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BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
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BACKGROUND & AIMS: Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment. METHODS: Two phase II, randomized, double-blind, placebo-controlled trials were conducted. Trial 1: outpatients with early decompensated cirrhosis randomized to placebo or rifaximin SSD once-nightly: IR 40 or 80 mg, SER 40 or 80 mg, or IR 80 mg plus SER 80 mg, for 24 weeks. Trial 2: inpatients with OHE randomized to lactulose plus placebo or rifaximin SSD: IR 40 mg once or twice daily or SER 80 mg once or twice daily for ≤14 days. Primary efficacy endpoint: time to cirrhosis complication-related hospitalization/all-cause mortality (Trial 1) or time to OHE resolution (Trial 2). RESULTS: In Trial 1 (n = 516), no significant difference in time to cirrhosis complication-related hospitalization/all-cause mortality vs placebo. In a post hoc analysis, time to all-cause hospitalization/all-cause mortality was improved with IR 40 mg vs placebo (15.4% [12/78] vs 27.7% [26/94]; P = .03). A Trial 2 prespecified interim analysis (n = 71) showed lactulose plus rifaximin SSD IR 40 mg bid significantly reduced median time to OHE resolution (21.1 hours) vs lactulose plus placebo (62.7 hours; P = .02). Trial 2 was subsequently terminated. CONCLUSION: Rifaximin SSD IR 40 mg may reduce hospitalizations in patients with cirrhosis and shorten duration of OHE during hospitalization-considered a negative finding, yet also hypothesis-generating. (ClinicalTrials.govNCT01904409; NCT03515044).
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Encefalopatía Hepática , Rifamicinas , Humanos , Adulto , Rifaximina/uso terapéutico , Lactulosa/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Comprimidos/uso terapéutico , Rifamicinas/uso terapéuticoRESUMEN
Treatment for chronic hepatitis B virus infection (cHBV) is mostly indefinite, with new finite-duration therapies needed. We report safety, pharmacokinetics and antiviral activity of the investigational HBV core inhibitor ABI-H2158. This Phase 1a/b study (NCT03714152) had three parts: Part A, participants received a single ascending oral dose of ABI-H2158 (5-500 mg) or placebo; Part B, participants received multiple doses of ABI-H2158 300 mg once (QD) or twice (BID) daily or placebo, for 10 days; Part C, cHBV patients received ABI-H2158 (100, 300, or 500 mg QD or 300 mg BID) or placebo, for 14 days. Ninety-three participants enrolled. In Parts A/B, there were no serious adverse events (SAEs) or deaths, and all treatment-emergent AEs (TEAEs) were Grade 1. In Part C, two patients had Grade 3 TEAEs unrelated to ABI-H2158; there were no deaths, SAEs or Grade 4 TEAEs. In Part A, median time to maximum ABI-H2158 plasma concentration (Tmax ) and mean terminal elimination half-life (t½ ) were 1-4 and 9.8-20.7 h, and area under the plasma concentration-time curve increased dose proportionally. In Part B, Day 10 Tmax was 2 h, mean t½ was 15.5-18.4 h, and exposure accumulated 1.7- to 3.1-fold. In Part C, Day 14 Tmax was 1 h, exposure accumulated 1.4- to 1.8-fold, and ABI-H2158 was associated with >2 log10 declines in HBV nucleic acids. In conclusion, ABI-H2158 in cHBV patients following 14 days of dosing was well tolerated and demonstrated potent antiviral activity. Safety and pharmacokinetics supported future QD dosing.
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Antivirales , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Método Doble Ciego , Relación Dosis-Respuesta a DrogaRESUMEN
INTRODUCTION: Ammonia levels are used to assess hepatic encephalopathy, but their levels are highly variable in clinical practice. METHODS: We studied factors associated with variation in ammonia values in cirrhotic patients without previous hepatic encephalopathy and healthy volunteers (HVs). RESULTS: Ammonia increased by 12% and 18% at 1 and 2 hour, respectively, after a protein meal in 64 cirrhotic patients (P < 0.001). In 237 HVs, ammonia levels varied significantly between sites (P < 0.0001). New site-specific ammonia upper limits based on HV levels using a strict analysis protocol differed from routinely used values. Correlation between paired fresh samples was high (r = 0.83) but modest between fresh and frozen samples (r = 0.62). DISCUSSION: Sample handling, processing, and protein intake impact ammonia levels across sites.
