[Primary biliary cirrhosis: 12-year experience in observation]. / Pervichnyi biliarnyi tsirroz: 12-letnii opyt nabliudeniia.

AIM: To ascertain initial signs of primary biliary cirrhosis (PBC), criteria of its early diagnosis, variants of the course, clinical picture and life quality of PBC patients. MATERIAL AND METHODS: 128 PBC patients were examined in the Central Research Institute of Gastroenterology from 1991 to 2002. Quality of life was assessed by SF-36 questionnaire adapted for patients with chronic cholestatic diseases of the liver. RESULTS: The patients complained of skin puritus (80%), jaundice (66%), fatigue (68.8%), weight loss (24.6%). The disease manifested with skin pruritus in 75.8%, jaundice--in 12.5% patients. Decompensated hepatic cirrhosis (Child-Pugh C) at first hospitalisation was diagnosed in 11.7% cases. The earliest and most significant biochemical markers of PBS were high activity of gammaglutamil-transpeptidase (GGTP) and alkaline phosphatase (AP). IgM level was high in 70.5% cases. Antimitochondrial antibodies were detected in 83.6% examinees. Overlapping with autoimmune hepatitis was seen in 9.4%. One-third of the patients had systemic symptoms. Quality of life deteriorated. CONCLUSION: PBC may be long asymptomatic. The absence of skin pruritus is not a sure sign of the disease absence. To detect PBC early, young and middle-aged women with unexplained weakness or skin pruritus should undergo a comprehensive examination including measurements of GGTP, AP, AMA, IgM, morphological investigation of liver tissue. PBC patients had low quality of life. This should be accounted for when treating patients, in determination of their working ability and for early referral for liver transplantation.

[Changes in the liver in glutenic enteropathy]. / Izmeneniia pecheni pri gliutenovoi énteropatii.

AIM: To evaluate frequency of clinical manifestations, biochemical and morphological alterations characteristic of liver affection in patients with glutenic enteropathy (GEP) in correlation with GE duration and severity of malabsorption syndrome (MAS). MATERIAL AND METHODS: 116 GEP patients have undergone clinico-laboratory examination, intestinoscopy with biopsy of jejunal mucosa, puncture biopsy of the liver with morphological examination of the specimens, ultrasonography of the liver. In addition, the immune status was assessed and tests for markers of hepatotropic viruses B and C were made. RESULTS: Clinical symptoms, typical for hepatic lesion in GEP patients, such as yellowness of the skin and scleras, palmar erythema, vascular stella and hepatomegaly were found in 7.2% cases. Hyperaminotransferasemia was detected in 48.4% of new cases of celiac disease, in 18.1% of patients on strict aglutenic diet. Aminotransferase hyperactivity detection was associated with severity of MAS. Morphological alterations in the liver in celiac disease are characterized by fat dystrophy, portal and periportal hepatitis, steatohepatitis or fibrosis. Combined therapy of celiac disease including strict aglutenic diet, correction of metabolic disturbances was not always effective in correction of metabolic processes in the liver. In new GEP cases early adequate therapy was most effective. CONCLUSION: The course of glutenic enteropathy is accompanied with clinicomorphological alterations in the liver. This necessitates use of drugs improving liver function.

[Clinico-morphological changes of the liver in patients with dyslipoproteinemia]. / Kliniko-morfologicheskie izmeneniia pecheni u bol'nykh s dislipoproteidemiei.

At present the disorders of lipid metabolism and connected diseases are studied insufficiently. Some disorders with the basis of lipid metabolism disorders are combined into the lipid distress-syndrome. The clinical study of 60 patients with expressed dislipoproteidemia (48 female and 12 male) in the age 46-79 years were made by the clinical observation, estimation of biochemical indexes, lipid blood spectrum, viral hepatitis markers, ultrasonic and liver biopsy. Obtained results showed that the patients with dislipoproteidemia had the expressed liver disorders which were typical for the clinical-morphological characteristics of non-alcoholic steatohepatitis. In patients with cardio-vascular pathology, atherosclerosis and dislipoproteidemia in 90% of cases the detected liver dystrophy can be considered as pre-stage of NASH.

