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Bibi S, Nisar M, Rafique S, Waqas M, Zahoor M, Idrees M, Nazir N, Ihsan M, Salmen SH, Alharbi SA, Khan A, Al-Harrasi A. Harnessing Nature's Gifts: Salix nigra and Its Potential for Combating Hepatitis C Virus (HCV). ACS OMEGA 2023; 8:42987-42999. [PMID: 38024752 PMCID: PMC10653063 DOI: 10.1021/acsomega.3c06193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 09/26/2023] [Indexed: 12/01/2023]
Abstract
Hepatitis C virus (HCV) causes various liver complications, including fibrosis, cirrhosis, and steatosis, and finally progresses toward hepatocellular carcinoma (HCC). The current study aimed to explore the antiviral activity of the traditional Pakistani medicinal plant Salix nigra (S. nigra) known as black willow against the hepatitis C virus (HCV). The anti-HCV activity of S. nigra was established against stable Hep G2 cell lines expressing the HCV NS3 gene. Various plant-derived compounds with anti-HCV activity were identified, making phytotherapy a promising alternative to conventional treatments due to their cost-effectiveness and milder side effects. The two extraction methods (Maceration and Soxhlet) and four solvents (n-hexane, methanol, ethyl acetate, and water) were used to obtain crude extracts from S. nigra. Cytotoxicity testing showed that methanol (CC50 25 μg/mL) and water (CC50 30 μg/mL) extracts were highly toxic, while ethyl acetate and n-hexane (CC50 > 200 μg/mL) extracts were nontoxic at low concentrations (10-50 μg/mL), making them suitable for further anti-HCV investigations. Stable transfection of the NS3 gene was successfully performed in Hep G2 cells, creating a cellular expression system for studying virus-host interaction. The ethyl acetate extract of S. nigra exhibited significant inhibition of NS3 gene expression (mRNA and protein levels). The phytochemical analysis of S. nigra was also performed using the high-performance liquid chromatography (HPLC) technique. The phytochemical analysis identified several polyphenolic substances in the extracts of S. nigra. Our results concluded that the extracts of S. nigra have significantly reduced the expression of the NS3 gene at mRNA and protein levels. These findings contribute to the global efforts to combat hepatitis C by offering plant-based treatment options for HCV management.
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Affiliation(s)
- Sadia Bibi
- Department
of Botany, University of Malakand, Dir (Lower), Chakdara 18800, Khyber
Pakhtunkhwa, Pakistan
| | - Mohammad Nisar
- Department
of Botany, University of Malakand, Dir (Lower), Chakdara 18800, Khyber
Pakhtunkhwa, Pakistan
| | - Shazia Rafique
- Division
of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Muhammad Waqas
- Department
of Biotechnology and Genetic Engineering, Hazara University Mansehra, Mansehra 2100, Pakistan
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat Al Mauz, P.O Box 33, 616Nizwa, Sultanate of Oman
| | - Muhammad Zahoor
- Department
of Biochemistry, University of Malakand, Dir (Lower), Chakdara 18800, Khyber
Pakhtunkhwa, Pakistan
| | - Muhammad Idrees
- Division
of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 54590, Pakistan
| | - Nausheen Nazir
- Department
of Biochemistry, University of Malakand, Dir (Lower), Chakdara 18800, Khyber
Pakhtunkhwa, Pakistan
| | - Mohammad Ihsan
- Department
of Botany, University of Malakand, Dir (Lower), Chakdara 18800, Khyber
Pakhtunkhwa, Pakistan
| | - Saleh H. Salmen
- Department
of Botany and Microbiology, College of Science, King Saud University, PO Box −2455, Riyadh 11451, Saudi Arabia
| | - Sulaiman Ali Alharbi
- Department
of Botany and Microbiology, College of Science, King Saud University, PO Box −2455, Riyadh 11451, Saudi Arabia
| | - Ajmal Khan
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat Al Mauz, P.O Box 33, 616Nizwa, Sultanate of Oman
| | - Ahmed Al-Harrasi
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat Al Mauz, P.O Box 33, 616Nizwa, Sultanate of Oman
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2
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Khan R, Ali A, Bibi S, Rafique S, Idrees M, Halim SA, Waqas M, Bahadar H, Uddin J, Khan A, Al-Harrasi A. Expression Profiling of the Tripartite Motif Family Genes in Chronic Hepatitis C Patients. ACS OMEGA 2023; 8:25370-25377. [PMID: 37483213 PMCID: PMC10357460 DOI: 10.1021/acsomega.3c02800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/01/2023] [Indexed: 07/25/2023]
Abstract
