RESUMO
BACKGROUND: As of 2019, the United States (US) was not on track to achieve targets for elimination, due to increasing incidence and treatment barriers. In 2020, the COVID-19 pandemic disrupted HCV services globally and in the US. As healthcare services normalize, there is an urgent need to reassess progress and evaluate scenarios that restore a pathway toward HCV elimination. METHODS: We updated a validated Markov model to estimate HCV-related morbidity and mortality in the US. Five scenarios were developed to bookend possible HCV outcomes in the wake of the pandemic. These included 1) return to pre-COVID-19 treatment forecasts; 2) achieve elimination targets through treatment and harm reduction; 3) long-term treatment disruptions; 4/5) achieve elimination targets through increased treatment without increased harm reduction, starting in either 2022 or 2025. FINDINGS: From 2014-2019, more than 1.2 million patients were treated for HCV in the US. Elimination targets in 2030 could be achieved in the US by treating an additional 3.2-3.3 million patients from 2020 to 2030, or by preventing new infections through expanded harm reduction programs and treating up to 2.7 million patients. Intervention scenarios could prevent over 30,000 HCC cases and over 29,000 liver-related deaths. INTERPRETATION: The US has made strides toward HCV elimination, but gains could be lost in the wake of the pandemic. However, it is still possible to avert nearly 30,000 deaths through increased harm reduction and increased treatment rates. This requires a coordinated effort from the entire HCV community.
Assuntos
COVID-19 , Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Estados Unidos/epidemiologia , Pandemias/prevenção & controle , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite C/tratamento farmacológico , HepacivirusRESUMO
Overt hepatic encephalopathy is a generally reversible neurologic complication of cirrhosis. Overt hepatic encephalopathy has been associated with poor hospitalization- and mortality-related outcomes, which is important given increasing hepatic encephalopathy-related hospitalizations over time. The aim of this narrative review is to provide an overview of hospital- and mortality-related outcomes in patients with overt hepatic encephalopathy and the pharmacologic therapies that may improve these outcomes. Guideline-recommended prophylaxis with lactulose (first-line therapy) or secondary prophylaxis with rifaximin plus lactulose decreases hospital admissions and mortality rates. Rifaximin or lactulose treatment was beneficial for reducing the hospitalization rate in patients with hepatic encephalopathy compared with no treatment. Further, retrospective studies have shown that rifaximin with or without lactulose was effective for decreasing the number of hepatic encephalopathy episodes, hepatic encephalopathy-related hospitalizations, and duration of hospitalization. Ornithine phenylacetate, an ammonia-reducing agent currently in development, is also being investigated in hospitalized patients with hepatic encephalopathy. Overall, data support that prophylaxis for the prevention of hepatic encephalopathy recurrence improves outcomes in patients with cirrhosis and a history of hepatic encephalopathy.
Assuntos
Fármacos Gastrointestinais/uso terapêutico , Encefalopatia Hepática/prevenção & controle , Lactulose/uso terapêutico , Ornitina/análogos & derivados , Rifaximina/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação , Mortalidade , Ornitina/uso terapêutico , Prevenção SecundáriaAssuntos
Hepatite C , Transplante de Fígado , Hepacivirus , Humanos , Padrão de Cuidado , Doadores de TecidosRESUMO
Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Anilidas/administração & dosagem , Anilidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular/métodos , Mutação , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , beta Catenina/genéticaRESUMO
OBJECTIVES: Our objective was to determine the safety, efficacy, and pharmacokinetics of telaprevir plus pegylated interferon alfa 2a and ribavirin for chronic, posttransplant genotype 1 hepatitis C virus infection. MATERIALS AND METHODS: A prospective, single-arm, multicenter, open-label, phase 2b study was conducted at 22 North American sites to assess the safety, efficacy, and pharmacokinetics of pegylated interferon alfa 2a, ribavirin, and twice daily telaprevir in liver transplant recipients with recurrent, chronic hepatitis C without cirrhosis. Baseline liver biopsies were read by a central pathologist. There were planned safety reviews after a sentinel cohort reached treatment weeks 4 and 16. Serial pharmacokinetic sampling was performed for calcineurin inhibitors, telaprevir, and ribavirin. RESULTS: Sixty-one patients were enrolled and received ≥ 1 dose of study medication; 37 (61%) achieved sustained virologic response. Thirteen of 18 treatment-naive patients (72%), 10 of 11 patients with no or minimal fibrosis (91%), 13 of 15 patients (87%) with interleukin 28B genotype CC, and 36 of 45 patients (80%) with either undetectable or unquantifiable hepatitis C virus RNA at treatment week 4 achieved sustained virologic response. Nine patients (15%) had ≥ 1 drug-related serious adverse event and 7 (11%) discontinued all study drugs due to an adverse event. There were no deaths or acute cellular rejection episodes. During telaprevir treatment, median doses of tacrolimus and cyclosporine were 0.5 mg weekly and 25 mg daily. Target exposures were achieved for telaprevir with twice daily dosing and for ribavirin with reduced initial dosing. CONCLUSIONS: Telaprevir combination therapy for posttransplant hepatitis C virus infection yielded superior efficacy than historical controls. Adverse events were similar to, but exceeded, those in immunocompetent patients. Calcineurin inhibitor dosing levels were substantially reduced with telaprevir.
