[Polish multicenter study on safety and efficacy of adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)]. / Wieloosrodkowe badanie bezpieczenstwa i skutecznosci preparatu dipiwoksyl adefowiru w leczeniu przewleklego wirusowego zapalenia watroby typu B u doroslych z opornoscia na lamiwudyne (HEP 2008).

Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.

sPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C and Association with Response to Antiviral Therapy.

AIM: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). METHODS: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. RESULTS: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<001) with no difference between responders and nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. CONCLUSIONS: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

[Serum levels of vascular endothelial growth factor in chronic hepatitis C patients treated with interferon alpha and ribavirin]. / Stezenie czynnika wzrostu sródblonka naczyn w surowicy krwi chorych z przewleklym wirusowym zapaleniem watroby typu C leczonych interferonem alfa i rybawiryna.

UNLABELLED: Liver fibrosis is a result of disturbed balance between extracellular matrix protein synthesis and degradation. Growth factors may play the meaningful role in pathogenesis of fibrosis. The aim of the study was the assessment of VEGF role in pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and evaluation of the influence of antiviral therapy on VEGF levels depending on treatment results. MATERIAL AND METHODS: Study group included 100 CHC patients with fibrosis (Scheuer: 1-4 points). Control group included 30 HCVAb-positive subjects with normal ALT, without fibrosis (Scheuer: 0 points). From all subjects blood samples were taken at the beginning of the study. From study group patients blood samples were also collected after the treatment with Rebetron. RESULTS: There was no significant difference in VEGF levels between CHC group and control group. Significant negative correlation between VEGF levels and inflammatory activity (R = -0.40; p < 0.01) and fibrosis stage (R = -0.30; p < 0.05) was observed. After antiviral treatment significant elevation of VEGF occurred in responders (112.8 vs. 315.03 pg/ml; p < 0.05), but not in non-responders. CONCLUSIONS: 1. Progression of liver lesions is correlated with reduction of VEGF levels. 2. Good therapeutic effect is connected with the elevation of VEGF levels. 3. Angiogenesis stimulation by VEGF probably is an important element in regenerative processes accompanying fibrosis regression.

Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-beta1, vascular endothelial growth factor, and basic fibroblast growth factor in patients with chronic hepatitis C.

AIM: To assess the role of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and to evaluate the influence of the antiviral therapy on above parameter levels depending on the treatment results (complete response or no response). METHODS: Study group included 100 patients with CHC, in whom fibrosis in liver specimens was assessed (Scheuer fibrosis score: 1-4 points). Control group included 30 subjects with antibodies anti-HCV present and persistently normal ALT level, without fibrosis (Scheuer fibrosis score: 0 points). Concentration of studied parameters was assayed in the serum by immunoenzymatic method before and after the therapy with interferon alpha-2b and ribavirin. RESULTS: TGF-beta1 levels were significantly higher in the study group compared to the control group (35.89 vs 32.37 ng/mL; P=0.023). Such differences were not found in VEGF and bFGF levels. In patients showing complete response (negative HCV RNA and normal ALT level), significant increase in VEGF (112.8 vs 315.03 pg/mL; P<0.05) and bFGF (2.51 vs 15.79 pg/mL; P=0.04) levels were found. Significant decrease in TGF-beta1 level was observed both in responders (37.44 vs 30.02 ng/mL; P=0.05), and in non-responders (38.22 vs 30.43 ng/mL; P=0.043). bFGF levels before the treatment were significantly lower (2.51 vs 5.94 pg/mL; P=0.04), and after the treatment significantly higher (15.79 vs 4.35 pg/mL; P=0.01) in patients with complete response than in those with no response. CONCLUSION: Among the analyzed parameters TGF-beta1 seems to play the most important role in the pathogenesis of fibrosis in CHC. Levels of this factor are significantly lower in subjects who do not have fibrosis developed in them. Good therapeutic effect in CHC patients is associated with significant changes in TGF-beta1, VEGF, and bFGF levels. bFGF seems to have the highest usefulness in the prognosis of treatment efficacy.

[Quantitative assessment of mRNA TGF-beta1 in liver tissue in connection with serum mean daily level of TGF-1 in chronic hepatitis B patient]. / Ocena ilosciowa mRNA TGF-beta1 w bioptacie watroby w powiazaniu ze sredniodobowym steeniem TGF-beta1 w surowicyz u chorych z przewleklym zapaleniem watroby typu B.