Hepatitis C virus (HCV) is one of the most prevalent pathogens which causes significant morbidity and mortality in 2% of the world's population. Several interferon-stimulated genes (ISGs) are involved in HCV clearance by interacting with the viral proteins. Among these ISGs, the tripartite motif (TRIM) family genes are elevated during HCV infection. This study aims to evaluate the expression of three TRIM family genes in chronic hepatitis C patients, distributed among different groups, including TRIM11, TRIM14, and TRIM25. A total of 242 participants were recruited in this study, including 182 infected patients, 37 naïve individuals, and 23 control individuals. Out of 182 infected patients, 100 achieved sustained virologic response (SVR), 61 achieved rapid virologic response (RVR), and 21 patients developed hepatocellular carcinoma (HCC), showing no response to the given treatments. Our results indicate highest expression levels of TRIM mRNA transcripts in the RVR group with the highest increase of 7.5 folds in TRIM25, 6.68 folds in TRIM14, followed by the data from patients of the SVR group. The elevation was also evident in other groups, i.e., SVR and HCC, in different patterns among all the three TRIM genes. In addition to elevation in expression levels, a linear correlation is observed between the TRIM mRNAs and viral loads of HCV. These results showed the potential role of TRIM family genes in HCV restriction.
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Affiliation(s)
- Ramisha Khan
- Molecular
Virology Laboratory, Centre for Applied Molecular Biology (CAMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
- Kinnaird
College for Women University, Lahore 54000, Pakistan
| | - Amjad Ali
- Department
of Biotechnology and Genetic Engineering, Hazara University, Mansehra 21120, Khyber Pakhtunkhwa, Pakistan
| | - Sadia Bibi
- Department
of Botany, University of Malakand, Chakdara Dir Lower 18800, Khyber Pakhtunkhwa, Pakistan
| | - Shazia Rafique
- Divison
of Molecular Virology, Center of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
| | - Muhammad Idrees
- Divison
of Molecular Virology, Center of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
| | - Sobia Ahsan Halim
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Muhammad Waqas
- Department
of Biotechnology and Genetic Engineering, Hazara University, Mansehra 21120, Khyber Pakhtunkhwa, Pakistan
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Haji Bahadar
- Institute
of Pharmaceutical Sciences, Khyber Medical
University, Peshawar 25120, Pakistan
| | - Jalal Uddin
- Department
of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Kingdom
of Saudi Arabia
| | - Ajmal Khan
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Ahmed Al-Harrasi
- Natural and
Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
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Riaz HA, Nishwa DE, Fatima A, Wahid B, Ali A, Kumari B, Idrees M. Risk of adverse outcomes following treatment with direct acting antiviral drugs in HCV infected patients with liver cirrhosis. Heliyon 2023; 9:e16169. [PMID: 37234654 PMCID: PMC10205523 DOI: 10.1016/j.heliyon.2023.e16169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 04/23/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Introduction Hepatitis C virus (HCV) is the second major cause of death in Pakistan. Previously, interferon-based regimens were considered highly recommended therapy for HCV patients. Since 2015, interferon-based therapy has been replaced with interferon-free therapy also known as Direct Acting Antiviral (DAA) drugs. The treatment response of interferon-free regimens has been reported as highly effective treatment option with more than 90% sustained virological response (SVR) in chronic HCV infected patients in western countries of the world. Objective This study aims to analyze the treatment response of DAA drugs in HCV-infected Pakistani population with liver cirrhosis. Methodology We collected the total 94 sample of the HCV infected patients, from June 2020 to September 2020. Forty-six (46) patients were cirrhotic, and forty-eight (48) patients were non-cirrhotic. Data was analyzed using IBM SPSS version 21 software. Conclusion The findings of our study suggest that the response rate was 82.60% in HCV cirrhotic patients and 68.75% in HCV non-cirrhotic patients. Our study showed that overall treatment response was independent of age and gender. We also observed some adverse effects such as hepatocellular carcinoma, portosystemic encephalopathy (PSE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), upper gastrointestinal bleeding (UGIB), ascites, among patients following treatment with interferon-free regimens.
