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Lee CSJ, Mateu-Gelabert P, Melendez YA, Fong C, Kapadia SN, Smith M, Marks KM, Eckhardt B. Reduced injection risk behavior with co-located hepatitis C treatment at a syringe service program: The accessible care model. PLoS One 2024; 19:e0308102. [PMID: 39208211 PMCID: PMC11361571 DOI: 10.1371/journal.pone.0308102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 07/14/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND The main mode of transmission of Hepatitis C in North America is through injection drug use. Availability of accessible care for people who inject drugs is crucial for achieving hepatitis C elimination. OBJECTIVE The objective of this analysis is to compare the changes in injection drug use frequency and high-risk injection behaviors in participants who were randomized to accessible hepatitis c care versus usual hepatitis c care. METHODS Participants who were hepatitis C virus RNA positive and had injected drugs in the last 90 days were enrolled and randomized 1:1 to an on-site, low threshold accessible care arm or a standard, referral-based usual care arm. Participants attended follow-up appointments at 3, 6, 9, and 12 months during which they answered questions regarding injection drug use frequency, behaviors, and treatment for opioid use disorder. PRIMARY OUTCOMES The primary outcomes of this secondary analysis are the changes in the frequency of injection drug use, high-risk injection behaviors, and receiving medication for opioid use disorder in the last 30 days. RESULTS A total of 165 participants were enrolled in the study, with 82 participants in the accessible care arm and 83 participants in the usual care arm. Participants in the accessible care arm were found to have a statistically significant higher likelihood of reporting a lower range of injection days (accessible care-by-time effect OR = 0.78, 95% CI = 0.62-0.98) and injection events (accessible care-by-time effect OR = 0.70, 95% CI = 0.56-0.88) in the last 30 days at a follow-up interview relative to those in the usual care arm. There were no statistically significant differences in the rates of decrease in receptive sharing of injection equipment or in the percentage of participants receiving treatment for opioid use disorders in the two arms. CONCLUSION Hepatitis C treatment through an accessible care model resulted in statistically higher rates of decrease in injection drug use frequency in people who inject drugs.
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Affiliation(s)
| | - Pedro Mateu-Gelabert
- City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America
| | - Yesenia Aponte Melendez
- City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America
| | - Chunki Fong
- City University of New York Graduate School of Public Health and Health Policy, New York, New York, United States of America
| | - Shashi N. Kapadia
- Weill Cornell Medicine, New York, New York, United States of America
| | - Melinda Smith
- Weill Cornell Medicine, New York, New York, United States of America
| | - Kristen M. Marks
- Weill Cornell Medicine, New York, New York, United States of America
| | - Benjamin Eckhardt
- New York University School of Medicine, New York, New York, United States of America
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Habas E, Farfar KL, Errayes N, Habas AM, Errayes M, Alfitori G, Rayani A, Elgara M, Al Adab AH, Elzouki A. Hepatitis Virus C-associated Nephropathy: A Review and Update. Cureus 2022; 14:e27322. [PMID: 36043014 PMCID: PMC9412079 DOI: 10.7759/cureus.27322] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection. The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits. Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes. Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.
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Sheu MJ, Liang FW, Lin CY, Lu TH. Changes in liver-related mortality by etiology and sequelae: underlying versus multiple causes of death. Popul Health Metr 2021; 19:22. [PMID: 33926463 PMCID: PMC8082829 DOI: 10.1186/s12963-021-00249-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/31/2021] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data. METHODS We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality. RESULT Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65-74 years. CONCLUSION The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.
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Affiliation(s)
- Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
- Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Fu-Wen Liang
- Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yih Lin
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
| | - Tsung-Hsueh Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Silva JM, Silva MJ, Calinas F, Nogueira PJ. Burden of Liver Cirrhosis in Portugal between 2010 and 2017. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 28:153-161. [PMID: 34056037 PMCID: PMC8138255 DOI: 10.1159/000510729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/26/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Liver cirrhosis is a prevalent disease in Portugal. Recent changes in alcohol consumption, as well as the wide use of direct-acting antivirals for hepatitis C since 2015, may be contributing to changes in the national burden of liver cirrhosis in the last few years. OBJECTIVES We aim to characterize the burden of cirrhosis in Portugal between 2010 and 2017. PATIENTS AND METHODS We analyzed all hospital admission episodes due to cirrhosis in Portugal Mainland between 2010 and 2017, registered in the national Diagnosis-Related Group database, according to etiology of cirrhosis. We also analyzed data on mortality and potential years of life lost from liver cirrhosis and chronic liver disease, retrieved from Statistics Portugal (National Institute for Statistics). RESULTS Between 2010 and 2017, a total of 51,438 admissions for liver cirrhosis occurred in Portugal. The annual number of admissions decreased (p = 0.044) during the analyzed period. The most frequent cause of cirrhosis was alcoholic liver disease, present in 78.9% of all admissions (n = 40,595), followed by chronic hepatitis C virus infection, present in 11.3% (n = 5,823). A male predominance was identified in the admissions for every analyzed cause of cirrhosis. Annual admissions for alcoholic cirrhosis remained stable (p = 0.075) during the 8-year period. The same stable tendency was observed in the number of admissions for cirrhosis caused by hepatitis C virus (p = 0.861) and alcohol plus hepatitis C virus infection (p = 0.082), although these admissions for hepatitis C-related cirrhosis increased until 2014-2015 and steadily decreased thereafter. Annual deaths due to liver cirrhosis and chronic liver disease decreased from 1,357 in 2010 to 1,038 in 2017 (p = 0.002). The number of potential years of life lost decreased as well in the period (p = 0.001). CONCLUSION The burden of cirrhosis, evaluated by hospital admissions, mortality, and potential years of life lost, decreased in Portugal between 2010 and 2017.
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Affiliation(s)
| | - Mário Jorge Silva
- Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Filipe Calinas
- Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Paulo Jorge Nogueira
- Instituto de Medicina Preventiva e Saúde Pública, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Public Health Research Centre, NOVA National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), NOVA National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal
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Fu H, Dong J, Sun Z, Zhang X, Yu A, Chen G, Li W. Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:648. [PMID: 32566585 PMCID: PMC7290620 DOI: 10.21037/atm-20-3074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). Methods We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. Results A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. Conclusions The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.
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Affiliation(s)
- Hua Fu
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Center of Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Zhide Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Xuejun Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Aijun Yu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Guoli Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Wei Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
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Orrego-Marín CM, Bedoya AM, Cardona Arias JA. Metaanálisis de la validez y el desempeño de las pruebas de tamización del virus de la hepatitis C en bancos de sangre, 2000-2018. ACTA BIOLÓGICA COLOMBIANA 2019. [DOI: 10.15446/abc.v24n3.79348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Este estudio evaluó la validez y desempeño del inmunodiagnóstico del virus de la hepatitis C (VHC), con base en estudios publicados en la literatura científica mundial. Se diseñó y validó un protocolo de búsqueda y selección de investigaciones en las fases de la guía PRISMA, se analizaron los parámetros de sensibilidad, especificidad, cocientes de probabilidad, razón de odds y curva ROC, en MetaDisc. Se tamizaron 4602 estudios, de los cuales sólo 545 se realizaron en bancos de sangre y 18 evaluaron la validez diagnóstica de las pruebas para el VHC. La mayoría de los estudios fueron de Europa y Asia, con un 78 % basados en determinación de anticuerpos. Los estudios con detección de anticuerpos se realizaron en 21 483 donantes sanos y 3 145 infectados en quienes se halló una sensibilidad de 97,8 % (IC 95 % = 97,3 - 98,2), especificidad 99,0 % (IC 95 % = 98,9 - 99,2), cociente de probabilidad positivo 75,4 (IC 95 % = 27,2 - 209,2) y negativo de 0,02 (IC 95 % = 0,01 - 0,07) y área bajo la curva de 99,8 %. Se concluye que la detección de anticuerpos presenta excelente validez, desempeño y utilidad diagnóstica para la detección del VHC en donantes de sangre y población general.