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Amoníaco/sangre , Ensayos Clínicos como Asunto , Encefalopatía Hepática/sangre , Cirrosis Hepática/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Voluntarios Sanos , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
In the current era of therapy with direct-acting antiviral (DAAs) drugs, achievement of a sustained virological response (SVR) is achievable in ⩾90% of hepatitis C-infected patients. SVR benefits are well-recognized with reductions in rates of liver complications, hepatocellular carcinoma and mortality. Additional benefits include reduced morbidity related to extrahepatic and systemic manifestations of hepatitis C such as renal, dermatologic, and metabolic complications. However, not all patients will derive all of these benefits and monitoring for progression is necessary, especially in those with more advanced fibrosis. To maximize the health benefits of SVR, counseling patients on best means to maintain good liver health and prevent reinfection are also important.
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Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Carcinoma Hepatocelular/prevención & control , Progresión de la Enfermedad , Hepatitis C Crónica/mortalidad , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/prevención & control , Neoplasias Hepáticas/prevención & control , Recurrencia , Factores de Riesgo , Respuesta Virológica SostenidaRESUMEN
PURPOSE OF REVIEW: Acute-on-chronic liver failure (ACLF), a syndrome precipitated by acute liver injury in patients with advanced cirrhosis, is associated with multiorgan dysfunction and high rates of mortality. Liver support systems have been developed in an attempt to improve survival of patients with ACLF by providing a bridge until recovery of the native liver function. RECENT FINDINGS: Nonbiological devices such as molecular adsorbent recirculating system (MARS) and fractionated plasma separation and adsorption (Prometheus) are effective in improving severe hepatic encephalopathy and cholestasis, have good safety and tolerability profiles and are frequently employed in patients with ACLD; however, randomized controlled trials (RCTs) failed to show improvement in survival. Biologic devices that incorporate hepatic cells in bioreactors are also under development. Recent data from pilot studies suggested improvement in survival rates in some groups of patients with ACLF; however, their effect on patient survival in RCT is still unknown. SUMMARY: Liver support systems are safe and well tolerated when used in management of patients with ACLF. Their use should continue in controlled clinical trials to explore their role in bridging patients to liver transplantation or recovery in well defined patient groups.
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Enfermedad Hepática en Estado Terminal/terapia , Fallo Hepático Agudo/terapia , Hígado Artificial , Diálisis Renal/instrumentación , Enfermedad Hepática en Estado Terminal/complicaciones , Humanos , Fallo Hepático Agudo/complicacionesRESUMEN
Fatty liver prevalence is increasing and becoming a global health burden. Chronic hepatitis B infection (CHB) is one of the most common chronic viral infections. Steatosis in CHB patients increases risk of cirrhosis and hepatocellular carcinoma. Data from studies on the interaction between CHB and nonalcoholic fatty liver disease are not conclusive. Liver biopsy is the gold standard for diagnosis of fatty liver; however, noninvasive diagnostic tests have been developed to diagnose and predict fibrosis in CHB/NAFLD. Treatment guidelines are not clear.
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Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/epidemiología , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Biopsia con Aguja , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Progresión de la Enfermedad , Femenino , Salud Global , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Inmunohistoquímica , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Masculino , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/terapia , Prevalencia , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
UNLABELLED: Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11-50) and CPT 13 (10-15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD + SMT (n = 39) or SMT alone (n = 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (P = 0.044) and was reached faster and more frequently than in the SMT group (P = 0.045). Subjects receiving ECAD tolerated treatment well with no unexpected adverse events. CONCLUSION: The use of ECAD may be associated with an earlier and more frequent improvement of HE (grade 3/4). Because this 5-day study was not designed to examine the impact of MARS on survival, a full assessment of the role of albumin dialysis awaits the results of additional controlled trials.