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Affiliation(s)
- Hafiza Arooba Riaz
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Dur E. Nishwa
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Ameer Fatima
- Hepatobiliary and Gastroenterology Unit, Sheikh Zayed Hospital, Lahore, Pakistan
| | - Braira Wahid
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Akhtar Ali
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia
| | - Babita Kumari
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Muhammad Idrees
- Division of Molecular Virology, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
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Kuriry H, Casey J, Krassenburg L, La D, Kuczynski M, Shah H, Janssen HLA, Hansen BE, Feld JJ. Spontaneous Clearance After Relapse Following Direct-Acting Antiviral Treatment for Chronic HCV Infection. Clin Gastroenterol Hepatol 2021; 19:2398-2406.e1. [PMID: 32629131 DOI: 10.1016/j.cgh.2020.06.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/11/2020] [Accepted: 06/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment. METHODS We performed a case-control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay. RESULTS Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (<4 log IU/mL in 11 of 12) and normal levels of alanine aminotransferase at the time of relapse, much like patients with an SVR12. There was no significant difference between the spontaneous clearance group and the SVR12 group in magnitude and breadth of HCV-specific T cell responses. CONCLUSIONS In a case-control study of patients who spontaneously cleared chronic HCV infection following a relapse after DAA therapy, we found that it is important to confirm viremia prior to retreatment after the relapse-particularly for individuals with low levels of HCV RNA and normal or near-normal levels of alanine aminotransferase after treatment.
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Affiliation(s)
- Hadi Kuriry
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Julia Casey
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Lisette Krassenburg
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Danie La
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Magdalena Kuczynski
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto Viral Hepatitis Care Network, Toronto, Ontario, Canada
| | - Hemant Shah
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto Viral Hepatitis Care Network, Toronto, Ontario, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto Viral Hepatitis Care Network, Toronto, Ontario, Canada
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto Viral Hepatitis Care Network, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto Viral Hepatitis Care Network, Toronto, Ontario, Canada.
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Naveed M, Ali A, Sheikh N, Rafique S, Idrees M. Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs. APMIS 2020; 128:326-334. [PMID: 31863490 DOI: 10.1111/apm.13024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022]
Abstract
Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.
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Affiliation(s)
- Mariam Naveed
- Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Department of Genetics, Hazara University, Mansehra, Pakistan
| | - Nadeem Sheikh
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
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6
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Wahid B. An unusual case of renal dysfunction and hepatocellular carcinoma following sofosbuvir therapy. Future Virol 2019. [DOI: 10.2217/fvl-2018-0158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
HCV is the major cause of morbidity and mortality worldwide with more than 185 million affectees. Currently, direct-acting antiviral drugs are being used as standard treatment approach that directly target HCV genes to eradicate virus and prevent cirrhosis. Accumulating evidence has reported that more than 90% HCV patients achieve sustained virological response. Adverse drug reactions of interferon-free regimens have not been studied yet. This is the first evidence of renal impairment and hepatocellular carcinoma following direct-acting antiviral drug therapy.