Assuntos
Antivirais/administração & dosagem , Antivirais/farmacocinética , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Adulto , Idoso , Antivirais/efeitos adversos , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Esquema de Medicação , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , América do Norte , Oligopeptídeos/efeitos adversos , Fenótipo , Polietilenoglicóis/administração & dosagem , Estudos Prospectivos , RNA Viral/sangue , RNA Viral/genética , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem , Resposta Viral Sustentada , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Doença Hepática Terminal/cirurgia , Hepatite C/tratamento farmacológico , Transplante de Fígado , Cuidados Pré-Operatórios/métodos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Doença Hepática Terminal/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Humanos , Cirrose Hepática/cirurgia , Cirrose Hepática/virologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Doadores de Tecidos , Listas de EsperaAssuntos
Antivirais/uso terapêutico , Doença Hepática Terminal/cirurgia , Hepatite C/tratamento farmacológico , Transplante de Fígado , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/tratamento farmacológico , Colestase/terapia , Colestase/virologia , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Doença Hepática Terminal/virologia , Rejeição de Enxerto/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/etiologia , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática/cirurgia , Cirrose Hepática/virologia , RecidivaRESUMO
Hepatitis C virus infection affects approximately 2.2 to 3.2 million Americans. In 2012, the Centers for Disease Control and Prevention recommended a one-time antibody test of all persons belonging to the 1945-1965 birth cohort. Efforts to implement this recommendation in clinical settings are in their infancy; this case study report therefore seeks to share the experiences of three sites that implemented interventions to increase birth-cohort testing through participation in the Birth-cohort Evaluation to Advance Screening and Testing for Hepatitis C. At each site, project managers completed standardized questionnaires about their implementation experiences, and a qualitative analysis was conducted of the responses. The testing interventions used in-person recruitment, mail recruitment, and an electronic health record prompt. Sites reported that early efforts to obtain stakeholder buy-in were critical to effectively implement and sustain interventions and that the intervention required additional staffing resources beyond those being used for risk-based testing. In each case, administrative barriers were more extensive than anticipated. For the electronic health record-based intervention, technological support was critical in achieving study goals. Despite these barriers, interventions in all sites were successful in increasing rates of testing and case identification, although future studies will need to evaluate the relative costs and benefits of each intervention.
Assuntos
Promoção da Saúde/organização & administração , Hepatite C/diagnóstico , Programas de Rastreamento/organização & administração , Atenção Primária à Saúde/organização & administração , Idoso , Centers for Disease Control and Prevention, U.S. , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados UnidosRESUMO
From December 2012 to March 2014, three randomized trials, each implementing a unique intervention in primary care settings (repeated mailing, an electronic health record best practice alert [BPA], and patient solicitation), evaluated hepatitis C virus (HCV) antibody testing, diagnosis, and costs for each of the interventions compared with standard-of-care testing. Multilevel multivariable models were used to estimate the adjusted risk ratio (aRR) for receiving an HCV antibody test, and costs were estimated using activity-based costing. The goal of this study was to estimate the effects of interventions conducted as part of the Birth-Cohort Evaluation to Advance Screening and Testing for Hepatitis C study on HCV testing and costs among persons of the 1945-1965 birth cohort (BC). Intervention resulted in substantially higher HCV testing rates compared with standard-of-care testing (26.9% versus 1.4% for repeated mailing, 30.9% versus 3.6% for BPA, and 63.5% versus 2.0% for patient solicitation) and significantly higher aRR for testing after controlling for sex, birth year, race, insurance type, and median household income (19.2 [95% confidence interval (CI), 9.7-38.2] for repeated mailing, 13.2 [95% CI, 3.6-48.6] for BPA, and 32.9 [95% CI, 19.3-56.1] for patient solicitation). The BPA intervention had the lowest incremental cost per completed test ($24 with fixed startup costs, $3 without) and also the lowest incremental cost per new case identified after omitting fixed startup costs ($1691). CONCLUSION: HCV testing interventions resulted in an increase in BC testing compared with standard-of-care testing but also increased costs. The effect size and incremental costs of BPA intervention (excluding startup costs) support more widespread adoption compared with the other interventions. (Hepatology 2017;65:44-53).
