|
1
|
Ismail B, Benrajab KM, Bejarano P, Ruiz P, Sears D, Tzakis A, Zervos XB. Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy. World J Hepatol 2022; 14:602-611. [PMID: 35582292 PMCID: PMC9055203 DOI: 10.4254/wjh.v14.i3.602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 12/16/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Persistent inflammation on histology after successful hepatitis C (HCV) treatment has been reported. However, data regarding the long-term impact in liver transplant recipients is limited, particularly after using direct-acting antiviral (DAA) therapies.
AIM To evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.
METHODS We conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014. All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy. Only patients with at least one liver biopsy at or after treatment were included. We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.
RESULTS Persistent inflammation was seen in 12/13 patients on end of treatment biopsy. Inflammation was still seen in the available five follow-up biopsies (range 38-48 wk after the end of treatment). Intrahepatic HCV RNA was undetectable in all biopsies. All patients had preserved graft function for a mean follow-up of 2.5 years, except one that developed chronic rejection.
CONCLUSION After successful HCV treatment with DAAs, liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA. The clinical outcome remained favorable in most patients. Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.
Collapse
Affiliation(s)
- Bahaaeldeen Ismail
- Division of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY 40536, United States
| | - Karim M Benrajab
- Division of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, KY 40536, United States
| | - Pablo Bejarano
- Department of Pathology, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Phillip Ruiz
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, United States
| | - Debbie Sears
- Department of Liver Transplant, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Andreas Tzakis
- Department of Liver Transplant, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | |
Collapse
|
|
2
|
Ejtehadi F, Farahvashi P, Shamsaeefar A, Niknam R, Sivandzadeh GR, Aminlari L, Motazedian N, Kazemi K, Nikoupour H, Nikeghbalian S, Eghlimi H, Taghavi A, Fattahi M, Bagheri Lankarani K, Malek-Hosseini SA. Clinical Course and Outcome of Liver Transplantation in Patients with Hepatitis C in Iran. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.108405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Hepatitis C is one of the most common causes of end-stage liver disease and liver transplant worldwide. In recent years, with the rapid advances in the treatment of hepatitis C by direct-acting antiviral drugs (DAAs), the clinical course of the disease as well as liver transplantation have had significant improvement. Also, DAAs have completely replaced interferon-based regimens in the treatment and prevention of HCV recurrence after liver transplant. Objectives: This is the first study that aimed to investigate the clinical course of liver transplantation in patients with hepatitis C in Iran. Methods: This retrospective study was conducted on patients with HCV liver transplantation within five years (2012 - 2017) with the age range of 18 to 65 years at Shiraz Organ Transplant Center. All demographic and clinical data were recorded. Pre-transplant viral load, disease recurrence, graft rejection, and mortality rate were the most important indices in this study. Results: Among 55 transplant patients, 49% had received hepatitis C treatment before liver transplantation and interferon-based regimens were more prevalent. Besides, HCV genotype 3, followed by genotype 1, was the most prevalent one. A liver biopsy was performed in patients with elevated liver enzyme levels. The numbers of patients with HCV recurrence at 2, 6, 12, and 24-month intervals were three, two, zero, and two patients, respectively. At these time intervals, eight, eight, one, and three cases of acute graft rejection were found, respectively. Eight patients died with a one-year survival rate of 85%. Sepsis and infectious complications were the most leading causes of death. Conclusions: This study is the first study of liver transplant patients with hepatitis C in Iran. In the five-year study period, rapid development was made in the treatment of HCV patients. It led to the introduction of DAAs, which replaced interferon-based therapies. The results of this study indicated the high success rate of liver transplantation in patients with hepatitis C in Iran. The results of this study could be used to compare the efficacy of DAAs in future research.
Collapse
|
|
3
|
Akiyama MJ, Lipsey D, Ganova-Raeva L, Punkova LT, Agyemang L, Sue A, Ramachandran S, Khudyakov Y, Litwin AH. A Phylogenetic Analysis of Hepatitis C Virus Transmission, Relapse, and Reinfection Among People Who Inject Drugs Receiving Opioid Agonist Therapy. J Infect Dis 2021; 222:488-498. [PMID: 32150621 DOI: 10.1093/infdis/jiaa100] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/03/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). METHODS We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. RESULTS There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 months after treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships. CONCLUSION This study highlights the use of next-generation sequencing as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors after SVR.
Collapse
Affiliation(s)
| | - Daniel Lipsey
- Montefiore Medical Center/Albert Einstein College of Medicine
| | | | - Lili T Punkova
- Centers for Disease Control, Division of Viral Hepatitis
| | - Linda Agyemang
- Montefiore Medical Center/Albert Einstein College of Medicine
| | - Amanda Sue
- Centers for Disease Control, Division of Viral Hepatitis
| | | | - Yury Khudyakov
- Centers for Disease Control, Division of Viral Hepatitis
| | - Alain H Litwin
- Prisma Health, University of South Carolina School of Medicine, Clemson University School of Health Research
| |
Collapse
|
|
4
|
Mathur P, Kottilil S. Hepatitis C Core Antigen Testing: Still an Effective Diagnostic Method for Global Elimination of Hepatitis C. Clin Infect Dis 2020; 70:674-675. [PMID: 30943285 DOI: 10.1093/cid/ciz273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 03/28/2019] [Indexed: 12/20/2022] Open
Affiliation(s)
- Poonam Mathur
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore
| |
Collapse
|
|
5
|
Akiyama MJ, Lipsey D, Heo M, Agyemang L, Norton BL, Hidalgo J, Lora K, Litwin AH. Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy. Clin Infect Dis 2020; 70:2695-2702. [PMID: 31346609 PMCID: PMC7456350 DOI: 10.1093/cid/ciz693] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 07/19/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. METHODS PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. RESULTS Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). CONCLUSIONS HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.
Collapse
Affiliation(s)
- Matthew J Akiyama
- Divisions of General Internal Medicine, Bronx, New York
- Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
| | - Daniel Lipsey
- Divisions of General Internal Medicine, Bronx, New York
| | - Moonseong Heo
- Department of Public Health Sciences, College of Behavioral, Social, and Health Sciences, Clemson University, South Carolina
| | | | - Brianna L Norton
- Divisions of General Internal Medicine, Bronx, New York
- Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
| | | | - Kiara Lora
- Divisions of General Internal Medicine, Bronx, New York
| | - Alain H Litwin
- Department of Medicine, University of South Carolina School of Medicine–Greenville, Greenville
- Department of Medicine, Prisma Health-Upstate, Greenville
- Clemson University School of Health Research, South Carolina
| |
Collapse
|
|
6
|
Alhilali KA, Al-Attar Z, Gibson A, Tailor A, Meng X, Monshouwer M, Snoeys J, Park BK, Naisbitt DJ. Characterization of Healthy Donor-Derived T-Cell Responses Specific to Telaprevir Diastereomers. Toxicol Sci 2020; 168:597-609. [PMID: 30649540 DOI: 10.1093/toxsci/kfz007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Telaprevir, a protease inhibitor, was used alongside PEGylated interferon-α and ribavirin to treat hepatitis C viral infections. The triple regimen proved successful; however, the appearance of severe skin reactions alongside competition from newer drugs restricted its use. Skin reactions presented with a delayed onset indicative of a T-cell mediated reaction. Thus, the aim of this study was to investigate whether telaprevir and/or its diastereomer, which is generated in humans, activates T-cells. Telaprevir in its S-configured therapeutic form and the R-diastereomer were cultured directly with peripheral blood mononuclear cells from healthy donors prior to the generation of T-cell clones by serial dilution. Drug-specific CD4+ and CD8+ T-cell clones responsive to telaprevir and the R-diastereomer were generated and characterized in terms of phenotype and function. The clones proliferated with telaprevir and diastereomer concentrations of 5-20 µM and secreted IFN-γ, IL-13, and granzyme B. In contrast, the telaprevir M11 metabolite did not stimulate T-cells. The CD8+ T-cell response was MHC I-restricted and dependent on the presence of soluble drug. Flow cytometric analysis showed that clones expressed chemokine receptors CCR4 (skin homing) and CXCR3 (migration to peripheral tissue) and 1 of 3 distinct TCR Vβs; TCR Vβ 2, 5.1, or 22. These data show the propensity of both R- and S-forms of telaprevir to generate skin-homing cytotoxic T-cells that may induce the adverse reactions observed in human patients.