[Interconnection in activity of lipid peroxidation reactions and functional status of the liver in patients with chronic hepatitis of viral etiology]. / Vzaimosviaz' aktivnosti reaktsii perekisnogo okisleniia lipidov i funktsional'nogo sostoianiia pecheni u bol'nykh khronicheskim gepatitom virusnoi étiologii.

There was a study of lipid peroxidation activity, ceruloplasmin level, bile acids content, and the liver detoxifying function state in 37 patients with chronic hepatitis types B and C of viral etiology. Changes of the indices under study were most apparent in patients with HCV. It was revealed that the degree of impairment of detoxifying and bile-producing functions of the liver are closely interrelated to the activity of the inflammatory reaction and lipid peroxidation processes. The increasing ceruloplasmin level in this category of patients hampers the reduction of the activity of lipid peroxidation processes, which is apparently related not only to the direct cytotoxic viral effect but also to the negative effect of superoxide ions on the cell membrane. Along with this, in cases of viral lesions of hepatocytes there are changes in the synthesis and conjugation of bile acids leading to the derangement of their correlation, their increased aggregate content and accumulation in tissues, which can also enhance the intensity of destruction of liver tissues and is an extra factor contributing to the intensification of lipid peroxidation processes.

[HGV and TTV - new hepatitis viruses]. / HGV i TTV - novye virusy gepatitov.

AIM: To examine clinical, immunological and morphological features of HGV- and TTV-infections in patients with chronic hepatic diseases (CHD) and assess efficiency of treatment of HGV-seropositive patients. MATERIAL AND METHODS: 202 patients with CHD were examined for markers of HBV-, HCV-, HGV- and TTV-infections. Some patients were subjected to puncture biopsy of the liver. Efficiency of interferon-alpha treatment of HGV and HBV/HCV coinfection was studied. RESULTS: HGV RNA and TTV DNA were detected in 19.8 and 11.8% of cases, respectively. Biochemical indices in patients with HGV and TTV monoinfections significantly differed from those in the control group while morphological changes in most of them corresponded to those with hepatitis. INF-alpha was given to 7 patients with HGV + HBV/HCV infections. A response was achieved in 3 months in 2 of them. CONCLUSION: The role of HGV and TTV in hepatic diseases pathology is still unclear. Further studies on detection and examination of patients infected with G and TT viruses are necessary. When choosing therapy, the presence of HGV RNA and TTV DNA in blood serum, virus genome in hepatocytes and histological changes in hepatic tissue should be considered.

[Drug addicts' liver]. / Pechen' narkomanov.

AIM: To assess condition of the liver in drug abusers. MATERIALS AND METHODS: Clinicobiochemical, immunological, virological and morphological hepatic tests were made in 144 patients with different forms of drug addiction. RESULTS: Hepatic diseases are rather common in drug addicts. They have some specific clinical features: weak clinical symptoms and laboratory ++indications, high incidence of viral hepatitides markers, repeated infection, initially absent definite evidence on immunological status disturbance, predominant morphologically inactive forms. Symptoms of hepatic disorders were found both in the period of active abuse and in abstinence. CONCLUSION: Young people with psychopathological behavior should be examined and followed up for detection of drug addiction and concomitant liver diseases.

[Activities of glutathione enzymes in liver biopsy specimens in chronic lesions of hepatocytes]. / Aktivnost' glutationzavisimykh fermentov v bioptate pecheni pri khronicheskom porazhenii gepatsitov.

The nonenzymatic conjugation of metabolites is decreased in chronic diseases of the liver, which is caused by decreased concentration of glutathione. The activities of glutathione enzymes are increased, this indicating the development of compensatory processes of mobilization of the second phase of detoxication, that is, increased conjugation under conditions of suppression of the cytochrome P-450 system. Measurement of liver glutathione transferase is a highly informative test for assessing the activity of the pathological process, particularly important in patients with chronic active hepatitis and cirrhosis of the liver.