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DeMartini KS, Schilsky ML, Palmer A, Fehon DC, Zimbrean P, O'Malley SS, Lee HB, Toll BA. Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study. Alcohol Clin Exp Res 2018; 42:761-769. [PMID: 29498753 DOI: 10.1111/acer.13603] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 01/22/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Many liver transplantation programs require documented alcohol sobriety prior to United Network for Organ Sharing (UNOS) listing. This pilot study examined the feasibility of the first mobile, alcohol relapse prevention intervention for liver transplant patients with alcoholic liver disease (ALD). METHODS This was a randomized 8-week pilot feasibility trial of a text message-based alcohol intervention. In-treatment assessment was conducted at 4 weeks (4W), and immediate posttreatment assessment was conducted at 8W. Participants were liver transplant candidates (N = 15) diagnosed with ALD who reported at least 1 drinking episode in the past year. Primary feasibility outcomes were percent of messages responded to and posttreatment intervention satisfaction ratings. Preliminary clinical efficacy outcomes were any biologically confirmed alcohol consumption, stress, abstinence self-efficacy, and alcohol craving. RESULTS On feasibility outcomes, participants responded to 81% of messages received and reported high rates of intervention satisfaction, looked forward to receiving the messages, and found it easy to complete the intervention. On preliminary efficacy outcomes, zero participants in the text message (TM) had positive urine alcohol tests at 8W. Two of the 6 participants in standard care (SC) tested positive at 8W. No effects were seen on craving. For stress, a condition × time interaction emerged. TM participants had less stress at 4W and 8W compared with SC at baseline. They maintained their stress level during the intervention. For self-efficacy, a trend for condition effect emerged. TM participants had higher self-efficacy than SC participants. CONCLUSIONS Participants reported high satisfaction with the intervention, looked forward to the messages, and found it easy to complete. Participants who received the intervention had better treatment outcomes than those who received standard care. They maintained higher levels of self-efficacy and lower stress. Mobile alcohol interventions may hold significant promise to help ALD liver transplant patients maintain sobriety.
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Affiliation(s)
- Kelly S DeMartini
- Department of Psychiatry, Smilow Cancer Hospital at Yale, Yale School of Medicine, New Haven, Connecticut
| | - Michael L Schilsky
- Departments of Medicine and Surgery, Divisions of Digestive Diseases and Transplantation and Immunology, Yale-New Transplantation Center, Yale School of Medicine, New Haven, Connecticut
| | - Amanda Palmer
- Moffitt Cancer Center, University of South Florida, Tampa, Florida
| | - Dwain C Fehon
- Liver Transplantation Center, Yale-New Haven Hospital, New Haven, Connecticut
| | - Paula Zimbrean
- Liver Transplantation Center, Yale-New Haven Hospital, New Haven, Connecticut
| | | | - Hochang B Lee
- Department of Psychological Medicine, Yale-New Haven Hospital, New Haven, Connecticut
| | - Benjamin A Toll
- Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina
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Samuel ST, Martinez AD, Chen Y, Markatou M, Talal AH. Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians. World J Hepatol 2018; 10:319-328. [PMID: 29527267 PMCID: PMC5838450 DOI: 10.4254/wjh.v10.i2.319] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Revised: 01/17/2018] [Accepted: 02/03/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To understand the role of knowledge as a promoter of hepatitis C virus (HCV) screening among primary care physicians (PCP). METHODS A 45-item online questionnaire assessing knowledge of HCV natural history, risk factors, and treatment was distributed to 163 PCP. Logistic regression, adjusted for survey responses, assessed associations between PCP knowledge of HCV natural history and treatment and birth cohort (i.e., birth between 1945 and 1965) screening. Response stratification and weighting were used to account for nonresponse and to permit extension of responses to the entire survey population. Associations between various predictors including demographic characteristics, level of training, and HCV treatment experience and HCV knowledge were assessed. RESULTS Ninety-one individuals (55.8%) responded. Abnormal liver enzymes (49.4%), assessment of HCV-related risk factors (30.6%), and birth cohort membership (20%) were the leading HCV screening indications. Most PCP (64.7%) felt that the combination of risk-factor and birth cohort screening utilizing a self-administered survey while awaiting the physician (55.3%) were the most efficient screening practices. Implementation of birth cohort screening was associated with awareness of the recommendations (P-value = 0.01), knowledge of HCV natural history (P-value < 0.01), and prior management of HCV patients (P-value < 0.01). PCP with knowledge of HCV treatment was also knowledgeable about HCV natural history (P-value < 0.01). Similarly, awareness of age-based screening recommendations was associated with HCV treatment knowledge (P-value = 0.03). CONCLUSION Comprehensive knowledge of HCV is critical to motivate HCV screening. PCP-targeted educational interventions are required to expand the HCV workforce and linkage-to-care opportunities as we seek global HCV eradication.
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Affiliation(s)
- Sandeep T Samuel
- Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY 14203, United States
| | - Anthony D Martinez
- Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY 14203, United States
| | - Yang Chen
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY 14214, United States
| | - Marianthi Markatou
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY 14214, United States
| | - Andrew H Talal
- Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY 14203, United States
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Draz MS, Shafiee H. Applications of gold nanoparticles in virus detection. Theranostics 2018; 8:1985-2017. [PMID: 29556369 PMCID: PMC5858513 DOI: 10.7150/thno.23856] [Citation(s) in RCA: 162] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 01/09/2018] [Indexed: 12/12/2022] Open
Abstract
Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications.
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Affiliation(s)
- Mohamed Shehata Draz
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Hadi Shafiee
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
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Lin ON, Chang C, Lee J, Do A, Martin M, Martin A, Nguyen MH. HCV Prevalence in Asian Americans in California. J Immigr Minor Health 2017; 19:91-97. [PMID: 26798070 DOI: 10.1007/s10903-016-0342-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The World Health Organization estimates that 170 million persons are infected with HCV worldwide, but only 22 million are from the Americas and Europe, compared to 94 million from Asia. HCV prevalence in the general US population is 1.6 %, but data for Asian Americans are limited. Our goal was to examine HCV prevalence in Asian Americans in a large ethnically diverse patient cohort seeking primary care at a free clinic in Northern California. A total of 1347 consecutive patients were seen from September 2009 to October 2012 and were studied via individual chart review using case report forms. HCV infection was defined as positive HCV antibody (anti-HCV) or HCV RNA by PCR. 699 out of 1347 patients were screened for HCV. Asian Americans comprised 57.2 % of these patients and 29 (4.1 %) patients tested positive for HCV. Of these 29 HCV-positive patients, 22 (75.9 %) were Asian, yielding a prevalence of 5.5 % for Asians and 2.3 % for non-Asians (P = 0.038). The highest HCV prevalence was seen in Vietnamese patients at 7.9 %, and 6.0 % in Chinese patients. Of the HCV-positive Asians, none had a history of intravenous drug use (IVDU), tattoos, or sexual exposure. On multivariate analysis, significant independent predictors for positive HCV infection were male gender (OR 2.53, P = 0.02) and presence of known risk factors (OR 21.1, P < 0.001). However, older age and Asian ethnicity were found to be significant predictors of HCV infection (OR 1.03, P = 0.05 and 2.31, P = 0.066, respectively). In our study, HCV prevalence in patients seeking routine primary care was 5.5 % in Asian Americans, which was over double the prevalence for non-Asians at 2.3 %. Known risk factors were also notably absent in Asian patients with HCV infection. The high prevalence of HCV in Asian-Americans is likely reflective of the higher prevalence of HCV in their countries of origin in Asia. Asian-Americans immigrants from endemic countries are at higher risk of HCV infection and should be screened for HCV, regardless of their exposure risk profile.