Collapse
Affiliation(s)
- Khetam Ali Alhilali
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK.,Department of Pharmacology, Al-Kindy College of Medicine, University of Baghdad, Al-Nahda District, Baghdad, Iraq
| | - Zaid Al-Attar
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK.,Department of Pharmacology, Al-Kindy College of Medicine, University of Baghdad, Al-Nahda District, Baghdad, Iraq
| | - Andrew Gibson
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK
| | - Arun Tailor
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK
| | - Xiaoli Meng
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK
| | | | - Jan Snoeys
- Janssen Research and Development, Beerse 2340, Belgium
| | - B Kevin Park
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK
| | - Dean J Naisbitt
- Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK
| |
Collapse
|
|
7
|
Todorovska B, Joksimovic N, Caloska-Ivanova V, Dimitrova-Genadieva M, Trajkovska M, Curakova E, Kiprijanovska S, Zafirova-Ivanovska B, Serafimoski V. Factors That Influence the Virological Response in Patients with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin. ACTA ACUST UNITED AC 2019; 38:25-33. [PMID: 28593897 DOI: 10.1515/prilozi-2017-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION The success of the antiviral treatment in patients with chronic hepatitis C depends on the factors related to the virus and the host. The aim of the study is the analysis of the antiviral therapy which is a combination of pegylated interferon and ribavirin, considering various factors that will identify the predictors of the sustained virological response. MATERIAL AND METHODS This retrospective study included 226 patients, divided in two groups. Patients with sustained virological response and patients without sustained virological response were compared in terms of the following factors: genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, metabolic abnormalities, obesity and fatty liver. RESULTS The rate of the sustained virological response is 83.6%, more frequently in patients with genotype 3, with evidenced statistical significance (90.54%). The factors that significantly contribute to sustained virological response are related to the age (p = 0.0001), genotype (p = 0.002), mode of transmission (p = 0.005), inflammatory changes in the liver (p = 0.028), body mass index (p = 0.022) and insulin resistance (p = 0.039). The high rate of sustained virological response is related to the younger age of the patients which indirectly means short Hepatitis C Virus infection duration, absence of advanced liver disease and lack of significant co-morbid conditions. Single confirmed independent predictors of sustained virological response are the age (OR 0.928, p = 0.0001) and genotype (OR 3.134, p = 0.005). CONCLUSIONS Factors that are related to the virological response are the age, genotype, mode of transmission, inflammatory changes in the liver, body mass index and insulin resistance, but still, independent predictors of sustained virologic response are the age and the genotype.
Collapse
Affiliation(s)
- Beti Todorovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Nenad Joksimovic
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Viktorija Caloska-Ivanova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | | | - Meri Trajkovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Elena Curakova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Sanja Kiprijanovska
- Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Sciences and Arts, Skopje
| | - Beti Zafirova-Ivanovska
- Institute of Epidemiology and Biostatistics, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | | |
Collapse
|
|
8
|
Akiyama MJ, Norton BL, Arnsten JH, Agyemang L, Heo M, Litwin AH. Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial. Ann Intern Med 2019; 170:594-603. [PMID: 30959528 PMCID: PMC6868527 DOI: 10.7326/m18-1715] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. OBJECTIVE To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. DESIGN Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). SETTING Three OAT programs in Bronx, New York. PARTICIPANTS Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n = 51), GT (n = 48), and SIT (n = 51). INTERVENTION 2 intensive interventions (DOT and GT) and 1 control condition (SIT). MEASUREMENTS Primary: adherence, measured by using electronic blister packs. Secondary: HCV treatment completion and SVR 12 weeks after treatment completion. RESULTS Mean age was 51 years; 65% of participants had positive results on urine drug testing during the 6 months before treatment, and 75% reported ever injecting drugs. Overall adherence, estimated from mixed-effects models using the daily timeframe, was 78% (95% CI, 75% to 81%) and was greater among participants randomly assigned to DOT (86% [CI, 80% to 92%]) than those assigned to SIT (75% [CI, 70% to 81%]; difference, 11% [CI, 5% to 18%]; Bonferroni-corrected P = 0.001). No significant difference in adherence was observed between participants randomly assigned to GT (80% [CI, 74% to 86%]) and those assigned to SIT (difference, 4.7% [CI, -2% to 11%]; Bonferroni-corrected P = 0.29). The HCV treatment completion rate was 97%, with no differences among groups (P = 0.53). Overall SVR was 94% (CI, 89% to 97%); the SVR rate was 98% in the DOT group, 94% in the GT group, and 90% in the SIT group (P = 0.152). LIMITATION These findings may not be generalizable to PWID not enrolled in OAT programs. CONCLUSION All models of onsite HCV care delivered to PWID in OAT programs resulted in high SVR, despite ongoing drug use. Directly observed therapy was associated with greater adherence than SIT. PRIMARY FUNDING SOURCE National Institute on Drug Abuse and Gilead Sciences.
Collapse
Affiliation(s)
- Matthew J Akiyama
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (M.J.A., B.L.N., J.H.A., L.A.)
| | - Brianna L Norton
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (M.J.A., B.L.N., J.H.A., L.A.)
| | - Julia H Arnsten
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (M.J.A., B.L.N., J.H.A., L.A.)
| | - Linda Agyemang
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York (M.J.A., B.L.N., J.H.A., L.A.)
| | | | - Alain H Litwin
- University of South Carolina School of Medicine-Greenville and Greenville Health System, Greenville, South Carolina, and Clemson University School of Health Research, Clemson, South Carolina (A.H.L.)
| |
Collapse
|
|
9
|
Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination: A population study of ex-substance users in Singapore. Hepatobiliary Pancreat Dis Int 2019; 18:143-148. [PMID: 30558838 DOI: 10.1016/j.hbpd.2018.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 11/28/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population. METHODS HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score. RESULTS A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P < 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients. CONCLUSIONS Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings.
Collapse
|
|
10
|
Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers. Clin Ther 2018; 40:1234-1245. [PMID: 29983266 DOI: 10.1016/j.clinthera.2018.05.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 05/09/2018] [Accepted: 05/09/2018] [Indexed: 12/23/2022]
Abstract
This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.
Collapse
|
|
11
|
Adekunle R, Jonchhe S, Ravichandran B, Wilson E, Husson J. Hepatitis C genotype change after transplantation utilizing hepatitis C positive donor organs. Transpl Infect Dis 2018; 20:e12925. [PMID: 29797655 DOI: 10.1111/tid.12925] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 01/07/2018] [Accepted: 01/14/2018] [Indexed: 12/15/2022]
Abstract
A shortage in organs for transplantation has led to the increased use of hepatitis C (HCV) infected donor organs for solid organ transplant recipients infected with HCV. However, the donor HCV genotype is not routinely checked or known prior to transplant. Here, we report 4 cases of genotype conversion after transplantation in patients receiving HCV infected donor organs. This change in genotype may potentially impact HCV progression as well as treatment choice for these patients.
Collapse
Affiliation(s)
- R Adekunle
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - S Jonchhe
- University of Maryland School of Pharmacy, Baltimore, MD, USA
| | - B Ravichandran
- University of Maryland School of Pharmacy, Baltimore, MD, USA
| | - E Wilson
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - J Husson
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
12
|
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.
Collapse
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.
| |
Collapse
|
|
13
|
Iqbal S, Yousuf MH, Yousaf MI. Dramatic response of hepatitis C patients chronically infected with hepatitis C virus genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study. World J Gastroenterol 2017; 23:7899-7905. [PMID: 29209131 PMCID: PMC5703919 DOI: 10.3748/wjg.v23.i44.7899] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 09/06/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023] Open
Abstract
AIM To prospectively evaluate the efficacy of sofobuvir (SOF) in hepatitis C patients infected with hepatitis C virus (HCV) genotype 3 in Pakistan.
METHODS The present study was performed with the coordination of gastroenterology and pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016. The total number of patients included in this study was 1375 and all of them were infected with HCV genotype 3. On the basis of drug combinations, all the patients were separated into two groups. The first group of patients was treated for 24 wk with SOF (Sovaldi® by Gilead Sciences) plus ribavirin (RBV) [Ribazol® by Getz Pharma Pakistan (PVT) Ltd], while the patients of the second group were treated with SOF + RBV + pegylated-interferon (pegIFN) alfa-2a (Ropegra by Roach) for 12 wk. HCV genotyping and viral load measurement were performed on fully automated Abbott Real-Time PCR system (Abbott m24sp automated nucleic acid extraction system and Abbott m2000rt amplification system; abbott Molecular, Des Plaines, IL, United States). For the assessment of sustained virological response (SVR), all HCV RNA negative patients were followed for 12 weeks after the treatment completion. Any patient with less than 12 IU/mL viral load after 12 wk of treatment completion was considered as a sustained virological responder (SVR-12).
