Subgroup analysis showed a significant effect of standard IFN dose vs nonstandard; IFN duration ≥48 weeks vs <48 weeks, and loss of efficacy >2 years of follow‐up. Similar findings were seen in HBsAg seroconversion, but only three studies reported HBsAg seroreversion. In conclusion, IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA, associated with standard dose of IFN and ≥48 weeks of therapy, although this effect faded over time.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Fonseca¹,

Ling

Al‐Siyabi

et al. 2020

Journal of Viral Hepatitis

View full text Add to dashboard Cite

show abstract

“…Thus, an uncertain or even lifelong period of NUC treatment may be needed for most patients with chronic HBV infection. Alternatively, PEG-IFN-α treatment can lead to HB e-antigen (HBeAg) clearance and HBsAg seroconversion in 10-30% of cases within a definite duration of therapy (6,9,10). Beside direct antiviral effects, the immunomodulatory property of IFN-α may ultimately induce an immune control of HBV.…”

Section: Introductionmentioning

confidence: 99%

Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection

Zhao

Chen

2020

Front. Immunol.

View full text Add to dashboard Cite

Functional cure" is being pursued as the ultimate endpoint of antiviral treatment in chronic hepatitis B (CHB), which is characterized by loss of HBsAg whether or not anti-HBs antibodies are present. "Functional cure" can be achieved in <10% of CHB patients with currently available therapeutic agents. The dysfunction of specific immune responses to hepatitis B virus (HBV) is considered the major cause of persistent HBV infection. Thus, modulating the host immune system to strengthen specific cellular immune reactions might help eliminate HBV. Strategies are needed to restore/enhance innate immunity and induce HBV-specific adaptive immune responses in a coordinated way. Immune and resident cells express pattern recognition receptors like TLRs and RIG I/MDA5, which play important roles in the induction of innate immunity through sensing of pathogen-associated molecular patterns (PAMPs) and bridging to adaptive immunity for pathogen-specific immune control. TLR/RIG I agonists activate innate immune responses and suppress HBV replication in vitro and in vivo, and are being investigated in clinical trials. On the other hand, HBV-specific immune responses could be induced by therapeutic vaccines, including protein (HBsAg/preS and HBcAg), DNA, and viral vector-based vaccines. More than 50 clinical trials have been performed to assess therapeutic vaccines in CHB treatment, some of which display potential effects. Most recently, using genetic editing technology to generate CAR-T or TCR-T, HBV-specific T cells have been produced to efficiently clear HBV. This review summarizes the progress in basic and clinical research investigating immunomodulatory strategies for curing chronic HBV infection, and critically discusses the rather disappointing results of current clinical trials and future strategies.

show abstract

“…Current approaches include de novo dual therapy in NA‐naïve CHB, or extension to PegIFN as “add‐on” or “switch‐to” therapy in “NA‐experienced” patients. Focusing on HBsAg clearance, Qiu et al performed a systematic review with meta‐analysis to evaluate combination therapy with NAs and PegIFN for CHB . The authors identified 24 studies that met inclusion criteria.…”

mentioning

confidence: 99%

Editorial: chronic hepatitis B combination therapy—emerging success as proof‐of‐concept for future hepatitis B eradication?

Nhu

Pockros

2018

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

Systematic review with meta‐analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

Cited by 53 publications

References 52 publications

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

The efficacy of hepatitis B treatments in achieving HBsAg seroclearance: A systematic review and meta‐analysis

Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection

Editorial: chronic hepatitis B combination therapy—emerging success as proof‐of‐concept for future hepatitis B eradication?

Contact Info

Product

Resources

About