An update on the management of chronic hepatitis D

Shah, Pir Ahmad; Choudhry, Saad; Reyes, Karen J. Campoverde; Lau, Daryl

doi:10.1093/gastro/goz052

Cited by 12 publications

(5 citation statements)

References 41 publications

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“…Conventional treatment for chronic HDV infection consists of long-term administration of standard or pegylated interferon alpha (peg-IFN-α), which leads to a sustained virological response (SVR) in only 20–30% of patients treated and is frequently associated with serious adverse reactions. Several new agents are now under clinical investigation: bulevirtide, lonafarnib and nucleic acid polymers [ 9 , 10 ]. These drugs target essential steps of the HDV viral cycle - like viral entry, the isoprenylation of the large viral antigen, and viral encapsidation.…”

Section: Introductionmentioning

confidence: 99%

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis

Maestro

Gómez-Echarte

Camps

et al. 2021

Viruses

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Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis, but little is known about the molecular mechanisms involved. We have recently developed an HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV), which developed a liver pathology very similar to the human disease and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression of HDV antigens (HDAgs), and we have characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and that L-HDAg is essential to produce the HDV infectious particle and inhibits its replication. We have also found that lack of L-HDAg resulted in the increase of S-HDAg expression levels and the exacerbation of liver damage, which was associated with an increment in liver inflammation but did not require T cells. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

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Section: Introductionmentioning

confidence: 99%

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis

Maestro

Gómez-Echarte

Camps

et al. 2021

Viruses

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“…In addition, detecting HDV-specific IgM or IgG with the ELISA is an indispensable approach, especially for the screening of a large range of HBsAg-positive populations. Nonetheless, the widow period for detection is relatively short ( 33 ). Anti-HDV IgM typically appears in serum at 2–3 weeks after the onset of symptoms and disappears by 2 months after acute HDV infection.…”

Section: Discussionmentioning

confidence: 99%

Digital Droplet PCR for Detection and Quantitation of Hepatitis Delta Virus

Zhang

Cao

et al. 2022

Clin Transl Gastroenterol

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INTRODUCTION: Hepatitis delta virus (HDV) far exceeds our expected level. There remains a lack of reliable quantitative assays for HDV RNA detection. We sought to develop a new method based on digital droplet polymerase chain reaction (ddPCR) for HDV quantitative detection. METHODS: With plasmid (pMD19T) containing HDV full genome, we determined the method for ddPCR-based HDV RNA quantification. To compare various assays for HDV detection, 30 cases diagnosed with hepatitis D and 14 controls were examined using enzyme-linked immunosorbent assay, reverse-transcriptase PCR (RT-PCR), and ddPCR. A total of 728 hepatitis B virus–related patients, including 182 patients with chronic hepatitis B, 182 with liver cirrhosis, 182 with hepatocellular carcinoma, and 182 with liver failure, were screened for HDV infection. RESULTS: The detection limit of ddPCR for HDV is significantly low, with lower limit of detection and lower limit of quantitation of 0.29 IU/mL (95% confidence interval: 1.93 × 10−3–1.22 IU/mL) and 8.76 IU/mL (95% confidence interval: 1.83–1.03 × 106 IU/mL), respectively. Among the 44 samples, the enzyme-linked immunosorbent assay detected 30 cases positive, ddPCR reported 24 samples, and RT-PCR reported 10 samples positive for HDV RNA. Moreover, the positive rates of anti-HDV were 1.1%, 3.3%, 2.7%, and 7.1% in patients with chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and liver failure, respectively; the detection rates of RT-PCR in HDV RNA were 0%, 16.67%, 15.4%, and 20%, respectively. However, the detection rates of ddPCR were 0%, 33.33%, 30.77%, and 60%, respectively. DISCUSSION: We establish a high sensitivity and specificity quantitative HDV RNA detection method based on ddPCR. Hepatitis B virus–related end-stage liver diseases, especially liver failure, are associated with a remarkably high rate of HDV infection.

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“…In addition, detecting HDV-speci c IgM or IgG with ELISA is an indispensable approach, especially for the screening of a large range of HBsAg-positive populations. Nonetheless, the widow period for detection is relatively short (30). Anti-HDV IgM typically appears in serum at 2 to 3 weeks after the onset of symptoms and disappears by 2 months after acute HDV infection.…”

Section: Discussionmentioning

confidence: 99%

Digital Droplet PCR (ddPCR) for Detection and Quantitation of Hepatitis Delt Virus

Zhang

Cao

et al. 2021

Preprint

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Background & Aims The prevalence of hepatitis delt virus (HDV) far exceeds our expected level, there remains a lack of reliable quantitative assays for HDV RNA detection. We sought to develop a new method based on digital droplet PCR (ddPCR) for HDV RNA quantitative detection. Methods With plasmid (pMD19T) containing HDV full-genome, we determined the method for ddPCR-based HDV RNA quantification. To compare various assays for HDV detection, 30 cases diagnosed hepatitis D and 14 controls were examined by ELISA, RT-PCR and ddPCR. 728 HBV-related patients including 182 chronic hepatitis B (CHB), 182 liver cirrhosis (LC), 182 hepatocellular carcinoma (HCC) and 182 liver failure (LF) were screened for HDV infection. Results The limit of detection of ddPCR for HDV is significantly low, which lower limit of detection (LLoD) and lower limit of quantitation (LLoQ) to be 5.51 copies/reaction (95% CI: 1.15–6.4*105) and 0.18 copies/reaction (95% CI: 0.0012151- 0.76436), respectively. Among the 44 samples, ELISA detected 30 cases positive for anti-HDV, ddPCR reported 24 samples and RT-PCR reported 10 samples positive for HDV RNA. Moreover, the positive rates of anti-HDV IgG were 1.1%, 3.3%, 2.7% and 7.1% in patients with CHB, LC, HCC, and LF; the detection rates of RT-PCR in HDV RNA were 0%, 16.67%, 15.4% and 20%, however, the detection rates of ddPCR were 0%, 33.33%, 30.77% and 60%. Conclusion We establish a high sensitivity and high specificity quantitative HDV RNA detection method based on ddPCR compared to RT-PCR. HBV-related end-stage liver disease, especially liver failure, are associated with a remarkably high rate of HDV infection.

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An update on the management of chronic hepatitis D

Cited by 12 publications

References 41 publications

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis

AAV-HDV: An Attractive Platform for the In Vivo Study of HDV Biology and the Mechanism of Disease Pathogenesis

Digital Droplet PCR for Detection and Quantitation of Hepatitis Delta Virus

Digital Droplet PCR (ddPCR) for Detection and Quantitation of Hepatitis Delt Virus

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