Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.

PURPOSE: The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly. METHODS: This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA. RESULTS: The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness. CONCLUSION: This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.

A randomized, open-label, comparative, 6-month trial of oral ultra-low doses of antibodies to tumor necrosis factor-alpha and diclofenac in rheumatoid arthritis.

Artrofoon (oral ultra-low doses of antibodies to TNF-alpha is a novel drug approved by the Russian Ministry of Health for the treatment of rheumatoid arthritis (RA). The aim of this study was to assess clinical efficacy and safety of artrofoon in RA compared with diclofenac. In a 6-month, randomized, open-label, comparative trial, 60 patients with active RA (eight men and 52 women aged 23 to 62, mean disease duration 10 years) received artrofoon (8 tablets daily, n = 30) or diclofenac (100 mg daily, n = 30). RA signs and symptoms as well as serum levels of inflammatory markers were evaluated before treatment and at months 1, 3 and 6. Most patients in the artrofoon group showed a 20% improvement in major RA symptoms by the end of the study. The clinical effect rose gradually reaching maximum at month 6. In the artrofoon group, 57% of the patients achieved an American College of Rheumatology (ACR) 20% criteria (ACR20) by month 6 versus 20% of those receiving diclofenac. In some patients in the artrofoon arm, serum proinflammatory cytokine levels significantly decreased (> or = 25% reduction). Diclofenac produced a less pronounced clinical effect, and no changes in cytokine profile. Unlike conventional nonsteroidal anti-inflammatory drugs, artrofoon produced no adverse effects and the overall tolerability and safety were excellent. A half-dose treatment with artrofoon (4 tablets daily) was able to sustain clinical improvements over a 6-month follow-up period. To conclude, artrofoon is a safe and effective treatment for rheumatoid arthritis that acts by influencing the inflammatory process.

Experimental and clinical study of the effect of artrofoon on proinflammatory cytokine production.

The effect of Artrofoon on the production of proinflammatory cytokines was evaluated in experiments on mice with collagen-induced arthritis and in a clinical study on patients with rheumatoid arthritis. Artrofoon produced an antiinflammatory effect on animals with collagen-induced arthritis and reduced clinical signs of inflammation in patients with rheumatoid arthritis. These changes were accompanied by a significant decrease in the production of tumor necrosis factor-alpha and interleukin-1beta.

The clinical significance of immune reactions with some streptococcal antigens in rheumatoid arthritis.

The level of antibodies and delayed-type hypersensitivity to the group specific polysaccharides and cell wall proteins of groups A, B, C and G streptococci was determined in 247 patients with rheumatoid arthritis (RA) as well as in healthy persons and in patients with other articular disorders by means of an enzyme linked immunosorbent assay, passive hemaglutination and leukocyte migration inhibition tests. An increase of the immune response to antigens of group B streptococcus was found in patients with RA. The greatest sensitization against these antigens was typical for high disease activity of short duration, and a rapidly progressive course of RA. High titers of antibodies to polysaccharide of group B streptococcus appeared in the synovial fluid in the early stages of the clinical development of RA. Values of immune response to streptococcal antigens correlated well with the titer of rheumatoid factor and the concentration of immunoglobulins and immune complexes. The presence of group B streptococcus in the urogenital tract appeared more often in patients with RA than in healthy persons. The possibility of a triggering role for immune reactions with antigens of group B streptococcus in the immunopathological process of RA is discussed, as well as the diagnostic significance of our results.