Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Matsumoto, Akihiro; Tanaka, Eiji; Suzuki, Yoshiyuki; Kobayashi, Mariko; Tanaka, Yasuhito; Shinkai, Noboru; Hige, Shuhei; Yatsuhashi, Hiroshi; Nagaoka, Shinya; Chayama, Kazuaki; Tsuge, Masataka; Yokosuka, Osamu; Imazeki, Fumio; Nishiguchi, Shuhei; Saito, Masaki; Fujiwara, Kei; Torii, Nobuyuki; Hiramatsu, Naoki; Karino, Yoshiyasu; Kumada, Hiromitsu

doi:10.1111/j.1872-034x.2011.00910.x

Cited by 56 publications

(73 citation statements)

References 41 publications

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“…The mechanism of action of nucleotide analogues barely influences the transcription of cccDNA to mRNA or translation to various viral proteins. Therefore, treatment with nucleotide analogues should still allow HBsAg, HBcrAg [Rokuhara et al, 2003;Tanaka et al, 2008;Matsumoto et al, 2012], and HBV RNA levels to function as surrogate markers of intrahepatic cccDNA. Nevertheless, the levels of cccDNA did not correlate with any of these markers in this study.…”

Section: Discussionmentioning

confidence: 98%

Impact of peginterferon alpha‐2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B

Hagiwara

Kudo

Osaki

et al. 2013

Journal of Medical Virology

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The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG-IFN) α-2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre-therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow-up period. Serum HBV DNA levels decreased by 5.2 and 3.3 log copies/ml (mean) by the end of the therapy and follow-up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4 log copies/µg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (>4.5 log copies/µg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse (P = 0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 98%

Impact of peginterferon alpha‐2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B

Hagiwara

Kudo

Osaki

et al. 2013

Journal of Medical Virology

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“…Despite serological resolution, HBV cccDNA remains in hepatocytes and circulating peripheral mononuclear cells [18, 19]. The necessary conditions of the cessation of antiviral therapy were reported [20, 21], and we think that the cessation of antiviral therapy could be performed safely if the serological HBV status is HBV-DNA(−), HBeAg(−) and/or HBsAg(−). This case fulfilled the necessary conditions and stopped antiviral therapy, but a low dose of immunosuppressive drugs was administered in order to prevent rejection and the fibrosis of the graft.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous resolution of de novo hepatitis B after living donor liver transplantation with hepatitis B core antibody positive graft: a case report

et al. 2016

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BackgroundHepatitis B core antibody (HBcAb)-positive graft is reported to cause de novo hepatitis B after liver transplantation with a probability of 38–100 % without prophylaxis. Hepatitis B surface antigen loss is reported to be achieved with a probability of only 3–8 % in the patients treated by antiviral agents. We present an extremely rare case of spontaneous resolution of de novo hepatitis B after living donor liver transplantation (LDLT) with HBcAb-positive graft.Case presentationAn 8-year-old female patient underwent LDLT for end-stage biliary atresia using an HBcAb-positive left lobe graft. After transplantation, she did not receive any prophylactic agents for hepatitis B. Two years after LDLT, she was diagnosed with chronic hepatitis B. Six years after LDLT, liver fibrosis and hepatitis activity were advanced and lamivudine was started. Two years after lamivudine administration, emergence of a lamivudine-resistant YMDD mutant was detected and adefovir dipivoxil was combined with lamivudine. Hepatitis B virus deoxyribonucleic acid (HBV-DNA) became undetectable soon after the addition of adefovir dipivoxil. Twelve years after transplantation, acute rejection occurred and steroid pulse therapy was performed, but hepatitis B did not become severe and HBV-DNA continued to be undetectable. Fifteen years after LDLT, she voluntarily discontinued medication of all drugs, including immunosuppressive agents and antiviral drugs for 1 year because of mental instability. After an interval of 1 year, liver function was normal and her serological HBV status was as follows: HBsAg(−), HBsAb(+), HBeAb(−), HBeAb(+), HBcAb(+) and HBV-DNA(−). From these results, we diagnosed her condition as spontaneous clearance of de novo hepatitis B. The patient is free of antiviral therapies and continues to take a low dose of immunosuppressive drugs and is leading a normal life.ConclusionsIn this case, HBsAg loss is finally achieved but we need to follow carefully for HBV reactivation with the fibrosis of the graft in mind.

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“…There is also early data suggesting that an >1 log on‐treatment reduction in HBsAg together with a low end‐of‐treatment HBsAg level (<100 IU/mL) can predict sustained viral suppression and HBsAg clearance among HBeAg‐negative patients who have stopped lamivudine therapy . Recently, a Japanese group has proposed a model using HBsAg and hepatitis B core‐related antigen levels to predicting relapse after the discontinuation of NA therapy . Further studies are needed to determine whether switching NA to IFN contributes to the safe discontinuation of the antiviral therapy, particularly in patients with decreased HBsAg levels during long‐term NA treatment .…”

Section: Theoretic Advantages Of Combination Therapymentioning

confidence: 99%

Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B

Wong

Chan

2014

Journal of Viral Hepatitis

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Chronic hepatitis B is one of the leading causes of cirrhosis and hepatocellular carcinoma globally. At present, seven drugs, including two interferons and five oral nucleos(t)ide analogues (NAs), have been approved for the treatment of chronic hepatitis B. Interferon works by immunomodulation, but is successful in less than a third of treated patients and is a relatively weak antiviral. NAs directly suppress the hepatitis B virus but have limited durability. Based on current data, combination of NA and interferon results in greater viral suppression but does not translate to off-treatment sustained response. Concomitant or sequential treatment also does not make a difference. Combining telbivudine and interferon also runs the risk of severe peripheral neuropathy. On the other hand, interferon switch or additional therapy in patients well controlled with NAs appears to improve the durability of off-treatment response. This article reviews current data on interferon and NA combination and discusses potential future developments.

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Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Cited by 56 publications

References 41 publications

Impact of peginterferon alpha‐2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B

Impact of peginterferon alpha‐2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B

Spontaneous resolution of de novo hepatitis B after living donor liver transplantation with hepatitis B core antibody positive graft: a case report

Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B

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