Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy

Matsumoto, Akihiro; Nishiguchi, Shuhei; Enomoto, Hirayuki; Kang, Jong Hon; Tanaka, Yasuhito; Shinkai, Noboru; Kurosaki, Masayuki; Enomoto, Masaru; Yokosuka, Osamu; Yatsuhashi, Hiroshi; Nagaoka, Shinya; Okuse, Chiaki; Kagawa, Tatehiro; Mine, Tetsuya; Takaguchi, Koichi; Saito, Satoru; Hino, Keisuke; Ikeda, Fusao; Sakisaka, Shotaro; Morihara, Daisuke; Miyase, Shiho; Tsuge, Masataka; Chayama, Kazuaki; Hiramatsu, Naoki; Suzuki, Yoshiyuki; Murata, Kazumoto; Tanaka, Eiji

doi:10.1007/s00535-017-1360-z

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…NAs are excellent drugs for suppressing the replication of HBV, but many patients need to receive long-term treatment. PEG-IFN is a possible therapeutic tool for successfully withdrawing NA treatment in HBV-infected patients, and we participated in two clinical studies on this point in Japan; however, the VR ratios were not high, being around 30% in both [26,27]. We therefore explored new factors associated with the treatment efficacy of PEG-IFN following NA treatment.…”

Section: Discussionmentioning

confidence: 99%

Section: Peg-ifn Therapy and Its Efficacymentioning

confidence: 99%

“…We previously participated in two prospective cohort studies regarding PEG-IFN monotherapy following NA treatment [26,27]. As mentioned in a previous study, the analysis of one study arm was considered to include minimal bias [26]. In the present study, we retrospectively analyzed the pooled patients who had been enrolled in these studies from our institute and whose liver histology had been assessed before PEG-IFN.…”

Section: Peg-ifn Therapy and Its Efficacymentioning

confidence: 99%

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Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Enomoto

Aizawa

Hasegawa

et al. 2020

IJMS

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Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0 × 10−4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Peg-ifn Therapy and Its Efficacymentioning

confidence: 99%

Section: Peg-ifn Therapy and Its Efficacymentioning

confidence: 99%

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Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Enomoto

Aizawa

Hasegawa

et al. 2020

IJMS

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“…This might be caused by differences in the included HBV genotypes, as HBV genotypes have specific geographic distributions and can affect the response to IFNα therapy. 22,23 The outcomes of sequential therapy have been unsatisfactory in Japanese studies (including ours), [24][25][26][27][28] at least in part because genotype C is the most prevalent type of HBV, and is associated with a low likelihood of a favorable response to IFNα treatment.…”

Section: H Epatitis B Virus (Hbv) Infection Affects Nearly 250mentioning

confidence: 90%

Sequential therapy involving an early switch from entecavir to pegylated interferon‐α in Japanese patients with chronic hepatitis B

Enomoto

Nishiguchi

Tamori

et al. 2018

Hepatology Research

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“…peg-IFN monotherapy was also found to be efficient for HBsAg loss and seroconversion, but combination therapy was thought to cause more adverse events [12][13] . However, other studies have reported that the therapeutic efficacy of NAs combined with peg-IFN was better than monotherapy 14 .NAs are thought to directly inhibit HBV DNA replication, while peg-IFNα-2a as an immunomodulator can enhance the innate and adaptive immune responses to play a synergistic antiviral role 15,16 . In one study 10 , addition of NAs to peg-IFNα-2a therapy enhanced the virologic response in chronic hepatitis B patients who did not have an early response to peg-IFNα-2a.…”

Section: Discussionmentioning

confidence: 99%

ETV add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial

Yang

Chen

Wang

et al. 2019

Preprint

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Background and Aim The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding Peg-interferon to ongoing ETV treatment leads to a better curative effect or not. Methods Eligible HBV patients (n=144) were randomly divided (1:1) to receive either ETV monotherapy (n=70) or peg-interferon add-on therapy from weeks 26 to 52 (n=74). Patients were followed-up for 2 years. We evaluated hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response (SVR), transient elastography value, and histological scores. Results At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase (ALT)and aspartate aminotransferase (AST) levels and transient elastography values decreased significantly compared with baseline. Both group showed a favorable decrease in alpha fetoprotein(AFP) (monotherapy:23.4±77.3 vs 2.4±0.91, P=0.149; combination therapy: 33.3±96.9 vs 4.3±5.5,P=0.085) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 7.5±3.4 kPa [SD 1.9] vs. 12.8±13.9 kPa [SD 1.9], P=0.037). But this research didn’t show significant difference in HBsAg conversion rate (1.79% (1/56) vs 4.11% (3/73), P=0.632) as well as HBV-DNA sustained virologic response(93.2% vs 98.5%,P=0.15) between two groups. Conclusions Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better antiviral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.

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Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy

Abstract: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.

Cited by 17 publications

References 42 publications

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Sequential therapy involving an early switch from entecavir to pegylated interferon‐α in Japanese patients with chronic hepatitis B

ETV add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial

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