To date, nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic diffuse liver disease. Under adverse conditions, its natural course involves progression from simple steatosis and nonalcoholic steatohepatitis (NASH) to the development of liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, there has been much convincing evidence that NAFLD is a multisystem disease that contributes to damage to extrahepatic organs and systems, primarily increasing the risk of cardiovascular diseases, type 2 diabetes, chronic kidney disease and other diseases. In particular, numerous studies in recent years indicate that NAFLD increased the risk of diabetes by at least twice. Currently, the complex and bidirectional relationship between NAFLD and type 2 diabetes are well studied. NAFLD, hepatic and systemic insulin resistance, gut dysbiosis and lipotoxicity are the main factors determining the development of diabetes mellitus in predisposed individuals. Once type 2 diabetes manifests clinically, the likelihood of progressive liver damage increases. Non-alcoholic fatty liver disease, which is associated with type 2 diabetes, is thought to be a sign of a severe clinical course with serious clinical consequences in the form of NASH, liver cirrhosis and HCC. This combination requires a more aggressive therapeutic strategy, HCC screening, and long-term follow-up. A vicious circle is formed, which leads to adverse clinical consequences, worsens the prognosis and requires an active diagnostic and treatment strategy.

Background. Emerging evidence suggests a strong interaction between the gut, gut microbiota and liver. Derangement of gut flora, particularly small intestinal bacterial overgrowth (SIBO), occurs in a large percentage of patients with non-alcoholic fatty liver disease (NAFLD) and plays an important role in its pathogenesis. Aim. Study of the frequency of SIBO in various forms of non-alcoholic fatty liver disease, as well as the possibilities of its pathomorphosis as a result of eradication of SIBO as a result of the use of rifaximin or multicomponent probiotic. Material and methods. There were investigated 125 patients with non-alcoholic fatty liver disease (70 men, 55 women aged 18 to 65 years, mean age 37±6.7 years) developed at obesity or type 2 diabetes mellitus, including 85 patients with liver steatosis (group1) and 40 patients with non-alcoholic steatohepatitis (group 2). Patients with concomitant SIBO (70 patients) was treated with rifaximin or multicomponent probiotic. As the main endpoints of the study, the frequency of achieving eradication of SIBO was evaluated (estimated from the results of a repeated H2-lactulose hydrogen test after treatment), as well as a decrease in the severity of liver steatosis by steatometry and a decrease / normalization of transaminase levels 3 months after the start of the treatment. Secondary endpoints included the change in BMI and the HOMA-IR index 3 months after the start of the treatment. Results. SIBO in patients with non-alcoholic fatty liver disease was significantly more frequent than in control (p <0.005), and in patients with non-alcoholic steatohepatitis – significantly more often than in patients with liver steatosis (80 % vs 47.1 %, P <0.01). Eradication of SIBO after use of rifaximin was recorded in 30 of 36 patients with non-alcoholic fatty liver disease (83.3 %), including 16 of 20 patients with steatosis (80 %) and 14 of 16 (87.5 %) patients with non-alcoholic steatohepatitis. In the group of patients taking multicomponent probiotics after treatment, eradication of SIBO was noted in 12 of 36 patients (33.3 %), including 7 patients with steatosis (35 %) and 5 patients (31.3 %) with non-alcoholic steatohepatitis Conclusion. The investigation shows that the eradication of small intestinal bacterial overgrowth has the positive influence on the natural course of NAFLD and use of rifaximine should be discussed as a perspective therapeutic strategy at this pathology

Клінічна ендокринологія та ендокринна хірургія 1 (53)

Non-alcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD), which in the absence of treatment can progress to the development of cirrhosis and hepatocellular carcinoma, as well as to increased mortality associated with these diseases. The main risk factors for the development of NAFLD and NASH are the presence of insulin resistance and obesity. Quite often NAFLD and NASH are associated with so-called extrahepatic manifestations, such as obstructive sleep apnea, hypertension, dyslipidemia, intestinal dysbiosis, genetic predisposition, sedentary lifestyle and consumption of certain foods. However, NAFLD and NASH are also associated with some endocrine diseases and conditions, including type 2 diabetes, polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or excess, hypercortisolism, vitamin D or prolactin deficiency. In many of these diseases, the key pathophysiological mechanism is insulin resistance. This review considers the putative pathophysiological mechanisms that play an important pathogenetic role in the development of NASH in these endocrine disorders.Unfortunately, our understanding of the pathophysiology of NAFLD in various endocrinopathies is far from complete. In addition, the natural course of NAFLD due to endocrine disorders compared to the course and consequences of “primary” NAFLD is still poorly understood. Therefore, in the coming years, further research into the pathophysiology and clinical features of NASH will be important to better understand the relationship between different endocrinopathies and NAFLD, which will help improve the treatment of this pathology.

The human gastrointestinal tract is inhabited by almost 100 trillion bacteria, more than 90 % of which belong to the phylotypes Bacteroidetes and Firmicutes. This is about the same as the entire human body contains. The complex network of microbes that inhabit the body regulates its health and is supported by a balance of genetic and dietary factors. For the proper existence and survival of microbial populations in the intestine, a strictly regulated intestinal barrier is required, the violation of which can lead to the systemic spread of microbes and their penetration into the portal bloodstream. The intestinal barrier includes physical, immunological and microbial components. When any aspect of the gut barrier is not working, even bacteria that normally promote health can wreak havoc and contribute to disease and damage. It is known that changes in the intestinal barrier, intestinal permeability, and gut microbiome (GM) are associated with many diseases, including liver pathology. To understand how GM changes can lead to liver disease, a comprehensive understanding of the physiology of the intestinal barrier is required. Because of the close anatomical and physiological relationship between the gut and the liver, there has been a lot of research into how changes in one organ affect another. This review considers the main components of the intestinal barrier and the mechanisms of its pathological changes, including increased intestinal permeability, as well as GM disorders and their role in the pathogenesis of liver diseases, such as alcoholic liver disease, non‑alcoholic fatty liver disease, drug‑induced liver damage, liver cirrhosis. and its complications. Existing and promising therapeutic strategies for modifying GM and the intestinal barrier, which can be used in the treatment of hepatic pathology, are also considered.