RESULTS A total of 1375 patients chronically infected with HCV genotype 3 were treated with two drug combinations SOF + RBV and SOF + RBV + pegIFN alfa-2a. On the basis of these drug combinations, patients were divided into two groups (first and second). Overall SVR-12 was excellent in both groups (99.17% and 97.91%). Older patients (> 40 years) of second group showed lower SVR-12 (93.46%) compared to first group older patients (98.79%), while in the younger patients of both groups, the SVR-12 rate was almost the same (99.54% in first group and 99.05% in second group). No such difference regarding SVR-12 rate was seen in males and females of first group patients (99.68% and 98.88%, respectively), while in second group the males were found to be better responders compared to females (98.96% and 95%). The SVR-12 rate in previously treated patients of first group was better (99.34%) than second group (93.70%), while naïve patients of second group were marginally better responders (99.25%) than first group (97.80%). Rapid viral response at week-4 was found to be a very effective predictor for assessing the SVR rate at this stage of therapy in both groups. Headache, anemia and fatigue were common side effects in both groups either treated with SOF + RBV or SOF + RBV + pegIFN alfa-2a, while the overall percentage of the side effects was higher in second group.
CONCLUSION The remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided a new way to look forward to eliminate hepatitis C from our region.
Collapse
Affiliation(s)
- Sajjad Iqbal
- Department of Pathology, Shalamar Hospital, Lahore 54840, Pakistan
| | - Muhammad Haroon Yousuf
- Department of Gastroenterology and Hepatology, Shalamar Hospital, Lahore 54840, Pakistan
| | | |
Collapse
|
|
14
|
Norton BL, Fleming J, Bachhuber MA, Steinman M, DeLuca J, Cunningham CO, Johnson N, Laraque F, Litwin AH. High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2017; 47:196-201. [PMID: 28811158 DOI: 10.1016/j.drugpo.2017.07.021] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 07/06/2017] [Accepted: 07/21/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. METHODS We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n=89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment. RESULTS Overall SVR rates were 95% (n=41/43) for non-PWUD and 96% (n=44/46) for patients actively using drugs and/or receiving OAT [p=0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n=15/15; p=1.0), those actively using drugs/not receiving OAT had 90% SVR (n=9/10; p=0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p=1.0). CONCLUSION Regardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT.
Collapse
Affiliation(s)
- Brianna L Norton
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States.
| | - Julia Fleming
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States
| | - Marcus A Bachhuber
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States
| | | | - Joseph DeLuca
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States
| | - Chinazo O Cunningham
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States
| | - Nirah Johnson
- New York City Department of Health, Viral Hepatitis Program, New York, NY, United States
| | - Fabienne Laraque
- New York City Department of Health, Viral Hepatitis Program, New York, NY, United States
| | - Alain H Litwin
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States
| |
Collapse
|
|
15
|
Ahn J, Liu B, Bhuket T, Wong RJ. Race/Ethnicity-Specific Outcomes Among Chronic Hepatitis C Virus Patients Listed for Liver Transplantation. Dig Dis Sci 2017; 62:1051-1057. [PMID: 28168576 DOI: 10.1007/s10620-017-4469-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 01/20/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC) and need for liver transplantation (LT). It is unclear if HCV-related LT outcomes vary by race/ethnicity. AIMS We aim to evaluate ethnic disparities specifically among patients with chronic HCV in the USA. METHODS Using data from the United Network for Organ Sharing 2003-2013 LT registry, we evaluated race/ethnicity-specific disparities in LT waitlist survival and probability of receiving LT among chronic HCV patients listed for LT. RESULTS Among 43,478 HCV patients listed for LT (70.0% non-Hispanic white, 10.8% black, 16.3% Hispanic, 2.9% Asian), HCV-related LT waitlist registrations increased by 21.5% from 2003 to 2013. During this period, the proportion of HCV patients with HCC increased by 237%, and in 2013, HCV patients with HCC accounted for 33.0% of HCV-related waitlist registrations. When stratified by race/ethnicity, Hispanics with HCV had significantly lower waitlist mortality (OR 0.83; 95% CI 0.74-0.94; p < 0.01) compared to non-Hispanic whites, but no significant differences were seen among blacks and Asians. Furthermore, compared to non-Hispanic whites, Hispanics were significantly less likely to receive LT (OR 0.58; 95% CI 0.53-0.62; p < 0.001), but no differences were seen among blacks or Asians. CONCLUSION Among patients with chronic HCV in the USA, the MELD score has reduced race/ethnicity-specific disparities in waitlist mortality. However, Hispanic HCV patients had significantly better waitlist survival and lower probability of receiving LT, possibly reflecting slower disease progression compared to non-Hispanic whites with chronic HCV.
Collapse
Affiliation(s)
- Joseph Ahn
- Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Benny Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA
| | - Taft Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA.
| |
Collapse
|
|
16
|
Cellar DF, Voster D, Fetters R, Twitchell E, Harper GW, Scott C. Personality, Coping, and Well-Being for People Living with Chronic Hepatitis C. Psychol Rep 2017; 118:649-67. [PMID: 27154384 DOI: 10.1177/0033294115625557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The present study examined the relationships between personality, coping strategies, and health ratings to extend past research to people living with chronic hepatitis C (HCV). Participants were 35 people (11 men, 24 women; M age = 49.6 yr., SD = 10.6) living with chronic hepatitis C for an average of 9.0 yr. (SD = 6.0) since diagnosis. Participants provided descriptions of stressful situations and responded to a personality inventory, Ways of Coping Questionnaire scales (planful problem solving and escape-avoidance) and SF36 Health Survey scales measuring physical functioning and mental health. The stressful situations were judgmentally clustered into seven dimensions (diagnosis/mortality, disclosure, stigma, social and work role functioning, compounding problems, and no stress). Correlational analyses indicated strong negative relationships between escape-avoidance coping and health measures. Emotional Stability and Extraversion were positively related to both health variables, and Extraversion was negatively related to escape-avoidance coping. The results suggest that research from other contexts that has examined these relationships tended to generalize to people living with HCV.
Collapse
Affiliation(s)
| | - Devon Voster
- DePaul University, USA; Loyola University Medical Center, USA
| | - Rachel Fetters
- DePaul University, USA; Loyola University Medical Center, USA
| | - Emily Twitchell
- DePaul University, USA; Loyola University Medical Center, USA
| | - Gary W Harper
- DePaul University, USA; Loyola University Medical Center, USA; University of Michigan, USA
| | - Cotler Scott
- DePaul University, USA; Loyola University Medical Center, USA
| |
Collapse
|
|
17
|
Wadhawan M, Vij V, Makki K, Bansal N, Kumar A. Early Acute Severe HCV Recurrence After Transplantation: From Universal Mortality to Cure. J Clin Exp Hepatol 2017; 7:28-32. [PMID: 28348468 PMCID: PMC5357714 DOI: 10.1016/j.jceh.2016.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 10/21/2016] [Indexed: 12/12/2022] Open
Abstract
Acute severe recurrence of hepatitis C virus (HCV) after solid organ transplant is associated with high mortality. Pegylated interferon and ribavirin are suboptimal in treatment of this severe form of recurrence. We report 4 cases of acute severe HCV recurrence (within 6 months after transplant), including 3 cases with fibrosing cholestatic hepatitis treated with sofosbuvir and ribavirin. All four patients achieved a rapid suppression of HCV RNA with a normalization of liver function tests within 4 weeks of starting therapy. All patients were HCV RNA negative at 12 weeks after stopping therapy. The combination was found to be safe as anemia was the only adverse effect, which developed in 2 patients (1 patient required blood transfusion, while another managed with erythropoietin). Sofosbuvir and ribavirin appear to be safe and efficacious in treatment of acute severe HCV recurrence after organ transplant.
