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1.
J Viral Hepat ; 2024 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-39425534

RESUMEN

International guidelines suggest cessation of nucleos(t)ide analogues (NA) independent of HBsAg loss in HBeAg-negative patients after 2-3 years of viral suppression. Detectable HBV-RNA levels at the time of NA cessation were linked to a better prediction of relapse after NA withdrawal in small cohorts of HBeAg-negative patients. This study proves the impact of HBV-RNA levels in the prediction of relapse in a large cohort of HBeAg-negative patients, mainly infected with genotype B or C. Serum levels of HBV-RNA, HBsAg, anti-HBc and HBcrAg were determined before NA withdrawal in 154 HBeAg-negative patients, participating either in a therapeutic vaccination trial (NCT02249988) or in an observational register trial (NCT03643172). Importantly, vaccination showed no impact on relapse. Endpoints of the study were virological relapse (HBV-DNA > 2000 IU/mL) or biochemical relapse (attendant ALT levels ≥ 2 × ULN) 24 weeks after NA cessation. Virological relapse occurred in 54.5% of patients (N = 84/154), including eight patients (10%) developing an ALT flare. Baseline HBV-RNA level did not differ significantly between relapsers and off-treatment responders (p = 0.92). No significant difference occurred in proportions of detectable HBV-RNA levels between off-treatment responders (N = 27/70; 38.6%) and relapsers (N = 31/84; 36.9%) (p = 0.99). Combining predefined HBsAg cut-offs (100 IU/mL, p = 0.0013), anti-HBc cut-offs (325 IU/mL, p = 0.0117) or HBcrAg cut-offs (2 log U/mL, p = 0.66) with undetectable HBV-RNA (HBsAg, p = 0.0057; anti-HBc, p = 0.085; HBcrAg, p = 0.60) did not improve relapse prediction. The value of HBV-RNA levels at timepoint of NA cessation for the prediction of relapse is limited in HBeAg-negative patients. Trial Registration: ABX 203-002: NCT02249988; Terminator 2: NCT03643172.

2.
Eur J Clin Pharmacol ; 79(2): 207-217, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36478283

RESUMEN

PURPOSE: To determine the nature and frequency of duplicate prescriptions (DPs) in the emergency department (ED) by utilization of a novel categorization of DPs which differentiates between appropriate DPs (ADPs) and potentially inappropriate DPs (PIDPs). METHODS: In this retrospective cohort study, adult patients who presented to the ED for internal medicine of a large university hospital in northern Germany in 2018 and 2019 were screened for the presence of DPs. Descriptive statistical methods were used to characterize the nature and frequency of PIDPs compared to the frequency of ADPs. RESULTS: A total of 4208 patients were enrolled into the study. The median age of the study population was 63 years (interquartile range (IQR) 48-77), 53.9% were female. The patients took a median of 5 drugs (IQR 3-9). 10.9% of the study population were affected by at least one PIDP (at least one grade-1 PIDP: 6.1%; at least one grade-2 PIDP: 4.5%; at least one grade-3 PIDP: 1.1%). Non-opioid analgesics accounted for the majority of grade-1 PIDPs, while inhalatives were most frequently responsible for grade-2 and grade-3 PIDPs. Nearly half of the study population (48.6%) displayed at least one ADP. CONCLUSION: PIDPs pose a frequent pharmacological challenge in the ED. The medication review should comprise a systematic screening for PIDPs with a particular focus on non-opioid analgesics and inhalatives. ADPs were detected more frequently than PIDPs, questioning the predominant notion in the medical literature that DPs are exclusively deleterious.


Asunto(s)
Analgésicos no Narcóticos , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Analgésicos no Narcóticos/uso terapéutico , Prescripción Inadecuada , Prescripciones de Medicamentos , Servicio de Urgencia en Hospital , Analgésicos Opioides/uso terapéutico , Pautas de la Práctica en Medicina
3.
J Hepatol ; 76(5): 1042-1050, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35092743

RESUMEN

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. METHODS: We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. RESULTS: We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p <0.001), and in patients with lower HBsAg (aHR 0.243, p <0.001) and HBV core-related antigen (HBcrAg) (aHR 0.718, p = 0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/ml) and HBcrAg (<2log vs. ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490-4.174, p = 0.001). CONCLUSIONS: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal. LAY SUMMARY: A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) - so-called functional cure - after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss.


Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , ADN Viral , Genotipo , Antígenos del Núcleo de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Probabilidad
4.
Clin Gastroenterol Hepatol ; 20(4): e784-e793, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33309804

RESUMEN

BACKGROUND & AIMS: Predictors of successful nucleo(s)tide analogue (NA) therapy withdrawal remain elusive. We studied the relationship between end-of-treatment levels of hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) and outcome after therapy cessation. METHODS: Patients who discontinued NA therapy in centers in Asia and Europe were enrolled. HBcrAg and HBsAg were measured at treatment cessation, and associations with off-treatment outcomes were explored. The SCALE-B (Surface antigen, Core-related antigen, Age, ALT, and tenofovir for HBV) score was calculated as previously reported. End points included sustained virologic response (VR; hepatitis B virus DNA level <2000 IU/mL), HBsAg loss, and alanine aminotransferase (ALT) flares (>3× upper limit of normal). Re-treated patients were considered nonresponders. RESULTS: We analyzed 572 patients, 457 (80%) were Asian and 95 (17%) were hepatitis B e antigen positive at the start of NA therapy. The median treatment duration was 295 weeks. VR was observed in 267 (47%), HBsAg loss was observed in 24 (4.2%), and ALT flare was observed in 92 (16%). VR (67% vs 42%) and HBsAg loss (15% vs 1.5%) was observed more frequently in non-Asian patients when compared to Asian patients (P < .001). Lower HBcrAg levels were associated with higher rates of VR (odds ratio [OR], 0.701; P < .001) and HBsAg loss (OR, 0.476; P < .001), and lower rates of ALT flares (OR, 1.288; P = .005). Similar results were observed with HBsAg (VR: OR, 0.812; P = .011; HBsAg loss: OR, 0.380; P < .001; and ALT flare: OR, 1.833; P < .001). Lower SCALE-B scores were associated with higher rates of VR, HBsAg loss, and lower rates of ALT flares in both Asian and non-Asian patients (P < .001). CONCLUSIONS: In this multicenter study, off-treatment outcomes after NA cessation varied with ethnicity. Lower levels of HBcrAg and HBsAg were associated with favorable outcomes. A risk score comprising both factors can be used for risk stratification.


Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , ADN Viral , Antígenos del Núcleo de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos
5.
Liver Int ; 42(12): 2674-2682, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36152268

RESUMEN

BACKGROUND AND AIMS: Low anti-HBc serum levels at the time of therapy cessation were linked to a higher relapse risk in predominantly HBeAg-positive cohorts. We investigated the association of anti-HBc levels with relapse in HBeAg-negative patients. METHODS: Serum levels of anti-HBc, HBsAg and HBcrAg were determined in 136 HBeAg-negative patients, participating in a vaccination trial (ABX-203, NCT02249988), before treatment cessation or vaccination. Importantly, vaccination showed no impact on relapse. The correlation between the biomarkers and their predictive value for relapse (HBV DNA >2000 IU/ml ± ALT >2xULN) was investigated. RESULTS: After therapy cessation 50% (N = 68) of patients relapsed. Median anti-HBc prior to treatment stop was significantly higher among relapsers compared to off-treatment responders (520 IU/ml vs. 330 IU/mL, p = .0098). The optimal anti-HBc cut-off to predict relapse was 325 IU/ml according to the Youden-Index. About 35% of patients with anti-HBc level < 325 IU/ml versus 60% of those with values ≥325 IU/mL relapsed (p = .0103; sensitivity 50%, specificity 75%). Combining the optimal cut-offs of HBsAg (>3008 IU/mL) or HBcrAg (≥1790 U/ml) with anti-HBc increased the proportion of patients with relapse to 80% (p < .0001) and 74% (p = .0006), respectively. CONCLUSION: In contrast to predominantly HBeAg-positive cohorts, in our cohort of HBeAg-negative patients lower anti-HBc levels are associated with a significantly lower relapse risk after nucleos(t)ide analogue cessation. The vast majority of included patients were either genotype B or C and the applicability to other genotypes has to be further evaluated. However, anti-HBc level as an indicator of the host response might be prospectively further explored for prediction models.


