Concomitant Non-alcoholic Fatty Liver Disease Research Articles

Assessment of the quality of life in patients with onychomycosis and mycosis of the feet with concomitant non-alcoholic fatty liver disease against the background of complex therapy

Background. Сurrently, much attention is paid to the quality of patients, which is a promising direction of life, allowing to put a complete and objective picture of the disease, determine the most stable method of treatment, and evaluate its results.
 Aims. To evaluate the effectiveness of complex therapy in patients with onychomycosis and mycosis of the feet with concomitant non-alcoholic severe liver disease (NAFLD) using a modified questionnaire-questionnaire of the combined index of quality of life (QL-Index).
 Methods. The combined index of quality of life (QL-Index) was determined in patients with onychomycosis and mycosis of the feet with with concomitant NAFLD before and after complex therapy.
 Results. Analysis of the results of assessing the presence of a combined index of quality of life in 117 patients with onychomycosis and foot mycosis with concomitant NAFLD before treatment showed that the presence of onychomycosis and mycosis of the feet in the majority of respondents has a strong impact on the lives of the respondents (69.2%). After the complex treatment, according to the results of the combined questionnaire-questionnaire of the quality of life index, it was revealed that social activity in patients with onychomycosis and foot mycosis with concomitant NAFLD increased, and the psycho-emotional state improved. The quality of life of patients has improved, which significantly increased the effectiveness of this complex treatment.
 Conclusion. The high efficacy and safety of complex therapy, which included the use of the systemic antimycotic itraconazole in combination with external antifungal drugs, a hepatoprotector and a prebiotic in patients with onychomycosis and mycosis of the feet with concomitant NAFLD.

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

Concomitant NAFLD Facilitates Liver Metastases and PD-1-Refractory by Recruiting MDSCs via CXCL5/CXCR2 in Colorectal Cancer

Background and AimsBoth Non-alcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effect of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated. MethodsWe observed the effect of concomitant NAFLD on CRLM in the mouse model, and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment, then tested the therapeutic application based on the mechanisms; finally we validated our findings in the clinical samples. ResultsHere we prove that in different mouse models, NAFLD induces F4/80+ Kupffer cells to secret chemokine CXCL5, then recruits CXCR2+ myeloid-derived suppressor cells (MDSCs) to promote the growth of CRLM. CRLM with NAFLD background are refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual-therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2+ MDSCs, as well as the hazard of liver metastases in CRC patients. ConclusionsCollectively, our findings highlight the significance of a selective CXCR2+/CD11b+/Gr-1+ subset myeloid cells in favoring the development of CRLM with NAFLD background, and identify a pharmaceutic medicine which is already available for the clinical trials and potential treatment.

Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status

Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain. To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD. This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023. The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD. After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]). In this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.

Abstract 12 — Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Study

Background Rheumatoid arthritis (RA) is a debilitating and financially burdensome disease because of frequent presence of comorbidities including metabolic and cardiovascular abnormalities. Growing evidence suggests a link between RA and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and explore the risk factors of developing NAFLD in RA population. Methods This population-based, cross-sectional study utilized data on US adults aged [Formula: see text]20 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, a representative sample of the general US population. Diagnosis of RA was derived from questionnaire data. NAFLD was defined by controlled attenuation parameter (CAP) scores of [Formula: see text]278 dB/m using vibration controlled transient elastography (VCTE) in the absence of other liver disease. Weighted multiple regression analysis was further performed to assess the independent risk factors. Results Of 2,848 people included in this study, 224 of them had self-reported RA. The prevalence of NAFLD in the overall sample was 41%, with a numerically higher prevalence in RA patients than those without arthritis (47% vs. 40%, p=0.30). Compared to those without NAFLD, RA patients with concomitant NAFLD had more prevalent metabolic comorbidities including obese (75% vs. 32%, p=0.006), central obesity (100% vs. 71%, p=0.008), diabetes (39% vs. 14%, p=0.003) and hyperlipidemia (88% vs. 76%, p=0.042). Regarding laboratory findings, RA patients with NAFLD exhibited higher levels of triglyceride (188 mg/dL vs. 131 mg/dL, p=0.010), fasting plasma glucose (131 mg/dL vs. 109 mg/dL, p=0.010) and HbA1c (5.77% vs. 6.41%, p=0.002). Meanwhile, elevated levels of liver enzymes (ALT: 29 U/L vs. 19 U/L, p=0.015; AST: 25 U/L vs. 19 U/L, p=0.007) and inflammatory indicator CRP (5.1 mg/dL vs. 3.4 mg/dL, p<0.001]) were more frequently reported in RA patients with NAFLD as compared with those without. Further, weighted multivariate logistic regression analysis showed that the presence of central obesity (adjusted OR=1.56 [95% CI 1.16-2.11], p=0.008) and diabetes (adjusted OR=1.28 [95% CI 1.07-1.54], p=0.014) were significantly associated with prevalent NAFLD in patients with RA. Conclusion In this population-based study, about one in two patients with RA had NAFLD, which is higher than its overall prevalence among general population. Central obesity and diabetes are predisposing factors for NAFLD in RA. Our results highlight the importance of active NAFLD screening in RA population, especially for high-risk subsets.