Collapse
Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- DAA's, sofosbuvir
- FCH, fibrosing cholestatic hepatitis
- Fibrosing cholestatic hepatitis
- GGTP, gamma glutamyl transpeptidase
- HCV, hepatitis C virus
- IHBR, intrahepatic biliary radicals
- Kidney transplant
- LFT, liver function tests
- LRLT, living-related liver transplant
- Liver transplant
- MMF, mycophenolate mofetil
- MRCP, magnetic resonance cholangiopancreatography
- POD, postoperative day
- TND, target not detected
Collapse
Affiliation(s)
- Manav Wadhawan
- Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India,Address for correspondence: Manav Wadhawan, Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India.Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases InstituteDelhi/NCRIndia
| | - Vivek Vij
- Department of Surgical Gastroenterology & Liver Transplant, Fortis Hospitals (Escorts & Noida), Delhi/NCR, India
| | - Kausar Makki
- Department of Surgical Gastroenterology & Liver Transplant, Fortis Hospitals (Escorts & Noida), Delhi/NCR, India
| | - Nalini Bansal
- Department of Pathology, Fortis Escorts Hospital, Delhi, India
| | - Ajay Kumar
- Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India
| |
Collapse
|
|
18
|
Calles DL, Collier MG, Khudyakov Y, Mixson-Hayden T, VanderBusch L, Weninger S, Miller TK. Hepatitis C virus transmission in a skilled nursing facility, North Dakota, 2013. Am J Infect Control 2017; 45:126-132. [PMID: 27816216 DOI: 10.1016/j.ajic.2016.08.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 08/23/2016] [Accepted: 08/23/2016] [Indexed: 01/20/2023]
Abstract
BACKGROUND From March-May 2013, 3 cases of acute hepatitis C virus (HCV) infection were diagnosed among elderly patients residing at the same skilled nursing facility (facility A) and who received health care at hospital X during their likely exposure period. METHODS We performed HCV testing of at-risk populations; quasispecies analysis was performed to determine relatedness of HCV in persons with current infection. Infection control practice assessments were conducted at facility A and hospital X. Persons residing in facility A on September 9, 2013, were enrolled in a case-control study to identify risk factors for HCV infection. RESULTS Forty-five outbreak-associated infections were identified. Thirty cases and 62 controls were enrolled in the case-control study. Only podiatry (odds ratio, 11.6; 95% confidence interval, 2.4-57.2) and international normalized ratio monitoring by phlebotomy (odds ratio, 6.7; 95% confidence interval, 1.7-26.6) at facility A were significantly associated with case status. Infection control lapses during podiatry and point-of-care testing procedures at facility A were identified. CONCLUSIONS HCV transmission was confirmed among residents of facility A. The exact mode of transmission was not able to be identified, but infection control lapses were likely responsible. This outbreak highlights the importance of prompt reporting and investigation of incident HCV infection and the need for adherence to basic infection control procedures by health care personnel.
Collapse
Affiliation(s)
- Dinorah L Calles
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA.
| | - Melissa G Collier
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Yury Khudyakov
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | - Tonya Mixson-Hayden
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
| | | | | | | |
Collapse
|
|
19
|
Norton BL, Beitin A, Glenn M, DeLuca J, Litwin AH, Cunningham CO. Retention in buprenorphine treatment is associated with improved HCV care outcomes. J Subst Abuse Treat 2017; 75:38-42. [PMID: 28237052 DOI: 10.1016/j.jsat.2017.01.015] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 01/26/2017] [Accepted: 01/27/2017] [Indexed: 12/19/2022]
Abstract
Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential.
Collapse
Affiliation(s)
- B L Norton
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States.
| | - A Beitin
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States
| | - M Glenn
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States
| | - J DeLuca
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States
| | - A H Litwin
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States
| | - C O Cunningham
- Montefiore Medical Center, Albert Einstein College of Medicine, Division of General Internal Medicine, Bronx, NY, United States
| |
Collapse
|
|
20
|
Velázquez F, Chelliah M, Clasby M, Guo Z, Howe J, Miller R, Neelamkavil S, Shah U, Soriano A, Xia Y, Venkatraman S, Chackalamannil S, Davies IW. Design and Synthesis of P2-P4 Macrocycles Containing a Unique Spirocyclic Proline: A New Class of HCV NS3/4A Inhibitors. ACS Med Chem Lett 2016; 7:1173-1178. [PMID: 27994759 DOI: 10.1021/acsmedchemlett.6b00321] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 10/17/2016] [Indexed: 01/07/2023] Open
Abstract
A new class of hepatitis C NS3/4A inhibitors was identified by introducing a novel spirocyclic proline-P2 surrogate onto the P2-P4 macrocyclic core of MK-5172 (grazoprevir). The potency profile of new analogues showed excellent pan-genotypic activity for most compounds. The potency evaluation included the most difficult genotype 3a (EC50 values ≤10 nM) and other key genotype 1b mutants. Molecular modeling was used to design new target compounds and rationalize our results. A synthetic approach based on the Julia-Kocienski olefination and macrolactamization to assemble the P2-P4 macrocyclic core containing the novel spirocyclic proline-P2 moiety is presented as well.
Collapse
Affiliation(s)
- Francisco Velázquez
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Mariappan Chelliah
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Martin Clasby
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Zhuyan Guo
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - John Howe
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Randy Miller
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Santhosh Neelamkavil
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Unmesh Shah
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Aileen Soriano
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Yan Xia
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Srikanth Venkatraman
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Samuel Chackalamannil
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| | - Ian W. Davies
- Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
| |
Collapse
|
|
21
|
Alghamdi AS, Alghamdi M, Sanai FM, Alghamdi H, Aba-Alkhail F, Alswat K, Babatin M, Alqutub A, Altraif I, Alfaleh F. SASLT guidelines: Update in treatment of Hepatitis C virus infection. Saudi J Gastroenterol 2016; 22 Suppl:S25-57. [PMID: 27538727 PMCID: PMC5004485 DOI: 10.4103/1319-3767.188067] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Faisal M Sanai
- Department of Medicine, Division of Gastroenterology, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Department of Hepatobiliary Sciences and Liver Transplantation King Abdulaziz Medical City, and King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faisal Aba-Alkhail
- Department of Medicine, Division of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Khalid Alswat
- Department of Medicine, Gastroenterology unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Adel Alqutub
- Department of Medical Specialties, Gastroenterology and Hepatology Section, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Department of Hepatobiliary Sciences and Liver Transplantation King Abdulaziz Medical City, and King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faleh Alfaleh
- Department of Medicine, Gastroenterology unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
|
22
|
Bifano M, Adamczyk R, Hwang C, Kandoussi H, Marion A, Bertz RJ. An open-label investigation into drug-drug interactions between multiple doses of daclatasvir and single-dose cyclosporine or tacrolimus in healthy subjects. Clin Drug Investig 2016; 35:281-9. [PMID: 25896946 PMCID: PMC4544506 DOI: 10.1007/s40261-015-0279-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background and Objective Chronic hepatitis C virus (HCV) infection is a major cause of liver transplantation. Drug–drug interactions (DDIs) with cyclosporine and tacrolimus hindered the use of first-generation protease inhibitors in transplant recipients. The current study investigated DDIs between daclatasvir—a pan-genotypic HCV NS5A inhibitor with clinical efficacy in multiple regimens (including all-oral)—and cyclosporine or tacrolimus in healthy subjects. Methods Healthy fasted subjects (aged 18–49 years; body mass index 18–32 kg/m2) received single oral doses of cyclosporine 400 mg on days 1 and 9, and daclatasvir 60 mg once daily on days 4–11 (group 1, n = 14), or a single oral dose of tacrolimus 5 mg on days 1 and 13, and daclatasvir 60 mg once daily on days 8–19 (group 2, n = 14). Blood samples for pharmacokinetic analysis [by liquid chromatography with tandem mass spectrometry (LC–MS/MS)] were collected on days 1 and 9 for cyclosporine (72 h), on days 1 and 13 for tacrolimus (168 h) and on days 8 and 9 (group 1) or on days 12 and 13 (group 2) for daclatasvir (24 h). Plasma concentrations were determined by validated LC–MS/MS methods. Results Daclatasvir did not affect the pharmacokinetic parameters of cyclosporine or tacrolimus, and tacrolimus did not affect the pharmacokinetic parameters of daclatasvir. Co-administration of cyclosporine resulted in a 40 % increase in the area under the concentration–time curve of daclatasvir but did not affect its maximum observed concentration. Conclusion On the basis of these observations in healthy subjects, no clinically relevant DDIs between daclatasvir and cyclosporine or tacrolimus are anticipated in liver transplant recipients infected with HCV; dose adjustments during co-administration are unlikely to be required.
Collapse
Affiliation(s)
- Marc Bifano
- />Bristol-Myers Squibb Research and Development, 311 Pennington Rock Hill Road, Hopewell, NJ 08534 USA
| | - Robert Adamczyk
- />Bristol-Myers Squibb Research and Development, 311 Pennington Rock Hill Road, Hopewell, NJ 08534 USA
| | - Carey Hwang
- />Bristol-Myers Squibb Research and Development, 311 Pennington Rock Hill Road, Hopewell, NJ 08534 USA
| | - Hamza Kandoussi
- />Bristol-Myers Squibb Research and Development, Lawrenceville, NJ USA
| | | | - Richard J. Bertz
- />Bristol-Myers Squibb Research and Development, 311 Pennington Rock Hill Road, Hopewell, NJ 08534 USA
| |
Collapse
|
|
23
|
Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition. Proc Natl Acad Sci U S A 2016; 113:7620-5. [PMID: 27298373 DOI: 10.1073/pnas.1602701113] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.