Asunto(s)
Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Humanos , Antivirales/uso terapéutico , Resultado del Tratamiento , Anticuerpos contra la Hepatitis B , Recurrencia , Virus de la Hepatitis B/genética , ADN Viral
6.
BMC Gastroenterol ; 21(1): 296, 2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-34284732

RESUMEN

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.


Asunto(s)
Antibacterianos , Infecciones Bacterianas , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Farmacorresistencia Bacteriana , Alemania/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico
7.
Z Gastroenterol ; 59(9): 954-960, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34507374

RESUMEN

BACKGROUND: The COVID-19 pandemic has caused a significant impact on the medical care of many diseases and has led to reduced presentations to the emergency department. Reduced presentations may be due to overwhelmed capacities of hospitals or collateral damage from fear of infection, lockdown regulations, or other reasons. The effect on patients with liver cirrhosis is not established. OBJECTIVE: We aim to assess the impact on the care of patients with liver cirrhosis in a tertiary center in Northern Germany. METHODS: All patients presenting to the emergency department with a diagnosis of cirrhosis between March 1 and May 31 from 2015-2020 were included. Reasons for presentation, duration of symptoms, the severity of liver disease, and 30-day mortality were assessed and compared between patients presenting during the COVID-19 pandemic and pre-COVID-19. RESULTS: Overall, 235 patients were included. Despite an overall decline in presentations to the emergency department by 11.7%, the frequency of patients presenting with liver cirrhosis has remained stable (non-significant increase by 19.5%). No significant difference could be detected for the MELD score, the CLIF-organ failure subscores, and the 30-day mortality before and during the COVID-19 pandemic. Up to 75% of patients with liver cirrhosis had symptoms >24 h before presenting to the emergency department. CONCLUSION: Despite the overall trend of reduced emergency presentations during the COVID-19 pandemic, the frequency of presentations of patients with liver cirrhosis did not decline. Morbidity and mortality were not affected in a setting of disposable healthcare resources. The late presentation to the emergency department in many cirrhotic patients may open opportunities for interventions (i.e., with early telemedicine intervention).


Asunto(s)
COVID-19 , Pandemias , Control de Enfermedades Transmisibles , Servicio de Urgencia en Hospital , Alemania/epidemiología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , SARS-CoV-2
8.
J Infect Dis ; 217(10): 1656-1666, 2018 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-29471497

RESUMEN

Background: Treatment with nucleos(t)ide analogues (NA) suppresses hepatitis B virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses, including natural killer (NK) cell responses, explaining virological events following NA treatment cessation remain elusive. Methods: In a single-center prospective trial, 15 HBeAg-negative CHB patients on long-term NA treatment underwent structured NA cessation and were studied longitudinally. The NK cell compartment was assessed using high-dimensional flow cytometry and correlated with the clinical course. Results: Unsupervised stochastic neighbor embedding analysis revealed NA-treated CHB patients to have a significantly affected NK cell compartment compared to controls. Cessation of NA treatment resulted in minor phenotypic alterations, but it significantly augmented NK cell natural cytotoxicity responses in the CHB patients. This increased NK cell functionality correlated with alanine aminotransferase flares in the patients and was particularly enhanced in patients experiencing HBsAg seroclearance at long-term follow-up. Conclusions: Increased NK cell function is associated with active hepatitis and HBsAg seroclearance following structured NA cessation. This adds to our knowledge of the immunological events that develop following cessation of NA treatment in CHB.


Asunto(s)
Antivirales/administración & dosificación , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Hepatitis B Crónica/tratamiento farmacológico , Células Asesinas Naturales/efectos de los fármacos , Nucleósidos/análogos & derivados , Nucleósidos/administración & dosificación , Alanina Transaminasa/metabolismo , Línea Celular , Línea Celular Tumoral , ADN Viral/metabolismo , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/metabolismo , Humanos , Células K562 , Hígado/metabolismo , Hígado/virología , Estudios Prospectivos
9.
J Infect Dis ; 218(9): 1480-1484, 2018 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-29893893

RESUMEN

Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.


Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Antígenos e de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/uso terapéutico , Adulto , Anciano , ADN Viral/genética , Femenino , Guanina/uso terapéutico , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Resultado del Tratamiento , Adulto Joven
10.
J Hepatol ; 69(3): 584-593, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29758333

RESUMEN

BACKGROUND & AIMS: Treatment with nucleos(t)ide analogues (NA) leads to hepatitis B virus (HBV) DNA suppression in most patients with chronic hepatitis B (CHB), but HBV surface antigen (HBsAg) loss rates are low. Upon NA discontinuation, HBV DNA can return rapidly with ensuing alanine aminotransferase flares and induction of cytokines. Several studies reported higher HBsAg loss rates after stopping therapy, but at present it is unclear if cell-mediated immune responses are altered after treatment discontinuation. The aim of this study was to characterise T cell responses during the early phase of virological relapse, following discontinuation of NA therapy in HBeAg-negative patients. METHODS: A total of 15 HBeAg-negative patients with CHB on long-term NA treatment were included in a prospective study and subjected to structured NA discontinuation. T cell responses were studied at the end of NA therapy and 4, 8 and 12 weeks thereafter. RESULTS: The T cell phenotype of patients with CHB on long-term NA therapy was markedly different compared to healthy individuals, but was only slightly altered after discontinuation of therapy. T cells from patients with HBsAg loss expressed low levels of KLRG1 and PD-1 at all time-points and high levels of Ki-67 and CD38 at week 12 after treatment cessation. In vitro peptide stimulated HBV-specific T cell responses were increased in several patients after NA cessation. Blocking of PD-L1 further enhanced HBV-specific T cell responses, especially after discontinuation of therapy. CONCLUSION: Relapse of active HBV replication after stopping therapy may trigger an immunological environment that enhances the responsiveness of HBV-specific T cells in vitro. Together with other immune interventions, this approach might be of interest for the development of novel therapeutic options to induce HBsAg loss in CHB. LAY SUMMARY: Relapse of hepatitis B virus replication after discontinuation of nucleos(t)ide analogue therapy in certain patients with chronic hepatitis B may alter the phenotype of T cells and enhance the responsiveness of hepatitis B virus-specific T cells to in vitro peptide stimulation. Blocking PD-L1 can further augment these hepatitis B virus-specific T cell responses. Interestingly, T cells of patients that subsequently achieve hepatitis B surface antigen loss are less exhausted at all time-points after stopping treatment and display a higher proliferative capacity 12-weeks after treatment discontinuation. These findings contribute to the understanding of the immunological events that occur during discontinuation of nucleos(t)ide analogue therapy.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B , Hepatitis B Crónica , Nucleósidos/uso terapéutico , Linfocitos T , Privación de Tratamiento , Adulto , Antivirales/uso terapéutico , ADN Viral/sangre , Femenino , Alemania , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Inmunidad Celular/efectos de los fármacos , Masculino , Persona de Mediana Edad , Recurrencia , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología
11.
J Viral Hepat ; 25(11): 1226-1235, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30187603

RESUMEN

The management of chronic hepatitis B virus (HBV) infection is challenged by its varying natural course and its stealthy nature. Not all HBV-infected patients will develop complications of infection; however, it is of utmost importance to identify patients who are at risk and require antiviral treatment and/or close surveillance. Hepatic inflammation and quantification of HBV DNA have guided treatment decisions in the last decade, and these guided interventions have been shown to reduce liver-related complications and death. Data on the quantification of additional HBV markers such as hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) and hepatitis B virus RNA (HBV RNA) have accumulated in recent years. Here, we review the current evidence of how to use these markers and discuss open issues that require additional research.