Crohn´s disease is an independent risk factor for liver fibrosis in patients with inflammatory bowel disease and non-alcoholic fatty liver disease

Background and aimsControversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. MethodsCross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. ResultsThe prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001–1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001–1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78–8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87–0.98)). ConclusionsAlthough we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.

Efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache with concomitant nonalcoholic fatty liver disease in climacteric women.

This study aimed to assess the efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache (CTTH) with concomitant nonalcoholic fatty liver disease (NAFLD) in climacteric women. In this study, we enrolled 150 climacteric women with CTTH and concomitant NAFLD. The participants were divided into three groups based on the random number table: medication group, acupuncture group, and acupuncture-medication group. Treatment continued for 2 months. The efficacy of CTTH was assessed based on the visual analog scale/score (VAS). The influence on NAFLD was assessed based on body mass index (BMI), controlled attenuation parameter (CAP), and the ratio of hepatic-splenic computed tomography (CT) value. The Participant Health Questionnaire-9 (PHQ-9) score was compared among the three groups. A total of 123 participants completed the trial, including 37 participants in the medication group, 41 participants in the acupuncture group, and 45 participants in the acupuncture-medication group. Results are summarized hereinafter. (1) The total clinical efficiency rates of the medication group, acupuncture group, and acupuncture-medication group were 89.19% (33 of 37), 90.24% (37 of 41), and 95.65% (44 of 46), respectively. (2) Except for the BMI of the medication group (P = 0.063), a significant difference in VAS, BMI, CAP, the ratio of hepatic-splenic CT value, and PHQ-9 score was found in the three groups (P < 0.01). (3) There was a significant difference in VAS, BMI, CAP, and PHQ-9 among the three groups (P < 0.01), with those in the acupuncture-medication group being superior. No difference in the ratio of hepatic-splenic CT value was found (P = 0.440). (4) The efficacy differed significantly among the three groups (χ2 = 8.130, P = 0.017), and it was significantly superior in the acupuncture-medication group (P = 0.008, P = 0.013). Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in treating CTTH in climacteric women compared with either acupuncture or medication. Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in subsiding the negative moods in participants with CTTH and concomitant NAFLD.

Fatty liver is associated with significant liver inflammation and increases the burden of advanced fibrosis in chronic HBV infection

BackgroundConcurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial.MethodsConsecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer’s score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3).ResultsAmong the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760.ConclusionsNAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.

Therapeutic potential of sodium selenite in patients with non-alcoholic fatty liver disease and hypertension disease