Collapse
|
|
24
|
Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 2016; 37:37-61. [PMID: 26650437 PMCID: PMC4740345 DOI: 10.1210/er.2015-1084] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
Collapse
Affiliation(s)
- Vijay Shivaswamy
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Brian Boerner
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Jennifer Larsen
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| |
Collapse
|
|
25
|
Simon RE, Pearson SD, Hur C, Chung RT. Tackling the hepatitis C cost problem: A test case for tomorrow's cures. Hepatology 2015; 62:1334-6. [PMID: 26359645 DOI: 10.1002/hep.28157] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 09/08/2015] [Indexed: 12/07/2022]
Affiliation(s)
| | | | - Chin Hur
- Harvard Medical School, Boston, MA.,GI Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.,Institute for Technology Assessment, Boston, MA
| | - Raymond T Chung
- Harvard Medical School, Boston, MA.,GI Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
|
26
|
Mohamad B, Hanouneh IA, Zein NN, Lopez R, Matloob A, Alkhouri N. Liver Transplant in Young Adults with Chronic Hepatitis C Virus: An Argument for Hepatitis C Treatment in Childhood. EXP CLIN TRANSPLANT 2015; 14:201-6. [PMID: 26476199 DOI: 10.6002/ect.2015.0092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES We sought to assess the characteristics of hepatitis C virus-positive young adults who received a liver transplant and to evaluate posttransplant outcomes. MATERIALS AND METHODS United Network for Organ Sharing database was conducted from 1989 to 2012, and retrospective analysis was performed on all hepatitis C virus-positive young adult patients (aged, 8-35 y) who underwent a liver transplant in the United States. RESULTS A total of 506 hepatitis C virus subjects were included. Average age at time of transplant was 30.1 ± 4.8 years. Median follow-up after first liver transplant was 46.1 months (13, 89.3 mo). During this time, 217 patients (42.8%) died at a mean age at the time of death of 34 ± 6.7 years including 176/ 506 (34.8%) after the first liver transplant, 34/71 (48.6%) after the second liver transplant, and 7/8 (87.5%) after the third liver transplant. The majority (65.7%) of retransplants were performed for hepatitis C virus recurrence. A mean of 1.15 liver transplants were performed per patient. Overall, 262 subjects were transplanted in the pre-Model for End-stage Liver Disease era, and 244 were transplanted post-MELD. Younger age, higher bilirubin, higher creatinine, hepatitis C carcinoma, shorter wait time, shorter cold ischemia time, nonwhite donor race, and the use of mycophenolate mofetil were significantly more common in the post-Model for End-stage Liver Disease era (all with P < .05). Importantly, 5-year patient and graft survival were not different between the pre- and post-Model for End-stage Liver Disease era. CONCLUSIONS Liver transplant in young adults for hepatitis C virus acquired during childhood has poor outcomes that did not improve in the post-Model for End-stage Liver Disease era. These findings should prompt more aggressive evaluation and treatment for hepatitis C virus in children.
Collapse
Affiliation(s)
- Bashar Mohamad
- From the Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | | | | | | | | | | |
Collapse
|
|
27
|
Pandya P, Rzouq F, Oni O. Sustained virologic response and other potential genotype-specific roles of statins among patients with hepatitis C-related chronic liver diseases. Clin Res Hepatol Gastroenterol 2015; 39:555-65. [PMID: 25835493 DOI: 10.1016/j.clinre.2015.02.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 01/18/2015] [Accepted: 02/05/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND While statins have shown antiviral effects in different studies, few data are available about their effect among different HCV genotypes. AIM To evaluate the effect of concomitant statin use on sustained virologic response (SVR) and other treatment outcomes among patients with HCV genotypes 1-3. METHOD Using US Department of Veterans Affairs database, multivariate (MV), propensity score matched (PSM) and repeated measures mixed model analyses were performed on patients who received combination therapy with Peg-IFN and Ribavirin for treatment of HCV genotypes 1-3 between October 2001-December 2011. Concomitant statin users were matched with non-users in each genotype and SVR rates were compared. Changes in serum ALT during treatment was assessed. RESULTS Of 37,611 treated patients, 236 genotype 1 (GT1), 78 genotype 2 (GT2) and 23 genotype 3 (GT3) statin users and non-users were used for PSM. SVR among GT1 patients was 22.8% (overall), significantly higher among statin users (26.3% vs. 19.5% P<0.01 from PSM; OR=1.49 CI 1.06-2.08 P=0.02 from MV). No significant impact of statin use was observed among GT2 (overall SVR - 55.8%, statin users vs. non-users - 53.9% vs. 57.7%, P=0.32), and GT3 (overall SVR - 58.7%, statin users vs. non-users - 60.9% vs. 56.2%, P=0.39) patients. Higher baseline LDL was positively associated with SVR while statin use reduced ALT during treatment in GT1 patients. CONCLUSION In view of additional benefits of statins, and the prohibitive cost of newer HCV therapies, statins could be a potential assist for hard-to-treat GT1 patients especially in resource-poor settings.
Collapse
Affiliation(s)
- Prashant Pandya
- Kansas City VA Medical Center, Department of Gastroenterology (Hepatology Division), Kansas City, MO, USA; University of Kansas Medical Center, Department of Internal Medicine, Kansas City, KS, USA
| | - Fadi Rzouq
- University of Kansas Medical Center, Department of Internal Medicine, Kansas City, KS, USA
| | - Olurinde Oni
- Kansas City VA Medical Center, Hepatology Research Unit, Kansas City, MO, USA.
| |
Collapse
|
|
28
|
Lepida A, Colombo M, Fernandez I, Abdurakhmanov D, Abrao Ferreira P, Strasser SI, Urbanek P, Mangia A, Calleja JL, Iraqi W, DeMasi R, Lonjon-Domanec I, Moreno C, Wedemeyer H. Final Results of the Telaprevir Access Program: FibroScan Values Predict Safety and Efficacy in Hepatitis C Patients with Advanced Fibrosis or Cirrhosis. PLoS One 2015; 10:e0138503. [PMID: 26398503 PMCID: PMC4580464 DOI: 10.1371/journal.pone.0138503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 08/29/2015] [Indexed: 12/12/2022] Open
Abstract
Background Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intention-to-treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. Trial Registration ClinicalTrials.gov NCT01508286
Collapse
Affiliation(s)
- Antonia Lepida
- Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Massimo Colombo
- Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita’ degli Studi di Milano, Milan, Italy
| | - Inmaculada Fernandez
- Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain
| | - Djamal Abdurakhmanov
- I.M. Sechenov First Moscow State Medical University, E.M. Tareev Clinic for Nephrology, Internal and Occupational Medicine, Moscow, Russia
| | - Paulo Abrao Ferreira
- Outpatient Clinic to HIV and Viral Hepatitis Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil
| | - Simone I. Strasser
- AW Morrow Gastroenterology and Liver Center, Royal Prince Alfred hospital and University of Sydney, Sydney, Australia
| | - Petr Urbanek
- Department of Internal Medicine, First Medical Faculty, Charles University, and Central Military Hospital Prague, Prague, Czech Republic
| | - Alessandra Mangia
- Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy
| | - José L. Calleja
- Gastroenterology, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, CIBERehd, Madrid, Spain
| | | | - Ralph DeMasi
- Janssen Research and development, Titusville, New Jersey, United States of America
| | | | - Christophe Moreno
- Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
- * E-mail:
| | | |
Collapse
|
|
29
|
Perumpail RB, Wong RJ, Scandling JD, Ha LD, Todo T, Bonham CA, Saab S, Younossi ZM, Ahmed A. HCV infection is associated with lower survival in simultaneous liver kidney transplant recipients in the United States. Clin Transplant 2015. [PMID: 26205329 DOI: 10.1111/ctr.12598] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The frequency of simultaneous liver kidney transplantation (SLKT) has been increasing over the past decade. Hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. Given the rising prevalence of HCV-related SLKT, it is important to understand the impact of HCV in this patient population. METHODS We conducted a retrospective cohort study using data from the United Network for Organ Sharing registry to assess adult patients undergoing SLKT in the United States from 2003 to 2012. Patient survival following SLKT was assessed using Kaplan-Meier methods and multivariate Cox proportional hazards models. RESULTS Patients infected with non-HCV have significantly lower survival following SLKT compared to non-HCV patients at three (three-yr survival: 71.0% vs. 78.9%, p < 0.01) and five yr (five-yr survival: 61.4% vs. 72.5%, p < 0.01). The results of multivariate regression analyses demonstrated that patients infected with HCV had significantly lower survival following SLKT than patients with non-HCV disease (HR 1.41, 95% CI, 1.19-1.67, p < 0.001). In addition, lower post-SLKT survival was noted among patients with diabetes (HR 1.34, 95% CI, 1.13-1.58, p < 0.001) and hepatocellular carcinoma (HR 1.60, 95% CI, 1.17-2.18, p < 0.01). CONCLUSIONS Hepatitis C infection is associated with lower patient survival following SLKT.
