RESUMEN
To analyze the modifications of CD4 T cell, CD4/CD8 ratio, and serum levels of soluble CD14 (sCD14) in HIV/HCV-coinfected patients after treatment with direct anti-HCV antiviral agents. Consecutive cases of HIV/HCV-coinfected patients, attended at the University Hospital, who achieved sustained virological responses with interferon-free hepatitis C antiviral drugs, were analyzed. Thirty-five percent of patients (n = 39) had been diagnosed with liver cirrhosis. The evaluation criteria were changes in CD4 T-cell counts and percentages and inflammation (measured by serum sCD14 levels) or immune activation indexes (determined by CD4/CD8 ratio) from beginning anti-HCV therapy to 12 months later. One hundred twelve patients were included (87% male; median age, 54 years; median time from the infection diagnosis, 22 years; previous drug users, 87%). Significant increases in CD4 T cell count and percentage were detected only in individuals without liver cirrhosis. No significant differences in CD4/CD8 ratios or sCD14 levels were observed in patients with or without cirrhosis. The proportion of patients with less than 500 CD4 T cell/mm3 before therapy who achieved more than 500 CD4 T cell/mm3 after it increased only in the group without liver cirrhosis. The finding that CD4 T cell count and percentage were improved only in patients without liver cirrhosis supports the idea that treatment against HCV in HIV/HCV-coinfected patients is needed in the early phases of liver disease.
Asunto(s)
Antivirales/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Coinfección/inmunología , Coinfección/virología , Infecciones por VIH/virología , Hepacivirus/inmunología , Receptores de Lipopolisacáridos/sangre , Cirrosis Hepática/inmunología , Recuento de Linfocito CD4/estadística & datos numéricos , Coinfección/tratamiento farmacológico , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica SostenidaRESUMEN
Loss of follow-up or reinfections hinder the expectations of hepatitis C eradication despite the existence of highly effective treatments. Moreover, the elimination of the infection does not imply the reversion of those chronic alterations derived from the previous infection by hepatitis C virus (HCV). This review analyzes the risk factors associated with loss to follow-up in diagnosis or treatment, and the possibility of reinfection. Likewise, it assesses the residual alterations induced by chronic HCV infection considering the liver alterations (inflammation, fibrosis, risk of decompensation, hepatocellular carcinoma, liver transplantation) and, on the other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia, non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, bone and cognitive alterations). Peculiarities present in subjects coinfected with human immunodeficiency virus are analyzed in each section.
RESUMEN
The objective of this work was to identify predictive factors of fibrosis regression after direct antiviral agents (DAAs) in HCV-monoinfected and HIV/HCV-coinfected patients. This was a prospective study of HCV-monoinfected (n = 20), HIV/HCV-co-infected (n = 66) patients and healthy controls (n = 15). Patients had started DAAs and achieved sustained virological response. Liver stiffness (LS) and serum concentrations of profibrotic transforming growth factor (TGF)-ß1 and CXC chemokine ligand 4 (CXCL4) and antifibrotic HGF hepatocyte growth factor (HGF) were analyzed at baseline (M0) and 12 months after starting DAAs (M12). A M12 LS achievement of ≤ 9.5 kPa was considered the cutoff point to discharge from a liver clinic. The LS decrease from M0 to M12 was 34%. No significant differences were observed in LS decline between HCV- and HIV/HCV-infected individuals. Changes of serum CXCL4, TGF-ß1 and HGF levels did not correlate with LS improvement. 16 out from 56 patients (28%) with a baseline LS > 9.5 achieved a M12 LS ≤ 9.5. HCV-monoinfected and HIV/HCV coinfected patients experienced a significant reduction of LS after sustained virological response. This improvement did not correlate with changes in serum profibrotic or antifibrotic markers. A 29% of those with a baseline LS > 9.5 achieved a LS under this cutoff point.
Asunto(s)
Antivirales/administración & dosificación , Coinfección/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Coinfección/sangre , Coinfección/patología , Coinfección/virología , Diagnóstico por Imagen de Elasticidad , Femenino , Estudios de Seguimiento , Infecciones por VIH/patología , Infecciones por VIH/virología , Voluntarios Sanos , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Factor de Crecimiento de Hepatocito/sangre , Humanos , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Factor Plaquetario 4/sangre , Estudios Prospectivos , Valores de Referencia , Respuesta Virológica Sostenida , Factor de Crecimiento Transformador beta1/sangreRESUMEN
OBJECTIVE: To define the course of HIV-HCV-coinfected patients with compensated and decompensated liver cirrhosis and to investigate the survival and the risk factors for death. PATIENTS AND METHODS: Ninety-two HIV-infected patients with HCV-related cirrhosis (50 of them without and 42 with previous decompensations) were prospectively followed up during a median period of 20 months. Clinical, biochemical, virological and immunological factors were analysed. Multivariate analyses were performed of those factors associated with decompensations and mortality. RESULTS: There were 168 readmissions due to liver-disease-related causes. A Child-Pugh index > or =6 in those without previous decompensations (hazard ratio [HR] 7.94, 95% confidence interval [CI] 1.59-39.58; P = 0.014), and Child-Pugh index > or =9 (HR 2.68, 95% CI 1.13-6.33; P = 0.003) and absence of HAART (HR 0.44, 95% CI 0.19-0.98; P = 0.048) in those with previous decompensations were independently associated with decompensation during the follow up. There were 27 deaths, 22 of them attributable to liver disease. Independent factors associated with liver-related mortality were a Child-Pugh index > or =9 (HR 6.24, 95% CI 2.31-16.85; P < 0.001), progression of Child-Pugh index during the follow up (HR 4.27, 95% CI 1.54-11.80; P = 0.008), more than one decompensation (HR 24.25, 95% CI 7.27-40.45; P < 0.001) and absence of HAART (HR 0.35, 95% CI 0.12-0.98; P = 0.002). CONCLUSIONS: Evolution from compensated to decompensated cirrhosis and death is influenced by markers of liver function and the absence of HAART. The importance of this last element must be adequately stressed.
Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Cirrosis Hepática/complicaciones , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Antivirales/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , VIH/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Masculino , Estudios Prospectivos , Factores de Riesgo , Carga ViralRESUMEN
OBJECTIVE: To find the survival and the predictors of death of HIV-infected patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD). DESIGN AND METHODS: A prospective cohort study set in the infectious diseases units of four tertiary care public hospitals in Andalucía, Spain. From a multicentric cohort of 2664 HIV/HCV-co-infected patients, all consecutive patients with HCV-related cirrhosis who presented with the first hepatic decompensation from January 1997 to June 2004 were followed-up and 153 patients were included. The survival and the demographic, HIV-related and liver-related factors associated with death were evaluated. RESULTS: Ninety-five (62%) patients died during the follow-up. In 79 (85%) individuals, the cause of death was liver related. The median survival time was 13 months. Independent predictors of survival were Child score [hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.08-1.37; P = 0.001], CD4+ cell count at decompensation lower than 100 cells/microl (HR, 2.48; 95% CI, 1.52-4.06; P < 0.001) and hepatic encephalopathy as the first hepatic decompensation (HR, 2.45; 95% CI, 1.41-4.27; P = 0.001). HAART was prescribed to 101 (66%) patients. The cumulative probability of survival in patients under HAART was 60% at 1 year and 40% at 3 years, versus 38 and 18%, respectively, in patients not treated with HAART (P < 0.0001). The HR (95% CI) of death in patients on HAART was 0.5 (0.3-0.9), (P = 0.03). CONCLUSIONS The survival of HIV/HCV-co-infected patients with ESLD is extremely poor. Immunosuppression and markers of severe liver disease predict liver-related mortality in these patients. HAART seems to be associated with a reduced liver-related mortality.
Asunto(s)
Infecciones por VIH/mortalidad , Hepatitis C/mortalidad , Cirrosis Hepática/mortalidad , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Enfermedad Crónica , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Masculino , Pronóstico , Estudios Prospectivos , España/epidemiología , Análisis de Supervivencia , Carga ViralAsunto(s)
Bacillus cereus/aislamiento & purificación , Bacteriemia/etiología , Infecciones por Bacterias Grampositivas/complicaciones , Enfermedad de Hodgkin/complicaciones , Rabdomiólisis/etiología , Choque Séptico/etiología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bacteriemia/microbiología , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Susceptibilidad a Enfermedades , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Resultado Fatal , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Huésped Inmunocomprometido , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Radioterapia Adyuvante/efectos adversos , Recurrencia , Rabdomiólisis/fisiopatología , Choque Séptico/microbiología , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.
Asunto(s)
Fibrosis/etiología , Infecciones por VIH/complicaciones , VIH , Hepacivirus , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/etiología , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Hepatitis C Crónica/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.
Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/etiología , Adulto , Alanina Transaminasa/metabolismo , Recuento de Linfocito CD4 , D-Alanina Transaminasa , Progresión de la Enfermedad , Femenino , VIH , Infecciones por VIH/inmunología , Hepatitis C Crónica/inmunología , Humanos , Incidencia , Cirrosis Hepática/enzimología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/inmunología , Masculino , Análisis MultivarianteRESUMEN
OBJECTIVE: Analysis of the influence of portal hypertension on intestinal permeability in HIV-infected patients with hepatitis C virus (HCV)-related cirrhosis and of the prognostic significance of consequent macrophage activation. METHODS: Twenty HIV-monoinfected patients, 70 patients with HIV-HCV coinfection, 20 of them with compensated and 50 with decompensated cirrhosis, and 20 healthy controls were evaluated for intestinal permeability [measured by lipopolysaccharide-binding protein (LBP) serum levels], macrophage activation [soluble CD14, soluble tumour necrosis factor receptor 55 Kd, and interleukin 6 (IL-6)], and activation of the rennin-angiotensin-aldosterone axis. Patients with decompensated cirrhosis were monitored for a median period of 429 days to analyze the prognostic factors implicated in survival. RESULTS: Patients with decompensated cirrhosis show increased LBP levels compared with HIV-monoinfected patients. Patients with increased LBP concentration showed elevated soluble CD14, soluble tumour necrosis factor receptor 55 Kd, and IL-6 levels. Twenty-two patients died, from liver-related causes, during the follow-up, and 2 more underwent liver transplantation. Child-Pugh index, CD4 T-cell count, plasma aldosterone and serum IL-6 concentrations independently predicted liver-related mortality. CONCLUSIONS: Increased intestinal permeability, as measured by serum LBP levels, observed in patients with HIV infection is significantly higher in patients with decompensated liver cirrhosis. Proinflammatory cytokines (IL-6) are prognostic markers of HIV-HCV-coinfected patients with decompensated cirrhosis.