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Affiliation(s)
- Braira Wahid
- Department of Life Sciences, School of Science University of Management and Technology C-II, Johar Town, Lahore, Pakistan
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Wahid B, Naeem N, Altaf S, Ilyas N. Increasing Prevalence of Untypable and Mixed Genotypes of Hepatitis C Virus in Pakistan: Latest Trends in 2018. Viral Immunol 2019; 32:192-194. [PMID: 30939104 DOI: 10.1089/vim.2018.0152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Hepatitis C virus (HCV) genotyping is a critical parameter that acts as predictor of treatment response. According to previously reported findings, about 11 million population of Pakistan are HCV infected. Accumulating data suggest that genotype is the most prevalent genotype and mixed and untypable genotypes are the least prevalent genotypes of HCV. We observed that overall prevalence of mixed genotype (5.03%) and untypable genotype (3.3%) of HCV is on constant rise. This study highlights that the emergence of novel quasispecies could be reason of treatment failure in patients receiving direct-acting antiviral drugs.
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Affiliation(s)
- Braira Wahid
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Nabiha Naeem
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Saba Altaf
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Nimra Ilyas
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
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Khan R, Khan A, Ali A, Idrees M. The interplay between viruses and TRIM family proteins. Rev Med Virol 2019; 29:e2028. [PMID: 30609250 DOI: 10.1002/rmv.2028] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 11/11/2018] [Accepted: 11/13/2018] [Indexed: 12/20/2022]
Abstract
Novel therapeutic options are urgently needed to improve the global treatment of viral infections. Tripartite motif (TRIM) family proteins are involved in various biological and cellular functions including differentiation, development, proliferation, oncogenesis, innate immunity, and viral autophagy. Various TRIM proteins show antiviral properties against different viral infections and are now transitioning from ubiquitin proteins to an efficient and emerging therapeutic class of proteins. TRIM proteins combat viruses by targeting them at pre/post transcription levels. This review summarizes the comprehensive roles of different TRIM proteins along with their expression systems and their applications towards antiviral therapeutics.
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Affiliation(s)
- Ramisha Khan
- Molecular Virology Laboratory, Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Amna Khan
- Institute of Quality and Technology Management, University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Molecular Virology Laboratory, Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan.,Department of Genetics, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Idrees
- Molecular Virology Laboratory, Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan.,Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan
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9
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Wahid B, Waqar M, Rasool N, Wasim M, Khalid I, Idrees M. Prevalence of thyroid stimulating hormone dysfunction among sofosbuvir-treated HCV-infected patients: A real-world clinical experience. J Med Virol 2018; 91:514-517. [PMID: 30229954 DOI: 10.1002/jmv.25319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 09/05/2018] [Indexed: 12/22/2022]
Abstract
Thyroid dysfunctions occur frequently among hepatitis C virus (HCV)-infected patients. Accumulating evidence has shown the higher incidence of thyroid dysfunctions in interferon-treated patients that was previously the standard of care therapy. However, the prevalence of thyroid disorders has not been studied in the recently developed interferon-free regimens or direct-acting antiviral (DAA) drugs-treated patients. We recruited 37 patients who had just completed 6 months long sofosbuvir-based treatment, and 26 interferon-treated patients were also included in the study. Serum thyrotropin level of all participants was measured using VIDAS. We observed thyroid dysfunctions in both pegylated interferon-experienced and DAA drug-experienced patients but the prevalence of hyperthyroidism was found significantly higher in patients treated with interferon-based regimen as compared with interferon-free regimens. This high prevalence of hypothyroidism in patients with HCV posttreatment highlights the need for regular periodic screening of patients during the treatment.
