scholarly journals Australia could miss the WHO hepatitis C virus elimination targets due to declining treatment uptake and ongoing burden of advanced liver disease complications

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257369
Author(s):  
Jisoo A. Kwon ◽  
Gregory J. Dore ◽  
Behzad Hajarizadeh ◽  
Maryam Alavi ◽  
Heather Valerio ◽  
...  
Keyword(s):  
Liver Disease ◽  
Decompensated Cirrhosis ◽  
Advanced Liver Disease ◽  
Virus Elimination ◽  
Individual Level ◽  
Direct Acting Antiviral ◽  
Treatment Uptake ◽  
Unrestricted Access ◽  
Chronic Hcv ◽  
Related Mortality

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia’s progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

Antibody Development to HCV Alternate Reading Frame Protein in Liver Transplant Candidate and its Computational Analysis

2020 ◽  
Vol 17 (2) ◽  
pp. 154-170 ◽  
Author(s):  
Zahra Musavi ◽  
Tayebeh Hashempour ◽  
Javad Moayedi ◽  
Behzad Dehghani ◽  
Farzaneh Ghassabi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Transplant ◽  
Chronic Patients ◽  
Advanced Liver Disease ◽  
Reading Frame ◽  
Alternate Reading Frame Protein ◽  
Physicochemical Features ◽  
Liver Transplant Candidate ◽  
Transplant Candidate ◽  
Chronic Hcv

Background:: HCV Alternate Reading Frame Protein (ARFP) is a frameshift product of HCV-core encoding. Here, we characterized specific anti-ARFP antibodies in Liver Transplant Candidate (LTC) and chronic HCV-infected patients. Methods:: The ARFP gene was cloned and the recombinant protein was purified using Nickel chromatography and confirmed by western blotting. ELISA was developed using recombinant core-1a, core- 1b, ARFP-1a protein, and 99-residue synthetic ARFP 1b peptide. By several Bioinformatics tools, general properties, immunogenic epitopes, and structures of these proteins were obtained. Results:: The seroprevalence of anti-core and anti-ARFP antibodies was 100% in LTC patients, but only 75.2% and 94.3% of chronic patients had evidence of anti-ARFP and anti-core antibodies, respectively. In-silico results demonstrated physicochemical features, antigen properties and potential interactors that could describe progression toward advanced liver disease. Conclusion:: As the first report, the prevalence of anti-ARFP antibodies in LTC patients is of the order of 100% and titer of anti-ARFP antibody was significantly higher in LTC patients compared to chronic individuals, suggesting the possible role of ARFP in the progression toward advanced liver disease. In addition, docking analysis determined several interactor proteins such as prefoldin 2, cathepsin B, vitronectin, and angiotensinogen that have an important role in progression to chronic infection and liver disease development.

Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease

Hepatology ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 827-838 ◽  
Author(s):  
Lisa I. Backus ◽  
Pamela S. Belperio ◽  
Troy A. Shahoumian ◽  
Larry A. Mole
Keyword(s):  
Liver Disease ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Advanced Liver Disease ◽  
Direct Acting Antiviral ◽  
Direct Acting

scholarly journals Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 367 ◽  
Author(s):  
Raoel Maan ◽  
Adriaan J. van der Meer
Keyword(s):  
Liver Disease ◽  
Treatment Options ◽  
Public Health Problem ◽  
Hcv Infection ◽  
New Drugs ◽  
European Medicines Agency ◽  
Major Public Health Problem ◽  
Advanced Liver Disease ◽  
Specific Patient ◽  
Chronic Hcv

Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.

Low Uptake of Direct-acting Antiviral Therapy Among Hepatitis C Patients With Advanced Liver Disease and Access to Care, 2014-2017

2020 ◽  
Vol 55 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Philip R. Spradling ◽  
Jian Xing ◽  
Loralee B. Rupp ◽  
Anne C. Moorman ◽  
Stuart C. Gordon ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Access To Care ◽  
Antiviral Therapy ◽  
Advanced Liver Disease ◽  
Direct Acting Antiviral ◽  
Direct Acting

Assessment of Liver Fibrosis after Direct-Acting Antiviral Therapy in Compensated and Decompensated HCV-related Liver Disease

2019 ◽  
Vol 4 (04) ◽  
Author(s):  
Mohammed Amin Mohammed ◽  
Nesreen Moustafa Omar
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Virologic Response ◽  
Post Treatment ◽  
Direct Acting Antiviral ◽  
Non Invasive ◽  
Apri Score ◽  
Fibrosis Regression ◽  
Chronic Hcv ◽  
Direct Acting

Background and Aim: Successful HCV eradication was associated with significant improvement in liver histology. Direct-acting antiviral (DAAs) therapy is associated with a significantly higher rate of sustained virologic response (SVR) compared to interferon-based therapies. Several non-invasive methods have been developed and validated with robust reliability and clinical applicability. Although these non-invasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy, use of these measures in monitoring fibrosis regression after HCV eradication with DAAs is currently limited. So, the aim was to assess the impact of DAAs on fibrosis regression in chronic HCV Egyptian patients with either compensated or decompensated liver disease. Patients and Methods: A total of 228 Egyptian chronic HCV patients eligible for treatment with DAAs were enrolled in this prospective study. All subjects selected from outpatient's Hepatology clinic of Mansoura university hospital received DAAs with different regimens after consent. The endpoint was a sustained virologic response at 12 (SVR12) weeks post-treatment. All participants were evaluated non-invasively by fibrosis-4 index (FIB-4), Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) score, and liver stiffness measurement (LSM) by fibroscan before DAAs treatment, at end of treatment (EOT), 6- and 12-months post-treatment. Results: SVR achieved by DAAs therapy was associated with significant improvement (p ˂0.05) of non-invasive fibrosis markers (FIB-4, APRI score, and LSM by fibroscan) from baseline compared to EOT, 6-and 12-months post-treatment among HCV patients with significant and advanced liver fibrosis. Conclusions: fibrosis regression after DAAs therapy regardless of fibrosis grade. Baseline LSM by fibroscan predicted fibrosis regression.

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