Prediction model for sustained hepatitis B e antigen seroconversion to peginterferon alfa‐2a in chronic hepatitis B

Zhu, Huilan; Wang, Changtai; Zhang, Yafei; Wei, Shaofeng; Xu, Li; Zhang, Zhenhua

doi:10.1111/jgh.13414

Cited by 14 publications

(17 citation statements)

References 35 publications

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“…However, NUCs and IFN-α alone or combined treatment are rare to achieve functional cure (Reijnders et al, 2010; Zoulim and Locarnini, 2012; Terrault et al, 2016; Revill et al, 2019). Extensive studies have identified host genetic genes, alanine aminotransferase (ALT) levels, HBV genotype, and HBV DNA, anti-HBc, and HBsAg levels as important predictors of treatment efficacy (Brouwer et al, 2014; Fan et al, 2016b; Zhu et al, 2016a). Accumulating evidence suggests that host genetics play an important role in the patient response to IFN-α or NUCs ( Table 3 ; Tables S1 , S5 , S6 ).…”

Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

Host Genetic Determinants of Hepatitis B Virus Infection

et al. 2019

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Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.

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Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

Host Genetic Determinants of Hepatitis B Virus Infection

et al. 2019

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“…Therefore, sustained HBeAg seroconversion is a satisfactory result after treatment of HBeAg-positive chronic hepatitis B, and it is associated with improved long-term prognosis[5,6]. A rapid decline in hepatitis B surface antigen (HBsAg) and HBeAg titers during treatment implies a high rate of HBeAg seroconversion, as has been documented with interferon treatment[12,13]. These features are valuable in predicting the therapeutic effects in chronic HBV infection.…”

Section: Introductionmentioning

confidence: 99%

Early hepatitis B viral DNA clearance predicts treatment response at week 96

Tan

Liu

et al. 2017

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AIMTo investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B.METHODSA total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response.RESULTSThe rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk.CONCLUSIONHepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

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“…ALT, HBeAg, and HBV DNA were subgrouped according to previous studies and their ability to predict the response to treatment was evaluated. [18,19] As shown in Table 2, ALT and HBV DNA levels were not statistically different between responders and non-responders ( P > .05). Notably, the incidence of HBeAg seroconversion was significantly higher among patients with HBeAg S/CO ≤ 500 (OR = 2.60, 95% CI: 1.16–5.83, χ 2 = 5.52, P = .02, PPV = 54.76%, NPV = 68.25%) at baseline, with HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47–7.73, χ 2 = 8.53, P = .003, PPV = 58.54%, NPV = 70.49%) or a higher than 10-fold HBeAg decline (OR = 3.55, 95% CI: 1.50–8.37, χ 2 = 8.67, P = .003, PPV = 62.16%, NPV = 68.33%) at 12 weeks, or with HBeAg S/CO ≤ 15 (OR = 10.35, 95% CI: 4.09–26.20, χ 2 = 28.03, P < .001, PPV = 64.29%, NPV = 85.19%) at 24 weeks.…”

Section: Resultsmentioning

confidence: 90%

Combination therapy based on pegylated interferon alfa improves the therapeutic response of patients with chronic hepatitis B who exhibit high levels of hepatitis B e-antigen at 24 weeks

Zhang

Liu

et al. 2019

Medicine

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Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16–5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47–7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50–8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09–26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.

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Prediction model for sustained hepatitis B e antigen seroconversion to peginterferon alfa‐2a in chronic hepatitis B

Abstract: We successfully established prediction models for PEG-IFN response in HBeAg-positive CHB.

Cited by 14 publications

References 35 publications

Host Genetic Determinants of Hepatitis B Virus Infection

Host Genetic Determinants of Hepatitis B Virus Infection

Early hepatitis B viral DNA clearance predicts treatment response at week 96

Combination therapy based on pegylated interferon alfa improves the therapeutic response of patients with chronic hepatitis B who exhibit high levels of hepatitis B e-antigen at 24 weeks

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