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Vieira Teixeira S, Prates G, Marcondes Fonseca LA, Casseb J. Can Persistent Infections with Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus, and Human T Lymphotropic Virus Type 1 Be Eradicated? AIDS Res Hum Retroviruses 2024; 40:127-133. [PMID: 37409405 DOI: 10.1089/aid.2022.0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2023] Open
Abstract
Persistent viruses are hard to be eradicated, even using effective medications, and can persist for a long time in humans, sometimes regardless of treatment. Hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and human T cell lymphotropic virus infections, the most common in our era, are still a challenge despite the increased knowledge about their biology. Most of them are highly pathogenic, some causing acute disease or, more often, leading to chronic persistent infections, and some of the occult, carrying a high risk of morbidity and mortality. However, if such infections were discovered early, they might be eradicated in the near future with effective medications and/or vaccines. This perspective review points out some specific characteristics of the most important chronic persistent viruses. It seems that in the next few years, these persistent viruses may have control by vaccination, epidemiological strategies, and/or treatment.
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Affiliation(s)
- Sandy Vieira Teixeira
- Laboratory of Medical Investigation in Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Gabriela Prates
- Laboratory of Medical Investigation in Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Luiz Augusto Marcondes Fonseca
- Laboratory of Medical Investigation in Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil
| | - Jorge Casseb
- Laboratory of Medical Investigation in Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Hospital das Clinicas HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil
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Bernal LA, Soti V. Hepatitis C Virus: Insights Into Its History, Treatment, Challenges, and Future Directions. Cureus 2023; 15:e43924. [PMID: 37614826 PMCID: PMC10443603 DOI: 10.7759/cureus.43924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2023] [Indexed: 08/25/2023] Open
Abstract
Hepatitis C virus (HCV) is a global public health concern with significant impacts. It primarily spreads through blood-to-blood contact, such as sharing needles among drug users. Given the wide prevalence of risk factors, HCV continues to pose a major threat. Hence, it is crucial to understand its characteristics, structure, and genotypes to prevent, treat, and potentially eradicate it. This narrative review aims to explore the history of HCV treatment, highlight the breakthroughs achieved with direct-acting antiviral (DAA) therapy, address potential barriers to HCV eradication, and discuss future treatment possibilities. For this article, relevant studies were identified using various databases, including PubMed, ClinicalTrials.gov, and Journal Storage. The literature search revealed that after identifying HCV and studying its characteristics, interferon alfa and ribavirin became primary treatment options. However, due to their limited coverage against different HCV genotypes, ethnic variations, and suboptimal sustained virological response, the development of DAAs became essential. Combining various DAAs, such as sofosbuvir and velpatasvir, for a duration of 12 weeks has become the standard HCV treatment, with effectiveness against most genotypes. Additionally, ongoing clinical trials have shown promising results for other drugs such as CDI31244/sofosbuvir/velpatasvir, sofosbuvir/coblopasvir, and daclatasvir/asunaprevir. Despite the success of DAAs and ongoing efforts to discover more effective treatments, the high costs of DAAs pose a significant challenge to eradicating HCV, as not all patients can afford these expensive therapies. Furthermore, the ability of HCV to mutate limits the potential for vaccine development. Therefore, it is crucial to focus on developing more cost-effective strategies to control the spread of HCV and create novel, highly effective, and affordable DAAs.
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Affiliation(s)
- Luis A Bernal
- Internal Medicine, Lake Erie College of Osteopathic Medicine, Elmira, USA
| | - Varun Soti
- Pharmacology and Therapeutics, Lake Erie College of Osteopathic Medicine, Elmira, USA
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Vincent JP, Nyamasege C, Wang S, Madec Y, Shimakawa Y. Prevalence of hepatitis B, C, and D virus infection in Haiti: A systematic review and meta-analysis. Front Public Health 2023; 10:1099571. [PMID: 36711383 PMCID: PMC9874305 DOI: 10.3389/fpubh.2022.1099571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 12/22/2022] [Indexed: 01/13/2023] Open
Abstract
Background Viral hepatitis causes an important global health burden. In 2016, the World Health Assembly adopted an objective to globally eliminate this as a public health threat by 2030. However, significant gaps exist between countries in their progress. Haiti is the last country that has introduced infant hepatitis B vaccines into the routine immunization program in the Region of the Americas, and its schedule still does not incorporate birth dose vaccines. As the first step to raise awareness of viral hepatitis in this country, we conducted a systematic review and meta-analysis to estimate the prevalence of hepatitis B (HBV), C (HCV), and D (HDV) viruses in Haiti. Methods We searched PubMed, EMBASE, Web of Science and Scopus for studies reporting the prevalence of HBV, HCV and HDV among Haitian, with no language restriction, published until November 30th, 2021. Prevalence was pooled via a random-effects meta-analysis using a generalized linear mixed model with the logit link. Results Of 453 articles retrieved, 25 studies were included: 16 reported the prevalence of hepatitis B surface antigen (HBsAg), three for anti-HCV antibody, and six for both HBsAg and anti-HCV. No study was found for HDV prevalence. The pooled prevalence of HBsAg was 0.7% [95% confidence interval (CI): 0.3-1.4, I 2 = 77.7%] among children, 3.5% (95% CI: 2.8-4.4, I 2 = 93.2%) in the general adult population and 7.4% (95% CI: 4.0-13.3, I 2 = 83.9%) in high-risk adult population. The pooled prevalence of anti-HCV antibody was 0.9% (95% CI: 0.6-1.4, I 2 = 93.5%) among the general population and 1.4% (95% CI: 0.4-4.2, I 2 = 0.0%) in high-risk adult population. No study reported the prevalence of anti-HCV antibody exclusively in children. Interpretation The prevalence of blood-borne hepatitis, particularly that of HBV, is substantial in Haiti. The introduction of birth dose hepatitis B vaccines and improving access to testing and treatment services should be urgently considered to meet the elimination goal. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298081, identifier: PROSPERO (CRD42022298081).
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Affiliation(s)
- Jeanne Perpétue Vincent
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France,*Correspondence: Jeanne Perpétue Vincent ✉
| | - Carolyn Nyamasege
- Department of Health and Human Services, Institute for Health Policy and Practice, University of New Hampshire, Concord, NH, United States
| | - Su Wang
- Viral Hepatitis Program, Cooperman Barnabas Medical Center, Livingston, NJ, United States
| | - Yoann Madec
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France,Yusuke Shimakawa ✉
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Patauner F, Stanzione M, Stornaiuolo G, Martone V, Palladino R, Coppola N, Durante-Mangoni E, Zampino R. Safety and Efficacy of Direct Antiviral Agents for Hepatitis C in Patients with Malignancies Other Than Liver Cancer: A Case Series. Pathogens 2022; 11:860. [PMID: 36014981 PMCID: PMC9414735 DOI: 10.3390/pathogens11080860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 01/27/2023] Open
Abstract
(1) Background: direct-acting antivirals (DAA) are the current standard of care for chronic hepatitis C. Oncologic patients remain among the most difficult-to-treat subgroups of hepatitis C virus (HCV)-infected patients due to their clinical frailty and complex therapeutic protocols received. (2) Methods: we retrospectively collected and analysed clinical data of 30 consecutive patients treated with DAA, between 2015 and 2022, for chronic HCV infection in the context of oncologic disease. (3) Results: most patients were females (63.3%), median age was 67 years, HCV genotype 1 was prevalent (60%), and median HCV RNA levels were 2.2 × 106 IU/mL. The most common malignancy was breast cancer (37%), and the chief oncologic drugs co-administered with DAAs were tamoxifen, platinum derivatives, cyclophosphamide, paclitaxel, rituximab and doxorubicin. Overall, 50% of patients had chronic hepatitis. A total of 76.7% underwent a sofosbuvir-based treatment. Sustained virological response 12 weeks after the end of therapy (SVR12) was reached in all patients. After SVR12, two patients died. DAA treatment was well tolerated; no patients had to stop DAA treatment or showed any adverse event or drug-drug interaction specifically attributable to DAAs. (4) Conclusions: DAA treatment should be promptly offered to oncologic patients with chronic hepatitis C in order to achieve aminotransferase normalization and viremia control, making antineoplastic therapy feasible and safe.
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Affiliation(s)
- Fabian Patauner
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
| | - Maria Stanzione
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Gianfranca Stornaiuolo
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Veronica Martone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
| | - Roberta Palladino
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali Dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Rosa Zampino
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
- Unit of Infectious and Transplant Medicine, AORN Ospedali Dei Colli-Monaldi Hospital, 80131 Naples, Italy
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Prevalence of Transfusion-Transmitted Infections (HCV, HIV, Syphilis and Malaria) in Blood Donors: A Large-Scale Cross-Sectional Study. Pathogens 2022; 11:pathogens11070726. [PMID: 35889972 PMCID: PMC9321235 DOI: 10.3390/pathogens11070726] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 06/04/2022] [Accepted: 06/24/2022] [Indexed: 11/27/2022] Open
Abstract
Blood plays a major role in transmitting infectious diseases such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), syphilis, malaria, and many others. Thus, this study sought to evaluate the distribution of HCV, HIV, syphilis, and malaria among blood donors in Yemen. This is a cross-sectional study, conducted on blood donors at the national center in Yemen. Blood donors’ specimens were serologically tested for the presence of anti-HCV and anti-HIV antibodies, as well as anti-Treponema pallidum, anti-Plasmodium falciparum, and anti-Plasmodium vivax. A total of 16,367 donors were included in this study. Based on the donor’s occupation, the study showed that the relative seroprevalence of anti-HCV Ab among the donors was statistically significant, and relatively high prevalence was found among military donors (2.8%). Positive HIV antibody tests were only reported in 33 male donors (0.2%), who were mostly manual workers. A remarkably high prevalence of anti-Treponema pallidum was observed among manual workers (3.1%). There was a statistically significant difference in the distribution of anti-malaria Ab based on residency and age groups. This study revealed that the prevalence of HCV, HIV, syphilis, and malaria among donors was 2.0%, 0.2%, 2.4%, and 0.7%, respectively. Further genotyping studies are necessary to provide a complete picture of the prevalence of transfusion-transmitted infections (TTIs).