Asunto(s)
Biomarcadores/sangre , Pruebas Diagnósticas de Rutina , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/diagnóstico , Antivirales/uso terapéutico , ADN Viral/sangre , Hepatitis B/sangre , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Antígenos de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Humanos , ARN Viral/sangre
12.
Liver Int ; 38(5): 834-841, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28960793

RESUMEN

BACKGROUND & AIMS: Ribavirin (RBV) is commonly used for the treatment of hepatitis C virus (HCV) infection. However, RBV is associated with a reduced quality of life (QOL). We aim to assess the impact of RBV on QOL in a real-world setting. METHODS: In a prospective study, QOL was measured by a SF-36 questionnaire in 174 patients. In all, 85 patients were treated with RBV and 89 patients without RBV. QOL was assessed at baseline, week 12 of treatment and 24 weeks after treatment. RESULTS: Patients treated with RBV were more likely to have HCV genotype 2 and 3 infection and cirrhosis (all P < .05). RBV-treated patients reported lower scores for several domains of QOL already at baseline. During HCV treatment, RBV-free treatment led to an increase in all measured dimensions of quality of life, whereas RBV treatment led to a decrease in the emotional and physical functioning. After treatment, all dimensions for QOL showed improvement across the study cohort, regardless whether RBV was part of the treatment regimen. However, 28.8%-45.2% of treated patients perceive a sustained reduction in their physical or mental capacity after treatment, not related to RBV usage or SVR, but related to older age (P = .03) and cirrhosis (P = .02). CONCLUSIONS: During treatment, RBV leads to a reduced QOL, whereas RBV-free treatment leads to an increased QOL. After treatment, QOL strongly increases in both, RBV and RBV-free treated patients. Some patients perceive a sustained reduction in QOL, which seems unrelated to treatment.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Ribavirina/uso terapéutico , Anciano , Femenino , Hepacivirus , Hepatitis C/complicaciones , Humanos , Interferón-alfa , Cirrosis Hepática/virología , Masculino , Salud Mental , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento
13.
Br J Clin Pharmacol ; 84(5): 961-971, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29345798

RESUMEN

AIMS: Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications. METHODS: This post hoc analysis pooled data from nine studies which evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of frequently used concomitant medications of interest (CMOIs) were analysed [antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs (LLDs)] and categorized as amber or green according to their DDI potential with SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant medications not recommended to be coadministered with SMV were not included. The composite primary endpoint was defined as the frequency of either discontinuation, interruption or dose modification of the CMOI during 12 weeks of SMV treatment. RESULTS: Few patients met the composite endpoint in the various subgroups. Patients on amber CMOIs tended to experience CMOI modification more often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference in the frequency of adverse events between patients taking green and those taking amber CMOIs. CONCLUSIONS: In this large pooled analysis, coadministration of the evaluated commonly prescribed medications with known or potential PK interactions with SMV was manageable and resulted in few adjustments of concomitant medications. Our method could serve as a blueprint for the evaluation of the impact of DDIs.


Asunto(s)
Ansiolíticos/efectos adversos , Anticolesterolemiantes/efectos adversos , Antihipertensivos/efectos adversos , Antihipertensivos/farmacología , Interacciones Farmacológicas , Quimioterapia Combinada/efectos adversos , Simeprevir/farmacocinética , Ansiolíticos/farmacología , Anticolesterolemiantes/farmacología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Inhibidores de Proteasas/farmacocinética
14.
J Infect Dis ; 214(10): 1492-1497, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27609808

RESUMEN

This prospective study investigated viral and host markers after stopping long-term therapy with nucleos(t)ide analogues in noncirrhotic patients with hepatitis B e antigen-negative chronic hepatitis B. After stopping therapy, 13 of 15 patients experienced a virological relapse. Rebound of hepatitis B virus DNA and hepatitis B core-related antigen was associated with induction of plasma tumor necrosis factor, interleukin (IL) 10 , IL-12p70, CXCL10 and subsequent decline in hepatitis B surface antigen (HBsAg), with 20% HBsAg loss after long-term follow-up. The peak levels of hepatitis B virus DNA and hepatitis B core-related antigen after cessation of therapy were positively correlated with the level of HBsAg decline at week 48. Thus, stopping or interrupting NA treatment should be further investigated as a strategy to accelerate HBsAg loss.


