Combination Of Non-alcoholic Fatty Liver Disease Research Articles

NONALCOHOLIC FATTY LIVER DISEASE IS A CORNERSTONE OF THE CARDIOVASCULAR CONTINUUM

Cardiovascular diseases (CVD) are the leading cause of mortality in most countries worldwide, including Uzbekistan. The main direction in preventing diseases and complications of the cardiovascular system (CVS) is the timely detection and correction of risk factors (RF). Non-alcoholic fatty liver disease (NAFLD) is considered one of the RFs of CVD development, including coronary artery disease (CAD). Data from numerous studies demonstrate increased cardiovascular risks and accelerated progression of liver pathology in the combination of NAFLD and CAD, however, some studies have not confirmed the worsening of outcomes. An association between NAFLD and CAD, atherosclerosis, cardiac rhythm disturbances, arterial hypertension, chronic heart failure and other CVDs has been identified. However, data from meta-analyses should be interpreted with caution due to the use of different diagnostic methods and the heterogeneity of studies included in them. Further studies are needed to clarify the relationship between CVDs and NAFLD further

CARDIOMETABOLIC RISK PREDICTION IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE COMBINED WITH SUBCLINICAL HYPOTHYROIDISM

One of the most common diseases of our time is non-alcoholic fatty liver disease (NAFLD). Recently published research results indicate that patients with NAFLD along with traditional risk factors for cardiovascular diseases (CVD) have "new" risk factors such as endothelial dysfunction (ED), carotid intima-media thickness (CIMT), an increase in the CRP level, as well as risk factors combined into the Framingham scale. It is also known that combination of NAFLD with subclinical hypothyroidism (SH) forms an abnormal metabolic phenotype, which is associated with cardiometabolic risk factors. The study of cardiometabolic predictors and vascular markers in patients with NAFLD in combination with SH will provide an opportunity to improve the strategy of cardiovascular events prevention in such comorbid patients.

Synergistic effect of non-alcoholic fatty liver disease and history of gestational diabetes to increase risk of type 2 diabetes.

Whether non-alcoholic fatty liver disease (NAFLD) improves risk prediction for subsequent type 2 diabetes mellitus (T2DM) in women with prior gestational diabetes mellitus (pGDM) is uncertain. We examined the combined effects of NAFLD and pGDM on risk prediction for incident T2DM. This retrospective cohort study included 97,347 Korean parous women without diabetes mellitus at baseline whose mean (SD) age was 39.0 (7.8) years. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident T2DM according to self-reported pGDM and ultrasound-diagnosed NAFLD at baseline. When combined with conventional diabetes risk factors, the incremental predictive ability of NAFLD and pGDM to identify incident T2DM was assessed. During a median follow-up of 3.9 years, 1,515 cases of incident T2DM occurred. Multivariable-adjusted HRs (95% confidence intervals [CIs]) for incident T2DM comparing pGDM alone, NAFLD alone, and both NAFLD and pGDM to the reference (neither NAFLD nor pGDM) were 2.61 (2.06-3.31), 2.26 (1.96-2.59), and 6.45 (5.19-8.00), respectively (relative excess risk of interaction = 2.58 [95% CI, 1.21-3.95]). These associations were maintained after adjusting for insulin resistance, body mass index, and other potential confounders as time-dependent covariates. The combination of NAFLD and pGDM improved risk prediction for incident T2DM (based on Harrell's C-index, also known as the concordance index, and net reclassification improvement) compared to conventional diabetes risk factors. In conclusion, NAFLD synergistically increases the risk of subsequent T2DM in women with pGDM. The combination of NAFLD and pGDM improves risk prediction for T2DM.

Pathogenetic role of fetuin-A in formation of metabolic disorders and systemic inflammation in patients with non-alcoholic fatty liver disease