Liver parenchyma damage is associated with significant activation of oxidative stress. Correction of oxidative stress can be a promising direction in the treatment of arterial hypertension. It has been established that in patients with hepatopathies, lower concentrations of selenium are found in blood and erythrocytes, which gives reason to consider selenium as a potential therapeutic agent in patients with liver pathology.&#x0D; Objective — to determine the therapeutic potential of sodium selenite in patients with non‑alcoholic fatty liver disease in combination with hypertension.&#x0D; Materials and methods. 100 patients with nonalcoholic fatty liver disease (NAFLD) were included in the study: the main group — 49 patients (67.3% women, median age is 51.0 years) with concomitant NAFLD and arterial hypertension (HTN), the comparison group — 51 patients (58.8% women, median age is 52.0 years) with NAFLD isolated course. The control group included 20 practically healthy people (55.0% women, median age is 51.0 years). Among the patients of the main group, the first degree of HTN was diagnosed in 28.6% of patients (14 people), the second degree — 71.4% (35 people). Among these patients, 32.7% (16 people) had the first stage of HTN, 67.3% (33 people) had the second stage. In the main group, 55.1% of patients had steatosis, 44.9% had steatohepatitis. In the comparison group, 58.8% had steatosis, 41.2% had steatohepatitis (χ2=0.141, p=0.707). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured according to the standard method (kinetic method). Gamma‑glutamine transpeptidase (GGTP) was measured by the enzymatic colorimetric method, alkaline phosphatase (AP) by the colorimetric method. Selenium and selenoprotein P (Sel P) levels were determined using the immunofluorescence method. Ultrasound examination of the liver was performed according to the standard method on an empty stomach.&#x0D; Results. Body mass index corresponded to normal or increased body weight: in the main group — 27.8 [26.6; 28.5] kg/ m2 and 27.3 [24.2; 28.3] kg/ m2 in the comparison group, in the control group — 24.3 [21.9; 26.0] kg/ m2. In patients of the main group was determined a significant (p &lt;0.001) predominance of ALT levels (45 [43.0; 47.5] U/ L), AST levels (53 [51.0; 56.0] U/ L), AP levels (285.7 [217.6; 321.1] U/ L) and GGTP levels (96.2 [75.0; 108.9] U/ L) opposite to comparison group (respectively 36 [34.0; 39.0] U/ L, 41 [40.0; 45.0] U/ L, 215.5 [183.2; 246.7] U/ L and 65.5 [51.5; 76.8] U/ L) and control group levels (respectively 25.5 [24.0; 30.8] U/ L, 23 [19.3; 26.0] U/ L, 129.2 [116.9; 140.6] U/ L and 22.6 [16.1; 31.7] U/ L). A two‑fold decrease in selenoprotein P levels was obtained in patients with NAFLD and HTN compared to patients with NAFLD (19.7 [8.0; 26.7] ng/ mL and 43.1 [41.3; 45.4] ng/ mL respectively, p &lt;0.001), and selenium in one and a half times compared to patients with NAFLD (43.5 [39.9; 49.1] g/ L and 67.2 [61.5; 77.4] g/ L respectively, p &lt;0.001). The highest Sel P median levels (71.0 [54.3; 76.1] ng/ ml and selenium levels (108.0 [96.9; 118.8] g/ L) registered in the control group (p &lt;0.001). Evaluating the data on selenium metabolism and liver tests depending on the intake of sodium selenite, a significant increase in the levels of Sel P (53.6 [43.1; 60.4] ng/ ml, p &lt;0.001) and selenium (89.1 [63, 4; 99.5] g/ L, p &lt;0.009), as well as a decrease in AST levels (41.7 [32.6; 43.2] U/ l, p &lt;0.001) in the group with isolated NAFLD, while in the group with NAFLD and HTN comorbid course, no significant changes in the studied parameters were detected.&#x0D; Conclusions. The obtained results provide a basis for sodium selenite use in the therapy of patients with NAFLD. Further research on the duration of such therapy and sodium selenite dosing regimen in patients with a comorbid course of NAFLD and HTN is a promising and relevant direction.&#x0D;

THERMOGRAPHIC EVALUATION OF GOUT COURSE IN COMBINATION WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND TREATMENT

Summary. Gout is an urgent problem today, as its prevalence has doubled in recent decades. Disorders of thermoregulation and regional blood flow are an important clinical and pathogenetic manifestation of gout, which can be assessed by recording infrared radiation.&#x0D; The aim – to evaluate the thermographic semiotics of gout and thermographic indicators of its course in concomitant non-alcoholic fatty liver disease (NAFLD) and the effectiveness of their treatment.&#x0D; Material and Methods. 74 male gout patients were examined. They were divided into 2 groups. Group I included 38 patients with gout without liver damage, group II – 36 patients with NAFLD. Both groups were divided into subgroups: IA and IIA who received basic therapy, IB and IIB who additionally received carbon enterosorbent. The control group consisted of 20 healthy individuals. Thermographic study was performed using a thermal imager ULIRvision TI 120.&#x0D; Results. The temperature gradient of symmetrical areas in healthy individuals (control group) was (0.37±0.04) °C. In all patients before treatment thermograms shows a zone of intense hyperthermia with clear contours, which exceeded the size of the visible hyperemia in the affected joint. The temperature gradient in patients with gout without liver damage was (3.99±0.17) °C, and in patients with concomitant NAFLD – (4.41±0.14) °C (p&gt;0.05). On thermograms after treatment in most patients of both groups there was still a zone of hyperthermia. It was smaller in area and intensity, the clarity of the contours was lost. Therapy results were significantly better in patients receiving basic therapy with enterosorbent, but they still did not meet the norm (p&lt;0.05).&#x0D; Conclusion. Thermography makes it possible to determine the change in local temperature of the affected joints at gout during exacerbation, to establish the location and prevalence of the pathological process and to assess the effectiveness of treatment.

