[Cytokines and the liver in health and disease]. / Tsitokini i cheren drob pri zdrave i bolest.

Cytokines are a group of proteins with autocrine, paracrine and endocrine activities which provide communication among hepatic cells and other cells and tissues of the man. Active in minute quantities, the cytokines activate and regulate homeostasis and cellular repair through effects on cell growth, differentiation and receptor expression and cell-mediated immunity. Cytokines--IL-1, IL-2, IL-6, IL-8 IL-10, IL-12, TNF-alfa, PDGF and others, modulate liver metabolism in health and disease, physiological and pathologic liver functions and the evolution of liver inflammation and injury to hepatic fibrosis and liver cirrhosis. Data concerning the use of a recombinant form of Interleukin-10 and Interleukin-12 in the treatment of chronic liver disease (chronic viral hepatitis, fibrosis, cirrhosis, alcoholic liver disease) and cell-mediated immunity regulation are widely discussed in the review.

[Sodium in clinics and complications of liver cirrhosis]. / Natriiat v klinikata i uslozheniiata na chernodrobnata tsiroza.

The changes in sodium homeostasis most frequently are expression of water-electrolyte balance disturbances in patients with liver cirrhosis. Hyponatremia of water excess is found in 35% of the patients with cirrhosis and ascites. This disturbance is most frequently connected with raised antidiuretic hormone (vasopressin) secretion and is realized by including of nonosmotic stimulating mechanisms. The vasopressin plays a leading role in pathogenesis of disturbed water metabolism in the liver cirrhosis. Some patients with hepatorenal syndrome are established with highest plasma vasopressin concentrations. Gene expression of the regulation of kidney vasopressin-sensitive water channels (aquaporin-2 proteins) is also raised in the liver cirrhosis. Using in practice vasopressin-type 2 (V-2) receptor antagonists gives hopeful results in medical treatment of water-electrolyte disturbances in patients with advanced liver cirrhosis.

[The immunological changes and prognosis of cholestatic jaundice in choledocholithiasis]. / Imunologichni promeni i prognoza na kholestatichnata zhultenitsa pri kholedokholitiaza.

Fifty-six patients presenting choledocholithiasis are covered by the study. They are distributed in groups according to total serum bilirubin values, as follows: with total serum bilirubin < 20 mumol/l--17; 20 to 50 mumol/l--13; 50 to 80 mumol/l--9; and > 80 mumol/l--17 cases. Sixty healthy, sex and age matched individuals serve as controls. The immunocompetent cells are determined flow cytometrically with FACS TAR (BECTON DICKINSON). A panel of monoclonal antibodies (Becton Dickinson) is used, including: Leu4 (anti-CD3+)--T-lymphocytes; Leu3a (anti-CD4+)--helper/inducer lymphocytes; Leu2a (anti-CD8+)--suppressor/cytotoxic cells; Leu11a (anti-CD16+)--cells with a natural killer activity; Leu12 (anti-CD19+)--B-lymphocytes. As shown by the obtained results there are no changes in cell-mediated immune response among choledocholithiasis patients with normal values of total serum bilirubin. Parallel to increasing the degree of cholestatic jaundice (ChJ) severity, the absolute values of lymphocytes and their subpopulations decrease. The deficit is most clearcut in patients presenting the highest degree cholestasis, as compared to healthy individuals ((Ly: 1690 +/- 174/2277 +/- 186; CD3+: 956 +/- 119/1793 +/- 67; CD4+: 607 +/- 83/988 +/- 80; CD8+: 239 +/- 52/639 +/- 85; CD16+: 146 +/- 38/367 +/- 55; CD19+: 181 +/- 33/200 +/- 13. In 11 cases with early restored biliary drainage (by the 21st day of ChJ), total serum bilirubin decreases within 10 days after the operation (choledochoduodenoanastomosis), whereas lymphocytes and their subpopulations show an increase in absolute values. Two months after choledochoduodenoanastomosis, the total serum bilirubin and the lymphocyte subpopulations being examined regain their normal values. In two instances with rather late biliary drainage recovery (30 days after ChJ) the total serum bilirubin and lymphocyte subpopulations under study show no tendency whatsoever towards normalization at 10 days postoperatively. The results of the study demonstrate that the poor prognosis among ChJ patients is also related to inhibition of the cell-mediated immune response. The early biliary drainage recovery (at 21 days of ChJ) exerts a more favourable effect on the immune system, and improves the prognosis of the clinical course run by the pathological process.

[The European consensus on hepatitis C]. / Evropeiski konsensus za khepatit C.

