Treatment of hepatitis B virus with combination therapy now and in the future

Emery, Joel; Feld, Jordan J.

doi:10.1016/j.bpg.2017.04.007

Cited by 20 publications

(23 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, even with effective treatment, HCC still may develop . Efforts currently are underway to develop new antiviral agents for HBV infection . It is interesting to note that although universal vaccination against HBV infection is recommended in the United States, it cannot impact HBV‐attributable HCC occurring among individuals who already are chronic HBV carriers.…”

Section: Discussionmentioning

confidence: 99%

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013

Shiels

Engels

Yanik

et al. 2019

Cancer

View full text Add to dashboard Cite

Background In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear. Methods Data from the Surveillance, Epidemiology, and End Results–Medicare linkage (SEER‐Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66 years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age‐standardized incidence rates of HCV‐attributable, HBV‐attributable, and HCV/HBV‐unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence. Results Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV‐attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV‐attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV‐unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV‐attributable and HBV‐attributable HCC were noted among individuals aged 66 to 75 years, men, and individuals of Asian ancestry. Conclusions Among Americans aged ≥66 years, HCC rates increased rapidly between 2001 and 2013. Although HCV‐attributable cases contributed substantially to this increase, rates of HBV‐attributable and HCV/HBV‐unrelated HCC also rose during this period.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013

Shiels

Engels

Yanik

et al. 2019

Cancer

View full text Add to dashboard Cite

show abstract

“…Design of trials of combination therapies for chronic HBV Combination therapy will be an essential strategy to improve efficacy and the likelihood of HBV functional cure. 109 Many combinations can be envisioned. A key question is whether 2 or even 3 antiviral drugs have additive or synergistic effects on HBV replication.…”

Section: Prioritisation Of Patient Populations For Studymentioning

confidence: 99%

Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference‡

Cornberg

Lok

Terrault

et al. 2020

Journal of Hepatology

Self Cite

243

122

View full text Add to dashboard Cite

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in > − 30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.

show abstract

“…The selective pressure driven by the drug promotes the expansion of resistant viral strains, shifting the viral population from drug sensitive to resistant (Clutter, Jordan, Bertagnolio, & Shafer, 2016;Garbelli, Riva, Crespan, & Maga, 2017). To prevent the emergence of resistant strains, novel antiviral treatments combine multiple drugs targeting different viral enzymes (Broder, 2010;Emery & Feld, 2017;Valuev-Elliston & Kochetkov, 2017). However, a broad catalogue of antivirals is required to make this strategy feasible, and this is only available for a small number of viruses such as HIV.…”

mentioning

confidence: 99%

Unconventional RNA‐binding proteins step into the virus–host battlefront

2018

View full text Add to dashboard Cite

The crucial participation of cellular RNA-binding proteins (RBPs) in virtually all steps of virus infection has been known for decades. However, most of the studies characterizing this phenomenon have focused on well-established RBPs harboring classical RNA-binding domains (RBDs). Recent proteome-wide approaches have greatly expanded the census of RBPs, discovering hundreds of proteins that interact with RNA through unconventional RBDs. These domains include protein-protein interaction platforms, enzymatic cores, and intrinsically disordered regions. Here, we compared the experimentally determined census of RBPs to gene ontology terms and literature, finding that 472 proteins have previous links with viruses. We discuss what these proteins are and what their roles in infection might be. We also review some of the pioneering examples of unorthodox RBPs whose RNA-binding activity has been shown to be critical for virus infection. Finally, we highlight the potential of these proteins for host-based therapies against viruses. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

show abstract

Treatment of hepatitis B virus with combination therapy now and in the future

Cited by 20 publications

References 78 publications

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013

Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference‡

Unconventional RNA‐binding proteins step into the virus–host battlefront

Contact Info

Product

Resources

About