[Principles of treatment of different forms of alcoholic liver disease: A review].

The review considers the principles of treatment of various forms of alcoholic liver disease from the point of view of the evidence base and clinical recommendations. The main therapy for severe alcoholic hepatitis is systemic glucocorticosteroids, their effect on survival is increased by the addition of antioxidants (N-acetylcysteine, ademethionine). The effect of ademetionine on the life expectancy of patients with alcoholic cirrhosis of Child-Pugh class A and B has been proven. The treatment of patients with mild forms of alcoholic liver disease is not well developed, and the evidence base for most of the drugs used is modest.

[Mixed steatohepatitis: more questions than answers (part 2)].

In this review, we discussed the epidemiological and pathogenetic aspects of mixed steatohepatitis (SH), developed due to non-alcoholic fatty liver disease, metabolic associated fatty liver disease, drug-induced liver injury. We discussed the mechanisms of the mutually aggravating influence of etiological factors. Drugs can cause steatosis and SH, as well as contribute to the progressive course of existing SH, primarily of metabolic origin. The issues of interaction of pathogenetic factors, peculiarities of diagnostics and perspectives of pathogenetic and symptomatic treatment are considered. Therapy of mixed SH is based on avoidance of hepatotoxic drugs and lifestyle modification, medications with demonstrated efficacy (such as ademetionine) in certain SH might be used.

[Evaluating the efficacy of diet therapy with protein component modification at Wilson disease].

Wilson disease (WD) is a rare hereditary disorder of copper metabolism, based on of the ATP7B gene mutation, resulting in defect of cooper excretion, which leads to accumulation of cooper in tissues and internal organs (especially in the liver and brain). The basic principle of diet therapy for patients with WD is a diet with reduced copper content, adherence to which is accompanied by significant dietary restrictions, so patients with WD, compared to other liver diseases, represent the most difficult contingent for adjustment of diet. The aim: to assess of the effect of diet therapy with modification of the protein component on nutritional status of patients with WD. Material and methods. The study included 33 patients (15 men and 18 women, 31.4±10.2 years old) with WD. All patients had liver damage: non-cirrhotic stages (NCC) - in 12 (36.3%) patients, liver cirrhosis (LC) - in 21 (63.7%) patients. Out of the last, 14 (66.7%) patients had compensated LC, 7 (33.3%) patients had decompensated LC. The average age of the patients. All patients were divided into two groups, comparable by body mass index. For 2 months outpatients of the 1st group (n=17) received a specialized diet with a modification of the protein component, made by incorporating 20 g of dry composite protein mix (containing 50% protein in the form of milk protein concentrate, 4% dietary fiber) into the daily diet. Outpatients of the 2nd group (n=16) received the same diet without modification. All patients were provided anthropometry, including shoulder circumference and triceps skin-fold measurement, and analysis of the body mass composition with bioimpedance analyzer, the index of lean mass was additionally calculated. Clinical and biochemical blood tests were also conducted for all patients. Results and discussion. As a result of the diet therapy, statistically significant (p<0.05) changes were observed in patients of the 1st group who received a diet with a modification of the protein component: an increase in the index of lean mass (by 3.0%) and circumference of the shoulder muscles (by 2.3%), serum total protein and albumin (by 7.9 and 6.1%), an increase in the absolute number of lymphocytes (by 18.8%) and decrease in serum total bilirubin (by 20.2%). A statistically significant decrease in the level of free copper was observed in both groups (by 2.1 and 1.8 fold). Conclusion. The use of a specialized diet with a modification of the protein component, based on the inclusion of a protein composite dry mix in the diet, improves the nutritional status indicators in patients with Wilson disease.

[Mixed steatohepatitis: more questions than answers (Part 1)].

The term steatohepatitis is used for a heterogeneous group of diseases of various etiologies, characterized by a similar morphological picture. Earlier the diagnosis of non-alcoholic fatty liver disease implied the exclusion of other causes of steatohepatitis, in recent years it has been suggested that a combination of various etiological variants of steatohepatitis is possible. The review considers the terminological, epidemiological and pathogenetic aspects of the most common combination: metabolic and alcoholic genesis, the issues of the mutual influence of etiopathogenetic factors and the identification of the predominant process. Issues of existing and prospective pathogenetic and symptomatic therapy are discussed in detail. Treatment of steatohepatitis is based on the elimination of known causal factors and lifestyle modification; therapy includes medications, that have been proven to be effective in certain types of steatohepatitis and symptomatic therapy as well.