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Affiliation(s)
- Braira Wahid
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Muhammad Waqar
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nouman Rasool
- Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan.,Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Muhammad Wasim
- Department of Medicine, Khyber Teaching Hospital, Peshawar KPK, Pakistan
| | - Ifrah Khalid
- Division of Molecular Virology, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
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10
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Wahid B, Waqar M, Saleem K, Shafi F, Rehman Z, Hanif I, Ahmad HM, Wasim M, Sajjad, Wahid K, Idrees M. Poor response to direct-acting antiviral therapy in HCV-infected elderly population: a real-life cohort study based on GeneXpert® technology. Future Virol 2018. [DOI: 10.2217/fvl-2017-0158] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Aim: This study aimed to determine the efficacy of direct-acting antiviral drugs in different ethnicities and elderly population of Pakistan. Methods: We used GeneXpert® technology to quantify HCV RNA and evaluated treatment response in different cohorts that included HCV patients classified on the basis of their age-group and ethnicity. Results: The findings of our study suggest that 76% of nonresponder patients were older than 55 years of age which shows that age is the predictor of treatment outcome of direct-acting antiviral drugs. In addition to this, no differences were observed in overall efficacy by ethnicity. Conclusion: Treatment-regimen sofosbuvir+ribavirin has a limited effect on older patients; therefore, practitioners and healthcare professionals need to reconsider treatment options for elderly populations.
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Affiliation(s)
- Braira Wahid
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Muhammad Waqar
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Komal Saleem
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Faiza Shafi
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
| | - Zobaria Rehman
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Iqra Hanif
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
| | - Hafiza Maleeha Ahmad
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
| | - Muhammad Wasim
- Department of Medicine, Khyber Teaching Hospital, Peshawar, Pakistan
| | - Sajjad
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Hazara University, Mansehra, Pakistan
| | - Khansa Wahid
- Lahore College for Women University, Jail Road, Lahore, Pakistan
| | - Muhammad Idrees
- Genome Centre for Molecular Based Diagnostics & Research, Al-Sudais Plaza Abdalian Cooperative Society, Lahore, Pakistan
- Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
- Hazara University, Mansehra, Pakistan
- Division of Molecular Virology & Diagnostics Center of Excellence in Molecular Biology (CEMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
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11
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Saleem K, Wahid B, Ali A, Rafique S, Naz Z, Usman S, Idrees M. Unexpected Response Profiles Seen in Hepatitis C Virus-Infected Patients Treated with Sofosbuvir Plus Ribavirin: Five Case Reports. Viral Immunol 2018; 31:480-483. [PMID: 29694794 DOI: 10.1089/vim.2017.0199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Direct-acting antivirals (DAAs) have been proved as potent agents in the new era of Hepatitis C therapeutics. DAA has evolved to prove highly efficacious treatment rates and sustained virological response in hepatitis C virus (HCV)-treated patients and has shown minimal side effects, but in this study, we reported five cases that showed unusual response toward the use of DAA. The diagnosis was an unusual response of abruptly high viral titers and liver function tests (LFTs) in patients who received DAA combination therapy. The patients received sofosbuvir (400 mg) and ribavirin for 6 months. Although 6-month long recommended DAA combination therapy with ribavirin cleared HCV after 6 months, during the treatment period, five patients experienced unusually and unexpectedly high viral loads and LFTs level in the middle of therapy tenure and then sudden decline of viral titers after completion of treatment. This is the first study to describe the unusual response shown by patients treated with sofosbuvir-based combined therapy that experienced abrupt and marked rise in viral loads during the initial months of treatment followed by sudden elimination of virus during last 2 months of treatment. Although satisfactory response to DAA is well reported, clinicians and policy makers should deliberate upon the exceptions and ensure the proper implementation of International guidelines with modifications according to this population, if necessary.
