HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

Xing, Tongjing; Xu, Huji; Cao, Lin; Ye, Maocong

doi:10.1371/journal.pone.0169444

Cited by 29 publications

(30 citation statements)

References 53 publications

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“…In the present study, up to 31.94% and 26.39% of patients achieved HBeAg loss and seroconversion at the second year of LdT + ADV combination therapy, respectively. Evidence from a network meta‐analysis showed that LdT treatment, whether short term or long term, was associated with higher HBeAg seroconversion compared with the other NAs …”

Section: Discussionsupporting

confidence: 63%

“…Evidence from a network meta-analysis showed that LdT treatment, whether short term or long term, was associated with higher HBeAg seroconversion compared with the other NAs. 28 Considering the lower rates of HBeAg loss and seroconversion in the LAM + ADV and ETV + ADV groups in the present study, we speculated that the relatively high rate of HBeAg seroconversion in LdT + ADV may be related to the effect of LdT. The advantage of…”

Section: Discussionmentioning

confidence: 63%

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Efficacy and safety of three adefovir‐based combination therapies in HBeAg‐positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy

Wang

Chen

Zhang

et al. 2017

Journal of Viral Hepatitis

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Although high potent nucleos(t)ide analogues are strongly recommended as first-line therapy for chronic hepatitis B (CHB) in China, some patients are still being treated with adefovir disoproxil (ADV), especially those low-income patients whose health insurance could not reimburse the drug cost. Therefore, the management of patients who have failed ADV therapy or who sustained renal damage during ADV therapy remains an important clinical problem in China. This retrospective study aimed to compare the efficacy and safety of lamivudine (LAM), telbivudine (LdT) or entecavir (ETV) add-on strategies to optimize the treatment of patients with prior suboptimal response to ADV monotherapy. A total of 277 eligible patients were included in this study, and the baseline characteristics were similar among the LAM + ADV (n = 116), LdT + ADV (n = 72) and ETV + ADV (n = 89) groups. At week 96, both the proportion of undetectable HBV DNA (81.03% for LAM + ADV, 84.72% for LdT + ADV and 88.76% for ETV + ADV; P = .317) and ALT elevation (5.17% for LAM + ADV, 4.17% for LdT + ADV and 4.49% for ETV + ADV; P = 1.000) were similar among the three groups; also, a significant decline in liver stiffness was observed in each group from baseline to week 96. At week 96, the rate of HBeAg seroconversion was significantly higher in LdT + ADV than in LAM + ADV (26.39% vs 13.79%, P = .031) and ETV + ADV (26.39% vs 10.11%, P = .007). During the 96 weeks, no obvious renal injury was reported in any of the three groups, but an improvement in eGFR was found in LdT + ADV compared with LAM + ADV and ETV + ADV. In summary, all three combination strategies provide good control of virus replication, but the LdT + ADV combination therapy may yield better HBeAg seroconversion and eGFR improvement.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 63%

Efficacy and safety of three adefovir‐based combination therapies in HBeAg‐positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy

Wang

Chen

Zhang

et al. 2017

Journal of Viral Hepatitis

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“…Despite the long-term follow-up, HBeAg seroconversion rates were lower in the NAs group. This finding was also demonstrated by Xing et al (24) that in long-term treatment with potent NAs, HBeAg seroconversion with the therapy was lower compared with spontaneous HBeAg seroconversion rate (25). The latest study conducted by Marcellin et al (26) in 2017 showed remarkable results of Peg-IFN treatment in long-term follow-up of CHB patients (26).…”

Section: Pegylated-interferon Entecavir Tenofovir Disoproxilmentioning

confidence: 53%

Does Pegylated-Interferon Still Have High Efficacy Treatment Properties Against Chronic Hepatitis B?

Yıldırım¹,

User²,

Sayan³

et al. 2018

vhd

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Amaç: Pegile-interferon (Peg-IFN) alfa 2a/2b ve nükleozid ve nükleotid analogları (NA), şu anda kronik hepatit B (KHB) tedavisi için onaylanmış iki tedavi yaklaşımıdır. Bugüne kadar birkaç çalışma Peg-IFN ve NA'lar arasındaki tedavinin etkinliğini karşılaştırmıştır. Bu çalışmada, 2006-2016 yılları arasında Türk KHB hastalarında Peg-IFN ve potent NA'ların (entekavir ve tenofovir disoproksil) kümülatif virolojik ve serolojik yanıtlarını karşılaştırarak etkinliklerini değerlendirmeyi amaçladık. Gereç ve Yöntemler: Retrospektif gözlemsel olan bu çalışmada KHB tanılı total 331 hasta (Peg-IFN tedavi grubu, n=62, entekavir tedavi grubu, n=131 ve tenofovir disoproksil tedavi grubu, n=138) değerlendirildi. Bulgular: Virolojik yanıt oranı Peg-IFN tedavi grubunda 12. ayda (%90), NA tedavi grubundan (entekavir için %80, tenofovir disoproksil için %76) daha yüksekti (p<0,05). Peg-IFN'nin 24. ayda kalıcı viral yanıt (KVY) oranı %61 idi (p<0,001). Hepatit B e antijen serokonversiyonu Peg-IFN grubunda (%25) NA grubuna (entekavir için %16, tenofovir disoproksil için %13) göre belirgin yüksekti. Hepatitis B yüzey antijeni (HBsAg) serokonversion oranı Peg-IFN grubunda NA tedavi grubuna göre daha yüksekti (%7,9 vs %0,9 ve %0) (p<0,001). HBsAg serokonversiyonundan sonra anti-HBs titreleri altı aydan fazla korundu. Sonuç: KHB hastalarının uzun sureli takibinde Peg-IFNtedavisi, NA'larına göre daha yüksek KVY ile daha yüksek HBsAg ve HBeAg serokonversiyon ile ilişkili bulundu. Peg-IFN hepatit B virüsün tedavi edildiği yeni bir döneme kadar KHB hastalarında ilk seçenek tedavi yaklaşımı olarak görünmektedir.

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“…Initially, nucleoside analogues had a low genetic barrier and were prone to resistance, but recently, the high genetic barrier agents, ETV, tenofovir fumarate and TAF are not only potent, 54 but also have low levels of resistance and are relatively safe 55 . In addition to their effectiveness in viral suppression, they are also able to achieve HBeAg seroconversion, 56 but the rates of HBsAg loss are low. However, a pooled estimate of their efficacy in achieving HBsAg loss has not been performed.…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

Cited by 29 publications

References 53 publications

Efficacy and safety of three adefovir‐based combination therapies in HBeAg‐positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy

Efficacy and safety of three adefovir‐based combination therapies in HBeAg‐positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy

Does Pegylated-Interferon Still Have High Efficacy Treatment Properties Against Chronic Hepatitis B?

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

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