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Affiliation(s)
- Oliver N Lin
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA
| | - Christine Chang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA
| | - Joyce Lee
- Stanford University School of Medicine, Stanford, CA, USA
| | - Ailinh Do
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA
| | - Marina Martin
- Division of General Medical Discipline, Stanford University Medical Center, Palo Alto, CA, USA.,Pacific Free Clinic, San Jose, CA, USA
| | - Andy Martin
- Pacific Free Clinic, San Jose, CA, USA.,Stanford Center for Clinical Informatics, Palo Alto, CA, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA.
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11
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Mak SK, Sin HK, Lo KY, Lo MW, Chan SF, Lo KC, Wong YY, Ho LY, Wong PN, Wong AKM. Treatment of HCV in renal transplant patients with peginterferon and ribavirin: long-term follow-up. Clin Exp Nephrol 2017; 21:764-770. [PMID: 28083764 DOI: 10.1007/s10157-016-1364-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 11/23/2016] [Indexed: 11/24/2022]
Abstract
BACKGROUND In addition to the observation of an increased viremia among patients with chronic hepatitis C virus (HCV) infection who undergo renal transplantation, fibrosis and necroinflammatory activity have been noted to worsen comparing pre- and post-renal transplantation liver biopsies in some of these patients. Apart from the reported reduced patient and allograft survival rates, post-transplant diabetes mellitus, de novo glomerulonephritis, and an increased overall risk of infection have been observed. However, antiviral therapy for HCV is generally considered contraindicated among patients with solid organ transplants, with the main worry being the risk of acute rejection in relation to the use of interferon. We reported the long-term outcome of four renal transplant patients with chronic HCV infection who received peginterferon-based therapy. METHODS We collected the long-term follow-up data of four patients who completed the therapy with peginterferon in combination with ribavirin. Two of them had renal impairment at baseline. RESULTS With treatment, they had a significant improvement in terms of serum liver transaminase level, and two patients achieved the early virological response and the other two rapid virological response. All four patients achieved sustained virological response, with neither HCV flare up nor renal dysfunction during follow-up for a mean duration of 74.3 months after therapy. CONCLUSIONS These results suggest that sustained HCV virological response may be achieved without allograft dysfunction, in selected renal transplant patients using a peginterferon-based therapy.
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Affiliation(s)
- Siu-Ka Mak
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China.
| | - Ho-Kwan Sin
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kin-Yee Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Man-Wai Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Shuk-Fan Chan
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kwok-Chi Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Yuk-Yi Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Lo-Yi Ho
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Ping-Nam Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Andrew K M Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
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Cipriano LE, Weber TA. Population-level intervention and information collection in dynamic healthcare policy. Health Care Manag Sci 2017; 21:604-631. [PMID: 28887763 PMCID: PMC6208882 DOI: 10.1007/s10729-017-9415-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 08/10/2017] [Indexed: 12/09/2022]
Abstract
We develop a general framework for optimal health policy design in a dynamic setting. We consider a hypothetical medical intervention for a cohort of patients where one parameter varies across cohorts with imperfectly observable linear dynamics. We seek to identify the optimal time to change the current health intervention policy and the optimal time to collect decision-relevant information. We formulate this problem as a discrete-time, infinite-horizon Markov decision process and we establish structural properties in terms of first and second-order monotonicity. We demonstrate that it is generally optimal to delay information acquisition until an effect on decisions is sufficiently likely. We apply this framework to the evaluation of hepatitis C virus (HCV) screening in the general population determining which birth cohorts to screen for HCV and when to collect information about HCV prevalence.
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Affiliation(s)
- Lauren E Cipriano
- Ivey Business School, Western University, 1255 Western Road, London, ON, N6G 0N1, Canada.
| | - Thomas A Weber
- Ecole Polytechnique Fédérale de Lausanne, CDM-ODY 3.01, Station 5, CH-1015, Lausanne, Switzerland
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13
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Shoreibah M, Orr J, Jones D, Zhang J, Venkata K, Massoud O. Ledipasvir/sofosbuvir without ribavirin is effective in the treatment of recurrent hepatitis C virus infection post-liver transplant. Hepatol Int 2017; 11:434-439. [PMID: 28083718 DOI: 10.1007/s12072-016-9778-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 12/09/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIM Recurrent hepatitis C virus infection is a challenging complication post-liver transplant. Current guidelines recommend the combination of ribavirin and ledipasvir/sofosbuvir for 12 weeks for the treatment of recurrent HCV genotype 1 post-liver transplant. Data are limited on the use of ledipasvir/sofosbuvir without ribavirin. The aim of this study was to evaluate the use of ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus post-liver transplant. METHODS This is a retrospective study of liver transplant patients who received ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus in our liver center from 2014 to 2016. RESULTS A total of 60 patients were enrolled of which 70% were male, 88% Caucasian, age 60 ± 7 years, 15% cirrhotic, and 45% treatment-experienced with recurrent hepatitis C virus infection genotype 1 post-liver transplant. Treatment duration varied from 8 to 24 weeks. There were no serious adverse events and no discontinuation of treatment. A total of 71% of patients had undetectable serum hepatitis C virus at 4 weeks. However, irrespective of treatment duration, 100% of patients had undetectable serum hepatitis C virus at the end of treatment and 100% of patients achieved sustained viral response at 12 weeks. CONCLUSION Ledipasvir/sofosbuvir without ribavirin is an effective treatment of recurrent hepatitis C virus infection post-liver transplant. The entire group achieved sustained viral response at 12 weeks irrespective of the length of treatment. The combination of ledipasvir/sofosbuvir was well tolerated without serious adverse effects or discontinuation.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1808 7th Ave South, BDB 391, Birmingham, AL, 5294, USA
| | - Jordan Orr
- Department of Internal Medicine, Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, 1720 2nd Ave South, BDB 327, Birmingham, AL, 35294, USA.
| | - DeAnn Jones
- The University of Alabama at Birmingham, 1802 6th Ave South, Birmingham, 35233, AL, USA
| | - Jie Zhang
- The University of Alabama at Birmingham, 1802 6th Ave South, Birmingham, 35233, AL, USA
| | - Krishna Venkata
- Department of Medicine, Montgomery Internal Medicine Residency Program, University of Alabama at Birmingham, 2055 E. South Blvd., Suite 200, Montgomery, 36116, AL, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1808 7th Ave South, BDB 391, Birmingham, AL, 5294, USA
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14
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Ahmed KT, Almashhrawi AA, Ibdah JA, Tahan V. Is the 25-year hepatitis C marathon coming to an end to declare victory? World J Hepatol 2017; 9:921-929. [PMID: 28824743 PMCID: PMC5545137 DOI: 10.4254/wjh.v9.i21.921] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Revised: 06/04/2017] [Accepted: 07/07/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely.
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Affiliation(s)
- Khulood T Ahmed
- Khulood T Ahmed, Ashraf A Almashhrawi, Jamal A Ibdah, Veysel Tahan, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Ashraf A Almashhrawi
- Khulood T Ahmed, Ashraf A Almashhrawi, Jamal A Ibdah, Veysel Tahan, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Jamal A Ibdah
- Khulood T Ahmed, Ashraf A Almashhrawi, Jamal A Ibdah, Veysel Tahan, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Veysel Tahan
- Khulood T Ahmed, Ashraf A Almashhrawi, Jamal A Ibdah, Veysel Tahan, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
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15
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Barocas JA, Beiser M, León C, Gaeta JM, O'Connell JJ, Linas BP. Experience and Outcomes of Hepatitis C Treatment in a Cohort of Homeless and Marginally Housed Adults. JAMA Intern Med 2017; 177:880-882. [PMID: 28395004 PMCID: PMC5575839 DOI: 10.1001/jamainternmed.2017.0358] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Joshua A Barocas
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts2Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts
| | | | - Casey León
- Boston Health Care for the Homeless Program, Boston, Massachusetts
| | - Jessie M Gaeta
- Boston Health Care for the Homeless Program, Boston, Massachusetts
| | | | - Benjamin P Linas
- Division of Infectious Diseases, Boston Medical Center, Boston, Massachusetts5Boston University School of Medicine, Boston, Massachusetts
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16
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Poordad F, Lawitz E, Gutierrez JA, Guerrero J, Speeg K, Swenson ES. An HCV-positive recipient of an HCV-positive donor liver successfully treated before and immediately after liver transplant with daclatasvir, sofosbuvir, and ribavirin. Clin Case Rep 2017; 5:371-375. [PMID: 28396749 PMCID: PMC5378822 DOI: 10.1002/ccr3.841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Accepted: 10/31/2016] [Indexed: 01/14/2023] Open
Abstract
This case suggests that initiation of HCV therapy immediately after liver transplantation with well‐tolerated, all‐oral regimens may achieve a virologic cure in HCV‐positive recipients, thus preventing post‐transplant HCV recurrence and associated disease progression. This strategy may broaden utilization of HCV‐positive donor livers, potentially including HCV‐negative transplant recipients.