Non‑alcoholic fatty liver disease (NAFLD) remains the leading nosology among hepatic diseases around the world. Its complex pathogenesis is not still clearly understood. Besides metabolic changes one of potential mechanisms of NAFLD development is changes in hepatokines, fetuin‑A in particular, secretion and metabolism.
 Objective — to determine the role of fetuin‑A in the development and progression of NAFLD.
 Materials and methods. The study enrolled 78 NAFLD patients with metabolic disorders and 30 volunteers as a control group. Additionally to routine examination serum concentration of fetuin‑A was determined. Statistical processing was carried out using SPSS 21.
 Results. The results showed a statistically significant increase in fetuin‑A concentrations in NAFLD patients with concomitant MS (p < 0.05). There was a direct correlation between fetuin‑A levels and parameters of abdominal (WC and WHR, p < 0.05) and visceral obesity (VAT %, p < 0.05). Concentrations of fetuin‑A were higher in polymorbid patients, especially in the combination of NAFLD with type 2 diabetes mellitus and obesity. Fetuin‑A levels was associated with changes in carbohydrates and lipids parameters. Fetuin‑A positively correlated with glycated hemoglobin (r = 0.32, p < 0.05) and index HOMA (r = 0.36, p < 0.05). There was a positive correlation between fetuin‑A level and TG (r = 0.44, p < 0.05) and LDL cholesterol (r = 0.37, p < 0.05). Furthermore, an increase in fetuin‑A was associated with an increase in activity of ALT (r = 0.39, p < 0.05) and elevation of the level of TNF‑a (r = 0.33, p < 0.05). NAFLD patients with advanced stages of steatosis and fibrosis also demonstrated higher levels of fetuin‑A (p < 0.05).
 Conclusions. The obtained data indicate a significant pathogenetic role of fetuin‑A in the development and progression of NAFLD.

Prevalence and Specific Manifestations of Non-alcoholic Fatty Liver Disease (NAFLD) and Diabetes Mellitus Type 2 Association in a Moroccan Population: A Cross-sectional Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is recognized as a common cause of chronic liver disease worldwide. Its association with type 2 diabetes mellitus (T2DM) is known to increase the risk of degenerative complications of diabetes and the likelihood of developing severe hepatic injuries. The objective of this study was to assess the prevalence of NAFLD and to describe the characteristics of its association with T2DM. METHODS: This was a descriptive analytical study, involving patients with T2DM with no history of alcohol consumption, viral hepatitis, hepatotoxic medications, or other chronic liver diseases. The patients underwent an investigation of NAFLD including abdominal ultrasound, non-invasive biomarkers of liver fibrosis, elastography and ultrasound-guided liver biopsy. RESULTS: We collected data from 180 patients with a mean age of 59.3 ± 10.9 years with strong female predominance. The mean duration of diabetes progression was 9.2 ± 7.3 years. Hepatic sonography showed signs of NAFLD in 45.6% of cases. Non-invasive hepatic biomarkers indicated significant fibrosis in 18.3% of cases. Overall, 21% of patients underwent an elastography evaluation, revealing severe fibrosis or cirrhosis in 15.4% of patients. The diagnosis of NASH (Non-alcoholic steatohepatitis) was confirmed histologically in 3 patients. The overall prevalence of NAFLD was 45.6%. Patients with NAFLD had a statistically significant incidence of obesity, metabolic syndrome, hypertension, dyslipidemia, macrovascular complications, and hypertriglyceridemia (p < 0.05). CONCLUSIONS: The combination of NAFLD and T2DM is often found in patients with obesity or metabolic syndrome. The presence of NAFLD can be responsible for increased morbidity and important cardiovascular risks in patients with T2DM.

Non-alcoholic fatty liver disease and metabolic liver dysfunction in the new coronavirus infection COVID-19

Our study aimed to explore associated non-alcoholic fatty liver disease (NAFLD) and metabolic liver dysfunction influence on the severity of the new coronavirus infection COVID-19. Material and methods. The study design was a cross-sectional study. The research included 215 patients (39.50 % of men) aged 26–60 years who had undergone a new coronavirus infection COVID-19 at least two months ago. Participants were divided into three groups by severity of infection: mild (n = 99), moderate and severe (n = 116) by anamnesis. Hepatic steatosis index (HIS), body mass index (BMI), waist circumference, alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, systolic and diastolic pressure were calculated and abdominal ultrasound examination was done. Results. In the group with moderate and severe course of COVID-19, the proportion of patients diagnosed with NAFLDaccording to the HSI index was significantly higher compared to patients with mild coronavirus infection. Patients with mild COVID-19, who were diagnosed with NAFLD, had higher alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, BMI, systolic and diastolic pressure, waist circumference compared to patients without NAFLD. Similar differences persisted for patients with moderate and severe course. With the step-by-step exclusion of cardiometabolic parameters from the logistic regression model, the triglyceride content and BMI retained association with steatohepatosis according to ultrasound data, regardless of severity. When creating a similar model for the HSI index, significant correlation was shown for alanine aminotransferase activity in patients with mild COVID-19, for alanine aminotransferase activity and BMI – in patients with moderate and severe COVID-19. Conclusions. Patients with NAFLD have a more severe course of COVID-19. In addition, associations of the severity of COVID-19 with a combination of NAFLD and other cardiometabolic changes in the body, such as arterial hypertension, obesity, dyslipidemia, were revealed.