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Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol. Sci Rep 2022; 12:9942. [PMID: 35705594 PMCID: PMC9200852 DOI: 10.1038/s41598-022-13657-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 05/05/2022] [Indexed: 11/19/2022] Open
Abstract
Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84–4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.
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Omar ZMM, Ahmed AAN, El-Bakry MH, Ahmed MA, Hasan A. Metformin versus Silymarin as Hepatoprotective Agents in Mice Fibrotic Model Caused by Carbon Tetrachloride. ANNALES PHARMACEUTIQUES FRANÇAISES 2022; 80:659-668. [PMID: 35093389 DOI: 10.1016/j.pharma.2022.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 12/11/2021] [Accepted: 01/12/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To study metformin hepatoprotective effects compared to silymarin on hepatic fibrosis caused by carbon tetrachloride (CCl4) in mice. MATERIAL AND METHODS liver fibrosis in mice was achieved by intraperitoneal injection of 2 ml/kg of CCl4 dilution in olive oil [1:9 (v/v)] twice a week for 7 weeks followed by oral treatment with metformin (250 mg/kg/day) or silymarin (100 mg/kg/day) (a standard hepatoprotective drug). The changes that follow liver fibrosis were assessed by measurement of hepatic enzymes (ALT, AST and ALP), histopathological examination using hematoxylin and eosin stain, special stains, and α-smooth muscle actin (α-SMA) immunostaining, measuring oxidative stress markers (MDA, GSH, NOx and MnSOD) and transforming growth factor-beta 1 (TGF-β1) in liver. RESULTS liver fibrosis was obviously developed in mice after intraperitoneal injection with CCl4 for 7 weeks. Both silymarin and metformin treatment exhibited a significant decrease in the fibrotic changes and similarly an increase in endogenous antioxidants. Interestingly there is a significant difference between silymarin and metformin regarding both efficacy and potency. CONCLUSION These findings highlight the anti-inflammatory, antioxidant and antifibrotic effects of metformin in CCl4-induced hepatic fibrosis in mice, but silymarin is more beneficial.
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Affiliation(s)
| | | | | | - Mohammed Ahmed Ahmed
- Department of Pathology, Faculty of Medicine, Al- Azhar University, Assiut, Egypt
| | - Abdulkarim Hasan
- Department of Pathology, Faculty of Medicine, Al- Azhar University, Cairo, Egypt.
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Sudhindar PD, Wainwright D, Saha S, Howarth R, McCain M, Bury Y, Saha SS, McPherson S, Reeves H, Patel AH, Faulkner GJ, Lunec J, Shukla R. HCV Activates Somatic L1 Retrotransposition-A Potential Hepatocarcinogenesis Pathway. Cancers (Basel) 2021; 13:5079. [PMID: 34680227 PMCID: PMC8533982 DOI: 10.3390/cancers13205079] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/29/2021] [Accepted: 10/07/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.
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Affiliation(s)
- Praveen D. Sudhindar
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Daniel Wainwright
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Santu Saha
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Rachel Howarth
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Misti McCain
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Yvonne Bury
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK;
| | - Sweta S. Saha
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Stuart McPherson
- The Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton NE7 7DN, UK;
| | - Helen Reeves
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
- The Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton NE7 7DN, UK;
| | - Arvind H. Patel
- MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK;
| | - Geoffrey J. Faulkner
- Mater Research Institute, University of Queensland, Woolloongabba, QLD 4102, Australia;
- Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
| | - John Lunec
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Ruchi Shukla
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
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Wang YW, Lee WP, Huang YH, Hou MC, Lan KH. Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis. BMC Infect Dis 2021; 21:984. [PMID: 34548026 PMCID: PMC8454153 DOI: 10.1186/s12879-021-06657-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 09/04/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients. METHODS A systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL. RESULTS Six studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL. CONCLUSIONS For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.
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Affiliation(s)
- Ying-Wen Wang
- Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Wei-Ping Lee
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Keng-Hsin Lan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Gul N, Khan SU, Ali I, Khan FU. Transmission dynamic of stochastic hepatitis C model by spectral collocation method. Comput Methods Biomech Biomed Engin 2021; 25:578-592. [PMID: 34459684 DOI: 10.1080/10255842.2021.1970143] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
In this research work, we present an exciting mathematical analysis of a stochastic model, using a standard incidence function, for infectious disease hepatitis C transmission dynamics. In this model, we divided the infected population into three different classes with two different infection stages known as chronic class and acute class while the third is an isolation class. We also presents briefly the Legendre spectral method for the numerical solution to the proposed model. It is observed that the disease-free equilibrium is asymptotically stable, when basic reproduction number R0<1. It is also shown that the proposed model has a stable endemic equilibrium when the reproduction number R0>1. Also, sensitivity analysis is carried out to study and identify the effect of parameters on R0. Moreover, we have performed numerical simulations to study the influence of disease free equilibrium and endemic equilibrium. Legendre polynomial and Legendre weight function are used to solve the proposed stochastic system numerically. Numerical results are compared against the basic reproduction number.
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Affiliation(s)
- Naseeb Gul
- Department of Mathematics, City University of Science and Information Technology Peshawar, KP, Pakistan
| | - Sami Ullah Khan
- Department of Mathematics, City University of Science and Information Technology Peshawar, KP, Pakistan
| | - Ishtiaq Ali
- Department of Mathematics and Statistics, College of Science, King Faisal University, Al-Hasa, KSA
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Zakaria S, El-Sisi AE. Daclatasvir and Sofosbuvir Mitigate Hepatic Fibrosis Through Downregulation of TNF-α / NF-κB Signaling Pathway. Curr Mol Pharmacol 2021; 13:318-327. [PMID: 31951178 DOI: 10.2174/1874467213666200116114919] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 12/02/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatic fibrosis is the major issue in chronic liver diseases such as chronic hepatitis C virus (HCV). The newly approved direct acting antiviral (DAA) agents such as Sofosbuvir (SOF) and daclatasvir (DAC) have been found to be associated with decreased fibrotic markers in HCV patients. AIM This study tried to explore whether the reported antifibrotic effect of these drugs is antiviral dependent or drug induced. METHOD Hepatic fibrosis was induced by (0.5ml/kg) CCl4 IP twice a week for six weeks. SOF (20 mg/kg/d) and DAC (30 mg/kg/d) were added in the last four weeks of treatments. Liver functions, fibrotic markers such as Hyaluronic acid and metalloproteinase-9 were detected using immunoassay. The expression of TNF-α/NF-κB signaling pathway as well as Bcl-2 were done using immunoassay. RESULTS SOF and DAC exerted a potent antifibrotic effect evidenced by their activity against hyaluronic acid HA and metalloproteinase MMP-9 significantly (P≤0.001). This effect was further proved histopathologically where liver tissues from rats treated by drugs showed marked inhibition of collagen precipitation as well as inhibition of HSCs activation. This antifibrotic action was associated with decreased expression of TNF-α /NF-κB signaling pathway and induction of Bcl-2. CONCLUSION SOF/ DAC antifibrotic effect is independent of its antiviral activity. The molecular events associated with this effect were the downregulation of TNF-α / NF-κB signaling pathway and induction of Bcl-2.
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Affiliation(s)
- Sherin Zakaria
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kaferelsheikh University, Kaferelsheikh, Egypt
| | - Alaa E El-Sisi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
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12
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Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain. Pharmacol Rep 2021; 73:1680-1693. [PMID: 34218397 PMCID: PMC8254454 DOI: 10.1007/s43440-021-00301-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 06/18/2021] [Accepted: 06/18/2021] [Indexed: 12/13/2022]
Abstract
Background Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice. Methods Socially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1β, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels. Results CBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals. Conclusions Apparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD. Supplementary Information The online version contains supplementary material available at 10.1007/s43440-021-00301-8.
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13
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Qureshi N, Tadesse M, Tran N, Henderson S. Establishing an Epidemiologic Profile of Hepatitis C Virus Infection at the Los Angeles County Jail. Public Health Rep 2021; 136:726-735. [PMID: 33602004 DOI: 10.1177/0033354920988610] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
OBJECTIVE The hepatitis C virus (HCV) is the most common blood-borne infection in the United States. Although 2% to 3% of the global population is estimated to be infected with HCV, an estimated 18% of the US prison population may be infected. The objective of this study was to establish an epidemiologic profile of HCV infection in the largest urban jail system in the United States. METHODS We retrospectively analyzed 20 years of data on demographic characteristics, risk factors, and HCV positivity among 80 681 individuals incarcerated at the Los Angeles County Jail who were tested for HCV infection from January 1, 2000, through December 31, 2019. We used multivariate logistic regression analysis to determine predictors of HCV positivity. RESULTS Of the 80 681 individuals tested, 27 881 (34.6%) had positive test results for HCV infection. In the multivariate analysis, HCV positivity was most strongly associated with injection drug use (adjusted odds ratio [aOR] = 34.9; 95% CI, 24.6-49.5) and being born during 1946-1955 (aOR = 13.0; 95% CI, 11.9-14.2). Men were more likely than women to have HCV infection (aOR = 1.4; 95% CI, 1.3-1.5), and Hispanic (aOR = 4.2; 95% CI, 3.9-4.4) and non-Hispanic White (aOR = 3.8; 95% CI, 3.5-4.0) individuals were more likely than non-Hispanic African American individuals to have HCV infection. Noninjection drug use, homelessness, and mental health issues were also significantly associated with HCV positivity. CONCLUSION Even in the absence of resources for universal screening for HCV infection, the creation of a risk profile and its implementation into a screening program may be a beneficial first step toward improving HCV surveillance and establishing an accurate estimate of HCV infection in the incarcerated population.
