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1.
Int J Drug Policy ; 128: 104433, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703622

RESUMEN

BACKGROUND: The World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time. METHODS: All persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models. RESULTS: The prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective. CONCLUSION: The prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services.

2.
Subst Abuse Treat Prev Policy ; 19(1): 21, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532435

RESUMEN

BACKGROUND: Persons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances. METHODS: Data was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI). RESULTS: At baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement. CONCLUSIONS: More than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hepatitis C Crónica , Hepatitis C , Trastornos Relacionados con Sustancias , Humanos , Niño , Estudios Prospectivos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Hígado/patología , Cirrosis Hepática/epidemiología , Factores de Riesgo , Hepatitis C Crónica/epidemiología , Hepatitis C/complicaciones , Trastornos Relacionados con Sustancias/complicaciones
5.
Int J Drug Policy ; 123: 104279, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061225

RESUMEN

BACKGROUND: Norway aims to eliminate hepatitis C virus (HCV) infection within the end of 2023. Before the introduction of direct-acting antivirals, the prevalence of chronic HCV infection among people who inject drugs (PWID) in Oslo was 40-45 %. The primary aim of the study was to assess changes in HCV prevalence among PWID in Oslo from 2018 to 2021. The secondary aim was to assess change in prevalence in selected subgroups. METHODS: Point prevalence studies were conducted in 2018 and 2021 among PWID attending low-threshold health services in downtown Oslo. Assessments included blood samples analysed for anti-HCV and HCV RNA, and a questionnaire about drug use. Information about previous HCV treatment was only collected in the 2021 cohort. We calculated HCV RNA prevalence estimates for 2018 and 2021 and used logistic regression analysis to identify factors associated with detectable HCV RNA and previous HCV treatment. RESULTS: A total of 281 and 261 participants were included in 2018 and 2021, respectively. The median age was 40.6 and 44.0 years, 73.7 % and 72.8 % were men, and 74.5 % and 78.6 % reported recent (past four weeks) injecting drug use, respectively. HCV RNA prevalence decreased significantly from 26.3 % (95 % CI 21.3-31.9) in 2018 (74 of 281) to 14.2 % (95 % CI 10.2-19.0) in 2021 (37 of 261). The odds of detectable HCV RNA were significantly lower in 2021 compared to 2018 (aOR 0.41; 95 % CI 0.26-0.67). In the 2021 cohort, detectable HCV RNA was associated with recent amphetamine injecting (aOR 7.21; 95 % CI 1.41-36.95), and mixed heroin/amphetamine injecting (aOR 7.97; 95 % CI 1.55-41.07). The odds of previous treatment were lower among women (aOR 0.52; 95 % CI 0.27-1.00). CONCLUSION: A substantial decrease in HCV RNA prevalence among PWID in Oslo between 2018 and 2021 was observed. To reach elimination, adaptive services must be further developed.


Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Masculino , Humanos , Femenino , Adulto , Hepacivirus/genética , Estudios Transversales , Antivirales/uso terapéutico , Abuso de Sustancias por Vía Intravenosa/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/complicaciones , Prevalencia , Hepatitis C/tratamiento farmacológico , ARN/uso terapéutico , Anfetaminas
6.
Clin Infect Dis ; 78(3): 582-590, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-37992203

RESUMEN

BACKGROUND: We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID). METHODS: We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment. RESULTS: A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2-77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1-45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0-46.2]; risk ratio 1.9 [95% CI: 1.4-2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8-12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5-6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8-70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6-73.9]) during control conditions. CONCLUSIONS: An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation. Clinical Trials Registration. NCT04220645.


Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , ARN , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico
7.
Infect Dis (Lond) ; 56(1): 19-31, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37795955

RESUMEN

OBJECTIVE: To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups. METHODS: A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital. RESULTS: A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7-3.7, p = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin (n = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p < 0.001). No significant difference in the length of hospital stay was found for other sources of infection (n = 151), with a median of seven versus six days (p = 0.550) in the ESBL- and non-ESBL groups, respectively. CONCLUSION: There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin.