Poor glycaemic control and ectopic fat deposition mediates the increased risk of non-alcoholic steatohepatitis in high-risk populations with type 2 diabetes: Insights from Bayesian-network modelling.

An estimated 55.5% and 37.3% of people globally with type 2 diabetes (T2D) will have concomitant non-alcoholic fatty liver disease (NAFLD) and the more severe fibroinflammatory stage, non-alcoholic steatohepatitis (NASH). NAFLD and NASH prevalence is projected to increase exponentially over the next 20 years. Bayesian Networks (BNs) offer a powerful tool for modelling uncertainty and visualising complex systems to provide important mechanistic insight. We applied BN modelling and probabilistic reasoning to explore the probability of NASH in two extensively phenotyped clinical cohorts: 1) 211 participants with T2D pooled from the MODIFY study & UK Biobank (UKBB) online resource; and 2) 135 participants without T2D from the UKBB. MRI-derived measures of visceral (VAT), subcutaneous (SAT), skeletal muscle (SMI), liver fat (MRI-PDFF), liver fibroinflammatory change (liver cT1) and pancreatic fat (MRI-PDFF) were combined with plasma biomarkers for network construction. NASH was defined according to liver PDFF >5.6% and liver cT1 >800ms. Conditional probability queries were performed to estimate the probability of NASH after fixing the value of specific network variables. In the T2D cohort we observed a stepwise increase in the probability of NASH with each obesity classification (normal weight: 13%, overweight: 23%, obese: 36%, severe obesity: 62%). In the T2D and non-T2D cohorts, elevated (vs. normal) VAT conferred a 20% and 1% increase in the probability of NASH, respectively, while elevated SAT caused a 7% increase in NASH risk within the T2D cohort only. In those with T2D, reducing HbA1c from the 'high' to 'low' value reduced the probability of NASH by 22%. Using BNs and probabilistic reasoning to study the probability of NASH, we highlighted the relative contribution of obesity, ectopic fat (VAT and liver) and glycaemic status to increased NASH risk, namely in people with T2D. Such modelling can provide insights into the efficacy and magnitude of public health and pharmacological interventions to reduce the societal burden of NASH.

Features of clinical, biochemical, and sonographic parameters in patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease.

Introduction. Difficulties encountered in treating patients with chronic viral hepatitis C (CHC) are associated with the presence of concomitant liver pathology, namely fatty degeneration, which contributes to the progression of HCV infection. The above circumstances prompted the authorsled to thoroughly examine of this category of patients for further development of a new pathogenetically directed course of treatment. Objective. To study clinical, biochemical, and instrumental features of the course of liver disease in CHC patients with concomitant non-alcoholic fatty liver disease (NAFLD). Tested 339 patients with chronic hepatitis C with concomitant NAFLD; and 175 patients with СНС. Methodology: anamnestic, anthropometric and clinical, general clinical, biochemical, serological, and molecular genetic (markers of hepatitis C virus, HCV RNA PCR (qualitative and quantitative determination, genotyping), enzyme-linked immunosorbent assay, ultrasonographic examination of digestive organs, statistical methods. Conducted clinical, instrumental, and laboratory studies have shown that CHC patients with concomitant NAFLD are characterized by various disorders - a violation of the functional state of the liver, a violation of carbohydrate and lipid metabolism, an imbalance of the cytokine system, the presence of histological and non-inflammatory activity in the liver. The presence of concomitant NAFLD in patients with CHC aggravates the clinical picture, manifesting itself in a significant lipid metabolism disorder that provokes the rapid formation of liver fibrosis. An additional complicating factor is the development of insulin resistance, leading to persistent morphological changes in the liver parenchyma.

Association of PNPLA3 SNP With the Development of HBV-related Hepatocellular Carcinoma.