Аdеmethionine in the treatment of fatigue in liver diseases: a systematic review.

AIM: To systematize the published data on the treatment of hepatogenic fatigue with аdеmethionine. MATERIALS AND METHODS: Search was performed using databases PubMed, EMBASE, Embase®, Medline®, eLIBRARY.ru, published in 1952-2018. RESULTS: 16 articles were found on the use of аdеmethionine in liver diseases and the assessment of the dynamics of the symptom of fatigue, including 1 double-blind, randomized, placebo-controlled study, 3 open randomized studies; most of the works were multicenter open observation programs. The studies included 3238 patients (of which 2820 were included in the final data analysis) and a wide range of liver diseases: alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, cirrhosis of different causes, viral hepatitis, drug-induced liver injury. Different doses, routes of administration of аdеmethionine and the duration of the course were used. CONCLUSION: Ademethionine, regardless of the route of administration, is effective in the treatment of fatigue due to different liver disease in the short and long term. The dose-dependent effect of the drug and the possibility of maintaining post-effect after end of the treatment course should be assumed, but this requires further study in randomized clinical trials.

[Clinical features of inflammatory bowel disease (ulcerative colitis and Crohn's disease) in geriatric practice in Saint Petersburg.]

Objective - to identify the clinical features of inflammatory bowel disease (IBD) in elderly and senile patients in St. Petersburg. A retrospective analysis of medical charts of 208 patients over 60 years old with inflammatory bowel diseases (IBD) was carried out: 60% of them with ulcerative colitis (UC), 40% with Crohn's disease (CD). The control group consisted of 867 patients aged up to 60 years (UC- 524 patients, 60,4%; CD - 343 patients, 29,6%). Concomitant cardiovascular diseases were detected in 87% of patients, broncho-pulmonary - in 25%, diseases of the bones and joints - in 35%, pathology of the kidneys and urinary tract - in 26,5%, and liver - in 44%. Debut and recurrent IBD were often accompanied (33,6%) by a worsening of somatic pathology (versus 8,7% in other age groups of patients). It's took longer to verify diagnosis of IBD in older patients, than in patients of young and middle ages. Patients with distal localization of the pathological process (proctitis and left-sided colitis) prevailed among patients with UC, the inflammatory form of the disease dominated in patients with CD.

Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017).

The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient.

[CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF INTESTINAL LESIONS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS].

Objective: To compare the clinical, endoscopic picture and morphological changes of the intestinal mucosa in patients with primary sclerosing cholangitis (PSC). Materials and methods: 31 patients with PSC (women - 15 men - 16) were included in study group. The diagnosis of ulcerative colitis (UC) was established in 8 patients, Crohn's disease (CD) - in 5, unclassified colitis (UCC) - in 7, and 11 patients had no clinical and endoscopic signs of IBD. The control group consisted of 30 patients with IBD: UC - 20 patients, CD - 10 persons. All the patients performed ileocolonoscopy (ICS) with multiple biopsy and histological examination of material. Results: The prevalence of IBD in patients with PSC was 64.5%. IBD with PSC was characterized by extensive colitis with mild clinical activity. Morphological activity of IBD associated with PSC was usually moderate and severe. Morphological activity of disease in IBD/PSC group was lower than in UC alone (p < 0.05). IBD onset came before PSC symptoms (p < 0.05). Distal gradient of inflammation in colon predominated in IBD/PSC group when disease starts with IBD symptoms, in case of PSC symptoms - proximal gradient was more frequent. In IBD/PSC group affected ileum were detected in a third of cases, including CD ileitis - 60%, backwash ileitis in UC (NCC) in 26.7%, that was significantly frequently than in UC alone (p = 0.02). Within the IBD/PSC group 30% of patients with colitis were without damaging of rectum. In all the patients with PSC without clinical, endoscopic signs of colitis polymorphocellular infiltration of mucosa were founded. Eosinophilic infiltration of mucosa in group of PSC met significantly more frequently than in other study groups. Fibrosis of intestinal mucosa was founded significantly more frequently in group of PSC without IBD compared with UC/PSC and UC patients, but not with CD group. Conclusions: For IBD in PSC extensive colitis without lesions of the rectum, backwash ileitis are common. There are some morphological differences in the intestinal lesions within the IBD/PSC patients depending on the type of disease onset. There is a dissociation between low clinical activity and intensive morphological inflammation. When PSC had no clinical features of IBD, a microscopic ileocolitis (characterized by eosinophilic infiltration and fibrosis of the intestinal mucosa) without nosological classification was founded in all patients.