The European Association for the Study of the Liver (EASL) International Consensus on Hepatitis C made by 72 experts in hepatology, epidemiology and virology at the EASL Consensus Conference, Paris, February, 1999 and confirmed by the 34th EASL Annual Meeting, Naples, 8-12 april 1999, is widely reviewed. Some newest and more effective strategies for treatment of the chronic viral hepatitis C were discussed during the Naples EASL meeting. Higher doses interferons (interferon-alpha or consensus interferon) plus ribavirin (or combination ribavirin and amantadine) for a longer period--12 months, improved efficacy of the treatment of chronic hepatitis C. An ultrarapid HCV clearance by daily hgh-dose interferon-alpha induction therapy in the start of the management plus ribavirin was achieved and discussed in naive patients and in nonresponders to standard therapy. A gene therapy by an effective genetic vaccine against HCV infection was widely discussed, too. Hepatitis C is an enormous present and future health burden to the world. Not until 2010, the most of therapeutic problems in patients with chronic persisted HCV infection would be resolved.

[The extrahepatic manifestations in hepatitis C virus (HCV) infection]. / Izvunchernodrobni proiavi pri infektsiia s khepatit C virus (HCV).

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.

[The systemic and local immune responses in patients with alcoholic liver cirrhosis depending on hepatitis C viral infection (HCV)]. / Sistemen i lokalen imunen otgovor pri bolni s alkokholna chernodrobna tsiroza v zavisimost ot infektsiiata s khepatit C-virus (HCV).

The systemic and local immune response was studied in patients with alcoholic liver cirrhosis and the significance of the combined infection with HCV. To investigation were submitted 23 patients (16 males and 7 females) aged between 29 and 61 years with alcoholic liver cirrhosis. Of them 14 were anti-HCV(+) and 9 anti-HCV(-). As controls were used 36 clinically healthy individuals, matched by sex and age to the patients. The flow cytometric analysis of the lymphocyte (Ly) populations from the peripheral venous blood and of cells from liver aspirate obtained by blind liver biopsy according to Menghini, was performed with FacsTAR (Becton Dickinson). In the anti-HCV(-) patients, as compared to the controls (patients/controls) the Ly subpopulations were increased: CD3+/mm3:2010 +/- 738/1440 +/- 388; CD4+/mm3:1350 +/- 441/991 +/- 442; IL-2R+/mm3:133 +/- 78.5/31 +/- 20. In the anti-HVC(+) patients we established increased IL-2R+/mm3: 170 +/- 126 as compared with the controls and anti-HCV(-) patients. The suppressor/cytotoxic (CD8+) Ly with their suppressor (CD8+CD11b+) and cytotoxic (CD8+CD11b-) subpopulations and natural killers (CD16+) had a tendency to diminution in the anti-HCV(+) patients. In both examined groups the B (CD19+) Ly were non-significantly increased. The flow cytometric analysis of the cells from the liver specimen in 9 patients of whom 3 anti-HCV(-) and 6 anti-HCV(+) revealed that CD3+ on the average were 32.8% +/- 20.4% (from 9.2% to 65.1%); CD4+ were 21.1% +/- 7.4% (from 12.0% to 34.5%); CD8+ 22.6% +/- 11.8% (from 4.7% to 39.8%) and their values were higher in the anti-HCV(+) patients; the correlation CD4+/CD8+ = 1/1.09 +/- 0.6; CD16+ were 12.9% +/- 10.1% (from 1.9% to 34.8%); CD19+ varied from 3.2% to 27.8%; monocytes (CD14+) were 7.69% +/- 5.65 (from 2.0% to 15.8%) from the cells of the aspirate and their percentage contents was higher in the anti-HCV(+) patients. The results of out study revealed that in patients with alcoholic liver cirrhosis changes in the cell immune response were also observed and that they were more marked in infection with HCV.

[The treatment of primary biliary liver cirrhosis with ursodeoxycholic acid (preliminary report)]. / Lechenie na purvichnata biliarna chernodrobna tsiroza s urzodezoksikholeva kiselina (predvaritelno suobshtenie).