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Affiliation(s)
- Nazia Qureshi
- 5141 Correctional Health Services, Los Angeles County Department of Health Services, Los Angeles, CA, USA
| | - Martha Tadesse
- 5141 Correctional Health Services, Los Angeles County Department of Health Services, Los Angeles, CA, USA
| | - NgocDung Tran
- 5141 Correctional Health Services, Los Angeles County Department of Health Services, Los Angeles, CA, USA
| | - Sean Henderson
- 5141 Correctional Health Services, Los Angeles County Department of Health Services, Los Angeles, CA, USA
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14
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Lin CC, Liu TW, Yeh ML, Tsai YS, Tsai PC, Huang CF, Huang JF, Chuang WL, Dai CY, Yu ML. Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma. Clin Mol Hepatol 2020; 27:313-328. [PMID: 33317258 PMCID: PMC8046631 DOI: 10.3350/cmh.2020.0247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/10/2020] [Indexed: 12/19/2022] Open
Abstract
Background/Aims Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.
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Affiliation(s)
- Ching-Chih Lin
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ta-Wei Liu
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
| | - Ming-Lung Yu
- Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
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15
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Al Abri MZ, Farag MA, Al Mosawi AS, Al Awaidy ST. Socio-Demographic Characteristics and Patterns of Substance Use Disorder in Oman: A retrospective study of the National Registry Surveillance Programme between 2004 and 2018. Sultan Qaboos Univ Med J 2020; 20:e296-e303. [PMID: 33414933 PMCID: PMC7757916 DOI: 10.18295/squmj.2020.20.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/09/2020] [Accepted: 05/14/2020] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES Substance use disorder is a global challenge. Therefore, this study aimed to provide an updated view of socio-demographic characteristics and patterns of substance use in Oman. METHODS This retrospective descriptive study was conducted between 2004 and 2018. Data were retrieved from Oman's National Drug Addict Registry. The data collected included the socio-demographic characteristics of registered cases, the proportion of various psychoactive substances' consumption and their routes of administration, the associated sociodemographic determinants as well as comorbid conditions. RESULTS A total of 6,453 cases were registered during the study's timeframe. The majority of which were Omani (97.9%), male (98.7%), single (57.9%), unemployed (50.2%), had an education level below university (81.0%) and were adolescents and young adults (77.0%). Opiates were the most common substance used (66.6%) and more than half of the sample were polydrug users (51.0%). Injecting-drug users constituted 53.4% of the total registered cases. The proportion of people with hepatitis virus C, hepatits virus B and HIV among the registered cases were 46.9%, 5.1% and 3.7%, respectively. CONCLUSION The findings are in favour of rapidly escalating the introduction of a substance use preventive programme at all school levels as well as making opioid substitution therapy and other harm reduction programmes available in Oman.
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16
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Mercedes R, Brown J, Minard C, Tsai CM, Devaraj S, Munden M, Leung D. A Liver Biopsy Validation Pilot Study of Shear Wave Elastography, APRI, FIB-4, and Novel Serum Biomarkers for Liver Fibrosis Staging in Children With Chronic Viral Hepatitis. Glob Pediatr Health 2020; 7:2333794X20938931. [PMID: 32821773 PMCID: PMC7412911 DOI: 10.1177/2333794x20938931] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/12/2020] [Accepted: 05/26/2020] [Indexed: 01/04/2023] Open
Abstract
As liver biopsy in children poses inherent risks, noninvasive measures of liver fibrosis are needed. This was a cross-sectional, liver biopsy validation pilot study of 16 participants evaluating the ability of shear wave elastography, aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors, and novel serum biomarkers to stage liver fibrosis in children with chronic hepatitis B or C. There was very high intrasegmental shear wave speed variation in our participants and little correlation with fibrosis. APRI and monocyte chemoattractant protein (MCP-1) were higher in fibrosis stage F2-3 versus F0-1 (P = .02, P = .06, respectively). Soluble Fas (sFas) was lower in F2-3 versus F0-1 (P = .046). A logistic regression analysis calculated by (APRI × MCP-1)/sFas demonstrated an area under the receiver operating characteristic curve of 0.92 (P < .001), suggesting that this combination can differentiate fibrosis stage F0-1 from F2-3 in children with chronic viral hepatitis.
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Affiliation(s)
| | | | | | - Cynthia M Tsai
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
| | | | - Marthe Munden
- Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Daniel Leung
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
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17
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Cheng H, Xu C, Zhang D, Zhang Z, Liu J, Lv X. Multiclass identification of hepatitis C based on serum Raman spectroscopy. Photodiagnosis Photodyn Ther 2020; 30:101735. [PMID: 32171878 DOI: 10.1016/j.pdpdt.2020.101735] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/05/2020] [Accepted: 03/09/2020] [Indexed: 10/24/2022]
Abstract
Hepatitis C is a chronic infectious disease, and early detection and diagnosis are key to curing it. In this study, human serum Raman spectroscopy combined with a support vector machine (SVM) classification algorithm was used to identify multiple types of hepatitis C. The HCV genome is highly mutated and its nucleic acid sequence diversity is up to 30%, according to the homology of nucleotide sequences, the virus strains were divided into seven genotypes and more than 90 subtypes, there were geographical differences in the distribution of HCV of different genotypes, and hcv-1, 2 and 3 were widely prevalent in the world, the main prevalent HCV genotypes in China include 1b,2a,3a,3b and 6a. Combined with the characteristics of Urumqi, xinjiang, China as a multi-ethnic gathering area and the distribution characteristics of HCV genotypes in Urumqi, xinjiang reported in literature, HCV1, HCV2, HCV3a and HCV3b were selected as groups in this paper (Messina et al., 2015; Chen et al., 2017; Ohno et al., 1997). The serum Raman spectra of 55 healthy people, 55 hepatitis C virus cluster 1 (HCV1) patients, and 55 hepatitis C virus cluster 2 (HCV2) patients were collected. The normalized average Raman spectra of the three groups of serum, the differences in the average spectra between groups were plotted and analyzed. The attributions, similarities and differences in the main characteristic peaks in the three types of serum Raman spectra were described. The SVM (support vector machine) algorithm was combined with the normalized Raman spectral data to identify the three groups of serum with 91.1 % accuracy. Furthermore, serum Raman spectroscopy data from 17 hepatitis C virus genotype 3a (HCV3a) patients, 7 hepatitis C virus genotype 3b (HCV3b) patients, and 6 hepatitis C virus cluster 4 (HCV4) patients were also collected. Because of the small number of serum samples, the HCV3b and HCV4 patient sera were classified into one group to discriminate them from HCV3a patients. A model of HCV3a hepatitis was detected. As with the abovementioned groups of patients, the normalized mean Raman spectra of the HCV3a patients and HCV3b patients + HCV4 patients, the difference between the average spectra of the two groups were plotted and analyzed; the attributions, similarities and differences of the main characteristic peaks from these two groups of serum Raman spectra were described. The SVM algorithm was combined with the normalized Raman spectroscopy data to identify the two groups of patient sera with 90 % identification accuracy. This study shows that serum Raman spectroscopy combined with an SVM algorithm can be used for multiclass identification of hepatitis C.
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Affiliation(s)
- Hong Cheng
- The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Chunlei Xu
- The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Di Zhang
- The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China
| | - Zhaoxia Zhang
- The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.
| | - Jie Liu
- College of Information Science and Engineering, Xinjiang University, Urumqi 830046, China
| | - Xiaoyi Lv
- College of Information Science and Engineering, Xinjiang University, Urumqi 830046, China; School of Software, Xinjiang University, Urumqi 830046, China.
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18
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Shawon MAA, Yousuf MAK, Raheem E, Ahmed S, Dipti TT, Hoque MR, Taniguchi H, Karim MR. Epidemiology, clinical features, and impact of food habits on the risk of hepatocellular carcinoma: A case-control study in Bangladesh. PLoS One 2020; 15:e0232121. [PMID: 32339207 PMCID: PMC7185601 DOI: 10.1371/journal.pone.0232121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/07/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer mortality worldwide. Infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is the most predominant cause of HCC. Concerns arise for the presence of additional risk factors, as there is still a large proportion of patients without HBV or HCV infection. Previous studies have reported that higher intake of fruits and vegetables and reduced consumption of red/processed meat might play a protective role in HCC etiology, though the nationwide proof is limited. Hence, we studied multiple risk factors including food habit, lifestyle, and clinical implications of HCC patients in Bangladeshi. Demographic, clinical, and biochemical data, as well as data on food habits, were collected in this study. Our results indicated that a high intake of rice (AOR 4.28, 95% CI 1.48 to 14.07, p = 0.011), low intake of fruits (AOR = 4.41 95% CI 1.48-15.46; p = 0.012), leafy vegetables (AOR = 2.80, 95% CI 1.32-6.08; p = 0.008), and fish (AOR = 4.64 95% CI 2.18-10.23; p<0.001) increased the HCC risk. Moreover, a high intake of eggs (AOR = 2.07 95% CI 0.98-4.43; p = 0.058) also showed an increased risk. Roti, non-leafy vegetables, red meat, and tea were found to have no association with HCC risk. This study revealed that food habit patterns and lifestyle may have a profound effect on HCC development among Bangladeshi patients in addition to well established risk factors.
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Affiliation(s)
- M. Al-Amin Shawon
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - M. Abul Khair Yousuf
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Sium Ahmed
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - Tyeaba Tasnim Dipti
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - Mohammad Razuanul Hoque
- Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, Bangladesh
| | - Hiroaki Taniguchi
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - M. Rezaul Karim
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
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Bhatia M, Gupta E. Emerging resistance to directly-acting antiviral therapy in treatment of chronic Hepatitis C infection-A brief review of literature. J Family Med Prim Care 2020; 9:531-538. [PMID: 32318377 PMCID: PMC7113931 DOI: 10.4103/jfmpc.jfmpc_943_19] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 12/16/2019] [Accepted: 12/24/2019] [Indexed: 12/13/2022] Open
Abstract
Hepatitis caused by Hepatitis C virus (HCV) is a major cause of chronic liver disease. HCV is transmitted by injection drug use, blood transfusion, hemodialysis, organ transplantation and less frequently sexual intercourse. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular carcinoma. Globally, about 170 million people are infected with HCV. Since the discovery of this virus in 1989, the clinical management of chronic hepatitis C infection has undergone a paradigm shift from alpha interferon to direct-acting antiviral (DAA) therapy. However, resistance to many of these antiviral agents has been reported increasingly from all over the globe. This review article focuses on the emerging HCV resistance to DAAs and the relevance of in vitro DAA resistance testing in clinical practice.