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Albúminas , Encefalopatía Hepática/terapia , Cirrosis Hepática/complicaciones , Diálisis Renal , Adulto , Anciano , Algoritmos , Femenino , Encefalopatía Hepática/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Desintoxicación por Sorción , Resultado del TratamientoRESUMEN
BACKGROUND: There is a need for hepatitis C virus (HCV) therapies with excellent efficacy across genotypes and in diverse populations. Part A of the C-CREST-1 and C-CREST-2 trials led to the selection of a three-drug regimen of grazoprevir (MK-5172; an HCV NS3/4A protease inhibitor; 100 mg/day) plus ruzasvir (MK-8408; an NS5A inhibitor; 60 mg/day) plus uprifosbuvir (MK-3682; an HCV NS5B polymerase inhibitor; 450 mg/day). Part B of the studies tested this combination as a single formulation in different treatment durations in a broader population. METHODS: Part B of these randomised, phase 2, open-label clinical trials enrolled individuals from 15 countries who were chronically infected with HCV genotypes 1-6 (HCV RNA ≥10â000 IU/mL) with or without compensated cirrhosis. Those with genotype 1, genotype 2, genotype 4, or genotype 6 were treatment-naive; those with genotype 3 could be treatment-naive or treatment-experienced with pegylated interferon and ribavirin. Randomisation occurred centrally using an interactive voice response system and integrated web response system. Participants were randomly assigned to receive treatment for 8, 12, or 16 weeks with a fixed-dose combination of grazoprevir, ruzasvir, and uprifosbuvir with or without ribavirin. The primary endpoint was the proportion of participants achieving sustained virological response 12 weeks after the end of all study therapy (SVR12), defined as HCV RNA less than the lower limit of quantification (either target detected unquantifiable or target not detected [<15 IU/mL]). The trials are registered at ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. FINDINGS: 676 participants were randomly assigned between Feb 18, 2015, and Aug 16, 2016. In all 675 participants who received at least one dose of study drug (full analysis set), SVR12 for the 8-week regimen of grazoprevir, ruzasvir, and uprifosbuvir with and without ribavirin was achieved in 39 (93% [95% CI 81-99]) of 42 participants with genotype 1a, 45 (98% [88-100]) of 46 with genotype 1b, 54 (86% [75-93]) of 63 with genotype 2, 98 (95% [89-98]) of 103 with genotype 3, and seven (100% [59-100]) of seven participants with genotype 4. SVR12 for the 12-week regimen with and without ribavirin was achieved in 87 (99% [95% CI 94-100]) of 88 participants with genotype 1, 61 (98% [91-100]) of 62 with genotype 2, and four (100% [40-100]) of four with genotype 6. Among participants with cirrhosis who were infected with genotype 3, SVR12 for the 12-week regimen with and without ribavirin was achieved in 28 (97% [95% CI 82-100]) of 29 of those who were treatment-naive and 29 (100% [88-100]) of 29 who were treatment-experienced. SVR12 for the 16-week regimen with and without ribavirin was achieved in 26 (100% [95% CI 87-100]) of 26 participants with genotype 2 infection and 72 (96% [89-99]) of 75 participants with genotype 3 infection. The most common adverse events were headache (143 [22%] of 664), fatigue (129 [19%] of 664), and nausea (83 [13%] of 664). 16 (2%) of 664 participants had serious adverse events. INTERPRETATION: The combined regimen of grazoprevir (100 mg/day), ruzasvir (60 mg/day), and uprifosbuvir (450 mg/day) has the potential to provide a simplified treatment for HCV that is effective and well tolerated in most individuals infected with HCV, as well as a shorter duration of treatment in many individuals. FUNDING: Merck & Co, Inc.
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Antivirales/administración & dosificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Uridina/análogos & derivados , Adulto , Amidas , Antivirales/efectos adversos , Carbamatos , Ciclopropanos , Esquema de Medicación , Femenino , Genotipo , Hepatitis C Crónica/genética , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Humanos , Cirrosis Hepática/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pirrolidinas/administración & dosificación , Pirrolidinas/efectos adversos , Quinoxalinas/administración & dosificación , Quinoxalinas/efectos adversos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Sulfonamidas , Respuesta Virológica Sostenida , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Uridina/administración & dosificación , Uridina/efectos adversosRESUMEN
The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.