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Affiliation(s)
- Komal Saleem
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan
| | - Braira Wahid
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan
| | - Amjad Ali
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan
| | - Shazia Rafique
- 2 Centre of Excellence in Molecular Biology (CEMB), University of the Punjab , Lahore, Pakistan
| | - Zara Naz
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan
| | - Sana Usman
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan
| | - Muhammad Idrees
- 1 Centre for Applied Molecular Biology, University of the Punjab , Lahore, Pakistan .,3 Vice Chancellor Hazara University Mansehra , Mansehra, Pakistan
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Iqbal S, Yousuf MH, Yousaf MI. Dramatic response of hepatitis C patients chronically infected with hepatitis C virus genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study. World J Gastroenterol 2017; 23:7899-7905. [PMID: 29209131 PMCID: PMC5703919 DOI: 10.3748/wjg.v23.i44.7899] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 09/06/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023] Open
Abstract
AIM To prospectively evaluate the efficacy of sofobuvir (SOF) in hepatitis C patients infected with hepatitis C virus (HCV) genotype 3 in Pakistan.
METHODS The present study was performed with the coordination of gastroenterology and pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016. The total number of patients included in this study was 1375 and all of them were infected with HCV genotype 3. On the basis of drug combinations, all the patients were separated into two groups. The first group of patients was treated for 24 wk with SOF (Sovaldi® by Gilead Sciences) plus ribavirin (RBV) [Ribazol® by Getz Pharma Pakistan (PVT) Ltd], while the patients of the second group were treated with SOF + RBV + pegylated-interferon (pegIFN) alfa-2a (Ropegra by Roach) for 12 wk. HCV genotyping and viral load measurement were performed on fully automated Abbott Real-Time PCR system (Abbott m24sp automated nucleic acid extraction system and Abbott m2000rt amplification system; abbott Molecular, Des Plaines, IL, United States). For the assessment of sustained virological response (SVR), all HCV RNA negative patients were followed for 12 weeks after the treatment completion. Any patient with less than 12 IU/mL viral load after 12 wk of treatment completion was considered as a sustained virological responder (SVR-12).
RESULTS A total of 1375 patients chronically infected with HCV genotype 3 were treated with two drug combinations SOF + RBV and SOF + RBV + pegIFN alfa-2a. On the basis of these drug combinations, patients were divided into two groups (first and second). Overall SVR-12 was excellent in both groups (99.17% and 97.91%). Older patients (> 40 years) of second group showed lower SVR-12 (93.46%) compared to first group older patients (98.79%), while in the younger patients of both groups, the SVR-12 rate was almost the same (99.54% in first group and 99.05% in second group). No such difference regarding SVR-12 rate was seen in males and females of first group patients (99.68% and 98.88%, respectively), while in second group the males were found to be better responders compared to females (98.96% and 95%). The SVR-12 rate in previously treated patients of first group was better (99.34%) than second group (93.70%), while naïve patients of second group were marginally better responders (99.25%) than first group (97.80%). Rapid viral response at week-4 was found to be a very effective predictor for assessing the SVR rate at this stage of therapy in both groups. Headache, anemia and fatigue were common side effects in both groups either treated with SOF + RBV or SOF + RBV + pegIFN alfa-2a, while the overall percentage of the side effects was higher in second group.
CONCLUSION The remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided a new way to look forward to eliminate hepatitis C from our region.
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Affiliation(s)
- Sajjad Iqbal
- Department of Pathology, Shalamar Hospital, Lahore 54840, Pakistan
| | - Muhammad Haroon Yousuf
- Department of Gastroenterology and Hepatology, Shalamar Hospital, Lahore 54840, Pakistan
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Wahid B, Usman S, Ali A, Saleem K, Rafique S, Naz Z, Ahsan Ashfaq H, Idrees M. Therapeutic Strategies of Clustered Regularly Interspaced Palindromic Repeats-Cas Systems for Different Viral Infections. Viral Immunol 2017; 30:552-559. [DOI: 10.1089/vim.2017.0055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Braira Wahid
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Sana Usman
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Komal Saleem
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
| | | | - Hafiz Ahsan Ashfaq
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
- Vice Chancellor Hazara University, Mansehra, Pakistan
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