[Cytochrome P-450-dependent hydroxylation and activity of glutathione-dependent liver enzymes in chronic liver diseases]. / Tsitokhrom P-450-zavisimoe gidroksilirovanie i aktivnost' glutationzavisimykh fermentov pecheni pri ee khronicheskom povrezhdenii.

Repression of cytochrom P-450-dependent hydroxylation and demethylation in liver was demonstrated in bioptats of patients with chronic liver diseases. The inhibition of cytochrome P450 system was provoked by oxidative modification of proteins-enzymes in patients with chronic liver changes as was proposed at the same time. The activation of glutathione-dependent enzymes was revealed. So the intensification of conjugation and development processes was revealed as the compensation mechanisms of detoxication with chronic liver diseases.

[The clinical significance of the liver glutathione system in chronic lesions]. / Klinicheskoe znachenie sistemy glutationa pecheni pri ee khronicheskikh porazheniiakh.

It is shown that chronic hepatobiliary pathology is associated with a fall in spontaneous metabolite conjugation related to reduced concentration of hepatic glutathione. There was also enhanced activity of glutathione-dependent enzymes. This indicates progress of compensatory processes associated with mobilization of detoxication phase 2, i.e. stimulation of conjugation processes under depression of cytochrome P-450 system. The authors ascertain high informative value of hepatic glutathione transferase in assessment of disease activity in patients with chronic active hepatitis and hepatic cirrhosis.

[Activity of blood antioxidant enzymes in chronic liver damage]. / Aktivnost' antioksidantnykh fermentov krovi pri khronicheskikh porazheniiakh pecheni.

Patients with chronic hepatic disease have higher superoxide dismutase (SOD) activity and lower erythrocytic glutathione levels. There was a decrease in plasma SOD activity in cirrhosis, a feedback between the dismutase and oxidase activities of ceruloplasmin in cholestatic damages to the liver. Drug therapy resulted in positive dynamics in the levels of SOD, glutathione peroxidase, glutathione, ceruloplasmin, which is likely to be associated with the control of the enzymatic mechanisms of antioxidative protection. It is suggested that the enhanced erythrocytic SOD activity in hepatic diseases might trigger free radical oxidation.

[Cytochrome P-450-dependent hydroxylation in liver tissue of patients with hepatobiliary diseases]. / Osobennosti tsitokhrom P-450-zavisimogo gidroksilirovaniia v tkani pecheni bol'nykh s gepatobiliarnoi patologiei.

Chronic diseases of the liver were found to be associated with microsomal hydroxylation reactions inhibition, this inhibition depending on the disease activity and stage. Chronic cholestatic hepatitis and primary biliary cirrhosis are associated with a more marked suppression of these reactions, the degree of inhibition being in proportion with the cholestatic syndrome severity. Demethylation process was found inhibited in active liver cirrhosis and primary biliary cirrhosis. The authors believe that assessment of the rate of microsomal oxidation in a liver biopsy specimen will help objectively assess the first phase of cytochrome P-450 effected biotransformation (hydroxylation) in patients with chronic disease.

[The dynamics of the morphological liver changes in primary biliary cirrhosis (based on the data from repeat biopsies)]. / Dinamika morfologicheskikh izmenenii pecheni pri pervichnom biliarnom tsirroze (po materialam povtornykh biopsii).

Repeat biopsy examinations (38 specimens) from 18 patients with primary biliary cirrhosis (PBC) showed association of the most active PBC with pronounced ductule proliferation, especially with ductule necrosis. The semiquantitative R. Knodell technique allows defining most characteristic histological parameters and correlations. In 3 patients the biopsies helped detect a combination of PBC with viral hepatitis resultant in cirrhosis. Repeat biopsies contribute to specification of the initial diagnosis, to evaluation of PBC activity and progression.

