RESUMEN
BACKGROUND: Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression. AIM: To evaluate serum vitamin D as prognostic parameter in HCC, we performed a prospective cohort study. METHODS: HCC patients were prospectively recruited and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal-Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25(OH)D3 levels and overall survival (OS) was assessed in uni- and multivariate Cox regression models. RESULTS: Two-hundred patients with HCC were included. The mean follow-up time was 322 ± 342 days with a range of 1-1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25(OH)D3 concentration was 17 ± 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331-3.719, P = 0.002). Furthermore, very low 25(OH)D3 levels were associated with mortality independently from the MELD score and high alpha-Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model. CONCLUSIONS: We conclude that 25(OH)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.
Asunto(s)
Calcifediol/sangre , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Deficiencia de Vitamina D/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática/complicaciones , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D/epidemiología , alfa-Fetoproteínas/metabolismoRESUMEN
The levels of the liver-specific microRNA-122 (miR-122) circulating extracellularly in the blood have been shown to be increased upon liver damage. However, it is unknown if the levels of serum miR-122 are altered during antiviral therapy and reflect the therapeutic success. Here, we investigated miR-122 serum levels in patients with chronic hepatitis C virus (HCV) genotype 1 infection during antiviral therapy with pegylated interferon and ribavirin. Therefore, sera from 60 patients with chronic HCV infection genotype 1 showing sustained virological response (SVR), non-response or relapse to therapy obtained at baseline, 4, 12, 24 weeks, end of treatment and follow-up were analysed retrospectively for miR-122 content by quantitative real-time reverse transcription PCR. The time courses of miR-122 were correlated with HCV RNA as well as standard liver parameters. We found that while there was no relation between serum miR-122 and HCV RNA levels at baseline, the decline in HCV RNA upon beginning of the therapy closely correlated with the reduction of serum miR-122 in the three different patient groups. Moreover, the serum miR-122 level correlated well with alanine aminotransaminase, a marker of ongoing liver damage. At follow-up serum miR-122 levels remained low in SVR, but increased to baseline levels in patients not responding or showing relapse to therapy. In contrast, the serum concentration of the ubiquitously expressed miR-16 did not change during therapy. We conclude that the serum level of miR-122 well reflects the success of interferon/ribavirin therapy in patients with chronic HCV infection.