Asunto(s)
Antivirales/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Nucleósidos/administración & dosificación , Nucleótidos/administración & dosificación , Privación de Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/sangre , ADN Viral/sangre , Femenino , Antígenos del Núcleo de la Hepatitis B/sangre , Hepatitis B Crónica/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia
15.
Clin Infect Dis ; 62(5): 561-7, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26611779

RESUMEN

BACKGROUND: With the approval of direct-acting antivirals (DAAs), the management of drug-drug interactions (DDIs) has become an important challenge while treating individuals with hepatitis C. To date, the potential of causing DDIs for the recently approved DAAs has not been systematically investigated. We aimed to assess the clinical significance of DDI between the regular outpatient medications and DAA therapies in a large real-world cohort. METHODS: Overall, 261 hepatitis C virus monoinfected patients who were selected for DAA therapy at 2 intervals between 2011 and 2014 were asked about their regular outpatient medications. The potential for DDIs between all these drugs and sofosbuvir/ribavirin, ledipasvir/sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/simeprevir, ombitasvir/paritaprevir/ritonavir ± dasabuvir as well as boceprevir and telaprevir triple therapy was assessed using www.hep-druginteractions.org and the relevant prescribing information. RESULTS: The 261 patients took a median number of 2 drugs (range 0-15); 20% of patients did not take any medication. Sofosbuvir/ribavirin had the lowest risk to cause a potentially significant DDI (9.6%). In contrast, for ombitasvir/paritaprevir/ritonavir ± dasabuvir potentially significant DDIs could be expected in 66.3% of the patients. Significant DDIs for sofosbuvir/simeprevir would be expected in 31.4%, for sofosbuvir/daclatasvir in 36.8%, and for sofosbuvir/ledipasvir in 40.2%. Proton pump inhibitors, thyroid hormones, and dihydropyridine derivatives were frequently used and presented a risk of interacting with the antiviral regimen. CONCLUSIONS: A significant number of patients are at risk for DDIs if treated with the recently approved DAA regimens. A careful evaluation of potential DDI is essential to prevent adverse effects or unnecessary risk of treatment failure.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Estudios de Cohortes , Interacciones Farmacológicas , Pacientes Ambulatorios
16.
J Hepatol ; 65(3): 473-82, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27085252

RESUMEN

BACKGROUND & AIMS: The European Association for the Study of the Liver (EASL) guidelines recommend HCV RNA measurements at specific time points during sofosbuvir(SOF)-therapy. However, it remains unclear, how these results should be interpreted. We aimed to analyze whether on-treatment HCV RNA levels predict relapse comparing the CobasAmpliPrep/CobasTaqMan v2.0 (CAP/CTM) and Abbott RealTime HCV (ART) assays. METHODS: Samples were collected from 298 patients (HCV genotypes; GT1-5) at weeks (w) 0, 1, 2, 4, 8, 12, 16, 20 and 24 during SOF-based therapy at two university clinics and tested for HCV RNA level by CAP/CTM and ART. Patients were treated with SOF/ribavirin (RBV) 12/24 w (n=99), pegylated-interferon-alfa (PegIFN)/SOF/RBV 12 w (n=51), SOF/simeprevir (SMV)±RBV 12 w (n=69) or SOF/daclatasvir±RBV 12/24 w (n=79). RESULTS: HCV RNA levels during the first 4weeks of SOF/RBV therapy were significantly lower in GT3 patients who achieved SVR compared with those who relapsed. All GT3 patients with a week 2 result <45IU/ml by CAP/CTM achieved SVR but only 33% of those with ⩾45IU/ml (p=0.0003). Similar results were documented with ART and 60IU/ml as cut-off (SVR: 100% vs. 29%; p=0.0002). In contrast, HCV RNA levels during early treatment phases were not significantly related to relapse in patients treated with other SOF-based regimens. Residual HCV RNA was frequently detected by ART at later stages of therapy. However, SVR rates remained high in these patients. At the end of SOF/SMV±RBV therapy HCV RNA was detectable with ART in 20% of patients, of whom 92% achieved SVR. CONCLUSIONS: HCV RNA levels assessed at week 2 of SOF/RBV therapy can predict relapse in GT3-patients. Detectable HCV RNA results at later stages during SOF-based therapy may occur frequently with the more sensitive ART. However, this should not lead to treatment extension. LAY SUMMARY: We analyzed the predictive value of hepatitis C virus (HCV) RNA levels measured at different time points for treatment efficacy. We found that the level of HCV RNA measured at week 2 of antiviral therapy can be used to predict treatment success in patients with HCV genotype 3 infection treated with sofosbuvir and ribavirin but not in patients treated with other sofosbuvir-based regimens. Low level HCV RNA is frequently detected by the RealTime HCV assay during later stages of antiviral therapy. However, this is not associated with reoccurrence of HCV RNA after the end of treatment.