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Affiliation(s)
- Mohit Bhatia
- Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Ekta Gupta
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
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20
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The Prevalence of Hepatitis C Infection in Blood Donors: A Meta-Analysis and Systematic Review. IRANIAN RED CRESCENT MEDICAL JOURNAL 2020. [DOI: 10.5812/ircmj.94998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Acoustic radiation forced impulse-based splenic prediction model using data mining for the noninvasive prediction of esophageal varices in hepatitis C virus advanced fibrosis. Eur J Gastroenterol Hepatol 2019; 31:1533-1539. [PMID: 31689264 DOI: 10.1097/meg.0000000000001458] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Esophageal varices (EV) are serious complications of hepatitis C virus (HCV) cirrhosis. Endoscopic screening is expensive, invasive, and uncomfortable. Accordingly, noninvasive methods are mandatory to avoid unnecessary endoscopy. Acoustic radiation forced impulse (ARFI) imaging using point shear wave elastography as demonstrated with virtual touch quantification is a possible noninvasive EV predictor. We aimed to validate the reliability of liver stiffness (LS) and spleen stiffness (SS) by an ARFI-based study together with other noninvasive parameters for EV prediction in HCV patients. Also, we aimed to evaluate the diagnostic performance of a new simple prediction model (incorporating SS) using data mining analysis. PATIENTS AND METHODS This cross-sectional study included 200 HCV patients with advanced fibrosis. Labs, endoscopic, ultrasonographic, LS, and SS data were collected. Their accuracy in diagnosing EV was assessed and a data mining analysis was carried out. RESULTS Ninety patients (22/46% of F3/F4 patients) had EV (39/30/18/3 patients had grade I/II/III/IV, respectively). LS and SS by ARFI showed high significance in differentiating not only patients with/without EV (P = 0.000 for both) but also correlated with the grading of varices (R = 0.31 and 0.45, respectively; P = 0.000 for both). Spleen longitudinal diameter (SD), splenic vein diameter (SVD), platelets to spleen diameter ratio, LOK index, and FIB-4 score were the best ultrasonographic and biochemical predictors for the prediction of EV [area under receiver operating characteristic (AUROC) 0.79, 0.76, 0.76, 0.74, and 0.71, respectively]. SS (using ARFI) had better diagnostic performance than LS for the prediction of EV (AUROC = 0.76 and 0.70, respectively). The diagnostic performance increased using data mining to construct a simple prediction model: high probability for EV if [(SD cm) × 0.17 + (SVD mm) × 0.06 + (SS) × 0.97] more than 6.35 with AUROC 0.85. CONCLUSION SS by ARFI represents a reliable noninvasive tool for the prediction of EV in HCV patients, especially when incorporated into a new data mining-based prediction model.
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22
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Sakamaki A, Kamimura K, Fukui N, Watanabe H, Sakai N, Tominaga K, Mizuno K, Takamura M, Kawai H, Sugai T, Yamagiwa S, Someya T, Terai S. A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety. BMC Gastroenterol 2019; 19:85. [PMID: 31195993 PMCID: PMC6567614 DOI: 10.1186/s12876-019-1013-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 06/06/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Naoki Fukui
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Haruka Watanabe
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Norihiro Sakai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Kenichi Mizuno
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Takuro Sugai
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Toshiyuki Someya
- Division of Psychiatry, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510 Japan
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Transjugular Intrahepatic Portosystemic Shunt does not affect the efficacy and safety of direct-acting antivirals in patients with advanced cirrhosis: A real-life, case-control study. Dig Liver Dis 2019; 51:870-874. [PMID: 30824409 DOI: 10.1016/j.dld.2018.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 11/17/2018] [Accepted: 11/20/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a well-established treatment for complications of portal hypertension. AIMS To analyze the impact of TIPS on virologic response and safety profile in patients treated with direct-acting antivirals (DAAs). METHODS We analyzed data from HCV-positive cirrhotic patients treated with DAAs. Twenty-one patients with previous TIPS placement were compared with 42 matched subjects without TIPS. Logistic regression was used to identify predictors of hepatic function worsening and adverse events. RESULTS No differences were found between the two groups in particular regarding sustained virologic response (92.5 and 97.6% in TIPS vs no-TIPS, p = 0.559). Model for End-stage Liver Disease (MELD) of both TIPS and no-TIPS groups declined from baseline to week 24 of follow-up (from 12.5 ± 3.5 to 10.8 ± 3.4 and from 11.1 ± 3.5 to 10.3 ± 3.4, p = 0.044 and 0.025). There were no differences in adverse event rates. At univariate analysis, age was associated with MELD increase from baseline to week 24 (OR 1.111, 95% CI 1.019-1.211, p = 0.017), and patients with higher baseline MELD developed serious adverse events more frequently (OR 0.815, 95% CI 0.658-1.010, p = 0.062). Patients with or without TIPS did not show differences in transplant-free survival. CONCLUSION TIPS placement does not affect virologic response and clinical outcome of patients receiving DAAs.
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Stark JE, Cole J. Successful treatment of chronic hepatitis C virus infection in a patient receiving daily peritoneal dialysis. Am J Health Syst Pharm 2019; 74:1541-1544. [PMID: 28947525 DOI: 10.2146/ajhp160729] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Successful use of a 4-drug oral fixed-dose combination therapy to treat chronic hepatitis C in a patient receiving peritoneal dialysis (PD) is reported. SUMMARY New highly effective treatments for chronic hepatitis C virus (HCV) infection are now available, but safety and efficacy data on the use of anti-HCV therapies in patients with renal failure, particularly those requiring PD, remain limited. A 73-year-old black man with chronic HCV genotype 1a infection and stage 5 chronic renal disease requiring daily automated PD was referred for HCV treatment prior to renal transplantation. HCV treatment was initiated with paritaprevir-ritonavir-ombitasvir- dasabuvir, or "PrOD" (a combination tablet containing paritaprevir 75 mg, ritonavir 50 mg, and ombitasvir 12.5 mg to be taken once daily and a dasabuvir sodium 250-mg tablet to be taken twice daily), in conjunction with ribavirin 200 mg once daily. After a 12-week course of PrOD therapy, during which ribavirin therapy was tapered and then discontinued at week 10 and subcutaneous epoetin alfa was administered for anemia control from weeks 4 to 12, the patient's HCV viral load was undetectable; a sustained virologic response at 12 weeks (SVR12) was noted. CONCLUSION A patient with end-stage renal disease requiring PD was treated successfully for HCV genotype 1a infection with PrOD fixed-dose combination therapy plus ribavirin therapy. The patient achieved an SVR12 despite withdrawal of ribavirin at treatment week 10, with minimal adverse effects reported.
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Affiliation(s)
- Jennifer E Stark
- Department of Pharmacy, Veterans Health Care System of the Ozarks, Fayetteville, AR.
| | - Jennifer Cole
- Department of Pharmacy, Veterans Health Care System of the Ozarks, Fayetteville, AR
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Lapumnuaypol K, Thongprayoon C, Wijarnpreecha K, Cheungpasitporn W. Impact of hepatitis C sustained viral response on cardiovascular diseases: a meta-analysis. Hosp Pract (1995) 2019; 47:105-110. [PMID: 31018721 DOI: 10.1080/21548331.2019.1612066] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background: Hepatitis C virus-infected patients are found to have increased risks of cardiovascular disease (CVD)-related morbidity and mortality. However, the effect of treatment on cardiovascular risk remains unknown. We performed a systematic review and meta-analysis to assess the effect of Sustained Virologic Response (SVR) on cardiovascular outcome in chronic HCV-infected patients. Methods: A systematic review was conducted in MEDLINE, EMBASE, Cochrane databases from inception through November 2018 to identify studies that assessed the effect of SVR on CVDs. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: Seven cohort studies with a total of 53,841 HCV-infected patients with average follow-up time of 5 years were enrolled. When compared with HCV-infected patients who do not achieve SVR, patients with SVR have a reduced risk of overall CVDs with the pooled hazard ratio of 0.76 (95% confidence interval 0.61-0.94). Egger's regression asymmetry test was performed and showed no publication bias. Conclusions: Our study demonstrates a significant association between SVR after HCV treatment and reduced risk of overall CVDs.
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Affiliation(s)
- Kamolyut Lapumnuaypol
- Department of Internal Medicine, Albert Einstein Medical Center , Philadelphia , PA , USA
| | - Charat Thongprayoon
- Department of Nephrology and Hypertension, Mayo Clinic , Rochester , MN , USA
| | - Karn Wijarnpreecha
- Department of Gastroenterology, Mayo Clinic Hospital , Jacksonville , FL , USA
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center , Jackson , MS , USA
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26
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Ferreira GDSA, Watanabe ALC, Trevizoli NDC, Jorge FMF, Diaz LGG, Araujo MCCL, Araujo GDC, Machado ADC. Leukocytoclastic vasculitis caused by hepatitis C virus in a liver transplant recipient: A case report. World J Hepatol 2019; 11:402-408. [PMID: 31114644 PMCID: PMC6504854 DOI: 10.4254/wjh.v11.i4.402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/16/2019] [Accepted: 04/08/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Infection by the hepatitis C virus (HCV) is currently considered to be a global health issue, with a high worldwide prevalence and causing chronic disease in afflicted individuals. The disease largely involves the liver but it can affect other organs, including the skin. While leukocytoclastic vasculitis has been reported as one of the dermatologic manifestations of HCV infection, there are no reports of this condition as the first symptom of HCV recurrence after liver transplantation. CASE SUMMARY We report here a case of leukocytoclastic vasculitis in a liver transplant recipient on maintenance immunosuppression. The condition presented as a palpable purpura in both lower extremities. Blood and urine cultures were negative and all biochemical tests were normal, excepting evidence of anemia and hypocomplementemia. Imaging examination by computed tomography showed a small volume of ascites, diffuse thickening of bowel walls, and a small bilateral pleural effusion. Skin biopsy showed leukocytoclasia and fibrinoid necrosis. Liver biopsy was suggestive of HCV recurrence in the graft, and HCV polymerase chain reaction yielded 11460 copies/mL and identified the genotype as 1A. Treatment of the virus with a 12-wk direct-acting antiviral regimen of ribavirin, sofosbuvir and daclatasvir led to regression of the symptoms within the first 10 d and subsequent complete resolution of the symptoms. CONCLUSION This case highlights the difficulties of diagnosing skin lesions caused by HCV infection in immunosuppressed patients.