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Antivirales/uso terapéutico , Enfermedad Hepática en Estado Terminal , Virus de la Hepatitis B/genética , Hepatitis B/tratamiento farmacológico , Neoplasias Hepáticas , Replicación Viral/efectos de los fármacos , ADN Viral/análisis , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/epidemiología , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/prevención & control , Salud Global , Hepatitis B/complicaciones , Hepatitis B/virología , Humanos , Incidencia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & controlRESUMEN
OBJECTIVE: To determine the effect of co-infection on neuropsychological performance in relatively healthy hepatitis C virus (HCV)-alone patients when compared with HCV/HIV-co-infected patients. DESIGN: To test whether the burden of co-infection with HCV and HIV on the central nervous system results in increased cognitive deficits, we tested 47 HCV-alone and 29 HCV/HIV-co-infected patients on a neuropsychological screening battery of tests of attention, concentration and psychomotor speed. METHODS: The neuropsychological test performance of HCV-alone and HCV/HIV-co-infected patients was compared with normative samples. The test performance between HCV-alone and HCV/HIV-co-infected patients was also assessed. Patients with chronic liver disease were divided on the basis of disease severity as determined by fibrosis stage, according to the METAVIR system. Neuropsychological test performance was correlated with fibrosis stage. RESULTS: As previously reported, HCV patients independent of co-infection status demonstrated deficits on neuropsychological measures of attention, concentration and psychomotor speed. No significant differences were found between patients with HCV-alone and HCV/HIV-co-infected patients on the neuropsychological measures. There was a relationship between neuropsychological test performance and fibrosis stage. CONCLUSION: Relatively healthy patients with HCV (either alone or when co-infected with HIV) may have deficits in the domains of attention, concentration and psychomotor speed. In this study no significant differences were found between patients with HCV alone and HCV/HIV-co-infected patients on neuropsychological measures, but as previously demonstrated, greater fibrosis was associated with poorer performance.
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Trastornos del Conocimiento/virología , Infecciones por VIH/psicología , Hepatitis C Crónica/psicología , Adulto , Femenino , Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The objective of this study was to investigate the relationship of biopsychosocial variables to fatigue in patients with chronic hepatitis C (CHC) with the goal of identifying areas of possible intervention. METHOD: Ninety-four patients with CHC not on antiviral therapy completed a demographic questionnaire and measures of fatigue, health-related quality of life, and depression. Fibrosis stage and relevant medical information were obtained from medical records. RESULTS: A stepwise multiple regression analysis revealed that the most significant predictor of fatigue was poor social functioning, followed by poor physical functioning, greater depression, and female gender. Together, these variables accounted for 68% of the total variance in fatigue. DISCUSSION: Study findings suggest that treatment strategies for fatigue in patients with CHC should focus on increasing social functioning in addition to improving physical functioning and decreasing depressive symptoms. Research investigating the effectiveness of interventions targeting social functioning, such as support groups and supportive counseling, is recommended.
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Fatiga/psicología , Hepatitis C Crónica/psicología , Factores de Edad , Fatiga/etiología , Fatiga/prevención & control , Femenino , Estado de Salud , Hepatitis C Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores Sexuales , Trastornos Relacionados con SustanciasRESUMEN
Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has anti-inflammatory, antioxidant and anti-cancer activities. Although the precise mode of action of this compound is not yet elucidated, studies have shown that chemo-preventive action of curcumin might be due to its ability to induce apoptosis and to arrest cell cycle. This study investigated the cellular and molecular changes induced by curcumin leading to the induction of apoptosis in human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM) for 12-72 h. Curcumin inhibited the growth of both the cell lines in a concentration dependent manner. Growth inhibition of H1299 cell lines was both time and concentration dependent. Curcumin induced apoptosis in both the lung cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes remained unchanged up to 60 microM curcumin but showed decrease in expression levels at 80-160 microM. The data also suggest a p53 independent induction of apoptosis in lung cancer cells.
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Adenocarcinoma/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Curcumina/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Genes myc/fisiología , Humanos , Neoplasias Pulmonares/patología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína p53 Supresora de Tumor/fisiologíaAsunto(s)
Control de Enfermedades Transmisibles , Salud Global , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Prevalencia , Medición de RiesgoRESUMEN
Hepatitis C virus (HCV) is neurovirulent and has been shown to be associated with neuropsychological (NP) deficits in a subset of infected individuals. Despite these previous findings, little work has been done to examine neurobehavioral symptoms associated with HCV infection. We examined 34 HCV seropositive (HCV+) individuals and 35 healthy comparison participants (HCV-) with the self-rating form of the Frontal Systems Behavior Scale (FrSBe). Results showed that at the group level, only the FrSBe apathy subscale mean was clinically elevated (T score >65) among HCV+ persons; executive dysfunction, disinhibition, and total subscale means were not clinically elevated. At the individual level, a significantly higher proportion of HCV+ individuals than of HCV- individuals reported clinically elevated FrSBe T scores . Moreover, HCV+ individuals were nearly 3 times as likely to report clinically elevated FrSBe T scores of apathy, executive dysfunction, and disinhibition as compared to HCV- participants. A multiple regression that included substance use disorders, neuropsychological impairment, and age indicated that HCV status was an independent predictor of self-reported FrSBe total T scores. Across all participants, small, yet significant, correlations were found between elevated self-reported FrsBe T scores and dependence in activities of daily living. These results show that a subset of HCV-infected individuals report clinically elevated behavioral symptoms. Clinical implications for the assessment and management of elevated behavioral symptoms in HCV are discussed.