Collapse
Affiliation(s)
- Ryan B Perumpail
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital Campus, Oakland, CA, USA
| | - John D Scandling
- Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA
| | - Le Dung Ha
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Tsuyoshi Todo
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Clark A Bonham
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Sammy Saab
- Departments of Medicine and Surgery, UCLA, Los Angeles, CA, USA
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| |
Collapse
|
|
30
|
Zhang S, Bastian ND, Griffin PM. Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US. BMC Gastroenterol 2015; 15:98. [PMID: 26239358 PMCID: PMC4524433 DOI: 10.1186/s12876-015-0320-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 07/16/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments. METHODS A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers. RESULTS Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis. CONCLUSIONS For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30% reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions.
Collapse
Affiliation(s)
- Sai Zhang
- Department of Industrial Engineering, Penn State University, University Park, PA, 16803, USA.
| | - Nathaniel D Bastian
- Department of Industrial Engineering, Penn State University, University Park, PA, 16803, USA.
| | - Paul M Griffin
- School of Industrial and Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA, 30332-0205, USA.
| |
Collapse
|
|
31
|
Steinebrunner N, Sprinzl MF, Zimmermann T, Wörns MA, Zimmerer T, Galle PR, Stremmel W, Eisenbach C, Stein K, Antoni C, Schattenberg JM, Pathil A. Early virological response may predict treatment response in sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center "real-life" cohort. BMC Gastroenterol 2015; 15:97. [PMID: 26239732 PMCID: PMC4523924 DOI: 10.1186/s12876-015-0328-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 07/28/2015] [Indexed: 12/16/2022] Open
Abstract
Background The combination of sofosbuvir (SOF), ribavirin (RBV) and peg-interferon-alfa-2a (peg-IFN-alfa-2a) as well as the combination of SOF and RBV for the treatment of patients infected with hepatitis c virus (HCV) has improved rates of sustained virological response (SVR) considerably in recent trials. However, there is only limited data concerning the efficacy and safety in a “real-life” cohort. Methods We analyzed a cohort of 119 patients with chronic HCV infection treated at four investigational sites in Germany. All patients received either a combination treatment of SOF, RBV and peg-IFN-alfa-2a or SOF and RBV. Results The rates of SVR at 12 weeks after end of treatment (SVR 12) were as follows: Among 76 patients with genotype 1 infection the SVR 12 rate was 74 % (n = 56), among 14 patients with genotype 2 infection the SVR 12 rate was 79 % (n = 11), among 24 patients with genotype 3 infection the SVR 12 rate was 92 % (n = 22) and among 5 patients with genotype 4 infection the SVR 12 rate was 80 % (n = 4). Of all 26 patients with a relapse in our cohort, 69 % (n = 18) of these patients presented with liver cirrhosis and 58 % (n = 15) were treatment experienced. Notably, the level of HCV-RNA after 4 weeks of treatment was a significant predictor of treatment response in genotype 1 patients. Patients with HCV-RNA levels ≥ 12 IU ml-1 after 4 weeks of treatment achieved SVR 12 only in 30 % (n = 17/56, p < 0.0001) of cases and treatment response was even lower with SVR 12 of 25 % (n = 5/20, p = 0.0016) in the subgroup of patients with cirrhosis. Conclusion We observed a high rate of SVR 12 with SOF-based treatment regimes, however probably due to the high number of patients with liver cirrhosis and prior treatment experience, treatment response rates were lower than in previously published trials. In genotype 1 patients the analysis of early virological response may predict treatment response in SOF-based combination therapies.
Collapse
Affiliation(s)
- Niels Steinebrunner
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
| | - Martin F Sprinzl
- Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany.
| | - Tim Zimmermann
- Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany.
| | - Marcus A Wörns
- Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany.
| | - Thomas Zimmerer
- Department of Internal Medicine II, University Hospital Mannheim, Mannheim, Germany.
| | - Peter R Galle
- Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany.
| | - Wolfgang Stremmel
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
| | - Christoph Eisenbach
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
| | - Kerstin Stein
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital of Magdeburg, Magdeburg, Germany.
| | - Christoph Antoni
- Department of Internal Medicine II, University Hospital Mannheim, Mannheim, Germany.
| | - Jörn M Schattenberg
- Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany.
| | - Anita Pathil
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
| |
Collapse
|
|
32
|
Increasing Volume but Decreasing Mortality of Hospitalized Hepatitis C Patients in the United States, 2005 to 2011. J Clin Gastroenterol 2015; 49:620-7. [PMID: 25203363 DOI: 10.1097/mcg.0000000000000216] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Patients with hepatitis C virus infection often require hospitalization for progressive liver disease and complications, incurring high cost and risk of death. GOALS The aim of our study was to investigate recent trends in the economic burden and outcomes of patients hospitalized for hepatitis C in the United States. STUDY Patients with hepatitis C-associated hospitalization were identified from the Nationwide Inpatient Sample 2005 to 2011. We analyzed the in-hospital mortality, hospital service utilization, demographic, and clinical features of patients. A prognostic model to predict in-hospital survival and death with independent risk factors for mortality was developed. RESULTS A total of 607,279 cases of hepatitis C-associated hospitalization were identified. Over 7 years, the annual hospitalized volume increased by 28.8%. In-hospital mortality declined from 8.2% to 6.4%. Median length of stay (4 d) was unchanged but the inflation-adjusted hospital charges increased by 33.3%. Acute respiratory failure was the greatest independent risk factor for mortality [odds ratio (OR)=7.3; 95% confidence interval (CI), 7.0-7.5], followed by septicemia (OR=4.1; 95% CI, 4.0-4.3), renal failure (OR=3.4; 95% CI, 3.3-3.5), and acute liver failure (OR=2.9; 95% CI, 2.7-3.0). On the basis of the major risk factors for mortality, a risk-adjusted model was developed that could predict the in-hospital outcome of hepatitis C patients with an accurate rate of 89.2%. CONCLUSIONS Despite decreasing in-hospital mortality, both hospital volume and charges related to hepatitis C increased from 2005 to 2011. Use of a risk-adjusted model could help predict mortality and improve outcomes of hepatitis C inpatients.
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
Chou ML, Burnouf T, Chang SP, Hung TC, Lin CC, Richardson CD, Lin LT. TnBP⁄Triton X-45 treatment of plasma for transfusion efficiently inactivates hepatitis C virus. PLoS One 2015; 10:e0117800. [PMID: 25658612 PMCID: PMC4320006 DOI: 10.1371/journal.pone.0117800] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 01/01/2015] [Indexed: 12/17/2022] Open
Abstract
Risk of transmission of hepatitis C virus (HCV) by clinical plasma remains high in countries with a high prevalence of hepatitis C, justifying the implementation of viral inactivation treatments. In this study, we assessed the extent of inactivation of HCV during minipool solvent/detergent (SD; 1% TnBP / 1% Triton X-45) treatment of human plasma. Luciferase-tagged infectious cell culture-derived HCV (HCVcc) particles were used to spike human plasma prior to treatment by SD at 31 ± 0.5°C for 30 min. Samples were taken before and after SD treatment and filtered on a Sep-Pak Plus C18 cartridge to remove the SD agents. Risk of cytotoxicity was assessed by XTT cell viability assay. Viral infectivity was analyzed based on the luciferase signals, 50% tissue culture infectious dose viral titer, and immunofluorescence staining for HCV NS5A protein. Total protein, cholesterol, and triglyceride contents were determined before and after SD treatment and C18 cartridge filtration. Binding analysis, using patient-derived HCV clinical isolates, was also examined to validate the efficacy of the inactivation by SD. SD treatment effectively inactivated HCVcc within 30 min, as demonstrated by the baseline level of reporter signals, total loss of viral infectivity, and absence of viral protein NS5A. SD specifically targeted HCV particles to render them inactive, with essentially no effect on plasma protein content and hemostatic function. More importantly, the efficacy of the SD inactivation method was confirmed against various genotypes of patient-derived HCV clinical isolates and against HCVcc infection of primary human hepatocytes. Therefore, treatment by 1% TnBP / 1% Triton X-45 at 31°C is highly efficient to inactivate HCV in plasma for transfusion, showing its capacity to enhance the safety of therapeutic plasma products. We propose that the methodology used here to study HCV infectivity can be valuable in the validation of viral inactivation and removal processes of human plasma-derived products.