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Affiliation(s)
| | - Andre Luis Conde Watanabe
- Department of Liver Transplantation, Instituto de Cardiologia do Distrito Federal, Brasilia 70673-900, Brazil
| | | | | | - Luiz Gustavo Guedes Diaz
- Department of Liver Transplantation, Instituto de Cardiologia do Distrito Federal, Brasilia 70673-900, Brazil
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Estimation of hepatitis C prevalence in the Punjab province of Pakistan: A retrospective study on general population. PLoS One 2019; 14:e0214435. [PMID: 30943224 PMCID: PMC6447227 DOI: 10.1371/journal.pone.0214435] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 03/03/2019] [Indexed: 12/29/2022] Open
Abstract
Background Hepatitis C virus (HCV) infections are amongst the leading public health concerns in Pakistan with a high disease burden. Despite the availability of effective antiviral treatments in the country the disease burden in general population has not lowered. This could be attributed to the asymptomatic nature of this infection that results in lack of diagnosis until the late symptomatic stage. To better estimate and map HCV infections in the country a population-based analysis is necessary for an effective control of the infection. Methods Serologic samples of ~66,000 participants from all major cities of the Punjab province were tested for anti-HCV antibodies. The antibody-based seroprevalence was associated with socio-demographic variables including geographical region, age, gender and sex, and occupation. Results Overall serological response to HCV surface antigens was observed in over 17% of the population. Two of the districts were identified with significantly high prevalence in general population. Analysis by occupation showed significantly high prevalence in farmers (over 40%) followed by jobless and retired individuals, laborers and transporters. A significant difference in seroprevalence was observed in different age groups amongst sex and genders (male, female and transgender) with highest response in individuals of over 40 years of age. Moreover, most of the tested IDUs showed positive response for anti-HCV antibody. Conclusion This study represents a retrospective analysis of HCV infections in general population of the most populated province of Pakistan to identify socio-demographic groups at higher risk. Two geographical regions, Faisalabad and Okara districts, and an occupational group, farmers, were identified with significantly high HCV seroprevalence. These socio-demographic groups are the potential focused groups for follow-up studies on factors contributing to the high HCV prevalence in these groups towards orchestrating effective prevention, control and treatment.
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El-Sisi AE, Zakaria S. Potential Anti-Fibrotic Effect of Direct Acting Antiviral Drugs on CCl4 Induced Hepatic Fibrosis in Rats. EGYPTIAN JOURNAL OF BASIC AND CLINICAL PHARMACOLOGY 2019. [DOI: 10.32527/2019/101414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Affiliation(s)
- Alaa E. El-Sisi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Sherin Zakaria
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kaferelsheikh University, Kaferelsheikh, Egypt
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29
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Kumthekar A, Shull S, Lovejoy TI, Morasco BJ, Chang M, Barton J. Impact of hepatitis C treatment on pain intensity, prescription opioid use and arthritis. Int J Rheum Dis 2019; 22:592-598. [PMID: 30729702 DOI: 10.1111/1756-185x.13479] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 11/10/2018] [Accepted: 12/17/2018] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To assess the impact of direct acting anti-viral (DAA) therapy for hepatitis C virus (HCV) infection on changes in pain intensity and prescription opioid use among Veterans. METHODS We conducted a retrospective cohort study of Veterans with HCV who were seen in a rheumatology clinic at least once while receiving DAA therapy between January 1, 2010 and December 31st 2016. Demographic characteristics, HCV status, HCV treatment characteristics, numeric rating scale (NRS) pain scores and opioid prescription data were extracted from the electronic medical record. Pain scores were averaged over 6 months prior to HCV treatment and 6 months after completion of treatment. Prescription opioid dose was converted to a morphine equivalent daily dose (MEDD) and averaged across the two 6-month intervals. Generalized estimating equations were used to model the change in average pain and MEDD from pre- to post-HCV treatment. Effect size was assessed using Cohen's d. RESULTS A total of 121 Veterans, 91% male with average age of 59 were included. Average pre-treatment pain was 4.4 (SD 2.4). The average reduction in pain scores was 0.6 points (P = 0.02, Cohen's d = 0.22) after treatment. Among 67 patients prescribed chronic opioid therapy at baseline, average pre-treatment MEDD was 52.4 mg (SD = 62.5 mg) and post-DAA treatment average MEDD was 49.5 mg (SD = 69.3 mg), representing a decrease by 2.9 mg (P < 0.01, Cohen's d = 0.14). Opioid dose reduction was seen in 43/67 patients and 12 patients discontinued opioids entirely. CONCLUSION Among US Veterans, subjective pain scores had modest improvement and opioid prescriptions were mildly reduced following treatment with DAA.
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Affiliation(s)
- Anand Kumthekar
- Montefiore Medical Center, Albert Einstein College of Medicine, New York
| | - Sarah Shull
- Oregon Health and Science University, Portland, Oregon
| | - Travis I Lovejoy
- Oregon Health and Science University, Portland, Oregon.,VA Portland Health Care System, Portland, Oregon
| | - Benjamin J Morasco
- Oregon Health and Science University, Portland, Oregon.,VA Portland Health Care System, Portland, Oregon
| | - Michael Chang
- Oregon Health and Science University, Portland, Oregon.,VA Portland Health Care System, Portland, Oregon
| | - Jennifer Barton
- Oregon Health and Science University, Portland, Oregon.,VA Portland Health Care System, Portland, Oregon
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30
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Badawi A, Di Giuseppe G, Arora P. Cardiovascular disease risk in patients with hepatitis C infection: Results from two general population health surveys in Canada and the United States (2007-2017). PLoS One 2018; 13:e0208839. [PMID: 30540839 PMCID: PMC6291240 DOI: 10.1371/journal.pone.0208839] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 11/25/2018] [Indexed: 02/06/2023] Open
Abstract
The role of hepatitis C virus (HCV) infection in increasing the risk of cardiovascular disease (CVD) is controversial. The objective of the present study is to estimate the 10-year risk of CVD in HCV- positive subjects and describe their profile of cardiometabolic risk markers compared to HCV-negative subjects. We conducted a cross-sectional study to estimate 10-year CVD risk, calculated using the Framingham Risk Score (FRS), in participants from the Canadian Health Measures Survey (CHMS; 2007–2015, n = 10,115) and the US-National Health and Nutrition Examination Survey (NHANES; 2007–2016, n = 16,668). Subjects included in our analysis were aged 30 to 74 years with no prior history of CVD. FRS estimates, sociodemographic and cardiometabolic risk factors were compared between HCV- positive and -negative subjects in the two surveys. HCV-positive subjects had a distinct sociodemographic profile compared to their HCV-negative counterparts. Cardiometabolic risk factors, inflammatory markers and serum levels of micronutrients were comparable between the two survey populations, both in HCV-positive and -negative subjects. The average FRS in HCV-positive patients was in the range of “intermediate” 10-year CVD risk (i.e., 10–20%) and was significantly higher (P<0.01) than their HCV-negative counterparts who were within the “low” 10-year CVD risk range (i.e., ≤10%). Using a multivariable linear regression model adjusted for ethnicity, number of metabolic syndrome components and BMI, HCV infection was significantly associated with a 2.5–3.5% absolute risk increase of 10-year CVD (P<0.01). The results of the present study suggest a potential association between HCV infection and risk of subclinical and clinical CVD. The expansion of anti-HCV therapy may also contribute to reduced CVD risk and burden in patients with chronic HCV infection and should be explored further in other datasets and population modelling studies.
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Affiliation(s)
- Alaa Badawi
- Public Health Risk Sciences Division, Public Health Agency of Canada, Toronto, ON, Canada
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- * E-mail:
| | | | - Paul Arora
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Division of Enteric Diseases, National Microbiology Laboratory, Public Health Agency of Canada, Toronto, ON, Canada
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31
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Kalafateli M, Buzzetti E, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS. Pharmacological interventions for acute hepatitis C infection. Cochrane Database Syst Rev 2018; 12:CD011644. [PMID: 30521693 PMCID: PMC6517308 DOI: 10.1002/14651858.cd011644.pub3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. OBJECTIVES To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months.There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I2 = 0%). The proportion of people with any adverse events was higher with interferon-alpha and interferon-beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health-related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon-alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I2 = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons.Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. AUTHORS' CONCLUSIONS Very low quality evidence suggests that interferon-alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health-related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct-acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct-acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high-quality randomised clinical trials are required.