Comorbidity of NAFLD and GERD as a cardiometabolic phenomenon

The aim of the study was to study the cardiometabolic characteristics in individuals with an associated course of non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) in comparison with isolated cases of diseases.Materials and methods. The study included 120 patients (30 — with GERD, 30 — with NAFLD, 30 — with GERD + NAFLD. Work design — prospective parallel comparative study with 2 stages. Stage I — inclusion in the study, assessment of the main cardiometabolic, cardio vascular rice (CVR) according to the SCORE scale and the Framingham scale. Stage II — follow-up of the participants for 5 years, re-examination and riskmetry.Results. It has been shown that with a combination of NAFLD and GERD, the pathogenetic mechanisms involved in the formation of NAFLD (especially in steatohepatitis) affect the key characteristics of the metabolic profile and the state of the CV system to a greater extent than GERD. The total CVR values in this category of patients were: 4.8 — SCORE; 13.4 — on the Framingham scale. Over 5 years in this group, 10 (33% of the initial) newly diagnosed cases of CVD were verified: 6 — AH, 3 — IHD, 1 — AH + IHD. CVR for the NAFLD and GERD group increased: according to the SCORE scale — from low risk (4.8) to high (8.9), and according to the Framingham scale, the dynamics was even more negative (from 13.4 to 18.6).Conclusion. Kinds of cardiometabolic disorders in persons with comorbidity of NAFLD and GERD have been proven, which can form the prerequisites for structural cardiovascular changes, including the risks of CVD. This can be a rationale for carrying out additional preventive measures for the groups of patients under discussion, especially in the case of their associated course, as measures for the early preclinical diagnosis of CVR factors and for timely correction of the identified disorders.

THE ROLE OF RESISTIN IN THE PROGRESSION OF NON-ALCOHOLIC FATTY LIVER DISEASE

The aim of the research was to study the relationship between plasma concentrations of resistin and indicators of enzyme and pigment metabolism in patients with non-alcoholic fatty liver disease (NAFLD) and its combination with type 2 diabetes mellitus (DM-2). Materials and methods. On the base of Kharkiv Regional Hospital a total of 90 patients were examined, including patients with NAFLD (n = 20) and its combination with DM-2 with normal body weight (n = 20) and obesity (n = 50), as well as 20 healthy volunteers. A complex of clinical, laboratory and instrumental (including liver biopsy in 9 patients) examinations of patients was performed. Results. A direct relationship was established between the level of resistin and indicators of enzyme and pigment exchange in groups of patients with combined pathology. A significant increase of resistin plasma level, as well as disorders of the liver function were determined in all groups of patients in comparison with the controls. The most marked changes were revealed in patients with combination of NAFLD, DM-2 and obesity. Conclusions. The established relationship between the level of resistin and the indicators of the liver functional state suggests that an increase of resistin level may reflect the presence of impaired liver function in patients with NAFLD in combination with DM-2, predicting the progression of NAFLD. In order to detect the disorders of liver function in patients with DM-2, it is recommended to determine the level of resistin in patients with NAFLD, especially when concomitant obesity is present. Patients with resistin level (&gt; 8.06 ± 0.23 ng/ml) should be considered at risk of NAFLD progression.

Доцільність використання урсодезоксихолевої кислоти в лікуванні хворих на неалкогольну жирову хворобу печінки: клінічний випадок

Неалкогольна жирова хвороба печінки (НАЖХП) посідає провідне місце серед хронічних захворювань печінки. Поряд з цим патогенез НАЖХП на сьогодні не повністю вивчений. Деякі автори пропонують вважати НАЖХП однією зі складових метаболічного синдрому (МС), розглядаючи її як печінковий прояв МС. У статті подано сучасні погляди на лікування хворих із НАЖХП. Також висвітлено теоретичні аспекти використання урсодезоксихолевої кислоти (УДХК) і можливості її застосування у хворих із поєднанням НАЖХП і МС. Як приклад продемонстровано доцільність і ефективність призначення УДХК пацієнту Л. із НАЖХП і МС (порушення толерантності до глюкози, артеріальна гіпертензія, ожиріння). Призначення Урсофальку хворому Л. є патогенетично обґрунтованим з огляду на гіпохолестеринемічний, цитопротекторний, антиоксидантний, антихолестатичний та інші його позитивні ефекти. УДХК може розглядатись як ефективний і безпечний препарат у лікуванні не тільки хворих на НАЖХП, а й пацієнтів із МС, захворюваннями серцево-судинної системи й ожирінням.

