[New approaches to the pathogenesis, clinic, and treatment of hepatic encephalopathy].

This review article presents new approaches to the assessment of key pathogenesis factors, clinical features, and treatment of hepatic encephalopathy (HE) associated with liver cirrhosis. Various clinical variants of the course of HE in patients with cirrhosis of the liver areconsidered, which are important for the choice of treatment and prevention of repeated relapses of HE. Analyzed the ammonia hypothesis of pathogenesis and associated hyperammonemia, which is the basis of most modern treatment methods. These data on the activation of the adaptive pathway for removing ammonia in the form of glutamine are used in the further study of drugs that enhance the clearance of ammonia. The possibility of reducing GABA-ergic tone due to the effect of the antagonist on the neurosteroid site in the GABA receptor complex is emphasized.

Important problems in the diagnosis and treatment of primary sclerosing cholangitis (based on the Russian consensus on diagnosis and treatment autoimmune hepatitis. Moscow, 2018).

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.

[[The Modern View on Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease].]

The purpose of the review is to analyze modern data on pathogenesis, principles of treatment and future prospects treat- ment of nonalcoholic fatty liver disease (NAFLD). Modern ideas about the role of insulin resistance, oxidative stress gene polymorphisms in the pathogenesis of disease progression. This has led in recent years to a new strategy of treatment of the disease. Examines the role of physical load, modified diet, the weight loss. Substantiates the primary role of the use of insulin sensitizers, and agents with cytoprotective and antioxidant effect. The lack of the only effective drug for the treat- ment of NAFLD justifies the appropriateness of the appointment of combination therapy with exposure to various aspects of the pathogenesis. Elaborates on new drugs under clinical study.

[Cross-autoimmune syndromes in hepatology].

Along with the traditional autoimmune liver diseases--autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)--in clinical practice there are syndromes of autoimmune decussating. The term cross-syndrome means that in one patient there are signs of two different autoimmune liver diseases, that probably have a common pathogenesis. In line with the literature data and own experience of the diagnostic criteria there are different cross-syndromes: AIH and PBC, AIH and PSC; and also a combination of AIH and chronic hepatitis C. The most appropriate combinations and doses of prednisolone (budesonid), azathioprine and ursodesoxycholic acid, recommended for treatment of various options of cross-syndrome, as well as medical tactics in view of the conjunction of AIH and chronic hepatitis C, have been considered.

[Acute hepatitis in infectious diseases].

Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described.

[Parenteral acute viral hepatitis: current diagnosis, prevention and treatment].

Questions of diagnostics, feature of clinic, treatment and preventation of active virus hepatites with parenteral mechanism of transmission of an infection (hepatites B, C, D, G) which make up a significant number of all acute virus hepatites are considered. A wide circulation, features of modern diagnostics and frequency of progress of chronic forms define a problem of diagnostics and treatment of a virus hepatites, as one of important for domestic healthcare. Data about the importance and features serological markers of viruses of a hepatites B, C, D, G, are presented and their clinical interpretation is analyzed. Modern drug therapy is in detail resulted including preparations of interferon. The need of specific preventive actions, post-exposure preventive maintenance and passive immunization is considered.

[The evolution of ideas about nonalcohol fatty liver disease].

UNLABELLED: The aim of this study was to determine histological, clinical features and prognosis at patients with fatty gepatose and nonalcohol steatogepatite (NASG). The material of this study was analysis of clinical and laboratory manifestations in 74 patients with fatty gepatose of nonalcohol etiology that we have observed in 60-70th years of the twentieth century. All patients were performed liver puncture biopsy, 7 patients puncture performed twice, two--three times and two--four times. Thus we studded 91 punctate. Patients with fatty dystrophy I - II - III degree and I - II degree of fibrosis were included in the group of fat gepatose without inflammatory reaction (1st group, 54 patients), patients with fat-dystrophia II - III degree and III degree of fibrosis--in a group of fat gepatose with inflammatory reaction (Group 2, 20 patients). Patients classified earlier in a group of fat gepatose with inflammatory reaction, according to modern classification positions on histological characteristics of nonalcoholic steatogepatite. RESULTS: Functional disorders of liver are often not captured in conventional biochemical tests. It characterized by urobilinogenuriya, delayed retention of bromsulfalein, gipertriglitseridemiya. ALAT activity slightly increased in patients with fatty gepatose and exceeded norm in 1,5-2,5 times. While at NASG activity of this enzyme was more than half the enhanced AsAT, and gamma-GTP. Nonalcoholic steatogepatite did not have specific clinical and biochemical features. Assessment of inflammation and fibrosis degree using ultrasound liver is difficult and non-reliable. Therefore, NASG diagnosis based on represented data of liver puncture biopsy. In a lengthy check-up we have 42 patients with fat gepatose and NASG--stabilization process was defined in 34 people. Development of cirrhosis found in 5 patients. After repeat biopsy in these patients on a background of fat liver dystrophy encountered a picture of developing micronodular cirrhosis. In 3 of them had repeated liver puncture through 1.5 years. One patient puncture performed three times at intervals of 4.5 years, initial signs of cirrhosis found only in the last biopsy. Another patient moved 4 puncture for 6 years hemochromatosis as an iron overload syndrome, and initial signs of cirrhosis identified through 3 years, in next 3 years progression of morphological features of cirrhosis weren't found. CONCLUSION: Nonalcoholic steatogepatite is an independent disease, which should be remembered in differential diagnosis in patients with sustained ALAT and ASAT improvement in serum especially in presence of obesity, diabetes, hyperlipidaemia. The diagnosis was confirmed with biopsy of liver. Despite of oligosymptomatic course of the disease with long-term observation of more than one third of patients with evidence of progression of the process; cirrhosis development noted sixth of the patients, and more. Universally accepted treatment of NASG doesn't exists, although exclusion of provoking factors, therapy antioxidant drugs and ursodezoksiholevoy acid can have favorable effect. The study in 45 patients with NASG was adjusted an effective use of berlitione in the treatment of patients with nonalcoholic steatogepatite. At comparing different schemes of appointment preparations optimal effect were obtained in patients with berlitione dose 600 and 900 mg for two months.