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Affiliation(s)
- Maria Kalafateli
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Elena Buzzetti
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Douglas Thorburn
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryPond StreetLondonUKNW3 2QG
| | - Emmanuel Tsochatzis
- Royal Free Hospital and the UCL Institute of Liver and Digestive HealthSheila Sherlock Liver CentreLondonUK
| | - Kurinchi Selvan Gurusamy
- University College LondonDivision of Surgery and Interventional Science9th Floor, Royal Free HospitalRowland Hill StreetLondonUKNW3 2PF
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Inhibitory mechanism of 5-bromo-3-indoleacetic acid for non-structural-3 helicase hepatitis C virus with dynamics correlation network analysis. Comput Biol Chem 2018; 77:167-177. [DOI: 10.1016/j.compbiolchem.2018.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 09/03/2018] [Accepted: 10/06/2018] [Indexed: 01/20/2023]
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Ekouevi DK, Coffie PA, Tchounga BK, Poda A, Jaquet A, Dabis F, Eholie SP. Prevalence of hepatitis C among HIV-1, HIV-2 and dually reactive patients: A multi-country cross-sectional survey in West Africa. J Public Health Afr 2018; 9:871. [PMID: 30687482 PMCID: PMC6325423 DOI: 10.4081/jphia.2018.871] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023] Open
Abstract
Little is known on the impact of HIV-2 infection on HCV viral replication. The aim of the study was to compare HCV prevalence and viral replication based on HIV types in West Africa. A cross-sectional survey was conducted within the IeDEA HIV-2 West Africa cohort from March to December 2012. All HIVinfected adult patients who attended participating HIV clinics during the study period were included. Blood samples were collected and re-tested for HIV type discrimination, HCV serology and viral load. A total of 767 patients were enrolled: 186 HIV-1, 431 HIV-2 and 150 HIV-1&2 dually reactive. At time of sampling, 531 (69.2%) were on ART and median CD4+ cell count was 472/mm3. Thirty (3.9%, 95% CI 2.7-5.5) patients were anti-HCV positive (4.3% in HIV-1, 4.0% in HIV-1&2 dually reactive and 3.7% in HIV-2; p=0.91). Detectable HCV RNA was identified in 21 (70.0%) patients (100% in HIV-1 and HIV- 1&2 dually reactive vs. 43.8% in HIV-2; p=0.003). Systematic screening should be promoted and performed in this population, since HCV is now potentially curable in sub- Saharan Africa.
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Affiliation(s)
- Didier K Ekouevi
- Université de Lomé, Département de Santé Publique, Lomé-Togo.,ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France.,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire
| | - Patrick A Coffie
- ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France.,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire
| | - Boris K Tchounga
- ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France.,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire
| | - Armel Poda
- Université Polytechnique de Bobo, Institut Supérieur des Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.,Hôpital de Jour de Bobo, Service des Maladies Infectieuses (CHU Souro Sanou), Bobo-Dioulasso, Burkina Faso
| | - Antoine Jaquet
- ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France
| | - François Dabis
- ISPED, Université de Bordeaux & Centre INSERM U1219 - Bordeaux Population Health, Bordeaux, France.,Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire
| | - Serge P Eholie
- Programme PACCI, site de recherche ANRS, Abidjan, Côte d'Ivoire.,Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d'Ivoire.,Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire
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Determination of anti-HCV and quantification of HCV-RNA and IP-10 from dried blood spots sent by regular mail. PLoS One 2018; 13:e0201629. [PMID: 30063765 PMCID: PMC6067740 DOI: 10.1371/journal.pone.0201629] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 07/18/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND With the introduction of direct acting antivirals, treatment of hepatitis C virus (HCV) in hard-to-reach populations is now feasible. Therefore, new cost-effective and reliable test methods are needed. Determination of HCV antibodies and HCV-RNA from dried blood spots samples could represent one such method. Here we examined whether anti-HCV could be detected-and HCV-RNA quantified-from dried blood spots, sent by regular mail. We also investigated, if IP-10 determined from dried blood spots correlated with fibrosis progression appraised by transient elastography. METHOD Forty chronic HCV infected patients were consecutively enrolled. At baseline and after six months, dried blood spots were prepared from blood collected by venous puncture, dried for 4-6 hours, then stored in gas-impermeable plastic bags with a desiccator, before being sent by regular mail. At each visit, approximately six months apart, paired venous samples was obtained and analyzed for anti-HCV, HCV-RNA and IP-10. RESULTS Anti-HCV was found in 66/67 of the dried blood spots. Sixty-six paired samples were available for HCV-RNA analysis. A statistically significant correlation was found between log HCV-RNA concentrations in plasma, and log HCV-RNA obtained from (P < 0.0001, Pearson's R 0.6788, R2 0.4607). HCV-RNA, derived from DBS samples, was lower than the corresponding plasma concentration, reflected by a Bland-Altman bias of 3 with SD of bias ± 0.6472. We found no correlation between IP-10 and fibrosis progression. CONCLUSIONS We identified anti-HCV in 66/67samples, and quantified IP-10 and HCV-RNA from dried blood spots, dried at room temperature and sent by regular mail. HCV-RNA concentrations from the dried blood spots were lower than corresponding plasma values; a probable result of heparin coated test tubes. We found no correlation between IP-10 and fibrosis progression. Overall, dried blood spots could be a cost-effective and easy-to-use alternative to standard tests for the diagnosis of HCV infections.
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Lara J, Teka MA, Sims S, Xia GL, Ramachandran S, Khudyakov Y. HCV adaptation to HIV coinfection. INFECTION GENETICS AND EVOLUTION 2018; 65:216-225. [PMID: 30075255 DOI: 10.1016/j.meegid.2018.07.039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/25/2018] [Accepted: 07/30/2018] [Indexed: 02/07/2023]
Abstract
Human immunodeficiency virus (HIV) infection is rising as a leading cause of morbidity and mortality among hepatitis C virus (HCV)-infected patients. Both viruses interact in co-infected hosts, which may affect their intra-host evolution, potentially leading to differing genetic composition of viral populations in co-infected (CIP) and mono-infected (MIP) patients. Here, we investigate genetic differences between intra-host variants of the HCV hypervariable region 1 (HVR1) sampled from CIP and MIP. Nucleotide (nt) sequences of intra-host HCV HVR1 variants (N = 28,622) obtained from CIP (N = 112) and MIP (n = 176) were represented using 148 physical-chemical (PhyChem) indexes of DNA nt dimers. Significant (p < .0001) differences in the means and frequency distributions of 7 PhyChem properties were found between HVR1 variants from both groups. Linear projection analysis of 29 PhyChem features extracted from such PhyChem properties showed that the CIP and MIP HVR1 variants have a distinct distribution in the modeled 2D-space, with only ~1.3% of PhyChem profiles (N = 6782), shared by all HVR1 variants, being found in both groups. Probabilistic neural network (PNN) and naïve Bayesian (NB) classifiers trained on the PhyChem features accurately classified HVR1 variants by the group in cross-validation experiments (AUROC ≥ 0.96). Similarly, both models showed a high accuracy (AUROC ≥ 0.95) when evaluated on a test dataset of HVR1 sequences obtained from 10 patients, data from whom were not used for model building. Both models performed at the expected lower accuracy on randomly labeled datasets in cross-validation experiments (AUROC = 0.50). The random-label trained PNN showed a similar drop in accuracy on the test dataset (AUROC = 0.48), indicating that the detected associations were unlikely due to random correlations. Marked differences in genetic composition of HCV HVR1 variants sampled from CIP and MIP suggest differing intra-host HCV evolution in the presence of HIV infection. PhyChem features identified here may be used for detection of HIV infection from intra-host HCV variants alone in co-infected patients, thus facilitating monitoring for HIV introduction to high-risk populations with high HCV prevalence.
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Affiliation(s)
- James Lara
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States.
| | - Mahder A Teka
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States
| | - Seth Sims
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States
| | - Guo-Liang Xia
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States
| | - Sumathi Ramachandran
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States
| | - Yury Khudyakov
- Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30333, United States
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Morris MD, Brown B, Allen SA. Universal opt-out screening for hepatitis C virus (HCV) within correctional facilities is an effective intervention to improve public health. Int J Prison Health 2018; 13:192-199. [PMID: 28914118 PMCID: PMC5764160 DOI: 10.1108/ijph-07-2016-0028] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Purpose Worldwide efforts to identify individuals infected with the hepatitis C virus (HCV) focus almost exclusively on community healthcare systems, thereby failing to reach high-risk populations and those with poor access to primary care. In the USA, community-based HCV testing policies and guidelines overlook correctional facilities, where HCV rates are believed to be as high as 40 percent. This is a missed opportunity: more than ten million Americans move through correctional facilities each year. Herein, the purpose of this paper is to examine HCV testing practices in the US correctional system, California and describe how universal opt-out HCV testing could expand early HCV detection, improve public health in correctional facilities and communities, and prove cost-effective over time. Design/methodology/approach A commentary on the value of standardizing screening programs across facilities by mandating all facilities (universal) to implement opt-out testing policies for all prisoners upon entry to the correctional facilities. Findings Current variability in facility-level testing programs results in inconsistent testing levels across correctional facilities, and therefore makes estimating the actual number of HCV-infected adults in the USA difficult. The authors argue that universal opt-out testing policies ensure earlier diagnosis of HCV among a population most affected by the disease and is more cost-effective than selective testing policies. Originality/value The commentary explores the current limitations of selective testing policies in correctional systems and provides recommendations and implications for public health and correctional organizations.
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Affiliation(s)
- Meghan D Morris
- Department of Epidemiology & Biostatistics, University of California, San Francisco , San Francisco, California, USA
| | - Brandon Brown
- Center for Health Communities, University of California, Riverside , Riverside, California, USA
| | - Scott A Allen
- School of Medicine, University of California, Riverside , Riverside, California, USA
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Petruzziello A. Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma. Open Virol J 2018. [PMID: 29541276 PMCID: PMC5842386 DOI: 10.2174/1874357901812010026] [Citation(s) in RCA: 152] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) is one of the most prevalent primary malignant tumors and accounts for about 90% of all primary liver cancers. Its distribution varies greatly according to geographic location and it is more common in middle and low- income countries than in developed ones especially in Eastern Asia and Sub Saharan Africa (70% of all new HCCs worldwide), with incidence rates of over 20 per 100,000 individuals. Explanation The most important risk factors for HCC are Hepatitis B Virus (HBV) infection, Hepatitis C Virus (HCV) infection, excessive consumption of alcohol and exposition to aflatoxin B1. Its geographic variability and heterogeneity have been widely associated with the different distribution of HBV and HCV infections worldwide.Chronic HBV infection is one of the leading risk factors for HCC globally accounting for at least 50% cases of primary liver tumors worldwide. Generally, while HBV is the main causative agent in the high incidence HCC areas, HCV is the major etiological factor in low incidence HCC areas, like Western Europe and North America. Conclusion HBV-induced HCC is a complex, stepwise process that includes integration of HBV DNA into host DNA at multiple or single sites. On the contrary, the cancerogenesis mechanism of HCV is not completely known and it still remains controversial as to whether HCV itself plays a direct role in the development of tumorigenic progression.