[A new approach to the diagnosis of cholestasis by the activity of copper-containing enzymes]. / Novyi podkhod k diagnostike kholestaza po aktivnosti med'soderzhashchikh fermentov.

A reciprocal type of the relationship between superoxide dismutase (SOD) and hepatic ceruloplasmin levels in the liver and plasma has been demonstrated. This acts as an integrating mechanism of antioxidant resistance in hepatobiliary diseases. The value of SOD/ceruloplasmin ratio is presented which was low in primary biliary cirrhosis and chronic cholestatic hepatitis. A statistical significance for the differences between biochemical indices of cholestasis (bilirubin, cholesterol, alkaline phosphatase) was less than for SOD/ceruloplasmin ratio. The latter proved more informative in the diagnosis of cholestasis.

[Antioxidant liver enzymes in chronic liver disease]. / Antioksidantnye énzimy pecheni pri ee khronicheskom porazhenii.

Biopsy of the liver of 73 patients with chronic affection of the hepatobiliary system was conducted to study the enzymatic system of inactivation of the active forms of hepatic oxygen according to the stage of the chronic process. Reduced activity of superoxide dismutase and catalase and disruption of their relationship in chronic active hepatitis were revealed. Significantly diminished rate of inactivation of superoxide radicals was encountered in fibrosis and primary biliary cirrhosis. The informative importance of the catalase/NADP H-peroxidase index in appraising chronic affection of the hepatic tissue is shown. It is concluded that the interrelation of the antioxidative enzymes as a system of antioxidant protection of hepatocytes is impaired in chronic diseases of the liver.

[Enzyme system for dismutation of active forms of oxygen in the liver during chronic impairment of the hepatobiliary system]. / Enzimnaia sistema dismutatsii aktivnykh form kisloroda pecheni pri khronicheskom porazhenii gepatobiliarnoi sistemy.

A decrease in activity of main enzymes responsible for inactivation of reactive intermediates of oxygen was found in patients with chronic impairments of liver tissue. In chronic active hepatitis superoxide dismutase and catalase activities were decreased, while more pronounced alterations in the enzymatic activity were observed in primary biliary cirrhosis. Alterations in the rate of antioxidation enzymes activity correlated with severity of pathological process: less distinct alterations in superoxide dismutase and catalase activities were detected in adipose degeneration of liver tissue as compared with those in active chronic hepatitis, and, especially, in primary biliary cirrhosis. The data obtained by means of correlation analysis suggest that interrelationship of the antioxidation system components was deteriorated. The decrease in activity of these enzymes appears to be related to destructive alterations developed in chronic impairments of liver tissue.

[Determination of the superoxide dismutase activity in puncture biopsy specimens of the liver in chronic liver diseases]. / Opredelenie superoksiddismutaznoi aktivnosti v materiale punktsionnoi biopsii pecheni pri ee khronicheskom porazhenii.

Analysis of liver biopsy specimens from patients with chronic active hepatitis has shown reduced superoxide dismutase (SOD) and catalase activities. More profound changes were revealed in the patients with fibrosis, cirrhosis, and primary biliary cirrhosis. Suppressed activities of antioxidative enzymes and dissociation of their systemic interaction were found to be related to the pathologic process severity. Measurement of SOD activity in a biopsy specimen appears to be clinically valuable and may be used for the assessment of liver antioxidative defense in patients with liver conditions.

[Sarcoidosis and sarcoid-like granulomas in the liver]. / Sarkoidoz i sarkoidopodovnye granulemy v pecheni.

Based on examination of 2450 liver biopsy specimens it has been shown that different granulomas occur in 4% of all the biopsy specimens. Of these, sarcoid-like granulomas are detectable in 13.5% of cases. Diagnosis of liver sarcoidosis is always based on the clinicomorphological findings with regard to an injury to at least of one more organ or tissue characteristic for such a disease. Sarcoid impairment of the liver is not infrequently coupled with chronic liver disease. The greatest difficulties may occur in differential diagnosis between primary biliary cirrhosis and sarcoidosis.