RESUMEN
Most persons with chronic hepatitis C virus (HCV) infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) than national estimates (~25%).
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Alaska/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Sistema de Registros , Estados UnidosRESUMEN
Long-term prospective studies of the outcomes associated with hepatitis C virus (HCV) infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a starting point, we analyzed the development of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver-related death (LRD) according to fibrosis stage among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak = 0,1), moderate (Ishak = 2), or severe (Ishak = 3,4) fibrosis or cirrhosis (Ishak = 5,6). We examined time until development of ESLD, HCC, and LRD and report survival probabilities at 3, 5, 7, and 10 years. Of 407 persons, 39% (n = 150) had no/mild fibrosis, 32% (n = 131) had moderate fibrosis, 22% (n = 88) had severe fibrosis, and 9% (n = 38) had cirrhosis. The average time of follow-up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval [CI]: 0.4-6.8) of persons with no/mild fibrosis developed ESLD compared with 7.9% (95% CI, 4.0-15.2), 16.4% (95% CI, 9.6-27.2), and 49.0% (95% CI, 33.0-67.7) with moderate, severe fibrosis, and cirrhosis, respectively (P < 0.01). The 5-year outcome of HCC was 1.0% (95% CI, 0.1-7.0), 1.0% (95% CI, 0.1-6.6), 1.1% (95% CI, 0.2-7.7), and 13.4% (95% CI, 4.4-36.7) among persons with no/mild fibrosis, moderate fibrosis, severe fibrosis, and cirrhosis, respectively (P < 0.01). Five years after biopsy, 0.0% (95% CI, 0.0-14.8) of persons with no/mild fibrosis had suffered an LRD compared with 1.0% (95% CI, 0.2-7.5) of persons with moderate fibrosis, 4.7% (95% CI, 1.5-14.1) with severe fibrosis, and 16.3% (95% CI, 7.0-35.1) with cirrhosis (P < 0.01). CONCLUSION: For prevention of HCC, LRD, and ESLD in the short term, HCV therapy should target individuals who have more than mild fibrosis. (Hepatology 2017;66:37-45).
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Causas de Muerte , Enfermedad Hepática en Estado Terminal/epidemiología , Hepatitis C Crónica/epidemiología , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Anciano , Alaska/epidemiología , Biopsia con Aguja , Carcinoma Hepatocelular/fisiopatología , Carcinoma Hepatocelular/terapia , Estudios de Cohortes , Comorbilidad , Intervalos de Confianza , Bases de Datos Factuales , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/fisiopatología , Enfermedad Hepática en Estado Terminal/terapia , Femenino , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/terapia , Humanos , Inmunohistoquímica , Cirrosis Hepática/patología , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND & AIMS: Few studies have examined factors associated with disease progression in hepatitis C virus (HCV) infection. We examined the association of 11 risk factors with adverse outcomes in a population-based prospective cohort observational study of Alaska Native/American Indian persons with chronic HCV infection. METHODS: We collected data from a population-based cohort study of liver-related adverse outcomes of infection in American Indian/Alaska Native persons with chronic HCV living in Alaska, recruited from 1995 through 2012. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for end-stage liver disease (ESLD; presence of ascites, esophageal varices, hepatic encephalopathy, or coagulopathy), hepatocellular carcinoma (HCC), and liver-related death using a Cox proportional hazards model. RESULTS: We enrolled 1080 participants followed up for 11,171 person-years (mean, 10.3 person-years); 66%, 19%, and 14% were infected with HCV genotypes 1, 2, and 3, respectively. On multivariate analysis, persons infected with HCV genotype 3 had a significantly increased risk of developing all 3 adverse outcomes. Their aHR for ESLD was 2.1 (95% CI, 1.5-3.0), their aHR for HCC was 3.1 (95% CI, 1.4-6.6), and their aHR for liver-related death was 2.4 (95% CI, 1.5-4.0) compared with genotype 1. Heavy alcohol use was an age-adjusted risk factor for ESLD (aHR, 2.2; 95% CI, 1.6-3.2), and liver-related death (aHR, 2.9; 95% CI, 1.8-4.6). Obesity was a risk factor for ESLD (aHR, 1.4; 95% CI, 1.0-1.9), and diabetes was a risk factor for ESLD (aHR, 1.5; 95% CI, 1.1-2.2). Male sex was a risk factor for HCC (aHR, 3.6; 95% CI, 1.6-8.2). CONCLUSIONS: In a population-based cohort study of American Indian/Alaska Native persons with chronic HCV infection, we found those infected with HCV genotype 3 to be at high risk for ESLD, HCC, and liver-related death.
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Enfermedad Hepática en Estado Terminal/epidemiología , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Adulto , Alaska/epidemiología , Carcinoma Hepatocelular/mortalidad , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/mortalidad , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Humanos , Indígenas Norteamericanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. METHODS: AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. RESULTS: We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. CONCLUSIONS: In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.
Asunto(s)
Indio Americano o Nativo de Alaska/estadística & datos numéricos , Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Carbamatos/uso terapéutico , Fluorenos/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Alaska/epidemiología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: Chronic hepatitis C virus (HCV) infection diminishes immune function through cell exhaustion and repertoire alteration. Direct acting antiviral (DAA)-based therapy can restore immune cell subset function and reduce exhaustion states. However, the extent of immune modulation following DAA-based therapy and the role that clinical and demographic factors play remain unknown. METHODS: We examined natural killer (NK) cell, CD4+, and CD8+ T cell subsets along with activation and exhaustion phenotypes across an observational study of sofosbuvir-based treatment for chronic HCV infection. Additionally, we examined the ability of clinical variables and duration of infection to predict 12 weeks of sustained virologic response (SVR12) immune marker outcomes. RESULTS: We show that sofosbuvir-based therapy restores NK cell subset distributions and reduces chronic activation by SVR12. Likewise, T cell subsets, including HCV-specific CD8+ T cells, show reductions in chronic exhaustion markers by SVR12. Immunosuppressive CD4+ regulatory T cells decrease at 4-weeks treatment and SVR12. We observe the magnitude and direction of change in immune marker values from pretreatment to SVR12 varies greatly among participants. Although we observed associations between the estimated date of infection, HCV diagnosis date, and extent of immune marker outcome at SVR12, our regression analyses did not indicate any factors as strong SVR12 outcome predictors. CONCLUSION: Our study lends further evidence of immune changes following sofosbuvir-based therapy. Further investigation beyond SVR12 and into factors that may predict posttreatment outcome is warranted.