Assuntos
Hepatite C/diagnóstico , Hepatite C/economia , Idoso , Estudos de Coortes , Feminino , Custos de Cuidados de Saúde , Hepacivirus/imunologia , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes Sorológicos/economia , Testes Sorológicos/estatística & dados numéricosRESUMO
BACKGROUND: Hepatitis C virus (HCV) testing guidance issued by the Centers for Disease Control and Prevention in 1998 recommends HCV antibody (anti-HCV) testing for persons with specified risk factors. The purpose of this study was to determine the prevalence and predictors of anti-HCV positivity among primary care outpatients and estimate the proportion of unidentified anti-HCV-positive (anti-HCV+) persons using risk-based testing. METHODS: We analyzed electronic medical record data from a 4-site retrospective study. Patients were aged ≥18 years, utilized ≥1 outpatient primary care service(s) between 2005 and 2010, and had no documented evidence of prior HCV diagnosis. Among persons tested for anti-HCV, we fit a multilevel logistic regression model to identify patient-level independent predictors of anti-HCV positivity. We estimated the proportion of unidentified anti-HCV+ persons by using multiple imputation to assign anti-HCV results to untested patients. RESULTS: We observed 209 076 patients for a median of 5 months (interquartile range, 1-23 months). Among 17 464 (8.4%) patients who were tested for anti-HCV, 6.4% (n=1115) were positive. We identified history of injection drug use (adjusted odds ratio [95% confidence interval], 6.3 [5.2-7.6]), 1945-1965 birth cohort (4.4 [3.8-5.1]), and elevated alanine aminotransferase levels (4.8 [4.2-5.6]) as independently associated with anti-HCV positivity. We estimated that 81.5% (n=4890/6005) of anti-HCV+ patients were unidentified using risk-based testing. CONCLUSIONS: In these outpatient primary care settings, risk-based testing may have missed 4 of 5 newly enrolled patients who are anti-HCV+. Without knowing their status, unidentified anti-HCV+ persons cannot receive further clinical evaluation or antiviral treatment, and are unlikely to benefit from secondary prevention recommendations to limit disease progression and mortality.
Assuntos
Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Pacientes Ambulatoriais , Atenção Primária à Saúde , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: In 1998, the Centers for Disease Control and Prevention (CDC) published Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease, recommending HCV testing for populations most likely to be infected with HCV. However, the implementation of risk-based screening has not been widely adopted in health care settings, and 45% to 85% of infected U.S. adults remain unidentified. OBJECTIVES: To develop a better understanding of why CDC's 1998 recommendations have had limited success in identifying persons with HCV infection and provide information about how CDC's 2012 Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945-1965 may be implemented more effectively. DESIGN: Qualitative data were collected and analyzed from a multidisciplinary team as part of the Birth Cohort Evaluation to Advance Screening and Testing for Hepatitis C project. RESPONDENTS: Nineteen providers were asked open-ended questions to identify current perspectives, practices, facilitators, and barriers to HCV screening and testing. Providers were affiliated with Henry Ford Hospital, Mount Sinai Hospital, the University of Alabama, and the University of Texas Health Science Center. RESULTS: Respondents reported the complexity of the 1998 recommendations, and numerous indicated risk factors were major barriers to effective implementation. Other hindrances to hepatitis C testing included physician discomfort in asking questions about socially undesirable behaviors and physician uncertainty about patient insurance coverage. CONCLUSION: Implementation of the CDC's 2012 recommendations could be more successful than the 1998 recommendations due to their relative simplicity; however, effective strategies need to be used for dissemination and implementation for full success.
Assuntos
Hepatite C/diagnóstico , Programas de Rastreamento/organização & administração , Atenção Primária à Saúde/organização & administração , Centers for Disease Control and Prevention, U.S./normas , Fidelidade a Diretrizes , Hepatite C Crônica/diagnóstico , Humanos , Guias de Prática Clínica como Assunto , Fatores de Risco , Estados Unidos/epidemiologiaAssuntos
Hepacivirus/isolamento & purificação , Hepatite C , Transplante de Fígado , Complicações Pós-Operatórias/prevenção & controle , RNA Viral/metabolismo , Adulto , Idoso , Feminino , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/terapia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/virologia , Cuidados Pré-Operatórios , Estudos Retrospectivos , Prevenção SecundáriaRESUMO
BACKGROUND: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC. RESULTS: HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/µL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/µL before LT and <500/µL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics. CONCLUSION: Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Linfopenia/etiologia , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/diagnóstico , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high-risk donors (HRD) in addition to standard-risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post-transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self-reported and objective measures of recovery. Eighty-four patients provided baseline and six-month post-transplant data. There were generally no statistically significant differences at baseline or the six-month follow-up, suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.