Seven women, mean age 47.7 years, with primary biliary cirrhosis (6 patients in the II-III stage and I patient in IV stage of the disease) were treated in the course of 16 months with ursodeoxycholic acid (Ursofalk) 500 mg daily. At the end of the 3-d month of treatment the itching had passed in 3 of the patients and in the remaining 4 patients it had substantially decreased. In all patients the subjective complaints, dyspeptic syndrome, appetite and sleep improved. The serum concentrations of bilirubin, copper and cholesterol started to decrease and the serum activity of the enzymes alkaline phosphatase, ALAT and ASAT also decreased. In one patient the treatment was discontinued in the 6-th month because of allergic reaction. After 16 month treatment in the 6 patients who completed the treatment the itching passed and the working capacity improved. The serum concentrations of bilirubin, cholesterol, copper and IgG significantly fell (p less than 0.01), the serum activity of alkaline phosphatase, gamma glutamyl transpeptidase, ALAT and ASAT fell near the upper normal range. The hepatomegaly, splenomegaly, McLagan's flocculation test, serum concentration of IgM and the titer of the specific antimitochondrial antibodies (M2) did not change in spite of the treatment. The results show the ursodeoxycholic acid as a perspective therapeutic means for primary biliary cirrhosis which lowers or overcomes the syndrome of intrahepatic cholestasis and limits the activity of the cirrhotic process in the liver. Ursodeoxycholic acid is well tolerated.

[2 cases of primary hyperaldosteronism]. / Vurkhu dva sluchaiia s purvichen khiperaldosteronizum.

Two clinical cases of women with primary hyperaldosteronism are reported. The patients presented with arterial hypertension, muscular weakness and paresthesia. Severe hypokalemia was found which was resistant to intravenous infusions of potassium but was successfully treated with low daily doses (100-200 mg) of spironolacton, an aldacton antagonist, in the course of 3-4 days. In one of the patients the primary hyperaldosteronism was related to aldosterone secretion by the cells of a malignant corticosteroma, proved histologically. A successful operation led to full recovery of the patient. In the other patient there was an idiopathic form of primary hyper aldosteronism caused by bilateral hyperplasia of the suprarenal cortex. Contemporary diagnostic and therapeutic possibilities in primary hyperaldosteronism as well as the importance of the examination of potassium serum level and kaliuria in the patients with arterial hypertension for the timely and successful diagnosis and treatment of primary hyperaldosteronism are pointed out.

[Campylobacter (Helicobacter) pylori in chronic erosive gastritis, duodenitis and gastroduodenitis]. / Campylobacter (Helicobacter) pylori pri khronichnite erozivni gastriti, duodeniti i gastroduodeniti.

The presence and degree of manifestation of Campylobacter (Helicobacter) pylori in gastroduodenal mucosa were studied in 100 patients (56 men, mean age 51.4 years, and 44 women, mean age 46.5 years) with endoscopically proved chronic erosive gastritis (52 patients), erosive duodenitis (36 patients) and erosive gastroduodenitis (12 patients). The examinations revealed the presence of Campylobacter (Helicobacter) pylori in mean 77% of the patients with erosive gastritis, duodenitis and gastroduodenitis. Campylobacter (Helicobacter) pylori was found most often in patients with chronic erosive duodenitis--83.3%, whereas in the patients with erosive gastritis it was found in 73.07%. In 83.33% of the patients with chronic erosive gastritis, duodenitis and gastroduodenitis the campylobacter infection was well manifested--(++) according to Le Bodie et al (1987). The results allow the conclusion that one of the important pathogenetic factors of erosive gastritis, duodenitis and gastroduodenitis is the Campylobacter (Helicobacter) pylori infection of gastroduodenal mucosa.

[The cellular-humoral immune factors of patients with cholelithiasis uncomplicated and complicated by an inflammatory process]. / Prouchvane na kletuchno-khumoralni imunni faktori pri bolni s neuslozhnena i uslozhnena s vuzpalitelen protses zhluchnokamenna bolest.

82 patients-10 p. with uncomplicated cholelithiasis, 8 p. with chronic calculous cholecystitis, 34 p. with choledocholithiasis with stenosing papillo-odditis--and 30 healthy controls were examined, with monoclonal antibodies of the firm "Becton-Dickinson". The following immunocompetent cellular clones and subclones were examined: CD3+, CD16+, CD4+, CD8+, CD19+ CD4/CD8, HLA-DR+, CD3+. The results were read with analyzer for fluorescently marked activated cell clones "FACS-TAR". The serum IgA, IgM, IgG, C3-C4 complement fractions and circulating immune complexes were also examined. The analysis of the results shows that in the complicated cases of cholelithiasis with an inflammatory process in the biliary ducts several humoral and cellular immune factors take part.

[Pulmonary tumor embolism in primary cancer of the liver]. / Tumorna belodrobna emboliia pri purvichen rak na cherniia drob.

A case of a 73 years old man with macronodular liver cirrhosis, ascites, jaundice and a primary hepatocellular carcinoma is presented. The patient died suddenly and at the post mortem embolism of the pulmonary artery was found caused by tumor fragments. The tumor had infiltrated the wall and penetrated into the lumen of vena cava inferior.