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Affiliation(s)
- Fred Poordad
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Eric Lawitz
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Julio A Gutierrez
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Juan Guerrero
- Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Kermit Speeg
- Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Eugene S Swenson
- Bristol-Myers Squibb Research and Development Wallingford Connecticut USA
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17
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Chin M, Hogan C, Nguyen D. The Natural History of Hepatit is C Viral Infection: Clinical Evaluation and Monitoring. ACTA ACUST UNITED AC 2016. [DOI: 10.2174/1874220301603010052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease in the world and represents a substantial burden on global health systems and individual patient wellbeing. Routine screening for HCV in certain high-risk populations is appropriate. HCV can cause both an acute and chronic hepatitis, and manifests as a variety of hepatic and extrahepatic symptoms, largely influenced by a combination of host and viral factors. It can be difficult to predict clinical outcomes in individual cases. In those who suffer a chronic infection, progression to cirrhosis carries the risk of decompensation and hepatocellular carcinoma. The natural history of HCV infection and our understanding of risk factors that are predictive of disease progression are discussed.
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18
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Atla PR, Sheikh MY, Gill F, Kundu R, Choudhury J. Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis. Ann Gastroenterol 2016; 29:515-520. [PMID: 27708520 PMCID: PMC5049561 DOI: 10.20524/aog.2016.0072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Accepted: 06/23/2016] [Indexed: 12/23/2022] Open
Abstract
Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.
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Affiliation(s)
- Pradeep R Atla
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Muhammad Y Sheikh
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Firdose Gill
- Department of Medicine, Kaiser Permanente Fresno Medical Center (Firdose Gill), Fresno, California, USA
| | - Rabindra Kundu
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
| | - Jayanta Choudhury
- Division of Gastroenterology, Hepatology and Nutrition, University of California San Francisco, Fresno MEP (Pradeep R. Atla, Muhammad Y. Sheikh, Rabindra Kundu, Jayanta Choudhury), Fresno, California, USA
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19
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Felmlee DJ, Coilly A, Chung RT, Samuel D, Baumert TF. New perspectives for preventing hepatitis C virus liver graft infection. THE LANCET. INFECTIOUS DISEASES 2016; 16:735-745. [PMID: 27301929 PMCID: PMC4911897 DOI: 10.1016/s1473-3099(16)00120-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 01/29/2016] [Accepted: 02/15/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection.
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Affiliation(s)
- Daniel J Felmlee
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Hepatology Research Group, Peninsula School of Medicine and Dentistry, University of Plymouth, Plymouth, UK
| | - Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France
| | - Raymond T Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France.
| | - Thomas F Baumert
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
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20
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Spera AM, Eldin TK, Tosone G, Orlando R. Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women? World J Hepatol 2016; 8:557-565. [PMID: 27134703 PMCID: PMC4840161 DOI: 10.4254/wjh.v8.i12.557] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/09/2016] [Accepted: 03/22/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world's population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.
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Affiliation(s)
- Anna Maria Spera
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Tarek Kamal Eldin
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Grazia Tosone
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Raffaele Orlando
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
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21
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Ajlan A, Al-Jedai A, Elsiesy H, Alkortas D, Al-Hamoudi W, Alarieh R, Al-Sebayel M, Broering D, Aba Alkhail F. Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients. Can J Gastroenterol Hepatol 2016; 2016:2872371. [PMID: 27446833 PMCID: PMC4904700 DOI: 10.1155/2016/2872371] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 11/10/2015] [Indexed: 12/20/2022] Open
Abstract
Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1%) patients had detectable HCV RNA. Of the 36 patients, 2 (5.5%) relapsed and one died (2.75%). Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence.
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Affiliation(s)
- A. Ajlan
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - A. Al-Jedai
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
| | - H. Elsiesy
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Alkortas
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - W. Al-Hamoudi
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
- King Saud University, College of Medicine, Riyadh, Saudi Arabia
| | - R. Alarieh
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - M. Al-Sebayel
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Broering
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - F. Aba Alkhail
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Thong VD, Poovorawan K, Tangkijvanich P, Wasitthankasem R, Vongpunsawad S, Poovorawan Y. Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis. Intervirology 2016; 58:373-381. [PMID: 27010195 DOI: 10.1159/000444366] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 01/31/2016] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). METHODS Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11. RESULTS Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates. CONCLUSIONS Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.
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Affiliation(s)
- Vo Duy Thong
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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23
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Hernández D, Feaster DJ, Gooden L, Douaihy A, Mandler R, Erickson SJ, Kyle T, Haynes L, Schwartz R, Das M, Metsch L. Self-Reported HIV and HCV Screening Rates and Serostatus Among Substance Abuse Treatment Patients. AIDS Behav 2016; 20:204-14. [PMID: 25952768 PMCID: PMC4637257 DOI: 10.1007/s10461-015-1074-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Substance users are at increased risk for HIV and HCV infection. Still, many substance use treatment programs (SUTP) fail to offer HIV/HCV testing. The present secondary analysis of screening data from a multi-site randomized trial of rapid HIV testing examines self-reported HIV/HCV testing patterns and serostatus of 2473 SUTP patients in 12 community-based sites that had not previously offered on-site testing. Results indicate that most respondents screened for the randomized trial tested more than a year prior to intake for HIV (52 %) and HCV (38 %). Prevalence rates were 3.6 and 30 % for HIV and HCV, respectively. The majority of participants that were HIV (52.2 %) and HCV-positive (40.5 %) reported having been diagnosed within the last 1-5 years. Multivariable logistic regression showed that members of high-risk groups were more likely to have tested. Bundled HIV/HCV testing and linkage to care issues are recommended for expanding testing in community-based SUTP settings.
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Affiliation(s)
- Diana Hernández
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St, Rm 934, New York, NY, 10032, USA.
| | | | - Lauren Gooden
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St, Rm 934, New York, NY, 10032, USA
| | - Antoine Douaihy
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Raul Mandler
- National Institute on Drug Abuse, Bethesda, MD, USA
| | - Sarah J Erickson
- Department of Psychology, University of New Mexico, Albuquerque, NM, USA
| | - Tiffany Kyle
- The Center for Drug Free Living, Orlando, FL, USA
| | - Louise Haynes
- Medical University of South Carolina, Charleston, SC, USA
| | | | - Moupali Das
- School of Medicine, University of California, San Francisco, San Francisco, USA
| | - Lisa Metsch
- Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, 722 W. 168th St, Rm 934, New York, NY, 10032, USA
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Donnelly JP, Franco RA, Wang HE, Galbraith JW. Emergency Department Screening for Hepatitis C Virus: Geographic Reach and Spatial Clustering in Central Alabama. Clin Infect Dis 2015; 62:613-6. [PMID: 26611776 DOI: 10.1093/cid/civ984] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 11/19/2015] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a growing problem, disproportionately affecting those born between 1945 and 1965. Here, we demonstrate the wide geographic reach and surveillance potential of emergency department-based screening and identify areas of elevated HCV infection in central Alabama that were socioeconomically disadvantaged compared with surrounding communities.