Collapse
Affiliation(s)
- Ming-Li Chou
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Thierry Burnouf
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shun-Pang Chang
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ting-Chun Hung
- Department of Clinical Pathology, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chun-Ching Lin
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Christopher D. Richardson
- Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada
| | - Liang-Tzung Lin
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- * E-mail:
| |
Collapse
|
|
35
|
El-Kamary SS, Hashem M, Saleh DA, Ehab M, Sharaf SA, El-Mougy F, Abdelsalam L, Jhaveri R, Aboulnasr A, El-Ghazaly H. Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt. J Infect 2015; 70:512-9. [PMID: 25623176 DOI: 10.1016/j.jinf.2015.01.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 01/11/2015] [Accepted: 01/14/2015] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the world's highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening. METHODS Pregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed. RESULTS All 1250 pregnant women approached agreed to participate (100%) with a mean age of 27.4 ± 5.5 years (range:16-45). HCV antibodies and RNA were positive in 52 (4.2%) and 30 (2.4%) women respectively. After adjustment, only age (OR:1.08, 95%CI:1.002-1.16, p < 0.01), history of prior pregnancies (OR:1.20, 95%CI:1.01-1.43, p < 0.04), and working in the healthcare sector (OR:8.68, 95%CI:1.72-43.62, p < 0.01), remained significantly associated with chronic HCV infection. CONCLUSIONS Universal antenatal HCV screening was widely accepted (100%) and traditional risk-based screening alone would have missed 3 (10%) chronically infected women, thereby supporting universal screening of pregnant women whenever possible. Otherwise, risk-based screening should be modified to include history of prior pregnancy and healthcare employment.
Collapse
Affiliation(s)
- Samer S El-Kamary
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
| | - Mohamed Hashem
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Doa'a A Saleh
- Department of Public Health and Community Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Ehab
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sahar A Sharaf
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Fatma El-Mougy
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Lobna Abdelsalam
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ravi Jhaveri
- Division of Infectious Diseases, Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, NC, USA
| | - Ahmed Aboulnasr
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham El-Ghazaly
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| |
Collapse
|
|
36
|
Gaps in the hepatitis C continuum of care among sex workers in Vancouver, British Columbia: Implications for voluntary hepatitis C virus testing, treatment and care. Can J Gastroenterol Hepatol 2015; 29:411-6. [PMID: 26492129 PMCID: PMC4699605 DOI: 10.1155/2015/381870] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) eradication leads to reduced morbidity, mortality and transmission. Despite the disproportionate burden of HCV among sex workers, data regarding the HCV care continuum in this population remain negligible. METHODS Using baseline data from an ongoing cohort of women sex workers in Vancouver (An Evaluation of Sex Workers' Health Access, January 2010 to August 2013), the authors assessed HCV prevalence and engagement in the HCV care continuum within the past year. Multivariable logistic regression analyses were used to evaluate associations with recent (ie, in the past year) HCV testing. RESULTS Among 705 sex workers, 302 (42.8%) were HCV seropositive. Of these, 22.5% were previously unaware of their HCV status, 41.7% had accessed HCV-related care, 13.9% were offered treatment and only 1.0% received treatment. Among 552 HCV-seronegative sex workers, only one-half (52.9%) reported a recent HCV test. In multivariable analysis, women who self-identified as a sexual⁄gender minority (adjusted OR [aOR] 1.89 [95% CI 1.11 to 3.24]), resided in the inner city drug use epicentre (aOR 3.19 [95%CI 1.78 to 5.73]) and used injection (aOR 2.00 [95% CI 1.19 to 3.34]) or noninjection drugs (aOR 1.95 [95% CI 1.00 to 3.78]) had increased odds of undergoing a recent HCV test, while immigrant participants (aOR 0.24 [95% CI 0.12 to 0.48]) had decreased odds. CONCLUSIONS Despite a high burden of HCV among sex workers, large gaps in the HCV care continuum remain. Particularly concerning are the low access to HCV testing, with one-fifth of women living with HCV being previously unaware of their status, and the exceptionally low prevalence of HCV treatment. There is a critical need for further research to better understand and address barriers to engage in the HCV continuum for sex workers.
Collapse
|
|
37
|
Fu J, Wei J. Molecular dynamics study on drug resistance mechanism of HCV NS3/4A protease inhibitor: BI201335. MOLECULAR SIMULATION 2014. [DOI: 10.1080/08927022.2014.917298] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
38
|
Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [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: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
Collapse
Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
| | | |
Collapse
|
|
39
|
Norton BL, Voils CI, Timberlake SH, Hecker EJ, Goswami ND, Huffman KM, Landgraf A, Naggie S, Stout JE. Community-based HCV screening: knowledge and attitudes in a high risk urban population. BMC Infect Dis 2014; 14:74. [PMID: 24512462 PMCID: PMC3945609 DOI: 10.1186/1471-2334-14-74] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 01/28/2014] [Indexed: 12/11/2022] Open
Abstract
Background In an attempt to curtail the rising morbidity and mortality from undiagnosed HCV (hepatitis C virus) in the United States, screening guidelines have been expanded to high-risk individuals and persons born 1945–1965. Community-based screening may be one strategy in which to reach such persons; however, the acceptance of HCV testing, when many high-risk individuals may not have access to HCV specific medications, remains unknown. Methods We set out to assess attitudes about HCV screening and knowledge about HCV disease at several community-based testing sites that serve high-risk populations. This assessment was paired with a brief HCV educational intervention, followed by post-education evaluation. Results Participants (n = 140) were surveyed at five sites; two homeless shelters, two drug rehabilitation centers, and a women’s "drop-in" center. Personal acceptance of HCV testing was almost unanimous, and 90% of participants reported that they would still want to be tested even if they were unable to receive HCV treatment. Baseline hepatitis C knowledge was poor; however, the brief educational intervention significantly improved knowledge and increased acceptability of testing when medical access issues were explicitly stated. Conclusions Despite inconsistencies in access to care and treatment, high-risk communities want to know their HCV status. Though baseline HCV knowledge was poor in this population, a brief on-site educational intervention improved both knowledge and acceptability of HCV testing and care. These data support the establishment of programs that utilize community-based screening, and also provide initial evidence for acceptance of the implementation of the recently expanded screening guidelines among marginalized communities.
Collapse
Affiliation(s)
- Brianna L Norton
- Division of Infectious Diseases and International Health, Duke University Medical Center, Box 102358, Durham, NC 27710, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Perumalswami PV, DeWolfe Miller F, Orabee H, Regab A, Adams M, Kapelusznik L, Aljibawi F, Pagano W, Tong V, Dieterich DT. Hepatitis C screening beyond CDC guidelines in an Egyptian immigrant community. Liver Int 2014; 34:253-8. [PMID: 23890188 DOI: 10.1111/liv.12259] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Accepted: 06/17/2013] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Many Egyptian-born persons in the U.S. are at high risk of chronic hepatitis C virus (HCV) infection, yet are not aware of their infection and lack healthcare coverage or linkage to care. In this study, we target Egyptian-born persons living in the New York City area for screening and link to care. METHODS A unique partnership, the Hepatitis Outreach Network (HONE), combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. RESULTS Through four community-based screening events, 192 Egyptian-born persons were screened for HCV. Thirty (15.6%) persons were HCV positive. HCV antibody prevalence in those, whose national origin was Egypt, increased strongly with age and was associated with increasing number of years resident in Egypt and rural residents. Of the 30 Egyptian persons with HCV infection, 18 (60%) received a medical evaluation (2 with local providers and 16 at Mount Sinai). Of the HCV-infected persons evaluated, treatment was recommended in four and begun in three (75%). CONCLUSION Egyptian-born persons living in the New York City area have a high burden of HCV disease. HONE has successfully established targeted HCV screening in Egyptian-born persons through use of several unique elements that effectively link them to care.
Collapse
Affiliation(s)
- Ponni V Perumalswami
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Rossaro L, Torruellas C, Dhaliwal S, Botros J, Clark G, Li CS, Minoletti MM. Clinical outcomes of hepatitis C treated with pegylated interferon and ribavirin via telemedicine consultation in Northern California. Dig Dis Sci 2013; 58:3620-5. [PMID: 24154637 PMCID: PMC4591052 DOI: 10.1007/s10620-013-2810-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2012] [Accepted: 07/15/2013] [Indexed: 01/22/2023]
Abstract
BACKGROUND Patients in rural communities are less likely to receive treatment for their hepatitis C (HCV) infection. Telemedicine (TM) consultation can close the gap of access to specialists in remote and under-served areas. AIM To determine treatment response and side-effect profiles among HCV patients treated with pegylated interferon and ribavirin via TM consultation in different rural locations in Northern California compared with patients treated in traditional hepatology office visits. METHODS We performed a retrospective analysis of 80 HCV patients treated at different TM sites (TM, n=40) and at the University of California Davis Hepatology Clinic (HC, n=40) between 2006 and 2010, comparing baseline characteristics and clinical outcomes. RESULTS At baseline, response to therapy was similar for patients in both groups. Sustained virological response (SVR) was similar in both groups (TM: 55 vs. HC: 43%; p=0.36), and a higher proportion of patients treated via telemedicine completed treatment (TM: 78 vs. HC: 53%; p=0.03). TM patients had many more visits per week of therapy (TM: 0.61 vs. HC: 0.07; p<0.001). Neutropenia, GI side effects, fatigue, depression, weight loss, insomnia, and skin rash were similar in both groups. For HC patients incidence of anemia was significantly higher (53%) than for the TM group (25%; p=0.02). CONCLUSIONS The two groups had equivalent SVR. For the TM group therapy completion was superior and incidence of anemia was lower. This initial study suggests that, as a group, patients with HCV, can be safely and effectively treated via telemedicine.