Assuntos
Transtornos Cognitivos/fisiopatologia , Transplante de Fígado , Fígado/fisiopatologia , Doadores Vivos , Qualidade de Vida/psicologia , Estresse Psicológico/fisiopatologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Hepatopatias/fisiopatologia , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Obtenção de Tecidos e ÓrgãosRESUMO
UNLABELLED: Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). The aim of this study was to investigate the impact of peritransplant ALC on HCV recurrence following LT. A total of 289 LT patients between 2005 and 2011 were evaluated. Peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence based on METAVIR fibrosis score. When stratifying patients according to pre- and post-LT ALC (<500/µL versus 500-1,000/µL versus >1,000/µL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). Multivariate Cox regression analysis showed posttransplant ALC at 1 month remained an independent predictive factor for recurrence (P = 0.02, hazard ratio [HR] = 2.47 for <500/µL). When peritransplant ALC was persistently low (<500/µL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years) (P = 0.02, HR = 3.16). Furthermore, severe pretransplant lymphopenia (<500/µL) was an independent prognostic factor for overall survival (P = 0.01, HR = 3.01). The use of rabbit anti-thymocyte globulin induction (RATG) had a remarkable protective effect on HCV recurrence (P = 0.02, HR = 0.6) despite its potential to induce lymphopenia. Subgroup analysis indicated that negative effects of posttransplant lymphopenia at 1 month (<1,000/µL) were significant regardless of RATG use and the protective effects of RATG were independent of posttransplant lymphopenia. CONCLUSION: Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC.
Assuntos
Hepatite C/imunologia , Cirrose Hepática/etiologia , Transplante de Fígado , Complicações Pós-Operatórias/imunologia , Animais , Soro Antilinfocitário/farmacologia , Antivirais/uso terapêutico , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/mortalidade , Humanos , Terapia de Imunossupressão , Cirrose Hepática/epidemiologia , Contagem de Linfócitos , Linfopenia/complicações , Masculino , Michigan/epidemiologia , Período Perioperatório , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Coelhos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Carga Viral/efeitos dos fármacosRESUMO
There has been little research examining the effects of mental health before liver transplantation on quality of life (QOL) and recovery after transplantation. Therefore, the purpose of the current study was to examine how pretransplant depression and anxiety affect mental health, QOL, and recovery after transplantation. Eighty-two transplant recipients provided data when they were listed for transplantation and 6 months after transplantation. Pretransplant anxiety predicted posttransplant anxiety (P < 0.001), and there was a trend in predicting posttransplant depression (P = 0.06). Pretransplant depression predicted posttransplant depression (P = 0.03), and there was a trend in predicting posttransplant anxiety (P = 0.06). Additionally, pretransplant anxiety predicted posttransplant QOL for several domains, including Body Pain, Role Limitations Due to Emotional Problems, and Mental Health, as well as the Mental Health Composite Score (P < 0.05). However, in comparison with anxiety, pretransplant depression independently predicted outcomes for more QOL domains, which included Physical Functioning, Role Limitations Due to Physical Problems, General Health, Vitality, and Social Functioning, as well as the Physical Composite Score (P < 0.05). Patients with depression at the baseline were more likely to report incomplete recovery 6 months after transplantation (P < 0.001). With respect to baseline anxiety, there was a trend suggesting that these patients were also more likely to report incomplete recovery (P = 0.09). These findings highlight the importance of evaluating transplant candidates both before and after transplantation for anxiety and depressive symptoms. Once patients with these symptoms are identified, they can be referred for treatment, which may lead to better posttransplant outcomes for mental health, QOL, and recovery.