Asunto(s)
Bacteriemia , Infecciones por Escherichia coli , Sepsis , Adulto , Humanos , Escherichia coli , Tiempo de Internación , Infecciones por Escherichia coli/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Casos y Controles , Bacteriemia/tratamiento farmacológico , beta-Lactamasas , Factores de Riesgo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Sepsis/tratamiento farmacológico
8.
Sci Rep ; 13(1): 22590, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38114718

RESUMEN

Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1ß, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03681132.


Asunto(s)
Hepatitis B Crónica , Humanos , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Citocinas/uso terapéutico , Quimiocina CXCL10 , Antivirales/uso terapéutico , Recurrencia , Privación de Tratamiento , ADN Viral , Antígenos de Superficie de la Hepatitis B , Resultado del Tratamiento
9.
Int J Drug Policy ; 116: 104044, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149914

RESUMEN

BACKGROUND: Improving HCV treatment uptake among people who inject drugs (PWID) is crucial to achieving the WHO elimination targets. The aims were to evaluate HCV treatment uptake and HCV RNA prevalence in a large cohort of PWID in Norway. METHODS: Registry-based observational study where all users of the City of Oslo's low-threshold social and health services for PWID between 2010-2016 (n = 5330) were linked to HCV notifications (1990-2019) and dispensions of HCV treatment, opioid agonist treatment (OAT) and benzodiazepines (2004-2019). Cases were weighted to account for spontaneous HCV clearance. Treatment rates were calculated using person-time of observation, and factors associated with treatment uptake were analysed using logistic regression. HCV RNA prevalence was estimated among individuals alive by the end of 2019. RESULTS: Among 2436 participants with chronic HCV infection (mean age 46.8 years, 30.7% female, 73.3% OAT), 1118 (45.9%) had received HCV treatment between 2010-2019 (88.7% DAA-based). Treatment rates increased from 1.4/100 PY (95% CI 1.1-1.8) in the pre-DAA period (2010-2013) to 3.5/100 PY (95% CI 3.0-4.0) in the early DAA period (2014-2016; fibrosis restrictions) and 18.4/100 PY (95% CI 17.2-19.7) in the late DAA period (2017-2019; no restrictions). Treatment rates for 2018 and 2019 exceeded a previously modelled elimination threshold of 50/1000 PWID. Treatment uptake was less likely among women (aOR 0.74; 95% CI 0.62-0.89) and those aged 40-49 years (aOR 0.74; 95% CI 0.56-0.97), and more likely among participants with current OAT (aOR 1.21; 95% CI 1.01-1.45). The estimated HCV RNA prevalence by the end of 2019 was 23.6% (95% CI 22.3-24.9). CONCLUSION: Although HCV treatment uptake among PWID increased, strategies to improve treatment among women and individuals not engaged in OAT should be addressed.


Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Femenino , Persona de Mediana Edad , Masculino , Antivirales , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C/complicaciones , ARN/uso terapéutico , Noruega/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/complicaciones , Hepacivirus
10.
Crit Care ; 27(1): 9, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627655

RESUMEN

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).


Asunto(s)
COVID-19 , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , SARS-CoV-2 , ARN Viral , Tratamiento Farmacológico de COVID-19 , Método Doble Ciego
11.
Value Health ; 26(6): 883-892, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36646278

RESUMEN

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.


Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Hepacivirus , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Calidad de Vida , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología
14.
J Addict Dis ; 41(3): 213-224, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35920743

RESUMEN

BACKGROUND: In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). OBJECTIVE: To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection. METHODS: COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. RESULTS: Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37-10.63), vitality (MTD, 6.81; 95% CI, 1.88-11.75), and mental health (MTD, 5.17; 95% CI, 0.52-9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29-5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. CONCLUSION: HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02251990.