Collapse
|
|
42
|
Park C, Jiang S, Lawson KA. Efficacy and safety of telaprevir and boceprevir in patients with hepatitis C genotype 1: a meta-analysis. J Clin Pharm Ther 2013; 39:14-24. [DOI: 10.1111/jcpt.12106] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 09/30/2013] [Indexed: 12/18/2022]
Affiliation(s)
- C. Park
- College of Pharmacy; The University of Texas at Austin; Austin TX USA
| | - S. Jiang
- College of Pharmacy; The University of Texas at Austin; Austin TX USA
| | - K. A. Lawson
- College of Pharmacy; The University of Texas at Austin; Austin TX USA
| |
Collapse
|
|
43
|
Grasso A, Malfatti F, Testa R. Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C? World J Gastroenterol 2013; 19:6947-6956. [PMID: 24222938 PMCID: PMC3819530 DOI: 10.3748/wjg.v19.i41.6947] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 07/27/2013] [Accepted: 08/17/2013] [Indexed: 02/06/2023] Open
Abstract
The high rate of sustained viral response (SVR) to boceprevir or telaprevir-based triple therapy in hepatitis C (HCV)-related, non-cirrhotic naïve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used, unlike what is observed with the peginterferon and ribavirin schedules. This concept is strongly expressed by some opinion leaders on the basis of the data derived from sub-analyses of registrative trials as well as from a post-hoc analysis of the phase II C208 clinical trial. The perception of unrestrainable therapeutic success with the use of newer, more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir, an HCV NS5B polymerase inhibitor, as well as by the data from the phase II and III studies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors. However, a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the “world of trials”. Furthermore, many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment. Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients, an issue that will hopefully be investigated in further studies. This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.
Collapse
|
|
44
|
Gordon SC, Hamzeh FM, Pockros PJ, Hoop RS, Buikema AR, Korner EJ, Terrault NA. Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther 2013; 38:784-93. [PMID: 23981040 PMCID: PMC4553220 DOI: 10.1111/apt.12454] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 06/20/2013] [Accepted: 07/27/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND The effect of anti-viral treatment on downstream costs for hepatitis C virus (HCV)-infected patients is unknown. AIM To evaluate follow-up costs in patients with chronic HCV, stratified by liver disease severity. METHODS Using a US private insurance database, mean all-cause per-patient-per-month (PPPM) US (2010) medical costs were calculated for HCV-infected persons who did and did not receive anti-HCV treatment between January 2002 and August 2010. Analysis was stratified by liver disease severity [noncirrhotic disease (NCD), compensated cirrhosis (CC) or end-stage liver disease (ESLD)] defined by ICD-9 and CPT codes. RESULTS A total of 33 309 patients were included (78% NCD, 7% CC and 15% ESLD); 4111 individuals (12%) received anti-HCV treatment during the 2-year baseline period. Mean PPPM follow-up health care costs were significantly lower among treated patients with NCD ($900 vs. $1378 in untreated patients, P < 0.001) and ESLD ($3634 vs. $5071, P < 0.001) groups but not in the CC group ($1404 vs. $1795, P < 0.071; t-test). In a multivariable model adjusted for demographic characteristics, comorbidities, index date and geographical region, incremental cost ratios for total health care costs differed significantly (P < 0.001) between treated and untreated patients in the NCD and ESLD groups but not in the CC group. From this model, mean PPPM total health care costs between treated and untreated patients were $885 and $1370 in the NCD, $1369 and $1802 in the CC, and $3547 and $5137 in the ESLD groups, respectively. CONCLUSIONS Anti-HCV therapy was associated with lower follow-up US health care costs, and these savings were independent of baseline patient comorbidities and stage of disease.
Collapse
Affiliation(s)
| | | | | | | | | | | | - N. A. Terrault
- University of California at San Francisco, San Francisco, CA, USA
| |
Collapse
|
|
45
|
Fontana RJ, Hughes EA, Bifano M, Appelman H, Dimitrova D, Hindes R, Symonds WT. Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C. Am J Transplant 2013; 13:1601-5. [PMID: 23593993 DOI: 10.1111/ajt.12209] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Revised: 01/10/2013] [Accepted: 01/31/2013] [Indexed: 01/25/2023]
Abstract
Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.
Collapse
Affiliation(s)
- R J Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Princeton, NJ, USA.
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Nguyen LH, Nguyen MH. Systematic review: Asian patients with chronic hepatitis C infection. Aliment Pharmacol Ther 2013; 37:921-36. [PMID: 23557103 DOI: 10.1111/apt.12300] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2012] [Revised: 10/16/2012] [Accepted: 03/12/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans. AIM To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC. METHODS Using a PubMed search of 'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance. RESULTS Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes. CONCLUSIONS Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ≥2%.
Collapse
Affiliation(s)
- L H Nguyen
- Stanford University School of Medicine, Stanford, CA, USA
| | | |
Collapse
|
|
47
|
Donor diabetes mellitus is an independent risk factor for graft loss in HCV positive but not HCV negative liver transplant recipients. Dig Dis Sci 2013; 58:574-8. [PMID: 22923335 PMCID: PMC3670815 DOI: 10.1007/s10620-012-2345-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Accepted: 07/28/2012] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients. METHODS We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes. RESULTS Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts. CONCLUSION Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival.
Collapse
|
|
48
|
Seidenberg A, Rosemann T, Senn O. Patients receiving opioid maintenance treatment in primary care: successful chronic hepatitis C care in a real world setting. BMC Infect Dis 2013; 13:9. [PMID: 23298178 PMCID: PMC3548742 DOI: 10.1186/1471-2334-13-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Accepted: 12/21/2012] [Indexed: 01/14/2023] Open
Abstract
Background Injection drug users (IDUs) represent a significant proportion of patients with chronic hepatitis C (CHC). The low treatment uptake among these patients results in a low treatment effectiveness and a limited public health impact. We hypothesised that a general practitioner (GP) providing an opioid maintenance treatment (OMT) for addicted patients can achieve CHC treatment and sustained virological response rates (SVR) comparable to patients without drug dependency. Methods Retrospective patient record analysis of 85 CHC patients who received OMT for more than 3 months in a single-handed general practice in Zurich from January 1, 2002 through May 31, 2008. CHC treatment was based on a combination with pegylated interferon and ribavirin. Treatment uptake and SVR (undetectable HCV RNA 6 months after end of treatment) were assessed. The association between treatment uptake and patient characteristics was investigated by multiple logistic regression. Results In 35 out of 85 CHC patients (52 males) with a median (IQR) age of 38.8 (35.0-44.4) years, antiviral therapy was started (41.2%). Median duration (IQR) of OMT in the treatment group was 55.0 (35.0-110.1) months compared to the group without therapy 24.0 (9.8-46.3) months (p<0.001). OMT duration remained a significant determinant for treatment uptake when controlled for potential confounding. SVR was achieved in 25 out of 35 patients (71%). Conclusion In addicted patients a high CHC treatment and viral eradication rate in a primary care setting in Switzerland is feasible. Opioid substitution seems a beneficial framework for CHC care in this “difficult to treat” population.
Collapse
Affiliation(s)
- André Seidenberg
- Institute of General Practice and Health Services Research, University of Zurich, Zurich, Switzerland
| | | | | |
Collapse
|
|
49
|
Abstract
Chronic hepatitis C is a growing health problem worldwide that has attracted increased attention in recent years. Treatment with peginterferon and ribavirin combination had previously been the standard of care. In 2011, a new treatment with protease inhibitors, telaprevir and boceprevir was approved, and a new standard of care was defined. Previous predictors of response have been redefined, and while IL28B, fibrosis stage and hepatitis C virus viral load testing continue to have their value, viral kinetics during treatment defining viral response have emerged as the strongest predictor for achieving sustained virologic response with the new treatment. New therapies are expected in the near future, and current treatment predictors of response may soon change.
Collapse
Affiliation(s)
- Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Argentina
- Hepatology & Liver Transplant Unit. Hospital Universitario Austral, Argentina
| |
Collapse
|
|
50
|
Ridruejo E. Increased mortality in chronic HCV infection. Ann Hepatol 2012; 11:967-968. [DOI: 10.1016/s1665-2681(19)31429-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|