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Affiliation(s)
- John P Donnelly
- Department of Emergency Medicine Department of Medicine, Division of Preventive Medicine, University of Alabama School of Medicine Department of Epidemiology, School of Public Health, University of Alabama at Birmingham
| | - Ricardo A Franco
- Department of Medicine, Division of Infectious Diseases, University of Alabama School of Medicine, Birmingham
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Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase. Viruses 2015; 7:5571-86. [PMID: 26516899 PMCID: PMC4632402 DOI: 10.3390/v7102894] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Revised: 10/17/2015] [Accepted: 10/18/2015] [Indexed: 12/17/2022] Open
Abstract
The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.
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Dzyubak B, Venkatesh SK, Manduca A, Glaser KJ, Ehman RL. Automated liver elasticity calculation for MR elastography. J Magn Reson Imaging 2015; 43:1055-63. [PMID: 26494224 DOI: 10.1002/jmri.25072] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 09/25/2015] [Indexed: 12/12/2022] Open
Abstract
PURPOSE MR elastography (MRE) is a phase-contrast MRI technique that is used to quantitatively assess liver stiffness for staging hepatic fibrosis. The current approach requires manual selection of a region of interest (ROI) with good wave quality from which to measure stiffness. The purpose of this work was to develop and evaluate a fully automated approach for measuring hepatic stiffness from MRE images to further reduce measurement variability. MATERIALS AND METHODS An automated liver elasticity calculation (ALEC) algorithm was developed to address reader stiffness measurement variability. ALEC has three stages: initial tissue estimation, segmentation, and ROI cleanup. Stiffnesses measured by the algorithm were compared with technicians and an expert radiologist in a set of 121 clinical cases acquired at 1.5 Tesla. Intra-class correlation (ICC), Bland-Altman analysis, and a noninferiority test were performed to evaluate whether the algorithm can be used in place of manual analysis by technicians. RESULTS The stiffness measurement difference with the expert was 1.42% ± 11.17% (mean ± standard deviation) for the algorithm and 1.82% ± 13.65% for the technicians. The ICCs were 0.981 and 0.984, respectively. Both the algorithm and technicians were equivalent to the expert within a 5% significance margin (P < 0.01). The algorithm had no failures in the 119 cases that were considered analyzable by the human readers. CONCLUSION The results of this study show that the newly developed automated algorithm is able to measure stiffness in clinical liver MRE exams with an accuracy that is equivalent to that of an expert radiologist. ALEC may be useful for analysis of archived data and suitable for performing multi-center studies.
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Kurbanova N, Qayyum R. Association of Hepatitis C Virus Infection with Proteinuria and Glomerular Filtration Rate. Clin Transl Sci 2015; 8:421-4. [PMID: 26272111 DOI: 10.1111/cts.12321] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
AIM Despite several studies, the extent to which hepatitis C virus (HCV) infection is associated with chronic kidney disease (CKD) remains controversial. Thus, we examined the relationship between HCV and CKD using the continuous National Health and Nutrition Examination Survey (1999-2012). METHODS Specimens positive for anti-HCV antibodies were retested and confirmed with recombinant immunoblot assay (RIBA). Proteinuria was defined as urine albumin creatinine ratio > 30 mg/g. CKD was defined as estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2) . We used linear and logistic regression models to examine the association between HCV and outcomes with and without adjustment for age, sex, race, hypertension, diabetes mellitus, and body mass index and accounting for the complex survey design. RESULTS Of the 33,729 eligible participants, HCV infection was present in 659 (1.73%). In unadjusted and adjusted analyses, HCV was associated with proteinuria (OR = 1.40, p = 0.01 and OR = 1.50, p = 0.02, respectively). In both unadjusted and adjusted analyses, individuals with HCV had significantly higher GFR than individuals without (1.4 mL/min, p = 0.04 and 2.7 mL/min, p < 0.001, respectively). We did not find an association of HCV with CKD in adjusted or unadjusted analyses. CONCLUSION HCV infection is associated with proteinuria and high GFR but not with CKD. The biological mechanism of the observed association needs further study.
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Affiliation(s)
- Nargiza Kurbanova
- Community College of Baltimore County, School of Health Professions-Nursing, Catonsville, Maryland, USA
| | - Rehan Qayyum
- University of Tennessee College of Medicine at Chattanooga, Chattanooga, Tennessee, USA
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Whitehead NE, Hearn L, Trenz RC, Burrell LE, Latimer WW. Age cohort differences in illicit drug use and hepatitis C among African American substance users. J Addict Dis 2015; 33:314-21. [PMID: 25299749 DOI: 10.1080/10550887.2014.969605] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Identifying prognostic indicators for undiagnosed Hepatitis C is crucial to attenuate the negative impact of this disease. This study explored the influence of recent and more distal injection drug use on biologically confirmed Hepatitis C infection among a sample (N = 260) of older and younger African Americans. Data from the baseline assessment of the NEURO-HIV epidemiologic study was analyzed using confounder adjusted regression techniques. Older adults were more likely to test positive for Hepatitis C (OR = 2.80, 95% CI = 1.53-5.11) due to lifetime injection drug use (AOR = 5.37, 95% CI = 3.10-9.28). Clinical implications are discussed.
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Affiliation(s)
- Nicole Ennis Whitehead
- a Department of Clinical and Health Psychology, College of Public Health and Health Professions , University of Florida , Gainesville , Florida , USA
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Nguyen JT, Rich JD, Brockmann BW, Vohr F, Spaulding A, Montague BT. A Budget Impact Analysis of Newly Available Hepatitis C Therapeutics and the Financial Burden on a State Correctional System. J Urban Health 2015; 92:635-49. [PMID: 25828149 PMCID: PMC4524840 DOI: 10.1007/s11524-015-9953-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Hepatitis C virus (HCV) infection continues to disproportionately affect incarcerated populations. New HCV drugs present opportunities and challenges to address HCV in corrections. The goal of this study was to evaluate the impact of the treatment costs for HCV infection in a state correctional population through a budget impact analysis comparing differing treatment strategies. Electronic and paper medical records were reviewed to estimate the prevalence of hepatitis C within the Rhode Island Department of Corrections. Three treatment strategies were evaluated as follows: (1) treating all chronically infected persons, (2) treating only patients with demonstrated fibrosis, and (3) treating only patients with advanced fibrosis. Budget impact was computed as the percentage of pharmacy and overall healthcare expenditures accrued by total drug costs assuming entirely interferon-free therapy. Sensitivity analyses assessed potential variance in costs related to variability in HCV prevalence, genotype, estimated variation in market pricing, length of stay for the sentenced population, and uptake of newly available regimens. Chronic HCV prevalence was estimated at 17% of the total population. Treating all sentenced inmates with at least 6 months remaining of their sentence would cost about $34 million-13 times the pharmacy budget and almost twice the overall healthcare budget. Treating inmates with advanced fibrosis would cost about $15 million. A hypothetical 50% reduction in total drug costs for future therapies could cost $17 million to treat all eligible inmates. With immense costs projected with new treatment, it is unlikely that correctional facilities will have the capacity to treat all those afflicted with HCV. Alternative payment strategies in collaboration with outside programs may be necessary to curb this epidemic. In order to improve care and treatment delivery, drug costs also need to be seriously reevaluated to be more accessible and equitable now that HCV is more curable.
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Affiliation(s)
- John T. Nguyen
- />Brown University School of Public Health, Providence, RI USA
| | - Josiah D. Rich
- />Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI USA
- />Division of Infectious Diseases, Miriam Hospital, Providence, RI USA
- />Center for Prisoner Health and Human Rights, Providence, RI USA
- />Department of Epidemiology, Brown University School of Public Health, Providence, RI USA
| | | | - Fred Vohr
- />Medical Programs, Rhode Island Department of Corrections, Cranston, RI USA
| | - Anne Spaulding
- />Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA USA
| | - Brian T. Montague
- />Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI USA
- />Division of Infectious Diseases, Miriam Hospital, Providence, RI USA
- />Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, RI USA
- />The Miriam Hospital, Providence, RI USA
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Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009. PLoS One 2015; 10:e0132056. [PMID: 26167690 PMCID: PMC4500464 DOI: 10.1371/journal.pone.0132056] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 06/09/2015] [Indexed: 11/19/2022] Open
Abstract
We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV) infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA) facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001). For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness.