[Autoimmune Diseases of Digestive System].

Autoimmune diseases of digestive system refer to pathological conditions, caused by autoimmune mechanisms, and their etiology remains unknown. This is a group of relatively rare diseases, however, during the last years a marked tendency towards the raise in incidence andprevalence is observed, which led to an increase in number of clinical investigations on etiology, pathogenesis, and, accordingly, development of new diagnostic methods and therapies. Results of such trials shown, for example, that the pathogenesis of chronic cholestatic liver diseases is associated with nuclear receptors function, while the main etiological and pathogenic factor of inflammatory bowel diseases represents gut microbiota. Despite new achievements in autoinmune diseases of digestive system research, therapies are low effective and are accompanied by a huge number of adverse events. The fact that these diseases may lead to malignant tumors is also worth noting. For example, patients with primary sclerosing cholangitis have a 160 times higher risk of cholangiocellular carcinoma, while 10-14% ofpatients with celiac disease may develop malignancies of esophagus, small and large intestine. Thus, these diseases require further investigation with a purpose of more accurate diagnostic methods for the detection of disease at early stages and new effective and safe therapies development.

[THE ROLE OF NUTRITION IN THE GENESIS OF-HEPATIC OSTEODYSTROPHY IN PRIMARY BILIARY CIRRHOSIS].

THE PURPOSE: To evaluate the effect of diet on the development of hepatic osteodystrophy in patients with primary biliary cirrhosis. MATERIALS AND METHODS: In 24 women with PBC, including signs of autoimmune hepatitis (PBC/AIH)--9 persons and 19 women in the control group were analyzed the daily diet, body composition, as well as bone mineral density in the lumbar spine and femur by dual-energy X-ray adsorbtsiometrii (DEXA). THE RESULTS: In PBC incidence of osteoporosis and severe osteoporosis was 22.7% and 9.1%, respectively, and osteopenia--59.1%, with a lesion predominantly lumbar spine. Inadequate intake of calcium in patients with PBC is associated with lower density of the femur. The high protein content in the diet has a protective effect on bone mineral density, associating with the development of osteopenia.

[Role of transforming growth factor-beta in the development of some liver diseases].

AIM: To investigate the expression of transforming growth factor-beta 1 (TGF-beta1) in the liver tissue of patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and chronic hepatitis C (CHC). MATERIALS AND METHODS: Liver biopsy specimens were histologically and immunohistologically examined in 37 patients with verified liver diseases (12 with AIH, 15 with PBC, and 10 with CHC). RESULTS: The expression of TGF-beta1 in the non-parenchymal liver cells of the patients with AIH and PBC with liver cirrhosis was statistically significantly higher than in those without the latter (p = 0.01 and p = 0.04, respectively). There was a positive relationship between the stage of fibrosis and the absolute content TGF-beta1 and CD68+ cells in the portal tracts (r = 0.51). The higher expression of TGF-beta1 was found in the patients with HCV and AIH than in those with PBC (p = 0.03 and p < 0.05, respectively). There were no differences in the expression of TGF-beta1 in the patients with AIH as compared to those with CHC (p = 0.55). The number of CD68-positive macrophages was higher in CHC than in AIH and PBC (p = 0.004 and p = 0.01, respectively). In autoimmune liver diseases, TGF-beta1 was mainly expressed by the macrophages located in the portal tracts and, in CHC, within the hepatic lobules. CONCLUSION: The enhanced TGF-beta1 expression in the nonparenchymal liver cells in AIH and PBC with liver cirrhosis confirms the role of this cytokine in development of fibrosis in autoimmune liver diseases. That in hepatitis of various etiologies versus PBC suggests that the TGF-beta1 signaling pathway may play an important role in an inappropriate immune response in hepatitides; and the variations found in the location of the macrophages expressing TGF-beta1 reflect a difference in the mechanisms of lesions.