[Pathogenetic basis of pharmaceutical hepatitis induced by depakine in children].

42 children with epilepsy receved treatment by depakin drug. We defined the factors of lipid exchange processes of liver and their correlation between itself and with changes in immune status. The results of the studies indicated shaping the medical hepatitis with cholestatic syndrome on background of the long acceptance of depakin. Metabolic desadaptation was conditioned by glicolis activation in the condition of the oxygen deficit in tissue.

[Fatty hepatosis. Non-alcoholic steatohepatitis (evolution of the knowledge about clinico-morphological features, prognosis, treatment)].

AIM: To study histological, clinical features and prognosis in patients with fatty hepatosis (FH) and non-alcoholic steatohepatitis (NASH). MATERIAL AND METHODS: Clinical and laboratory data on 74 patients with FH of non-alcoholic origin were studied. All the patients have undergone puncture biopsy of the liver (a total of 91 biopsies). Patients with fatty dystrophy of the first, second and third degree and fibrosis of the first and second degree entered the group of fatty hepatosis without inflammation (group 1, n = 54), patients with fatty dystrophy of the second and third degree and fibrosis of the third degree were assigned to group 2 (n = 20), i.e. to the group of FH with inflammation. The latter group by modern histological characteristics belongs to NASH. RESULTS: Functional disorders of the liver were insignificant, urobilinogenuria, delayed retention of bromsulphalein, hypertriglyceridemia were observed. AlAT activity was insignificantly elevated in FH patients. It was elevated 1.5-2.5-fold in NASH, the activity of AsAT, gamma-GTP was high in half of the patients. NASH has no specific clinico-biochemical signs and its diagnosis is based on the data of puncture biopsy of the liver. Long-term follow-up of 42 patients with FH and NASH discovered stabilization of the process in 34 patients. Cirrhosis of the liver occurred in 5 patients. Repeated biopsies established association of fatty dystrophy with developing micronodular cirrhosis. CONCLUSION: NASH is an independent disease. This should be taken into consideration in differential diagnosis in patients with a stable rise of serum activity of AlAT and AsAT, especially in obesity, diabetes, hyperlipidemia. The diagnosis is verified at biopsy of the liver. In spite of scare symptoms, long-term follow-up detects progression of the disease in more than 1/3 of the patients. Cirrhosis arose in 1/6 of the patients. Standard NASH treatment is absent, though elimination of the provoking factors, therapy with antioxidant drugs and ursodesoxycholic acid produce a favourable effect.

[Clinical characteristics and risk factors of hepatic damage in lyme borrheliosis]. / Klinicheskaia kharakteristika i faktory riska porazheniia pecheni pri laim-borrelioze.

The study is based on the study of data on 33 patients with Lyme Borrelia infection in the presence of typical erythema migrans in whom elevated levels of serum bilirubin or transaminases were detected simultaneously with erythema or just shortly. The obligatory criterion was no history evidence of hepatitis and abnormal hepatic functional tests. Higher levels of serum aminotransferases were a major manifestation of Lyme hepatitis in the Sverdlovsk region. In 32 patients, ALT was increased, on the average, up to 176 U/l, and AST activity was up to 113 U/l within the first 2 weeks of the disease in the absence of clinical manifestations of hepatic and biliary diseases. There were changes in the levels of serum transaminases and bilirubin following 3- and 8-month antibiotic therapy. The presence of viruses A and C in moderate chronic hepatitis induced long-term increases in the activity of transaminases in 3 cases, as evidenced by histological studies of hepatic biopsy specimens.

[Clinical trial of heptral in patients with chronic diffuse liver disease with intrahepatic cholestasis syndrome]. / Otsenka éffektivnosti preparata geptral u bol'nykh s khronicheskimi diffuznymi zabolevaniiami pecheni s sindromom vnutripechenochnogo kholestaza.

Heptral (S-adenosine-L-methionine) was given to 32 patients with chronic diffuse diseases of the liver and intrahepatic cholestasis. 16 of them had primary biliary cirrhosis (PBC). Phase I of the treatment lasted 16 days when the drug was injected intravenously in a dose 800 mg/day. It was followed by phase 2--1600 mg/day taken for 16 days. A response was registered in the majority of patients. They had relieved symptoms of asthenia, skin pruritus, jaundice. The patients with liver cirrhosis and chronic hepatitis exhibited a statistically significant fall in ALT, AST and GGTP. PBS patients showed insignificant lowering of cholesterol, bilirubin. No resistance was noted in repeated courses. Heptral tolerance was satisfactory.