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Pipili C, Cholongitas E. Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand? World J Hepatol 2015; 7:1606-16. [PMID: 26140081 PMCID: PMC4483543 DOI: 10.4254/wjh.v7.i12.1606] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 05/18/2015] [Accepted: 06/01/2015] [Indexed: 02/06/2023] Open
Abstract
The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate ≤ 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
| | - Evangelos Cholongitas
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
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Kanda T, Yokosuka O, Omata M. Faldaprevir for the treatment of hepatitis C. Int J Mol Sci 2015; 16:4985-4996. [PMID: 25749475 PMCID: PMC4394460 DOI: 10.3390/ijms16034985] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2015] [Revised: 02/21/2015] [Accepted: 03/02/2015] [Indexed: 12/16/2022] Open
Abstract
The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and Drug Administration (FDA) approved the HCV NS3/4A protease inhibitor simeprevir and the HCV NS5B polymerase inhibitor sofosbuvir. Simeprevir or sofosbuvir in combination with pegylated interferon and ribavirin are available for clinical use. Faldaprevir, another HCV NS3/4A protease inhibitor that also has fewer adverse events than telaprevir or boceprevir, is under development. Of interest, faldaprevir in combination with pegylated interferon and ribavirin, and interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin provides high sustained virological response rates for HCV genotype 1 infection. The aim of this article is to review these data concerning faldaprevir. Faldaprevir in combination with pegylated interferon and ribavirin treatment appears to be associated with fewer adverse events than telaprevir or boceprevir in combination with pegylated interferon and ribavirin, and may be one of the therapeutic options for treatment-naive patients with HCV genotype 1. The interferon-free combination of faldaprevir and deleobuvir with ribavirin was effective for HCV genotype 1 infection and may hold promise for interferon-ineligible and interferon-intolerant patients.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Masao Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi 400-8506, Japan.
- University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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Organizing Pneumonia Associated with Pegylated Interferon α and Ribavirin Therapy. Case Rep Pulmonol 2015; 2015:794592. [PMID: 25705538 PMCID: PMC4325218 DOI: 10.1155/2015/794592] [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: 11/28/2014] [Accepted: 01/14/2015] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C virus infection is the leading cause of chronic liver disease in the United States of America. Pegylated interferon α and ribavirin combination is the mainstay of treatment. Severe pulmonary toxicities are rarely reported. We report here a case of severe form of organizing pneumonia secondary to pegylated interferon α therapy presenting as acute respiratory failure. Patient has near complete recovery with withdrawal of pegylated interferon α and steroid therapy. We report this case to raise the awareness of this rare but potentially life-threatening pulmonary complication of pegylated interferon α therapy.
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Cho YK, Kim YN, Song BC. Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection. Clin Mol Hepatol 2014; 20:368-75. [PMID: 25548743 PMCID: PMC4278068 DOI: 10.3350/cmh.2014.20.4.368] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 11/26/2014] [Accepted: 12/01/2014] [Indexed: 12/18/2022] Open
Abstract
Background/Aims This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. Methods Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. Results HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. Conclusions Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.
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Affiliation(s)
- Yoo-Kyung Cho
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Young Nam Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Byung-Cheol Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
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Narayanan S, Townsend K, Macharia T, Majid A, Nelson A, Redfield RR, Kottilil S, Talwani R, Osinusi A. Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C. Hepatol Int 2014. [PMID: 26202761 DOI: 10.1007/s12072-014-9574-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Triple therapy for the treatment of hepatitis C virus (HCV) with first-generation directly acting antiviral agents, the non-structural serine protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved sustained virologic response (SVR) rates. However, a high incidence of adverse events (AEs), high pill burdens and drug interactions remain significant barriers to successful completion of therapy. The aim of this study was to evaluate the AEs observed with BOC triple therapy in comparison to IFN-free sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1) individuals. METHODS We retrospectively evaluated HCV monoinfected, treatment-naïve or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR), were measured according to the DAIDS toxicity table (version 1.0). RESULTS BOC/IFN/RBV was associated with significantly more AEs, most commonly neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %) patients discontinued treatment early, but none (0 %) were because of AEs, while 60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %) because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV. CONCLUSIONS SOF/RBV treatment was associated with fewer side effects than BOC-based triple therapy, appearing to be a safer and more tolerable alternative for HCV GT-1 subjects. These results show that emerging IFN-free therapies may enhance patient adherence, allowing treatment of larger number of patients with improved efficacy.
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Affiliation(s)
- Shivakumar Narayanan
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Kerry Townsend
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA
| | - Thomas Macharia
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Adrian Majid
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Amy Nelson
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA
| | - Robert R Redfield
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shyam Kottilil
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
| | - Rohit Talwani
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Anu Osinusi
- Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.,Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA
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Tosone G, Maraolo AE, Mascolo S, Palmiero G, Tambaro O, Orlando R. Vertical hepatitis C virus transmission: Main questions and answers. World J Hepatol 2014; 6:538-548. [PMID: 25232447 PMCID: PMC4163737 DOI: 10.4254/wjh.v6.i8.538] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.
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Thong VD, Akkarathamrongsin S, Poovorawan K, Tangkijvanich P, Poovorawan Y. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication. World J Gastroenterol 2014; 20:2927-2940. [PMID: 24659883 PMCID: PMC3961978 DOI: 10.3748/wjg.v20.i11.2927] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/06/2014] [Accepted: 01/19/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.
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Phillip V, Saugel B, Ernesti C, Hapfelmeier A, Schultheiß C, Thies P, Mayr U, Schmid RM, Huber W. Effects of paracentesis on hemodynamic parameters and respiratory function in critically ill patients. BMC Gastroenterol 2014; 14:18. [PMID: 24467993 PMCID: PMC3906760 DOI: 10.1186/1471-230x-14-18] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 01/25/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Ascites is a major and common complication of liver cirrhosis. Large or refractory ascites frequently necessitates paracentesis. The aim of our study was to investigate the effects of paracentesis on hemodynamic and respiratory parameters in critically ill patients. METHODS Observational study comparing hemodynamic and respiratory parameters before and after paracentesis in 50 critically ill patients with advanced hemodynamic monitoring. 28/50 (56%) required mechanical ventilation.Descriptive statistics are presented as mean ± standard deviation for normally distributed data and median, range, and interquartile range (IQR) for non-normally distributed data. Comparisons of hemodynamic and respiratory parameters before and after paracentesis were performed by Wilcoxon signed-rank tests. Bivariate relations were assessed by Spearman's correlation coefficient and univariate regression analyses. RESULTS Median amount of ascites removed was 5.99 L (IQR, 3.33-7.68 L). There were no statistically significant changes in hemodynamic parameters except a decrease in mean arterial pressure (-7 mm Hg; p = 0.041) and in systemic vascular resistance index (-116 dyne·sec/cm5/m2; p = 0.016) when measured 2 hours after paracentesis. In all patients, oxygenation ratio (PaO2/FiO2; median, 220 mmHg; IQR, 161-329 mmHg) increased significantly when measured immediately (+58 mmHg; p = 0.001), 2 hours (+9 mmHg; p = 0.004), and 6 hours (+6 mmHg); p = 0.050) after paracentesis. In mechanically ventilated patients, lung injury score (cumulative points without x-ray; median, 6; IQR, 4-7) significantly improved immediately (5; IQR, 4-6; p < 0.001), 2 hours (5; IQR, 4-7; p = 0.003), and 6 hours (6; IQR 4-6; p = 0.012) after paracentesis. CONCLUSION Paracentesis in critically ill patients is safe regarding circulatory function and is related to immediate and sustained improvement of respiratory function.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Wolfgang Huber
- II, Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675 München, Germany.