Concomitant nonalcoholic fatty liver disease (NAFLD)/hepatic steatosis (HS) is suggested to increase the risk of hepatocellular carcinoma (HCC) in hepatitis virus B (HBV)-infected patients. Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 gene single-nucleotide polymorphism (SNP) is well-known to be associated with the development of NAFLD/HS; however, it is still unclear whether this SNP is related to the development of HCC in HBV-infected patients. We investigated a total of 202 HBV-infected patients who received percutaneous liver biopsy, and simultaneously assessed biopsy-proven HS, insulin resistance, and the PNPLA3 SNP status. We further investigated the relationships of these factors with the development of HCC in HBV-infected patients. Most of the enrolled cases (196/202: 97.0%) were non-cirrhotic patients. One hundred seventy-three patients (85.6%) received antiviral therapy. A Kaplan-Meier analysis showed that the incidence of HCC development in patients with HS was higher than that in patients without HS (p<0.01). An increased homeostasis model assessment as an index of insulin resistance (HOMA-IR) value (≥1.6) was associated not only with the presence of HS (p<0.0001) but also with the development of HCC (p<0.01). The PNPLA3 rs738409 SNP was also associated with the presence of HS (p<0.01) and the development of HCC (p<0.05) in HBV-infected patients. In addition to HS and IR, PNPLA3 rs738409 SNP was suggested to be associated with the development of HCC in Japanese patients with HBV infection.

Patients with NAFLD exhibit more advanced fibrosis in liver biopsy than patients with other chronic liver diseases.

Despite extremely high and seemingly rising prevalence of non-alcoholic fatty liver disease (NAFLD), awareness for this health condition is still low. In the present study we analyzed, if this is reflected in clinical routine for advanced diagnostic measures. Retrospective data of 93 patients with histologically determined fibrosis stage and confirmed etiology was analyzed. Patients were grouped according to chronic liver disease alone (n=40), concomitant chronic liver disease and NAFLD (n=29), or NAFLD alone (n=24). Fibrosis stage and presence of cirrhosis were main outcome measures. Patients with NAFLD were significantly older and had significantly higher body mass index and CAP-values than patients with chronic liver disease. Significantly higher fibrosis stages were observed in patients with NAFLD than in those with chronic liver disease alone (p=0.003). Presence of cirrhosis was significantly higher in patients with NAFLD than in patients with chronic liver disease (p=0.01). This was not associated with a significantly different age distribution over fibrosis stages between chronic liver disease and NAFLD. Undergoing liver biopsy 10 years earlier could have possibly prevented progression to cirrhosis in up to 7 patients with NAFLD. This could have potentially saved 35,000 € yearly health care resources. These findings suggest that the time course for development of liver fibrosis and cirrhosis is not fundamentally different between patients with NAFLD or with other chronic liver diseases. Higher rates of cirrhosis observed in patients with NAFLD could potentially be ameliorated by earlier diagnostic work-up and improved monitoring.

Adverse Effect of Nonalcoholic Fatty Liver Disease on the Therapeutic Response in Patients with Chronic Hepatitis B.

The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation. Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR). We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR. In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

Non-alcoholic fatty liver disease is not independently associated with Helicobacter pylori in a central European screening cohort.

The association between Helicobacter pylori (Hp) infection and non-alcoholic fatty liver disease (NAFLD) is subject of a contentious debate. Data mainly stem from Asian cohorts whereas European data are scarce. We, therefore, investigated an Austrian colorectal cancer screening cohort for an association between Hp and NAFLD. In total, 5338 consecutive participants undergoing screening colonoscopy at a single center in Austria were evaluated in this cross-sectional study. The primary risk factor was being Hp negative or positive. The primary endpoint was the presence of NAFLD defined by ultrasound (NAFLD; primary endpoint). Uni- and multivariable logistic regression models were fitted to obtain odds ratios (OR) and 95% confidence intervals (95%CI). Finally, this association was analyzed in a subgroup of 1128 patients in whom NAFLD was diagnosed by transient elastography (TE, secondary endpoint). NAFLD prevalence defined by ultrasound did not differ between Hp positive (48%) and negative patients (45%, P=0.097). Accordingly, in uni- (OR 1.12 95% CI 0.98-1.29; P=0.098) and multivariable analysis adjusting for different risk factors (aOR 0.96 95%CI 0.82-1.13; P=0.601) no independent association was found. On subgroup analysis, NAFLD diagnosed by TE was more prevalent in the Hp positive compared to the Hp negative group (49% vs. 38%, P=0.004) and these patients also had higher steatosis grades. However, after adjustment for risk factors, no independent association between Hp positivity and NAFLD diagnosed by TE (aOR 1.26 95%CI 0.89-1.78; P=0.194) was confirmed. In this Central European cohort, Hp-positivity was not associated with the diagnosis of NAFLD. Although Hp positive patients seem to be more likely to have a concomitant NAFLD diagnosis, this association might rather relate to a cardiometabolic risk phenotype than causality.