Asunto(s)
Hepatitis C , Antivirales , Genotipo , Hepacivirus , Humanos , Virus ARN , Simeprevir , Sofosbuvir
18.
Liver Int ; 35(7): 1845-52, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25556625

RESUMEN

BACKGROUND & AIMS: Several real world data demonstrated that eligibility for and tolerability of triple therapy against hepatitis C virus (HCV) infection with a first-wave protease inhibitor is limited. With the approval of sofosbuvir (SOF) effective treatment with and without pegylated interferon (PEG-IFN) has become available for most genotypes. However, no data are available regarding the added benefit of an interferon-free treatment concerning eligibility and tolerability in a real-world scenario. We aimed to assess the eligibility and safety of SOF based therapies in patients with primarily advanced cirrhosis, including decompensated cirrhosis, in a real-world setting. RESULTS: In total, 207 patients were evaluated for a SOF based treatment with and without PEG-IFN. Twenty-six patients did not receive treatment because of safety reasons. Common causes were severe concomitant cardiac disease and advanced renal disease. Autoimmune disease, thrombopaenia, anaemia or hepatic dysfunction did not preclude treatment. Eighty-four patients started treatment, 15 with decompensated cirrhosis. During the first 12 weeks hospitalization occurred in 11 patients most frequently because of typical complications of advanced liver disease. Risk factors for hospitalization were low platelet count and deteriorated liver function. Overall, 982 of 1008 planned treatment weeks (97%) were successfully completed within the first 12 weeks of therapy. CONCLUSION: With the better safety profile of interferon-free therapies, eligibility for HCV treatment will expand broadly, including patients with decompensated cirrhosis. Current limitations are renal failure and concomitant cardiac disease. Patients with advanced cirrhosis still have a high risk for hospitalization even with interferon-free therapies, but can continue HCV treatment in most cases.


Asunto(s)
Antivirales/uso terapéutico , Determinación de la Elegibilidad , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/uso terapéutico , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/diagnóstico , Hospitalización , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Selección de Paciente , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , Ribavirina/uso terapéutico , Factores de Riesgo , Sofosbuvir/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
20.
Int Health ; 16(2): 219-226, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37624102

RESUMEN

BACKGROUND: Post-exposure prophylaxis (PEP) is an effective tool to prevent infection with HIV. Patients seeking PEP after potential HIV exposure usually present to the emergency department (ED). Our study sought to determine the concordance of ED physicians' decisions on HIV-PEP with national guidelines (primary objective) and to assess the clinical relevance of drug-drug interactions (DDIs) between the HIV-PEP regimen and patients' concomitant medication (secondary objective). METHODS: We conducted a retrospective cohort study at the ED of Hannover Medical School, Germany. Between 1 January 2018 and 31 December 2019, 113 of 11 246 screened patients presented to the ED after potential HIV exposure and were enrolled in the study. RESULTS: The median age of the patients (82.3% male) was 30 y (IQR 25-35.5), 85.8% of potential HIV exposures were characterised as sexual and 85.0% presented within 72 h. ED physicians' decisions on HIV-PEP were concordant with national guidelines in 93.8%. No clinically relevant DDIs were detected. CONCLUSIONS: ED physicians' decisions on HIV-PEP were highly concordant with national guidelines. Approximately 1% of patient presentations to the ED were related to HIV exposure; therefore, training ED physicians on HIV transmission risk assessment and indications/contraindications for HIV-PEP is paramount.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Médicos , Humanos , Masculino , Femenino , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Profilaxis Posexposición/métodos , Estudios Retrospectivos , Servicio de Urgencia en Hospital , Fármacos Anti-VIH/uso terapéutico
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