Assuntos
Transplante de Fígado/psicologia , Saúde Mental , Qualidade de Vida , Adulto , Idoso , Ansiedade/psicologia , Depressão/psicologia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Shortened courses of treatment with pegylated interferon alfa and ribavirin for patients with hepatitis C virus infection who experience rapid virologic response can be effective in appropriately selected patients. The cost-effectiveness of truncated therapy is not known. OBJECTIVE: To assess the cost-effectiveness of response-guided therapy versus standard-duration therapy on the basis of best available evidence. METHODS: We developed a decision model for chronic hepatitis C virus infection representing two treatment strategies: 1) standard-duration therapy with pegylated interferon alfa and ribavirin for 48 weeks in patients with genotype 1 or 4 and for 24 weeks in patients with genotype 2 or 3 and 2) truncated therapy (i.e., 50% decrease in treatment duration) in patients with rapid virologic response. Patients for whom truncated therapy failed began standard-duration therapy guided by genotype. We used a Markov model to estimate lifetime costs and quality-adjusted life-years. RESULTS: In the base-case analysis, mean lifetime costs were $46,623 ± $2,483 with standard-duration therapy and $42,354 ± $2,489 with truncated therapy. Mean lifetime quality-adjusted life-years were similar between the groups (17.1 ± 0.7 with standard therapy; 17.2 ± 0.7 with truncated therapy). Across model simulations, the probability of truncated therapy being economically dominant (i.e., both cost saving and more effective) was 78.6%. The results were consistent when we stratified the data by genotype. In one-way sensitivity analyses, the results were sensitive only to changes in treatment efficacy. CONCLUSION: Truncated therapy based on rapid virologic response is likely to be cost saving for treatment-naive patients with chronic hepatitis C virus infection. Cost-effectiveness varied with small changes in relative treatment efficacy.
Assuntos
Antivirais/administração & dosagem , Antivirais/economia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Interferon-alfa/economia , Ribavirina/administração & dosagem , Ribavirina/economia , Adulto , Pesquisa Comparativa da Efetividade , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Humanos , Interferon-alfa/genética , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Polietilenoglicóis/economia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
GOALS: To evaluate the safety and efficacy of peginterferon-α-2b plus ribavirin in patients with recurrent hepatitis C after orthotopic liver transplant. BACKGROUND: Reinfection of liver allografts in hepatitis C virus -infected transplant recipients begins immediately after transplantation. Treatment of these patients is challenging because of poor tolerability. STUDY: A multicenter, open-label study enrolling patients with persistent viremia after primary orthotopic liver transplant for cirrhosis related to hepatitis C virus infection. Patients received peginterferon-α-2b (1.5 µg/kg/wk) plus ribavirin (400 to 1200 mg/d administered using a dose-escalating regimen and according to body weight) for 48 weeks. The primary endpoint was sustained virologic response (SVR). RESULTS: In total, 125 patients started treatment and 58.4% completed 48 weeks. SVR rate was 28.8% (G1, 23.8%; G2/3, 55.0%), end-of-treatment response rate was 40.8%, and relapse rate was 18.2%. SVR was 55% among patients who completed treatment. Genotype 2/3 infection, male sex, baseline hemoglobin>14 g/dL, 80:80:80 compliance, rapid virologic response (RVR), and complete early virologic response (cEVR) were predictors of SVR. SVR was higher among patients with RVR compared with those without RVR (83.3% vs. 25.7%; P=0.0098), and among patients with cEVR compared with those without EVR (66.7% vs. 1.8%; P<0.0001). Thirty-eight patients discontinued because of an adverse event and 69 required dose reduction or interruption. Anemia (74%) and neutropenia (30%) were common, and rejection was low (3.2%). CONCLUSIONS: SVR was low in this study. Anemia was a particular challenge in achieving maximal ribavirin therapeutic exposure and may account in part for the lower SVR.
Assuntos
Antivirais , Hepatite C/prevenção & controle , Interferon-alfa , Transplante de Fígado/efeitos adversos , Polietilenoglicóis , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Prevenção Secundária , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Black recipients undergoing liver transplantation (LT) for hepatitis C virus (HCV) have decreased patient and graft survival compared with white recipients, a finding that is primarily limited to black recipients of livers from white donors. The cause(s) for these discrepant outcomes are unclear but may be related to HCV disease recurrence. The rates of HCV-related disease recurrence and liver fibrosis progression among black and white liver transplant recipients have not been investigated. METHODS: In this study, we compared liver fibrosis progression between 105 black and 364 white recipients after HCV-related LT in a multisite cohort study and assessed the impact of donor race. RESULTS: At 6, 12, and 24 months after LT, there was a significantly higher percentage in the black recipient/white donor (B/W) group with severe fibrosis, defined as stage 3 or 4 (F3/F4), compared with all other recipient/donor race combinations. The adjusted odds ratio of developing F3/F4 for the B/W group was 2.54 (1.49-4.69; reference group, white recipient/white donor). Black recipients with black donors demonstrated a similar rate of progression to F3/F4 as white recipients. Patient survival was also decreased in the B/W group compared with other recipient/donor race combinations. CONCLUSION: African American recipients with white donors have more severe fibrosis progression after HCV-related LT. The mechanisms responsible for accelerating fibrosis progression in this high-risk race-mismatched group need to be investigated.