Monitoring of fibrosis process with the use of histopathologic studies on liver's bioptates is limited, so it is attempted to find reliable, obtained with less invasive methods, sensitive and reflecting fibrosis dynamics markers of this process. The aim of the study was simultaneously to assess liver's expression as well as circadian and mean daily TGF-betal concentration in serum of patients with chronic hepatitis type B in comparison to control group. Studies were performed on 50 patients (9 women, 41 men) aged 45.9 +/- 2.3 years with chronic hepatitis type B. Control group consisted of 20 patients (mean age 38.6 +/- 3.7 years), in which so called minimal changes without fibrosis were observed in histophatologic bioptate of liver. Blood for studies was collected every 4 houres during the day. Serum concentration of TGF-betal was assessed with the use of ELISA method, and expression of mRNA TGF-betal in liver with QRT-PCR method. No significant difference between circadian as well as mean daily serum TGF-betal concentration beetwen control group and the group with chronic hepatitis type B was shown. Increased expression of mRNA, TGF-betal in bioptate of liver of patients with chronic hepatitis type B in comparison to control group was noted. In "minimal changes" control group presence of significant positive correlation between expression of mRNA TGF-beta1 in liver and concentration of this cytokine in serum was shown, in the group of patients with chronic hepatitis B this connection was not noted.

[Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final report)]. / Pegylowany interferon alpha-2a z rybawiryna w leczeniu przewleklego wirusowego zapalenia watroby typu C (raport koncowy z badan).

UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

[Serum aminoterminal peptide of type III procollagen (PIIINP) and transforming growth factor-beta1 (TGF-beta1) levels in patients with chronic hepatitis B and C]. / Stezenia aminoterminalnego propeptydu prokolagenu typu III (PIIINP) oraz transformujacego czynnika wzrostu-beta 1 (TGF-beta 1) we krwi obwodowej chorych z przewleklym zapaleniem watroby typu B i C.

Fibrosis is the process accompanying majority of chronic diseases of liver, independent of etiological factor and leading to cirrhosis and hepatic failure. Monitoring fibrosis process by liver's biopsy is limited, so many attempts are undertaken to assess concentrations of definite proteins in blood, which could be easily accessible marker of intrahepatic process. It seems, that among others, determinations of blood concentration of aminoterminal propeptide of procollagen III--index of collagen's III synthesis and TGF-beta 1--cytokine of antiproliferative action and inhibiting hepatocytes' growth, yet inducing fibroblasts' growth and stimulating fibrosis process brings out such a possibility. The aim of the study was simultaneous determination of TGF-beta 1 and PIIINP concentration in blood of patients with chronic hepatitis B and C before interferone's therapy in comparison to healthy controls, assessment of the parameters in dependence on stage of liver fibrosis and determination of correlation between TGF-beta 1 and PIIINP. Studies were performed in 40 patients with chronic hepatitis B (CAH B) and 35 patients with chronic hepatitis C (CAH C). Significantly increased serum concentrations of TGF-beta 1 as PIIINP in both groups of patients (CAH B and CAH C; grading 2-3, staging 1-2) in comparison with control group was noted. Significant positive correlation of TGF-beta 1 and PIIINP serum concentrations in both groups of patients was observed. There was not significant changes in PIIINP serum levels in patients with hepatitis B and C in dependence on stage of liver fibrosis (staging 1 vs staging 2) but TGF-beta 1 serum levels was significantly increased in CAH B and C patients with higher stage of liver fibrosis process. On the base of obtained results, it seems that changes in TGF-beta 1 concentrations in blood reflect "grading" and "staging" and can be a marker of intensification of intrahepatic fibrosis process whereas PIIINP levels in blood have rather the relation with "grading".

[Cardiovascular effects of growth hormone deficiency in adults]. / Niedobór hormonu wzrostu u doroslych a uklad sercowo-naczyniowy.

The role of growth hormone (GH) in maintaining normal cardiovascular function and the influence of GH deficiency and GH replacement therapy on cardiovascular risk are presented.

Acromegaly and the risk of cancer.

Recent studies suggest that acromegaly might predispose to an increased risk of benign and malignant neoplasms, thus influencing the final outcome of the disease. The exact mechanism of neoplastic events in acromegaly has not been completely clarified. Several studies indicate an autocrine-paracrine role for growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the proliferation of normal and neoplastic cells. The paper reviews the results of molecular, clinical and epidemiological data supporting a role for GH-IGF-I action in colon, prostate, breast and lung carcinogenesis inpatients with acromegaly.