Research

Area 3

Cholestasis and bone pathology.

Team leader

Strategic objectives

1. Study of the epidemiology, pathogenesis, diagnosis and treatment of adult chronic cholestatic disorders and autoimmune hepatitis.

2. Knowledge of the pathogenic mechanisms underlying pruritus and osteoporosis in primary biliary cirrhosis.

3. Definition of the therapeutic potential of different artificial liver support procedures in liver failure.

4. Investigation of the pathogenic and therapeutic aspects of metabolic bone diseases.

Main lines of research


The research lines of this team are divided into two associated groups.

Grups

Cholestasis (Associated)

PARES, ALBERT

(ICMDM)

1. Epidemiology, natural history and therapeutic response of chronic cholestatic disorders in adults. Determination of the prevalence and incidence of cholestatic disorders in adults in Spain, and definition of the factors associated with the forms of presentation of primary biliary cirrhosis – particularly of its asymptomatic forms. Evaluation of the factors conditioning treatment response, and proposition of new treatment regimens in patients showing suboptimum response to ursodeoxycholic acid. Relevance of the anionic exchanger AE2.

2. Diagnosis of autoimmune hepatitis. Development of a new diagnostic procedure for autoimmune hepatitis, based on peptide mapping – a project conducted in collaboration with 6 centers in Europe and one in Israel.

3. Pruritus in chronic cholestasis and treatment response to albumin dialysis: proteomic analysis. Evaluation of treatment response based on albumin dialysis in patients with chronic cholestasis and refractory pruritus, and identification of the eliminated peptides and proteins using MARS. Study of the skin of these patients, in order to identify potential molecules associated with pruritus. Evaluation of the bile acid fractions and their eliminated conjugates based on the MARS system, and their relationship to diminished pruritus.

4. Pathogenesis of osteoporosis and fracture development in primary biliary cirrhosis and other chronic cholestatic disorders. In collaboration with the Bone Metabolic Diseases group, evaluation of the factors underlying fractures in primary biliary cirrhosis, and the proposal of new therapeutic modalities for increasing bone mass. Likewise, investigation is conducted into the repercussion of retained bile acids and bilirubin in cholestasis upon the development of bone disease.

5. Artificial liver support. Evaluation of the safety and efficacy of different bioartificial liver and hepatic support systems in treating acute liver failure and exacerbated chronic liver failure. An open-label, prospective randomized study versus conventional treatment involving cryopreserved human hepatocytes from organs not apt for transplantation.

Bone metabolic disease (Associated)

GUANYABENS, NURIA

(ICEMEQ)

6. Osteoporosis in premenopausal women and in males. Study of the clinical characteristics and mechanisms involved in the development of the disorder.

7. Osteoporosis in primary biliary cirrhosis. Clinical and “in vitro” analysis. Evaluation of the key factors in the low development of bone mass and the appearance of fractures, and proposal of new therapeutic protocols. In addition, evaluation of the effect of bilirubin and bile acids upon primary osteoblasts in culture.

8.Osteoporosis in liver transplantation. Evaluation of the hormonal changes regulating bone remodeling in this pathology.

9. Analysis of the efficacy of vertebroplasty. Evaluation of the clinical usefulness and the complications of this procedure in the treatment of pain secondary to recent vertebral fracture due to osteoporosis.

10. Evaluation of bone remodeling regulators. Evaluation of the role of sclerostin and, through this protein, investigation of the influence of osteocytes upon bone loss associated with glucocorticoid treatment and immobilization.