NON-ALCOHOLIC FATTY LIVER DISEASE AND HYPERTENSION: CLINICAL VARIABILITY OF COMORBIDITY

Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases; and considerable attention is paid to the comorbidity of NAFLD with hypertension (HT), which affects around one-third of the world's population. The combination of NAFLD with hypertension has been suggested to have a mutual potentiating effect, and hypertension affects the severity of NAFLD. The purpose: to study the features of the clinical manifestation of NAFLD in patients with hypertension. Materials and methods. The study included 115 patients with NAFLD at the stage of nonalcoholic steatohepatitis. The main group consisted of 63 patients with NAFLD and HT, the comparison group included 52 patients with isolated NAFLD, and the control group was composed of 20 healthy volunteers. The patients underwent anthropometric measurements, evaluation of biochemical markers of liver functional activity, lipid profile and carbohydrate metabolism changes, C-reactive protein (CRP) levels. Results. A significant increase in the proportion of patients with active complaints in the group of patients with NAFLD with HT (subjective signs of liver damage, manifestations of dyspeptic and asthenic syndrome) was detected. Significant differences were found in almost all anthropometric indicators in both groups of patients with NAFLD in comparison with the control group. The level of CRP had significant differences and was 7.90 mg/l (95% CI = 7.96-8.75 mg/l), 6.55 mg/l (95% CI = 6.47-7.57 mg/l) and 2.07 (95% CI = 1.83-2.85 mg/l) in patients with NAFLD and HT, isolated NAFLD and the control group, respectively (p &lt;0.001). Fasting glucose levels were significantly higher in both groups of examined patients with NAFLD compared with controls. Significant differences were found in the levels of total cholesterol, VLDL cholesterol, HDL cholesterol and atherogenic factor in patients with NAFLD depending on concomitant HT. There was no significant difference between LDL cholesterol and triglycerides in the two groups of patients with NAFLD. Conclusions. Based on the obtained data, it can be stated that GC in patients with NAFLD determines important deviations in the clinical manifestation of the disease and can be considered as a trigger factor for the progression of NAFLD.

Non-alcoholic fatty liver disease and psoriasis: random combination or regular relationship?

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. Recent observational studies have shown that the prevalence of NAFLD is remarkably higher in psoriatic patients (occurring in up to 50 % of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls. The use of drug therapy in patients with a combination of NAFLD and psoriasis with the inclusion of the drug Legalon is pathogenetically justified.

Неалкогольна жирова хвороба печінки та коморбідні захворювання: диференційований підхід до призначення антиоксидантів

Актуальність роботи зумовлена широкою розповсюдженістю неалкогольної жирової хвороби печінки (НАЖХП), частим поєднанням її із іншими коморбідними захворюваннями та неоднозначністю рекомендацій щодо лікування таких пацієнтів. Дослідження поєднаного перебігу НАЖХП та субклінічного гіпотиреозу (СГ) пов’язано із широким розповсюдженням тиреоїдної патології в регіонах, ендемічних щодо дефіциту йоду.&#x0D; Матеріал та методи. Обстежено 137 осіб, 20 із яких склали контрольну групу практично здорових. Для верифікації діагнозів використано комплекс клінічних та інструментально-лабораторних методів дослідження відповідно до діючих клінічних протоколів. Лабораторне дослідження прооксидантно-антиоксидантної системи крові проводилося із використанням спектрофотометричних методів за методикою, розробленою Науковим центром радіаційної медицини АМН України.&#x0D; Результати та їх обговорення. За умови приєднання супутньої патології у пацієнтів із НАЖХП спостерігається не тільки активація перекисного окислення ліпідів (ПОЛ), а й пригнічення антиоксидантного захисту (АОЗ). У випадках приєднання до НАЖХП на фоні порушення вуглеводного обміну ще й субклінічного гіпотиреозу процеси ПОЛ достовірно активуються, а АОЗ – пригнічується (порівняно з пацієнтами, що мають тільки субклінічний гіпотиреоз), хоча у пацієнтів із ізольованим субклінічним гіпотиреозом рівень МДА достовірно не відрізнявся від здорових. Після вираховування фактору АОЗ та ранжування пацієнтів у порядку спадання його значення виявлено, що хворі, які страждали на ізольовану НАЖХП, в переважній більшості мали незначне пригнічення АОЗ, що не обгрунтовує доцільність антиоксидантної терапії. Натомість, пацієнти із НАЖХП та коморбідною патологією характеризувалися помірним та значним пригніченням АОЗ, що дає підстави рекомендувати для їх лікування препарати з антиоксидантною дією. Такий диференційований підхід до призначення терапії на основі стану антиоксидантної системи дозволяє оптимізувати лікування та уникати поліпрагмазії.&#x0D; Висновок. Активація ПОЛ та пригнічення системи АОЗ у хворих із НАЖХП посилювалися за умови поєднаної патології. Для пацієнтів із НАЖХП обгрунтованим є диференційований підхід щодо призначення антиоксидантів: їх слід рекомендувати особам, які мають коморбідну патологію, натомість хворі із ізольованою НАЖХП в переважній більшості не потребують призначення антиоксидантної терапії.