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Affiliation(s)
- Arnolfo Petruzziello
- Department of Pathology, Virology and Molecular Biology Unit, Istituto Nazionale Tumori- IRCCS Fondazione G. Pascale, Naples, Italy
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Dai CY, Tsai YS, Chou WW, Liu T, Huang CF, Wang SC, Tsai PC, Yeh ML, Hsieh MY, Huang CI, Vanson Liu SY, Huang JF, Chuang WL, Yu ML. The IL-6/STAT3 pathway upregulates microRNA-125b expression in hepatitis C virus infection. Oncotarget 2018; 9:11291-11302. [PMID: 29541414 PMCID: PMC5834265 DOI: 10.18632/oncotarget.24129] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 12/01/2017] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND/AIMS MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection. RESULTS High expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression. The interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays an inducible effect on miR-125b gene expression. STAT3 siRNA or inhibitor could reduce HCV replication. MATERIALS AND METHODS HCV replicon cells Con1 (type 1b) and Huh7/Ava5 (type 1b) were treated with 17-hydroxy-jolkinolide B (HJB) or STAT3 siRNA. Cell viability assay and Renilla Luciferase Assay were used. Fragments of the miR-125b-1 promoter were constructed for the luciferase reporter assay. PSMB8, PSMB9, miR-125b-1, and miR-125b-2 expression was determined using TaqMan® Gene Expression Assays. Western blot analysis was performed to assess protein abundance. CONCLUSIONS This study elucidates a novel pathway for miR-125b in the pathogenesis of chronic HCV infection and suggests it as a possible target for treating HCV infection.
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Affiliation(s)
- Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wen-Wen Chou
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tawei Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chi Wang
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Yin Vanson Liu
- Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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Batista AD, Barros CJP, Costa TBBC, de Godoy MMG, Silva RD, Santos JC, de Melo Lira MM, Jucá NT, Lopes EPDA, Silva RO. Proton nuclear magnetic resonance-based metabonomic models for non-invasive diagnosis of liver fibrosis in chronic hepatitis C: Optimizing the classification of intermediate fibrosis. World J Hepatol 2018; 10:105-115. [PMID: 29399284 PMCID: PMC5787674 DOI: 10.4254/wjh.v10.i1.105] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 11/16/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To develop metabonomic models (MMs), using 1H nuclear magnetic resonance (NMR) spectra of serum, to predict significant liver fibrosis (SF: Metavir ≥ F2), advanced liver fibrosis (AF: METAVIR ≥ F3) and cirrhosis (C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C (CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients (61%) presented SF, 28 (40%) AF and 18 (26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27 (39.7%) and 25 (38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.
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Affiliation(s)
- Andrea Dória Batista
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | - Carlos Jonnatan Pimentel Barros
- Department of Fundamental Chemistry, Center for Exact and Nature Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | - Tássia Brena Barroso Carneiro Costa
- Department of Fundamental Chemistry, Center for Exact and Nature Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | | | - Ronaldo Dionísio Silva
- Department of Fundamental Chemistry, Center for Exact and Nature Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | - Joelma Carvalho Santos
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | | | - Norma Thomé Jucá
- Department of Pathology, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | - Edmundo Pessoa de Almeida Lopes
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
| | - Ricardo Oliveira Silva
- Department of Fundamental Chemistry, Center for Exact and Nature Sciences, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
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Sagnelli E, Alessio L, Sagnelli C, Gualdieri L, Pisaturo M, Minichini C, Di Caprio G, Starace M, Onorato L, Scotto G, Macera M, Coppola N. Clinical Findings of HCV Chronic Infection in Undocumented Immigrants and Low-Income Refugees in Three Areas of Southern Italy. Ann Hepatol 2018; 17:47-53. [PMID: 29311411 DOI: 10.5604/01.3001.0010.7534] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM In recent decades, Italy has become a land of immigration from countries suffering a socio-economic crisis. The aim of this study was to perform an organized screening to identify and offer care to immigrants with HCV infection. MATERIAL AND METHODS The screening, performed from 2012 to 2015, involved 1,727 immigrants in the Campania and Apulia regions in southern Italy. RESULTS Screening was accepted by 1,727 (85%) out of 2,032 immigrants interviewed; 70 (4.1%) of the 1,727 were anti-HCV-positive, all unaware of their serological condition, 31 (44.3%) of whom were HCV-RNA-positive and 39 negative. The 31 HCV-RNA-positive immigrants were further investigated at a third-level clinic of infectious diseases. The HCV viral load was 2.6 x 107 ± 7.7 x107 IU/mL, and 35.5% showed HCV-genotype 1a or 1b, 23.8% genotype 2 and 22.6% genotype 3. Two immigrants had liver cirrhosis and, in accordance with the Italian Healthcare Authority guidelines, received an interferon-free regimen and achieved a sustained virological response (SVR); 18 had chronic hepatitis, 6 of whom with a high risk of progression and received interferonbased therapy, with SVR in 4, whereas 12 at low risk were put on a waiting list for future interferon-free treatment, once licensed. The remaining 11 HCV-RNA-positive immigrants were considered HCV inactive chronic carriers and were included in a long-term observational program. CONCLUSION The screening program can be considered successful since it was accepted by 85% of the subjects interviewed and identified 70 anti-HCV-positive immigrants, all unaware of their clinical and virological condition.
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Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | - Loredana Alessio
- Medical Center, Centro Sociale ex Canapificio, Caserta; Medical Center, Centro di Accoglienza "La tenda di Abramo", Caserta, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | - Luciano Gualdieri
- Medical Center, Centro per la Tutela della Salute degli Immigrati, Naples, Italy
| | - Mariantonietta Pisaturo
- Medical Center, Centro Sociale ex Canapificio, Caserta; Medical Center, Centro di Accoglienza "La tenda di Abramo", Caserta, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | - Giovanni Di Caprio
- Medical Center, Centro Sociale ex Canapificio, Caserta; Medical Center, Centro di Accoglienza "La tenda di Abramo", Caserta, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | | | - Margherita Macera
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy
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Helal TESA, Ehsan NA, Radwan NA, Abdelsameea E. Relationship between hepatic progenitor cells and stellate cells in chronic hepatitis C genotype 4. APMIS 2018; 126:14-20. [PMID: 29155473 DOI: 10.1111/apm.12787] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 09/24/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection represents a major health problem in many areas of the world, especially Egypt. Hepatic progenitor cells (HPCs) and hepatic stellate cells (HSCs) have been implicated in fibrosis progression in chronic HCV. The aim of this study was to investigate the role of HPCs and HSCs in chronic HCV infection and the relationship between both cell types. This retrospective study was conducted on 100 chronic HCV patients. Immunohistochemistry was performed on liver tissue sections for cytokeratin 19 (progenitor cell markers), smooth muscle actin (stellate cell markers), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta (TGF-ß). The necroinflammatory activity was significantly related to the number of isolated HPCs and TGF-ß expression (p = 0.003 and p = 0.001 respectively). Advanced stages of fibrosis showed significantly increase number of HPCs (p = 0.001), higher ratio of HSCs (p = 0.004), more expression of TGF-ß (p = 0.001) and MMP-9 (p = 0.001). There was a significant direct correlation between immunoexpression of HPCs and HSCs for isolated cells (r = 0.569, p = 0.001) and ductular reaction (r = 0.519, p = 0.001). Hepatic progenitor cells and stellate cells play a significant role in the development and progression of fibrosis in chronic HCV. More interestingly, the significant direct correlation between HPCs and HSCs suggests a synergistic interrelation.
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Affiliation(s)
| | - Nermine Ahmed Ehsan
- Department of Pathology, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Nehal Ahmed Radwan
- Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Eman Abdelsameea
- Department of Hepatology, National Liver Institute, Menoufia University, Menoufia, Egypt
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I Mehrez M, Sa Fattah D, Aa Azeem N, A Saleh M, M Mostafa K. Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients. Euroasian J Hepatogastroenterol 2017; 7:154-157. [PMID: 29201799 PMCID: PMC5670260 DOI: 10.5005/jp-journals-10018-1238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 09/11/2017] [Indexed: 11/23/2022] Open
Abstract
Aim: The aim of this article is to assess HFE C282Y gene mutations as a predictor of sustained virological response (SVR) to anti-hepatitis C virus (HCV) treatment in Egyptian patients. Materials and methods: One hundred and forty chronic hepatitis C (CHC) patients were divided into two groups: 70 patients achieved SVR and 70 patients were nonresponders (NRs). All patients were subjected to quantitative polymerase chain reaction (PCR) at baseline, 12 and 24 weeks after therapy commencement. Deoxyribonucleic acid (DNA) sequencing for HFE (C282Y) was done by restriction fragment length polymorphism PCR. Results: Sixty five patients did not have mutation and 5 patients had C282Y mutation (GA) with SVR. While 45 NRs had heterozygous C282Y mutation (GA), 4 patients (5.7%) had homozygous mutation (AA) and 21 patients (30%) had no mutation (GG). The parameters of elevated iron [transferrin saturation (TS; p < 0.001), S iron (p < 0.02), total iron binding capacity (TIBC; p < 0.001), transferrin (p < 0.016), and soluble transferrin receptor (sTfR; p-value, 0.001)] were significantly associated with C282Y mutation. However, there was no significant difference regarding ferritin values and C282Y mutation in NR patients. Conclusion: Iron overload was frequently detected in CHC patients and associated with C282Y mutation, while biochemical markers of iron overload and C282Y HFE mutation were negative prognostic factor. How to cite this article: Mehrez MI, Fattah DSA, Azeem NAA, Saleh MA, Mostafa KM. Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients. Euroasian J Hepato-Gastroenterol 2017;7(2):154-157.