Asunto(s)
Antivirales , Hepatitis C Crónica , Adulto , Humanos , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepacivirus , Analgésicos Opioides/uso terapéutico , Amidas/uso terapéutico , Calidad de Vida
15.
J Addict Dis ; 41(1): 53-63, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35356868

RESUMEN

BACKGROUND: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. OBJECTIVES: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. METHODS: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. RESULTS: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810). CONCLUSIONS: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.


Asunto(s)
Metadona , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Metadona/sangre , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/genética
16.
Scand J Gastroenterol ; 58(3): 264-268, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36063075

RESUMEN

BACKGROUND AND AIMS: The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. METHOD: This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). RESULTS: We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22-73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. CONCLUSION: We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Ribavirina/uso terapéutico , Antivirales/uso terapéutico , Hepacivirus/genética , Estudios Retrospectivos , Quimioterapia Combinada , Hepatitis C/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C Crónica/complicaciones , Genotipo
17.
Ann Intern Med ; 175(9): 1221-1229, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35939812

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs. OBJECTIVE: To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT). DESIGN: A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688). SETTING: 55 clinical trial sites in 13 countries. PATIENTS: Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT. INTERVENTION: No treatments were administered. MEASUREMENTS: Serum samples were assessed for HCV reinfection. Urine drug screening was performed. RESULTS: Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up. LIMITATIONS: Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown. CONCLUSION: Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle-syringe sharing. PRIMARY FUNDING SOURCE: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.


Asunto(s)
Hepatitis C Crónica , Reinfección , Asunción de Riesgos , Adolescente , Adulto , Analgésicos Opioides/uso terapéutico , Estudios de Cohortes , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Reinfección/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología
18.
Liver Int ; 42(6): 1268-1277, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35362660

RESUMEN

BACKGROUND & AIMS: New models of HCV care are needed to reach people who inject drugs (PWID). The primary aim was to evaluate HCV treatment uptake among HCV RNA positive individuals identified by point-of-care (POC) testing and liver disease assessment in a peer-driven decentralized mobile clinic. METHODS: This prospective study included consecutive patients assessed in a mobile clinic visiting 32 small towns in Southern Norway from November 2019 to November 2020. The clinic was staffed by a bus driver and a social educator offering POC HCV RNA testing (GeneXpert®), liver disease staging (FibroScan® 402) and peer support. Viremic individuals were offered prompt pan-genotypic treatment prescribed by local hospital-employed specialists following a brief telephone assessment. RESULTS: Among 296 tested individuals, 102 (34%) were HCV RNA positive (median age 51 years, 77% male, 24% advanced liver fibrosis/cirrhosis). All participants had a history of injecting drug use, 71% reported past 3 months injecting, and 37% received opioid agonist treatment. Treatment uptake within 6 months following enrolment was achieved in 88%. Treatment uptake was negatively associated with recent injecting (aHR 0.60; 95% CI 0.36-0.98), harmful alcohol consumption (aHR 0.44; 95% CI 0.20-0.99), and advanced liver fibrosis/cirrhosis (aHR 0.44; 95% CI 0.25-0.80). HCV RNA prevalence increased with age (OR 1.81 per 10-year increase; 95% 1.41-2.32), ranging from 3% among those <30 years to 55% among those ≥60 years. CONCLUSIONS: A peer-driven mobile HCV clinic is an effective and feasible model of care that should be considered for broader implementation to reach PWID outside the urban centres.


Asunto(s)
Consumidores de Drogas , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Antivirales/uso terapéutico , Ciudades , Femenino , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Unidades Móviles de Salud , Estudios Prospectivos , ARN , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología
20.
Harm Reduct J ; 18(1): 102, 2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34641896

RESUMEN

BACKGROUND: There is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium. METHODS: This observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test. RESULTS: Eighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3-56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4-2.0). CONCLUSION: Reinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe. Trial registration clinicaltrials.gov NCT04251572, Registered 5 Feb 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04251572 .


Asunto(s)
Consumidores de Drogas , Hepatitis C Crónica , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Adulto , Antivirales/uso terapéutico , Bélgica/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Recurrencia , Reinfección , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Abuso de Sustancias por Vía Intravenosa/epidemiología
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