Peripheral blood dendritic cells in alcoholic and autoimmune liver disorders.

Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N = 26) and primary biliary cirrhosis (N = 20). DCs isolated from the peripheral blood of recruited participants were stained with monoclonal antibodies against blood dendritic cell antigens (BDCAs) and estimated using the flow cytometry. Myeloid DCs were defined as BDCA-1(+)/CD19(-) cells, and lymphoid DCs as BDCA-2(+)/CD123(+) cells. Total numbers of circulating DCs in subjects with some liver diseases were markedly lower than in the healthy participants (p = 0.03). There was a significantly lower percentage of circulating BDCA-2(+)/CD123(+) (p = 0.02), and a tendency for the percentage of circulating BDCA-1(+)/CD19(-) cells to decrease in patients with liver diseases compared to the controls (p = 0.09). These results may suggest that decreased numbers of DCs may be responsible for reduced adaptive immune responses and increased susceptibility to infections and cancer development observed in patients exposed to alcohol. Moreover, numerical abnormalities of DCs may contribute to the breakdown of self-tolerance, a feature of autoimmune diseases.

Prevalence of spontaneous bacterial peritonitis in asymptomatic inpatients with decompensated liver cirrhosis - a pilot study.

PURPOSE: To assess the prevalence of spontaneous bacterial peritonitis (SBP) in asymptomatic patients with decompensated liver cirrhosis. MATERIAL AND METHODS: Patients (pts) with symptoms of decompensation of liver cirrhosis, ascites, and no signs indicating SBP were included to our study. Exclusion criteria include: 1/ clinical symptoms of infection, 2/ developing de novo or worsening hepatic encephalopathy, 3/ gastrointestinal bleeding within the last month, 4/ renal failure, 5/ antibiotic treatment or norfloxacin prophylaxis at admission. About 60 ml of ascitic fluid were drawn for lab examination. Pathologic assessment for atypical cells was also performed. RESULTS: 37 patients fulfilled inclusion criteria. Their mean age was 56.2 ± 12.1. The Child-Pugh classification revealed 13 (35.1%) patients of class B and 24 (64.9%) patients of class C. The mean Model for End-Stage Liver Disease score in this group was 16.6 ± 6.8. The mean ascitic protein content was 1.85 ± 1.09 g/dL and mean neutrophil count 144.8 ± 445.1/mm3. Ascitic fluid analysis revealed: signs of bacterascites in 6 of 37 (16.2%) pts; neutrocytic ascites in 1 of 37 (2.7%) pts; and 2 of 37 (5.4%) pts met criteria for SBP. C-reactive protein level was the best predictor of infection [SBP(+) 47.9 ± 40.9 versus SBP(-) 11.7 ± 5.1; p= 0.0005]. CONCLUSIONS: The prevalence of SBP in asymptomatic cirrhotics with ascites is low. We observed the trend towards more frequent occurrence of the infection in patients suffered from severe liver disease (Child-Pugh C group).

Non-variceal upper gastrointestinal bleeding--guidelines on management.

In gastroenterology non-variceal upper gastrointestinal bleeding is health hazard. Frequency of occurrence accounts for 40-150 cases per 100000 inhabitants with death rate of 7-14%. Researches which goal is to improve treatment effectiveness as well as to establish standardized procedures for managing patients with symptoms of non-variceal upper gastrointestinal bleeding; have been conducted since many years. At the moment of admission, designed standards enable appropriate elaboration of patients' health state, referral to the right clinic and implementation of the most accurate treatment methods. Increase of suppression of primary bleeding as well as prevention of recurrence is associated with dynamic development of endoscopic treatment methods as well as with optimization of pharmacological treatment. In significant percentage, efficiency of non - variceal bleedings treatment depends on clinic's character (availability of equipment, experience of personnel) and on cooperation between several specialists (including gastroenterologist, surgeon, anesthetist, operative radiologist). Aim of the work is to present the latest evaluation of the mentioned subject, based on accessible literature. This work includes the basic principles for determination of bleeding intensity and risk of its recurrence as well as directions referring to fluids resuscitation and to monitoring of patients. Information on currently applied endoscopic methods for inhibition of non variceal upper gastrointestinal bleeding (injection, mechanical and thermo-coagulation techniques), comparison of their efficiency and possibility of application is provided in the work. The paper work also presents the newest directives for pharmacological treatment and guidelines for possible surgical treatment.

Pathophysiology of portal hypertension.

