Bone mineral density, bone turnover markers and cytokines in alcohol-induced cirrhosis.

AIMS: Liver cirrhosis is a risk factor for osteoporosis. However, the pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis (AC) is not well understood. Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL-2R), activation markers of cellular immunity, correlate with clinical activity and severity of the AC. The aim of this study is to evaluate the association of these soluble markers with the development of osteoporosis in patients with AC. METHODS: We studied 33 consecutive patients with AC and 24 healthy volunteers. Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay. Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay. We also determined serum levels of osteocalcin and bone alkaline phosphatase as biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D-Pyr) as marker of bone resorption. RESULTS: Patients with AC had reduced BMD (expressed as z-score) in all sites (LS: P < 0.001 and FN: P < 0.05). Serum concentrations of sTNF-R55 were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.001). Serum levels of sTNF-R55 positively correlated with D-Pyr urinary excretion (r = 0.354; P = 0.01). Serum levels of sIL-2R were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.05). CONCLUSIONS: There is a relation between activation of the cellular immunity and osteoporosis in AC. Bone mass loss could be related to the increased bone resorption found in these patients.

[Soluble interleukin-2 and tumor necrosis factor receptor in liver cirrhosis. Relationship with clinical severity and prognosis]. / Receptores solubles de la interleucina 2 y del factor de necrosis tumoral en la cirrosis hepática de diversas etiologías. Relación con el pronóstico y la gravedad clínica.

BACKGROUND AND OBJECTIVE: The mechanism responsible for the beginning and progression of hepatic injury in liver cirrhosis of viral and alcoholic etiology are unknown currently. However, there are abnormalities in the immune system which may be implied in the pathogenesis. PATIENTS AND METHOD: The concentrations of the soluble receptor of tumor necrosis factor (sTNF-R55) and the soluble receptor of interleukin-2 (sIL-2R) in 49 cirrhotic patients were determined by enzyme-linked inmunoassay. Patients were grouped according to the etiology (33 alcoholic and 16 viral) and prognosis (Child-Pugh classification) and they were compared with the values obtained in 26 healthy non-drinkers who made up the control group. RESULTS: The concentrations of sTNF-R55 and sIL-2R were significantly higher in both groups of patients when compared with controls. We found significant differences in sTNF-R55 concentrations in viral and alcoholic but not in sIL-2R concentrations. There was a positive correlation between the concentrations of both receptors and the degrees of Child-Pugh classification, as well as with albumin, total bilirubin and alkaline phosphatase (all of them parameters related to the severity and prognosis of liver cirrhosis). CONCLUSIONS: The serum concentrations of soluble receptors of tumor necrosis factor and interleukin-2 correlate with the prognosis of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T lymphocytes, monocytes and macrophages, in liver cirrhosis.

Receptores solubles de la interleucina 2 y del factor de necrosis tumoral en la cirrosis hepática de diversas etiologías. Relación con el pronóstico y la gravedad clínica / Soluble interleukin-2 and tumor necrosis factor receptor in liver cirrhosis. Relationship with clinical severity and prognosis

FUNDAMENTO Y OBJETIVO: Los mecanismos responsables del inicio y la progresión de las lesiones hepáticas en la cirrosis hepática de etiología viral y alcohólica no se conocen completamente en la actualidad, pero existen evidencias de la intervención de alteraciones del sistema inmunitario y de la producción de citocinas en la patogenia de estos procesos. PACIENTES Y MÉTODO: Se han determinado mediante enzimoinmunoanálisis las concentraciones séricas del receptor soluble del factor de necrosis tumoral (sTNF-R55) y del receptor soluble de la interleucina 2 (sIL-2R) en 49 pacientes diagnosticados de cirrosis hepática. Se agruparon según su etiología (33 casos de cirrosis alcohólica y 16 de cirrosis viral) y pronóstico (siguiendo la clasificación de Child-Pugh) y los valores séricos se compararon con los obtenidos en 26 sujetos sanos no bebedores que formaban el grupo control. RESULTADOS: Las concentraciones séricas de sTNF-R55 y de sIL-2R han sido significativamente más altas en el grupo de pacientes. No se han encontrado diferencias significativas en las concentraciones de sIL-2R entre las cirrosis hepáticas de etiologías viral y alcohólica, pero sí en las concentraciones de sTNF-R55. Existe una correlación entre las concentraciones de ambos receptores y los grados de Child-Pugh, así como con la albúmina, la bilirrubina total y la fosfatasa alcalina, todos ellos parámetros relacionados con la gravedad y el pronóstico de la cirrosis. CONCLUSIONES: Las concentraciones séricas de sTNF-RSS y de sIL-2R se correlacionan con el pronóstico de la cirrosis hepática con independencia de su etiología. Este hecho puede ser reflejo de la estimulación de las células T y de los monocitos y macrófagos e indicaría que el mecanismo de destrucción hepatocelular puede estar más relacionado con la persistencia de la respuesta inmunitaria que con el daño directo producido por el alcohol o los virus de la hepatitis B o C (AU)