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Affiliation(s)
- Mai I Mehrez
- Department of Hepatology, National Hepatology and Tropical Medicine Institute, Cairo, Egypt
| | - Dina Sa Fattah
- Department of Medical Biochemistry and Molecular Biology, Cairo University, Cairo, Egypt
| | - Naglaa Aa Azeem
- Department of Medical Biochemistry, Beni Suef University, Beni Suef, Egypt
| | - Mohamed A Saleh
- Department of Hepatology, National Hepatology and Tropical Medicine Institute, Cairo, Egypt
| | - Khadiga M Mostafa
- Department of Medical Biochemistry, Beni Suef University, Beni Suef, Egypt
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Latini A, Orsini D, Ambrifi M, Colafigli M, Zaccarelli M, Cristaudo A. Classical Kaposi's sarcoma concurrent with ledipasvir-sofosbuvir therapy for hepatitis C infection. GIORN ITAL DERMAT V 2017; 154:593-594. [PMID: 29192474 DOI: 10.23736/s0392-0488.17.05788-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Alessandra Latini
- Unit of Infectious Dermatology and Allergology, San Gallicano Institute for Cancer Research and Care, Rome, Italy
| | - Diego Orsini
- Unit of Infectious Dermatology and Allergology, San Gallicano Institute for Cancer Research and Care, Rome, Italy -
| | - Marina Ambrifi
- Unit of Infectious Dermatology and Allergology, San Gallicano Institute for Cancer Research and Care, Rome, Italy
| | - Manuela Colafigli
- Unit of Infectious Dermatology and Allergology, San Gallicano Institute for Cancer Research and Care, Rome, Italy
| | - Mauro Zaccarelli
- Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy
| | - Antonio Cristaudo
- Unit of Infectious Dermatology and Allergology, San Gallicano Institute for Cancer Research and Care, Rome, Italy
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44
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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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45
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Andreoni M, Babudieri S, Bruno S, Colombo M, Zignego AL, Di Marco V, Di Perri G, Perno CF, Puoti M, Taliani G, Villa E, Craxì A. Current and future challenges in HCV: insights from an Italian experts panel. Infection 2017; 46:147-163. [PMID: 29098647 DOI: 10.1007/s15010-017-1093-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 10/25/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages. METHODS A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens. RESULTS AND CONCLUSIONS Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated due to accumulating new data. Such recommendations may not be applicable to all healthcare settings for a variety of reasons. Moreover, some gaps still remain and the spectrum of patients to be treated is also evolving.
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Affiliation(s)
- Massimo Andreoni
- Infectious Diseases, Polyclinic of Rome Tor Vergata, Rome, Italy
| | - Sergio Babudieri
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Savino Bruno
- Humanitas University and Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Massimo Colombo
- Humanitas Clinical and Research Center, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Anna L Zignego
- Department of Experimental and Clinical Medicine, Interdepartmental Centre MASVE, University of Florence, Florence, Italy
| | - Vito Di Marco
- Sezione di Gastroenterologia e Epatologia, DiBiMIS, University of Palermo, Palermo, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy
| | - Carlo F Perno
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Massimo Puoti
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Gloria Taliani
- Infectious and Tropical Diseases Unit, Umberto I Hospital-"Sapienza" University, Rome, Italy
| | - Erica Villa
- Department of Internal Medicine, Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Antonio Craxì
- Gastroenterology and Liver Unit, DiBiMIS, University of Palermo, Palermo, Italy.
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46
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Alzubiedi S, Saleh MI. Predictors of Severe Thrombocytopenia Secondary to Peginterferon Alfa-2a Treatment in Subjects With Hepatitis C Virus Infection. Am J Ther 2017; 24:e670-e675. [DOI: 10.1097/mjt.0000000000000356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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47
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Chew KW, Liu CY, Ambale-Venkatesh B, Liao D, Horwich TB, Lima JAC, Bluemke DA, Paul Finn J, Butt AA, Currier JS. Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons. J Int Med Res 2017; 45:1693-1707. [PMID: 28606026 PMCID: PMC5805202 DOI: 10.1177/0300060517708919] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart
failure in human immunodeficiency virus (HIV)-coinfected persons is unknown.
The objective was to characterize cardiac function and morphology in
HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on
antiretroviral therapy without known cardiovascular disease or diabetes
mellitus underwent cardiac magnetic resonance imaging and spectroscopy for
measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these,
10 had untreated HCV coinfection and eight had HIV monoinfection. Global
systolic and diastolic function in the cohort were normal, and median
myocardial fat content was 0.48% (interquartile range 0.35–1.54). Left
ventricular (LV) mass index and LV mass/volume ratio were significantly
greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected
group. In the HIV-monoinfected group, there was more myocardial fibrosis as
measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected
patients in cardiac structure and morphology. Larger studies are needed to
examine whether HIV and HCV independently contribute to mechanisms of heart
failure.
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Affiliation(s)
- Kara W Chew
- 1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Chia-Ying Liu
- 2 National Institutes of Health, Bethesda, MD, USA.,3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Diana Liao
- 1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Tamara B Horwich
- 1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - João A C Lima
- 3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David A Bluemke
- 2 National Institutes of Health, Bethesda, MD, USA.,3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - J Paul Finn
- 4 Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Adeel A Butt
- 5 VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.,6 Weill Cornell Medical College, Doha, Qatar and New York, NY, USA.,7 Hamad Healthcare Quality Institute and Hamad Medical Corporation, Doha, Qatar
| | - Judith S Currier
- 1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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48
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El Serafy MA, Kassem AM, Omar H, Mahfouz MS, El Said El Raziky M. APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis. Arab J Gastroenterol 2017; 18:51-57. [PMID: 28579340 DOI: 10.1016/j.ajg.2017.05.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/27/2017] [Accepted: 05/07/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. PATIENTS AND METHODS Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. RESULTS Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). CONCLUSION APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.
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Affiliation(s)
- Magdy Amin El Serafy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Abdel Meguid Kassem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
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Wilson H, Brener L, Jackson LC, Saunders V, Johnson P, Treloar C. HCV knowledge among a sample of HCV positive Aboriginal Australians residing in New South Wales. PSYCHOL HEALTH MED 2017; 22:625-632. [PMID: 27268000 DOI: 10.1080/13548506.2016.1189582] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Australian Aboriginal and Torres Strait Islanders are overrepresented in both the prevalence and incidence of the hepatitis C (HCV). HCV knowledge has been associated with a range of positive health behaviours. HCV knowledge has previously been investigated as a single construct; however examining different knowledge domains (i.e. transmission, risk of complications, testing and treatment) separately may be beneficial. This study investigated whether having greater HCV knowledge in different domains is associated with self-reported positive health behaviours. 203 Aboriginal people living with HCV completed a survey assessing HCV knowledge, testing and care, lifestyle changes since diagnosis and treatment intent. Respondents' knowledge was relatively high. Greater knowledge of risk of health complications was associated with undertaking more positive lifestyle changes since diagnosis. Respondents testing and treatment knowledge was significantly associated with incarceration, lifestyle changes since diagnosis and future treatment intentions. This study illustrates the importance of ensuring that knowledge is high across different HCV domains to optimise a range of positive health behaviours of Aboriginal people living with HCV. Future health promotion campaigns targeted at Aboriginal people living with HCV could benefit from broadening their focus from prevention to other domains such as testing and treatment.
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Affiliation(s)
- Hannah Wilson
- a Centre for Social Research in Health , Sydney , Australia
| | - Loren Brener
- a Centre for Social Research in Health , Sydney , Australia
| | | | | | | | - Carla Treloar
- a Centre for Social Research in Health , Sydney , Australia
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50
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Improvements in brain and behavior following eradication of hepatitis C. J Neurovirol 2017; 23:593-602. [PMID: 28560632 DOI: 10.1007/s13365-017-0533-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 04/19/2017] [Accepted: 05/02/2017] [Indexed: 01/18/2023]
Abstract
Despite recent advances in treatment, hepatitis C remains a significant public health problem. The hepatitis C virus (HCV) is known to infiltrate the brain, yet findings from studies on associated neurocognitive and neuropathological changes are mixed. Furthermore, it remains unclear if HCV eradication improves HCV-associated neurological compromise. This study examined the longitudinal relationship between neurocognitive and neurophysiologic markers among healthy HCV- controls and HCV+ adults following successful HCV eradication. We hypothesized that neurocognitive outcomes following treatment would be related to both improved cognition and white matter integrity. Participants included 57 HCV+ participants who successfully cleared the virus at the end of treatment (sustained virologic responders [SVRs]) and 22 HCV- controls. Participants underwent neuropsychological testing and, for a nested subset of participants, neuroimaging (diffusion tensor imaging) at baseline and 12 weeks following completion of HCV therapy. Contrary to expectation, group-level longitudinal analyses did not reveal significant improvement in neurocognitive performance in the SVRs compared to the control group. However, a subgroup of SVRs demonstrated a significant improvement in cognition relative to controls, which was related to improved white matter integrity. Indeed, neuroimaging data revealed beneficial effects associated with clearing the virus, particularly in the posterior corona radiata and the superior longitudinal fasciculus. Findings suggest that a subgroup of HCV+ patients experienced improvements in cognitive functioning following eradication of HCV, which appears related to positive changes in white matter integrity. Future research should examine whether any additional improvements in neurocognition and white matter integrity among SVRs occur with longer follow-up periods.
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