Entecavir Treatment of Chronic Hepatitis D

Kabaçam, Gökhan; Önder, Fatih; Yakut, Mustafa; Seven, Gülseren; Karataylı, Senem Ceren; Karataylı, Ersin; Savaş, Berna; İdilman, Ramazan; Bozdayı, A. Mithat; Yurdaydın, Cihan

doi:10.1093/cid/cis459

Cited by 51 publications

(29 citation statements)

References 20 publications

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“…Four-week administration of ETV strongly reduced HBV viremia and intrahepatic HBV DNA levels, but had no impact on circulating HBsAg, HDV viremia and intrahepatic HDV loads. These results are in line with data from clinical trials showing that 1-year treatment with peg-IFN-α 4 but not with nucleoside analogs, like ETV 20 , reduced HDV viremia in infected patients 20 .…”

Section: Discussionsupporting

confidence: 87%

Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Giersch

Homs

Volz

et al. 2017

Sci Rep

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Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species. Peg-IFNα and peg-IFNλ reduced HDV viremia (1.4 log and 1.2 log, respectively) and serum HBsAg levels (0.9-log and 0.4-log, respectively). Intrahepatic quantification of genomic and antigenomic HDV RNAs revealed a median ratio of 22:1 in untreated mice, resembling levels determined in HBV/HDV infected patients. Both IFNs greatly reduced intrahepatic levels of genomic and antigenomic HDV RNA, increasing the amounts of HDAg- and antigenomic RNA-negative hepatocytes. ETV-mediated suppression of HBV replication (2.1-log) did not significantly affect HBsAg levels, HDV productivity and/or release. In humanized mice lacking adaptive immunity, IFNs but not ETV suppressed HDV. Viremia decrease reflected the intrahepatic reduction of all HDV markers, including the antigenomic template, suggesting that intracellular HDV clearance is achievable.

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Section: Discussionsupporting

confidence: 87%

Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Giersch

Homs

Volz

et al. 2017

Sci Rep

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“…Translation of bench side work to clinical practice has not occurred in CDH, and several attempts to benefit from the progress in CHC or CHB treatment have proved disappointing. In this context, famciclovir, lamivudine, adefovir, and entecavir were without effect in CDH (7)(8)(9)(10)(11)(12) or provided no additional benefit when combined with IFNα over IFN monotherapy in the case of ribavirin and lamivudine (6,10,13,14). Peg-IFNα-adefovir combination also had no additional effect over peg-IFNα monotherapy in terms of virologic, biochemical and histologic responses, but appeared to be better compared to monotherapy in decreasing quantitative hepatitis B surface antigen (HBsAg) levels (11).…”

Section: Introductionmentioning

confidence: 96%

Pegylated interferon-based treatment in patients with advanced liver disease due to chronic delta hepatitis

Kabaçam

Dalekos²,

Çakalǒglu³

et al. 2012

Turk J Gastroenterol

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Amaç: ‹leri delta hepatitinde interferonlar›n güvenilirlik ve etkinli¤i araflt›r›lmam›flt›r. Çok merkezli bir klinik çal›flman›n bu alt analizinin amac›, kronik delta hepatitine ba¤l› ileri karaci¤er hastal›¤› olan ve ileri hastal›¤› olmayan hasta gruplar›n›, 48 haftal›k interferon alfa-2a (180 μgAnahtar kelimeler: Siroz, hepatitis delta, pegile interferon, tedavi Background/aims: The safety and efficacy of interferons in advanced delta hepatitis have not been explored. The aim of this subanalysis of a multicenter clinical trial was to compare the efficacy and safety of 48 weeks of pegylated interferon alpha-2a (180 μg weekly) with or without adefovir (10 mg daily) in patients with chronic delta hepatitis-induced advanced liver disease and in those with non-advanced liver disease. Materials and Met

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“…However, increasing studies reveal an ineffectiveness of these nucleoside/nucleotide analogues and the poor response rate to interferons [24,25]. …”

Section: Introductionmentioning

confidence: 99%

High Prevalence and Significance of Hepatitis D Virus Infection among Treatment-Naïve HBsAg-Positive Patients in Northern Vietnam

Ratsch

Toàn

et al. 2013

PLoS ONE

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BackgroundHepatitis D virus (HDV) infection is considered to cause more severe hepatitis than hepatitis B virus (HBV) monoinfection. With more than 9.5 million HBV-infected people, Vietnam will face an enormous health burden. The prevalence of HDV in Vietnamese HBsAg-positive patients is speculative. Therefore, we assessed the prevalence of HDV in Vietnamese patients, determined the HDV-genotype distribution and compared the findings with the clinical outcome.Methods266 sera of well-characterized HBsAg-positive patients in Northern Vietnam were analysed for the presence of HDV using newly developed HDV-specific RT-PCRs. Sequencing and phylogenetic analysis were performed for HDV-genotyping.ResultsThe HDV-genome prevalence observed in the Vietnamese HBsAg-positive patients was high with 15.4% while patients with acute hepatitis showed 43.3%. Phylogenetic analysis demonstrated a predominance of HDV-genotype 1 clustering in an Asian clade while HDV-genotype 2 could be also detected. The serum aminotransferase levels (AST, ALT) as well as total and direct bilirubin were significantly elevated in HDV-positive individuals (p<0.05). HDV loads were mainly low (<300 to 4.108 HDV-copies/ml). Of note, higher HDV loads were mainly found in HBV-genotype mix samples in contrast to single HBV-infections. In HBV/HDV-coinfections, HBV loads were significantly higher in HBV-genotype C in comparison to HBV-genotype A samples (p<0.05).ConclusionHDV prevalence is high in Vietnamese individuals, especially in patients with acute hepatitis B. HDV replication activity showed a HBV-genotype dependency and could be associated with elevated liver parameters. Besides serological assays molecular tests are recommended for diagnosis of HDV. Finally, the high prevalence of HBV and HDV prompts the urgent need for HBV-vaccination coverage.

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Entecavir Treatment of Chronic Hepatitis D

Cited by 51 publications

References 20 publications

Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Both interferon alpha and lambda can reduce all intrahepatic HDV infection markers in HBV/HDV infected humanized mice

Pegylated interferon-based treatment in patients with advanced liver disease due to chronic delta hepatitis

High Prevalence and Significance of Hepatitis D Virus Infection among Treatment-Naïve HBsAg-Positive Patients in Northern Vietnam

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