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Actividades Cotidianas/psicología , Síntomas Conductuales/etiología , Síntomas Conductuales/virología , Hepatitis C/complicaciones , Hepatitis C/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estadísticas no ParamétricasRESUMEN
PURPOSE: Treatment persistence and cost of therapy for patients with chronic hepatitis C (CHC) treated with peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin were evaluated. METHODS: This retrospective database analysis used eligibility, pharmacy, and medical claims data from a large U.S. health plan for patients with CHC treated with peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin from January 2002 through June 2006. For the purposes of this analysis, the study population included all hepatitis C virus (HCV) genotypes. Comparable groups for assessment of outcomes were constructed using propensity score matching to reduce the effect of known sources of bias. Outcome variables included treatment persistence and annualized overall and HCV-attributable health care costs. RESULTS: A total of 1783 matched pairs were analyzed. Compared with patients receiving peginterferon alfa-2a plus ribavirin, patients receiving peginterferon alfa-2b plus ribavirin were 18% less likely to be persistent with therapy at week 48 (p = 0.013). During the first six months of follow-up, mean all-cause costs (p = 0.0368) and HCV-attributable costs (p < 0.0001) were significantly lower for peginterferon alfa-2a plus ribavirin than for peginterferon alfa-2b plus ribavirin. Mean annualized all-cause costs (p = 0.0060) and HCV-attributable costs (p = 0.0167) over the entire follow-up period were significantly lower for patients treated with peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin. CONCLUSION: Analysis of information from a health care claims database suggests that treating CHC with peginterferon alfa-2a plus ribavirin may improve treatment persistence and help reduce the health care costs imposed by CHC compared with treatment with peginterferon alfa-2b plus ribavirin.
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Antivirales/economía , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/economía , Interferón-alfa/economía , Interferón-alfa/uso terapéutico , Polietilenglicoles/economía , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud , Humanos , Interferón alfa-2 , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Excipientes Farmacéuticos , Polietilenglicoles/química , Proteínas Recombinantes , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A primary obstacle to early diagnosis and treatment of hepatic encephalopathy (HE) is the lack of a well-validated, standardized assessment method. The purpose of this study was to present preliminary validity data on a new method of grading HE, the Hepatic Encephalopathy Scoring Algorithm (HESA), which combines clinical impressions with neuropsychological performances to characterize HE. Participants were 49 inpatients admitted for complications of end stage liver disease. Each participant's level of HE was graded using HESA and the West Haven Criteria (WHC) by independent raters blinded to each other's rating. A moderately strong association was found between the two grading methods (r = 0.60), and individual HESA clinical and neuropsychological indicators were good discriminators among grades. The results also suggest HESA may be more sensitive to mental status impairment in the middle grades of HE than WHC. These findings suggest HESA holds promise as a multi-method approach to grading all levels of HE.
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Algoritmos , Encefalopatía Hepática/diagnóstico , Índice de Severidad de la Enfermedad , Adulto , Árboles de Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Encuestas y CuestionariosRESUMEN
The hepatitis C virus (HCV) is a common blood-borne illness that affects up to 2% of the world's population and almost 4 million Americans. Cognitive impairment, or difficulty with thinking, has become a well-established symptom in persons with end stage liver disease. It was previously assumed that cognitive impairment was a consequence of cirrhosis-associated hepatic encephalopathy. Recent evidence, however, suggests that approximately one-third of people with chronic HCV experience cognitive impairment even in the absence of cirrhosis and that its occurrence is unrelated to other indices of liver function, such as laboratory values, viral load, and genotype. In the present review, evidence outlining the presence of cognitive deficits associated with HCV, possible etiological factors, effects of antiviral therapy, and co-infection with human immunodeficiency virus (HIV) is presented. Implications of these findings and directions for future work are discussed.