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Daw MA, El-Bouzedi A. Prevalence of hepatitis B and hepatitis C infection in Libya: results from a national population based survey. BMC Infect Dis 2014; 14:17. [PMID: 24405790 PMCID: PMC3893419 DOI: 10.1186/1471-2334-14-17] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Accepted: 01/02/2014] [Indexed: 12/14/2022] Open
Abstract
Background Libya is one of the largest countries in Africa and has the longest coast in the Mediterranean basin facing southern Europe. High rates of prevalence of viral hepatitis have been observed in various regions in Africa, but the prevalence in Libya is not well documented. We report on a large-scale nationwide study that evaluated the epidemiology of hepatitis B and hepatitis C in Libya and assessed the risk factors involved. Methods A cross-sectional study was carried out in 2008 on 65,761 individuals all over Libya. The country was divided into 12 regions according to the population density and sampling within each region was carried out under the supervision of the National Centre for Prevention of Infectious Diseases. Serum samples were collected from both males and females of all ages in both urban and rural areas and tested for HBsAg for hepatitis B and anti-HCV antibody for hepatitis C. Prevalence rates were determined in regions and in different groups and correlated with different demographic and risk factors involved in the spread of these viruses. Results The prevalence of hepatitis B and hepatitis C viruses varied regionally across the country. The overall prevalence of hepatitis B was 2.2% (95% CI 2.1%-2.3%) and was higher among males than females (1.4:1.0). Hepatitis C virus (HCV) prevalence was 1.2% (95% CI 1.1-1.3) and it increased gradually after the age of 30 years (0.7-0.9% for < 30 years; 3.6% for ≥ 60 years). Prevalence of HBsAg was 0.8-0.9% below the age of 10 years, and higher but similar in older age groups (2.3-2.7%). There was an association between literacy and prevalence of hepatitis, particularly for HCV. Hospital admission, surgical operation, blood transfusion, and intravenous drug use were the main risk factors, and they were associated independently with a higher prevalence rate of viral hepatitis. Conclusions Libya may be considered an area of low-intermediate endemicity for hepatitis B virus infection, with lower rates in young age groups, and an area of low endemicity for hepatitis C. The prevalence of hepatitis B and C across Libya is not homogeneous, with indications of the effect of the higher rates in some neighbouring countries. Libya should adopt full coverage national plans and guidelines to face the future consequences of viral hepatitis, particularly hepatitis C virus.
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Affiliation(s)
- Mohamed A Daw
- Department of Medical Microbiology, Faculty of Medicine, Tripoli, Libya.
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Amjad M, Moudgal V, Faisal M. Laboratory Methods for Diagnosis and Management of Hepatitis C Virus Infection. Lab Med 2013. [DOI: 10.1309/lmasroyd8brs0gc9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Liu X, Yang X, Lee CA, Moustafa IM, Smidansky ED, Lum D, Arnold JJ, Cameron CE, Boehr DD. Vaccine-derived mutation in motif D of poliovirus RNA-dependent RNA polymerase lowers nucleotide incorporation fidelity. J Biol Chem 2013; 288:32753-32765. [PMID: 24085299 DOI: 10.1074/jbc.m113.484428] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that a conformational change of motif D leads to efficient and faithful nucleotide addition by bringing Lys-359 into the active site where it serves as a general acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a drastic change so close to Lys-359 might alter RdRp function and contribute in some way to the attenuated phenotype of Sabin type I. Here we present our characterization of the T362I RdRp. We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro. Using NMR, we show that this change in nucleotide incorporation fidelity correlates with a change in the structural dynamics of motif D. A recombinant PV expressing the T362I RdRp exhibits normal growth properties in cell culture but expresses a mutator phenotype in cells. For example, the T362I-containing PV is more sensitive to the mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I change was sufficient to cause a statistically significant reduction in viral virulence. Collectively, these studies suggest that residues of motif D can be targeted when changes in nucleotide incorporation fidelity are desired. Given the observation that fidelity mutants can serve as vaccine candidates, it may be possible to use engineering of motif D for this purpose.
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Affiliation(s)
| | | | - Cheri A Lee
- the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
| | - Ibrahim M Moustafa
- the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
| | - Eric D Smidansky
- the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
| | | | - Jamie J Arnold
- the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
| | - Craig E Cameron
- the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
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Macarthur KL, Smolic R, Smolic MV, Wu CH, Wu GY. Update on the Development of Anti-Viral Agents Against Hepatitis C. J Clin Transl Hepatol 2013; 1:9-21. [PMID: 26357602 PMCID: PMC4521270 DOI: 10.14218/jcth.2013.007xx] [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: 03/12/2013] [Revised: 05/14/2013] [Accepted: 05/14/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase III/IV clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options.
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Affiliation(s)
| | | | | | - Catherine H. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 2013; 310:804-11. [PMID: 23982366 PMCID: PMC4254410 DOI: 10.1001/jama.2013.109309] [Citation(s) in RCA: 240] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
IMPORTANCE The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations. OBJECTIVE To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics. DESIGN, SETTING, AND PATIENTS Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012). INTERVENTIONS In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. MAIN OUTCOMES AND MEASURES The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]). RESULTS In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events. CONCLUSION AND RELEVANCE In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01441180.
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Affiliation(s)
- Anuoluwapo Osinusi
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
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Abstract
Background Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States, with approximately 3.2 million Americans being chronically infected. Rates of HCV-related end-stage liver disease and its associated morbidity and mortality have yet to peak, so there is a pressing need for more effective and tolerable HCV treatment. HCV genotypes 1, 4, 5, and 6 are considered difficult to treat, and the need for improved therapies is especially great for persons infected with these genotypes. Current strategies for HCV treatment Current therapy for genotype 1 HCV infection includes triple therapy with pegylated interferon, ribavirin, and a NS3/4A protease inhibitor. Sustained virologic response (SVR) rates with triple therapy range from 42% to 75%, a vast improvement over pegylated interferon and ribavirin therapy alone. However, response rates remain suboptimal, and triple therapy is associated with significant adverse effects and is only indicated for genotype 1 HCV infection. Novel drugs for HCV treatment HCV drug development is proceeding at a rapid pace to meet this need. Novel direct acting antiviral agents in several classes, including new NS3/4A serine protease inhibitors, NS5A replication complex inhibitors, NS5B polymerase inhibitors, interferon lambda, and microRNAs, are in varying stages of development. These new therapeutic agents promise SVR rates of up to 100% with durations as short as 12 weeks and, often, fewer adverse effects. Conclusion New drug development in HCV is proceeding at an unprecedented pace. Novel agents promise higher SVR rates, shorter duration of therapy, and fewer adverse effects than have been possible with HCV therapy to date.
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Affiliation(s)
- Emily J Cartwright
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Lesley Miller
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother 2013; 57:5216-24. [PMID: 23939896 DOI: 10.1128/aac.00874-13] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
GSK2485852 (referred to here as GSK5852) is a hepatitis C virus (HCV) NS5B polymerase inhibitor with 50% effective concentrations (EC50s) in the low nanomolar range in the genotype 1 and 2 subgenomic replicon system as well as the infectious HCV cell culture system. We have characterized the antiviral activity of GSK5852 using chimeric replicon systems with NS5B genes from additional genotypes as well as NS5B sequences from clinical isolates of patients infected with HCV of genotypes 1a and 1b. The inhibitory activity of GSK5852 remained unchanged in these intergenotypic and intragenotypic replicon systems. GSK5852 furthermore displays an excellent resistance profile and shows a <5-fold potency loss across the clinically important NS5B resistance mutations P495L, M423T, C316Y, and Y448H. Testing of a diverse mutant panel also revealed a lack of cross-resistance against known resistance mutations in other viral proteins. Data from both the newer 454 sequencing method and traditional population sequencing showed a pattern of mutations arising in the NS5B RNA-dependent RNA polymerase in replicon cells exposed to GSK5852. GSK5852 was more potent than HCV-796, an earlier inhibitor in this class, and showed greater reductions in HCV RNA during long-term treatment of replicons. GSK5852 is similar to HCV-796 in its activity against multiple genotypes, but its superior resistance profile suggests that it could be an attractive component of an all-oral regimen for treating HCV.