[The chologon-sorbitol functional test under ultrasonic control in pathology of the gallbladder and biliary tract]. / Khologon-sorbitolov funktsionalen test pod ultrazvukov kontrol pri patologiiata na zhluchniia mekhur i zhluchnite putishta.

The degree of the filling up and the dilation of the gall bladder, its functional state as well as the passibility of d. cysticus are evaluated by ultrasound examination and computer determination of the surface and dimensions of the gall bladder. 546 patients, 20-78 years of age (484 women and 62 men) were examined by a pharmacodynamic functional test with chologon (acidum dehydrocholicum) in a dose of 10 mg/kg body mass and sorbitol (in 116 patients) in a dose of 20 g in 100 ml of water. The functional test is easily performed in the course of the ultrasound examination and side effects were registered. The test allows the assessment of the functional state of the gall bladder, the passibility of d. cysticus, the degree and mechanism of the filling up of the gall bladder and the bile ducts with bile. The better filling up of the gall bladder with bile after application of chologon (by passable d. cysticus) ensures better conditions for detecting microgallstones in the gall bladder as well as of diseases linked with its wall--cholesterosis, cancer and polypi of the bladder, etc.

[Ziksorin in the treatment of unconjugated familial functional jaundice--the Gilbert-Meulengracht syndrome]. / ziksorin pri lechenieto na nekoniugiranata familna funktsionalna zhultenita--sindroma na Gilbert--Meulengracht.

Zixoryn (Flumezinolum) is a new enzyme inductor without the adverse effects of the other known substances with similar inductor activity (phenobarbitals, DDT derivates, etc.). It was applied to 12 patients with unconjugated nonhemolytic familial jaundice--Gilbert-Meulengracht's syndrome. The dose was 600 mg'6 capsules of 100 mg taken as a single dose) once in a week in the course of 2 months. This treatment led to a 50% reduction of the hyperbilirubinemia in all patients treated. In the patients with initial bilirubin level under 35 mmol/l Zixoryn led to normalization of the bilirubin level with a normal ratio between the conjugated and unconjugated fractions. The discontinuance of Zixoryn treatment led in the course of 20-25 days to a gradual rise of bilirubin to its previous pathologic level. No side effects were registered in the patients treated with Zixoryn. Zixoryn is a new effecient drug for treatment through enzyme induction of bilirubin transport and glucuronizing enzyme systems in the hepatocytes. It is especially useful, in patients with high unconjugated hyperbilirubinemia as well as in patients with deterioration of the disease with an increase of the bilirubin level--total and unconjugated.

[Campylobacter pylori in patients with chronic gastritis and gastric and duodenal peptic ulcer]. / Campylobacter pylori pri bolni s khronichni gastriti, iazvena bolest na stomakha i duodenuma.

The presence of Campylobacter pylori was studied in biopsy material from gastric mucosa taken by guided biopsy during fiber gastroduodenoscopy from 101 patients with chronic gastritis (n = 50), peptic gastric ulcer (n = 28), peptic duodenal ulcer (n = 7), gastric cancer (n = 10) and gastric polyposis (n = 6). Campylobacter pylori was found in various quantity--moderate (++) and considerable ( )--in 64% of the patients with chronic gastritis, in 85.7% of the patients with peptic gastric ulcer and in 100% of the patients with peptic duodenal ulcer as well as in half of the patients with gastric cancer and polyposis. The quantity of Campylobacter pylori correlated with the severity of the inflammatory process and the degree of atrophy of the gastric antral mucosa. A tendency toward seasonal incidence of Campylobacter pylori infection of gastric mucosa was established: 78.69% of the patients examined during spring time (April-May) and 60.0% of the patients examined during winter time (January-February) had Campylobacter pylori infection. This explains to a certain extent the seasonal exacerbations of the pathological process in chronic gastritis and peptic ulcer. The development of a well expressed chronic atrophic gastritis is in direct relation with the greater quantity of Campylobacter pylori in the gastric mucosa. The study reveals the pathogenetic relations between the presence and quantity of Campylobacter pylori and the development and evolution of chronic gastritis and peptic gastric and duodenal ulcer.

[Cardiac metastasis in primary cancer of the liver]. / Surdechna metastaza pri purvichen rak na cherniia drob.

A rare case of a 77-year-old man with primary liver cancer and an isolated metastasis in the right atrial endocardium is presented. The metastasis was 30/40 mm large and occupied a considerable part of the atrial cavity. Clinically the disease was manifested by progressing chronic right ventricular failure, ending with a total heart failure. The diagnosis was made at the post mortem examination. The rarity of the case is pointed out. The possibility of a correct diagnosis while the patient was still alive is discussed.