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.

scholarly journals Liver Transplant Candidate Unsuitability: A Review of the British Columbia Experience

2006 ◽  
Vol 20 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Jaber Alali ◽  
Alnoor Ramji ◽  
Jin K Ho ◽  
Charles H Scudamore ◽  
Siegfried R Erb ◽  
...  
Keyword(s):  
Social Support ◽  
British Columbia ◽  
Liver Disease ◽  
Liver Transplant ◽  
Chart Review ◽  
Community Intervention ◽  
Retrospective Chart Review ◽  
Patients Âgés ◽  
Liver Transplant Candidate

BACKGROUND: Every centre has contraindications to liver transplantation and declares patients unsuitable for medical or nonmedical reasons. To date, there has been no published review of any centre’s experience.METHODS: A retrospective chart review was completed from 1997 to 2001, inclusive of all patients referred for liver transplant to the British Columbia Transplant Society who were declared unsuitable for transplantation, as well as the reasons for unsuitability.RESULTS: One hundred fifty patients were considered to be unsuitable for transplantation. During this period, 167 transplants were performed and 737 patients were referred for candidacy. Data were missing on three patients; analysis was performed on the remaining 147. Patients’ ages ranged from 15 to 72 years, and 33.3% were female. The most common primary liver disease was hepatitis C (n=53, 35%), followed by alcoholic liver disease (n=35, 24%) and autoimmune liver diseases (n=23, 16%). Medical contraindications constituted 74 patients (49.0%) and the most common reasons for unsuitability were no need of a liver transplant (29 patients [39%]), exclusion due to hepatoma or extrahepatic malignancy (20 patients [27%]) and multisystem failure (12 patients [16%]). Nonmedical contraindications constituted 73 patients. Failure to meet minimal alcohol criteria comprised the largest group (n=39, 53.4%) followed by inadequate social support (n=12, 16.4%), failure to follow up medical assessment (n=10, 13.7%) and drug abuse (n=6, 8.2%).CONCLUSIONS: Although many patients were declined for transplantation, the proportion is relatively small compared with the number of referred patients. Nonmedical reasons, including failure to meet alcohol criteria and lack of social support, remain a significant reason for unsuitability in British Columbia. Community intervention before transplant referral is recommended.

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.

Sign in / Sign up

Export Citation Format

Share Document