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Afshar M, Martinez AD, Gallo RL, Hata TR. Induction and exacerbation of psoriasis with Interferon-alpha therapy for hepatitis C: a review and analysis of 36 cases. J Eur Acad Dermatol Venereol 2013; 27:771-8. [PMID: 22671985 PMCID: PMC3443510 DOI: 10.1111/j.1468-3083.2012.04582.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Interferon-alpha (IFN-α) therapy is used to treat hepatitis C infection. The exacerbation and occurrence of psoriasis in hepatitis C patients treated with IFN-α is increasingly recognized, but the distinct associated features, aetiology and management have not been reviewed. OBJECTIVE To review all published cases of hepatitis C patients who developed psoriasis while receiving IFN-α therapy. METHODS The review was conducted by searching the PubMed database using the keywords 'hepatitis C' AND 'psoriasis.' In addition, references to additional publications not indexed for PubMed were followed to obtain a complete record of published data. RESULTS We identified 32 publications describing 36 subjects who developed a psoriatic eruption while receiving IFN-α therapy for hepatitis C. Topical therapies were a commonly employed treatment modality, but led to resolution in only 30% of cases in which they were employed solely. Cessation of IFN-α therapy led to resolution in 93% of cases. Hundred per cent of those who developed psoriasis while on IFN-α therapy responded to systemic therapy and were able to continue the drug. CONCLUSION Further studies and analysis of IFN-α-induced lesions are necessary to clarify the role of IFN-α and the hepatitis C virus in the development of psoriatic lesions.
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Affiliation(s)
- M Afshar
- Division of Dermatology, Department of Medicine, University of California, San Diego, USA.
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Zalesak M, Francis K, Gedeon A, Gillis J, Hvidsten K, Kidder P, Li H, Martyn D, Orne L, Smith A, Kwong A. Current and future disease progression of the chronic HCV population in the United States. PLoS One 2013; 8:e63959. [PMID: 23704962 PMCID: PMC3660594 DOI: 10.1371/journal.pone.0063959] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Accepted: 04/09/2013] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.
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Affiliation(s)
- Martin Zalesak
- Trinity Partners, LLC, Waltham, Massachusetts, United States of America.
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Jin YJ, Lee JW, Lee JI, Park SH, Park CK, Kim YS, Jeong SH, Kim YS, Kim JH, Hwang SG, Rim KS, Yim HJ, Cheong JY, Cho SW, Lee JS, Park YM, Jang JW, Lee CK, Sohn JH, Yang JM, Han S. Multicenter comparison of PEG-IFN α2a or α2b plus ribavirin for treatment-naïve HCV patient in Korean population. BMC Gastroenterol 2013; 13:74. [PMID: 23627926 PMCID: PMC3644280 DOI: 10.1186/1471-230x-13-74] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 04/22/2013] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Two recent Italian studies suggested that Pegylated-interferon (PEG-IFN) alfa-2a achieves a higher sustained virological response (SVR) rate than PEG-IFN alfa-2b. We intended to compare the efficacy and safety of PEG-IFN alfa-2a with those of PEG-IFN alfa-2b in Korean patients with chronic hepatitis C virus (HCV). METHODS This retrospective, multi-center trial was conducted on 661 treatment-naïve chronic HCV patients. Patients received PEG-IFN alfa-2a (180 μg/week; n=402) or PEG-IFN alfa-2b (1.5 μg/kg/week; n=259) with ribavirin (800-1200 mg/day) for 24 or 48 weeks according to HCV genotypes. RESULTS Early virologic response and sustained virologic response (SVR) rates were not significantly different between two PEG-IFN groups both in patients with HCV genotype 1 (all P-values>0.05) and 2/3 (all P-values>0.05). SVR rates were not different between two groups in each categorized baseline characteristics: age (years) (≤ 50 and >50), HCV viral load (IU/mL) (≤ 7 × 10(5) and >7 × 10(5)), and hepatic fibrosis (F0-2 and F3-4) (all P-values >0.05). In additional analysis for 480 patients who sufficiently complied with treatment doses and duration (80/80/80 rule) and propensity-score matched analysis, SVR rates were not different between two groups both in patients with HCV genotype 1 and 2/3 (all P-values >0.05). Adverse event rates were similar between two groups. CONCLUSIONS Unlike the Western data, efficacy and safety of PEG-IFN alfa-2a were similar to those of PEG-IFN alfa-2b in chronically HCV-infected Korean patients regardless of age, HCV viral load, and hepatic fibrosis.
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Affiliation(s)
- Young-Joo Jin
- Department of Internal Medicine, Incheon, South Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Incheon, South Korea
- Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam, South Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, Incheon, 400-711, Republic of Korea
| | - Jung il Lee
- Department of Internal Medicine, Incheon, South Korea
| | - Sang Hoon Park
- Inha University School of Medicine, Incheon, South Korea
| | - Choong Kee Park
- Hallym University Kangnam Sacred Heart Hospital, Seoul, South Korea
| | - Young Seok Kim
- Hallym University Sacred Heart Hospital, Anyang, South Korea
| | | | - Yun Soo Kim
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ju Hyun Kim
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | | | - Kyu Sung Rim
- Gachon University Gil Medical Center, Incheon, South Korea
| | - Hyung Joon Yim
- CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | | | - Sung Won Cho
- Korea University College of Medicine, Ansan, South Korea
| | - June Sung Lee
- Ajou University School of Medicine, Suwon, South Korea
| | - Young Min Park
- Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Jeong Won Jang
- Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam, South Korea
| | - Chun Kyon Lee
- Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, South Korea
| | - Joo Hyun Sohn
- National Health Insurance Corporation Ilsan Hospital, Goyang, Suwon, Republic of Korea
| | - Jin Mo Yang
- Guri Hospital, Hanyang University College of Medicine, Guri, St.Vincent Hospital, The Catholic University College of Medicine, Suwon, Republic of Korea
| | - Seungbong Han
- Department of Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Azevedo FKSFD, Azevedo CCSFD, Souto FJD. Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil. Mem Inst Oswaldo Cruz 2013; 107:217-23. [PMID: 22415261 DOI: 10.1590/s0074-02762012000200011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Accepted: 10/24/2011] [Indexed: 11/22/2022] Open
Abstract
In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4%) had cirrhosis and HCV genotype 1 predominated (64.3%). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.
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Ali T, Kaitha S, Mahmood S, Ftesi A, Stone J, Bronze MS. Clinical use of anti-TNF therapy and increased risk of infections. Drug Healthc Patient Saf 2013; 5:79-99. [PMID: 23569399 PMCID: PMC3615849 DOI: 10.2147/dhps.s28801] [Citation(s) in RCA: 167] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated.
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Affiliation(s)
- Tauseef Ali
- OU Physicians Center for Inflammatory Bowel Disease, University of Oklahoma Health Sciences Center
- Department of Internal Medicine, University of Oklahoma Health Sciences Center
| | - Sindhu Kaitha
- Department of Internal Medicine, University of Oklahoma Health Sciences Center
| | - Sultan Mahmood
- Department of Internal Medicine, University of Oklahoma Health Sciences Center
| | - Abdul Ftesi
- Integris Baptist Hospital, Oklahoma City, Oklahoma, USA
| | - Jordan Stone
- Department of Internal Medicine, University of Oklahoma Health Sciences Center
| | - Michael S Bronze
- Department of Internal Medicine, University of Oklahoma Health Sciences Center
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