In last years significant progress in recognizing mechanisms of portal hypertension pathophysiology was done. However, some unclear topics in this disease still exist. Portal hypertension is primarily caused by the increase in resistance to portal outflow and secondly by an increase in splanchnic blood flow. Portal hypertension is associated with changes in the intrahepatic, systemic, and portosystemic collateral circulation. Alterations in vasoreactivity (vasodilation and vasoconstriction) play a central role in the pathophysiology of portal hypertension by contributing to increased intrahepatic resistance, hyperdynamic circulation, and expansion of the collateral circulation. Among vasoactive substances which are activated in portal hypertension nitric oxide (NO) is considered as the most important vasodilator. Endothelin-1 and cyclooxygenase-derived prostaglandins are the main vasoconstrictor factors. The imbalance between the hyperresponsiveness and overproduction of vasoconstrictors and the hyporesponsiveness and impaired production of vasodilators are the mechanisms responsible of the increased vascular one in the sinusoidal area of the liver. New concepts in the pathophysiology of portal hypertension find the significant role of hepatic stellate cells activated by endothelial factors which cause vascular remodeling as an adaptive response of the portal vessels wall. The most frequent causes of portal hypertension include portal vein thrombosis, storage diseases of the liver, hepatic cirrhosis (independent of etiology), hepatic veins thrombosis and schistosomiasis. Understanding the pathophysiology of portal hypertension could be of great utility in preventing and curing the complications of portal hypertension, such as esophageal varices, hepatic encephalopathy, ascites.

The role of adenosine receptors for pancreatic blood flow in caerulein-induced acute pancreatitis.

PURPOSE: The aim of our study was to evaluate the possible influence of adenosine receptors agonists and antagonists on pancreatic blood flow (PBF) and the development of acute pancreatitis (AP) in rats. MATERIAL AND METHODS: Ninety male Wistar rats were subdivided into ten equal groups, nine rats in each. The study was carried out in two stages. In the first one the first group (control) received i.v. saline infusion for 12 hours. The groups 2-5 (the first stage) received i.v. caerulein infusion as in the first group, but with pretreatment with: in the second group--DPCPX (A1 receptor antagonist), in the third group--CGS 21680 (A2 receptor agonist), in the fourth group--ZM 241385 (A2 receptor antagonist), in the fifth group--IB-MECA (A3 receptor agonist). In the second stage the first group received i.v. caerulein infusion at the dose of 5 micrograms/kg/h for 12 hours. The groups 2-5 (the second stage) received i.v. caerulein infusion as in the first group, but with pretreatment with: in the second group--DPCPX (A1 receptor antagonist), in the third group--CGS 21660 (A2 receptor agonist), in the fourth group--ZM 241385 (A2 receptor antagonist), in the fifth group--IB-MECA (A3 receptor agonist). Pancreatic blood flow was measured by laser Doppler flowmetry. Pancreatic inflammation was evaluated by serum alpha-amylase activity, pancreatic weight and histological changes in the pancreatic tissue. RESULTS: We observed a significant attenuation of serum alpha-amylase activity increase (19.1 +/- 2.8 kIU/L vs 30.12 +/- 2.64 kIU/L), pancreatic weight (expressed as percentage of rat's body weight--0.85 +/- 0.16% vs 1.25 +/- 0.14%), and improvement of PBF (79.8 +/- 6.1% vs 60.1 +/- 3.6%), a reduced degree of pancreatic tissue damage (oedema, leukocyte infiltration, vacuolisation of acinar cells) in the third group (CGS 21680 + caerulein) compared with the first group in the second stage (only caerulein infusion). Neither agonists nor antagonists exerterd any appreciable effects on measured parameters in healthy rats. CONCLUSIONS: Pretreatment with A2 receptors agonist seems to be protective against the damage to the pancreas during the course of caerulein-induced acute pancreatitis in rats. This effect could be due to improvement of pancreatic blood flow. This finding could have some therapeutic implications.

Impact of interferon-alpha therapy on the serum level of alpha-fetoprotein in patients with chronic viral hepatitis.

PURPOSE: Assessment of the long-term effect of interferon-alpha (IFN-alpha) treatment on the serum level of hepatocarcinogenesis marker--alpha-fetoprotein (AFP), in patients (pts) with chronic viral hepatitis (c.v.h.) type B and C. MATERIAL AND METHODS: Thirty seven pts (21 with HCV and 16 with HBV infection; 20 women, 17 men, aged 24-62) were included in the study. The pts were administered IFN-alpha in the dose of 9-15 MU per week, thrice weekly, for 16 weeks (HBV group) and 24-52 weeks (HCV group). The effectiveness of IFN-alpha treatment was evaluated on the basis of the HBV DNA and HCV RNA level in the blood. The serum AFP values were determined before and 4-7 years after IFN-alpha treatment. RESULTS: The baseline serum AFP level was increased in 26 out of 37 pts (70%) (14/21 from HCV group; 12/16 from HBV group). After the 4-7 years' follow-up it remained elevated only in 2 out of 37 pts (5%). AFP values significantly decreased after IFN-alpha treatment (17.58 +/- 19.09 IU/ml vs 7.95 +/- 21.78 IU/ml; p < 0.05; normal range 0-5 IU/ml) in both HBV and HCV, responder and non-responder groups. CONCLUSIONS: IFN-alpha therapy significantly decreases the serum AFP level in patients with chronic viral hepatitis B and C. Its beneficial clinical effects have been observed both in responders and in non-responders. It could diminish the risk of liver carcinogenesis, however further studies are required to elucidate this issue.