Helicobacter pylori infection combined with non-alcoholic fatty liver disease increase the risk of atherosclerosis: Focus in carotid artery plaque.

Atherosclerosis has severe consequences on human health. Carotid artery plaques are a condition typically caused by atherosclerosis. Previous studies showed that nonalcoholic fatty liver disease (NAFLD) and Helicobacter pylori (H pylori) are risks factors for carotid artery plaque formation. We hypothesize that the combination of NAFLD with H pylori infection increases the risk of carotid artery plaque formation.A total of 4669 subjects aged > 40 years who underwent routine health checkups between January 2006 and December 2015 were retrospectively reviewed. A serial examination, including abdominal ultrasound, carotid artery ultrasound and esophago-gastroduodenoscopy (EGD), and biopsy urease testing, was conducted.In total, 2402 subjects were enrolled. There were no differences in H pylori infection status among patients with or without NAFLD. There was a trend of more participants with both NAFLD and H pylori infection (number [N]=583) presenting carotid artery plaque (N = 187,32.08%) than participants without NAFLD and H pylori infection (N = 589) who presented plaque formation (N = 106, 18.00%). Participants who had both H pylori infection and NAFLD had the highest risk of any carotid artery plaque (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.413–2.636) based on a multivariate logistic regression analysis. This analysis also showed that age >60 years, male sex, low-density lipoprotein (LDL) >130 mg/dL, and H pylori infection were independent risk factors for concomitant NAFLD and carotid artery plaque formation.The combination of H pylori infection and NAFLD increases carotid artery plaque formation. H pylori eradication and NAFLD control may be warranted to prevent carotid artery plaque formation.

Abstract P141: Non-alcoholic Fatty Liver Disease, Insulin Resistance, and the Risk of Incident Ischemic Heart Disease and Stroke - The Kangbuk Samsung Health Study

Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and with other metabolic abnormalities, but the association of NAFLD with the risk of clinical cardiovascular disease (CVD) is controversial. Furthermore, the risk associated with the combination of NAFLD and IR has not been evaluated in prospective studies. The aim of this study was to evaluate the association of NAFLD with or without IR on the incidence of coronary heart disease (CHD) and stroke. Methods: We performed a cohort study in 166,126 adults without CVD at baseline who underwent a health checkup exam during 2008 - 2011 and were followed-up through December 31, 2012 (average follow-up of 3.2 years). NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. IR was defined as a homeostasis model assessment of IR (HOMA-IR) value ≥ 2.5. Incident hospitalizations for CHD events and strokes were ascertained through data linkage with the Korean Health Insurance Review and Assessment Service (HIRA) database. Results: At baseline, the prevalence of NAFLD and of IR were 25.1 and 6.3%, respectively. During follow-up, 831 participants developed CHD and 582 subjects developed stroke. After adjusting for age, sex, center, year of screening exam, BMI, smoking, alcohol intake, physical activity, family history of CVD, and education, the hazard ratios (95 % confidence intervals) for CHD comparing NAFLD without IR, IR without NAFLD, and NAFLD with IR vs. no NAFLD without IR were 1.07 (0.91 - 1.27), 1.19 (0.74 - 1.91) and 1.55 (1.18 - 2.03), respectively. The corresponding hazard ratios for stroke were 0.93 (0.75 - 1.16), 1.40 (0.83 - 2.35) and 1.82 (1.32 - 2.52), respectively. The P-values for the interaction of NAFLD and IR for CHD and stroke were 0.48 and 0.28, respectively. These associations did not differ by clinically relevant subgroups. Conclusions: The combination of NAFLD and IR was associated with an increased incidence of CHD and of stroke, but this was not observed in those with either NAFLD or IR alone. The combination of NAFLD and IR may identify individuals at high cardiometabolic risk who may need to receive more intensive preventive intervention.