Особливості структурно-функціональних порушень серця при коморбідності неалкогольної жирової хвороби печінки та гіпертонічної хвороби

The purpose of the study was to establish the features of structural and functional remodeling of the heart in patients with non-alcoholic fatty liver disease in combination with hypertension. Materials and methods. The study included 211 patients, of whom 121 had comorbidity of non-alcoholic fatty liver disease and hypertension, 60 patients had isolated non-alcoholic fatty liver disease, and 30 patients had isolated hypertensive disease. The control group consisted of 20 healthy individuals. To study the structural and functional properties of the myocardium, patients underwent ultrasound of the heart according to conventional methods. Results and discussion. Examination of patients showed that the mass of the left ventricular myocardium in both groups of patients with hypertension were significantly higher than in the control group and the non-alcoholic fatty liver disease group (p &lt; 0.001). The presence of comorbidity with non-alcoholic fatty liver disease did not lead to a further increase in left ventricular myocardial mass in patients with hypertension (p &gt; 0.05). It was found that patients with hypertension in the presence and absence of non-alcoholic fatty liver disease are characterized by an increase in the volume of the left and right atria, as well as the diameters of the left atrium and aorta, compared with the control and the non-alcoholic fatty liver disease groups. At the same time, there were no significant differences between the groups of patients with hypertension in terms of both the presence and absence of comorbidity (p &gt; 0.05). In addition, the main indicator of systolic function of the left ventricle – ejection fraction – was evaluated. This figure was significantly lower in the two groups of patients with hypertension than in the control group and the non-alcoholic fatty liver disease group (p &lt; 0.001). The presence of comorbidity with non-alcoholic fatty liver disease did not affect this indicator (p &gt; 0.05). Among the two groups of patients with hypertension, patients with concentric hypertrophy significantly prevailed. There was a significant increase in the value of a very important integral indicator of diastolic function E / e in patients of all groups, which significantly distinguished them from the control group (p &lt; 0.001). This indicated the presence of diastolic dysfunction in these patients. There is no significant difference in the geometry of the heart and the types of transmitral blood flow between patients with hypertension depending on the presence of concomitant non-alcoholic fatty liver disease. Conclusion. Thus, there is no significant difference between the indicators of left ventricle systolic function in the groups of patients with comorbidity and isolated hypertension. At the same time, there were signs of deterioration of diastolic function in the comorbidity group, which was manifested by an increase in E / e. Deterioration of diastolic function was recorded in the group of isolated non-alcoholic fatty liver disease. These facts may indicate the influence of non-alcoholic fatty liver disease itself on the formation of diastolic dysfunction, both in the presence of hypertension and in its absence. The presence of concomitant non-alcoholic fatty liver disease does not affect transmitral blood flow in patients with hypertension

Features of myocardial damage indexes in patients with metabolic syndrome and nonalcoholic fatty liver disease

Background: Metabolic syndrome (MetS) is a cluster of several risk factors and is considered major risk for the development of cardiovascular disease. Metabolic syndrome patients often have concomitant nonalcoholic fatty liver disease (NAFLD), and two coming together of these two conditions increases the risk of myocardial damage.

Search for a way to improve the serum albumin binding function and the functional state of the liver when hypertension combined with non-alcoholic fatty liver disease

Recently, there has been a significant increase in interest in research on hypertension (HT), primarily due to its high prevalence. The interest in studying this problem is also exacerbated by the often insufficient effectiveness of existing treatments. The effect of concomitant pathologies on HT, in particular non-alcoholic fatty liver disease (NAFLD), remains poorly understood. The aim of the study – to evaluate the changes in the serum albumin binding function (SABF) and its relationship with the biochemical parameters of the blood when HT and HT combined with NAFLD and to suggest ways of medical correction of the detected disorders. Material and methods. 76 individuals with stage 2 HT with degree 2–3 arterial hypertension were examined. They were divided into two groups. Group 1 included 28 patients with HT without concomitant diseases who received basic hypertension therapy, and group 2 included patients with concomitant NAFLD. The latter in turn was divided into two subgroups: 2a – 27 patients who in addition to basic HT therapy received additional Antral hepatoprotector 200 mg three times a day for 2 months, and 2b – 21 patients who received only basic HT therapy. All of them underwent a standard clinical examination, as well as SABF, protein fractions, and liver function indicators. The comparison group consisted of 25 healthy individuals, comparable in age and sex. Results and Discussion. Patients in group 1 showed moderate changes in the functional state of the liver, but they did not exceed the norm, patients in group 2 – a significant decrease in SABF, as well as protein metabolism (decrease in total protein, albumin, albumin-globulin ratio and increase globulins) and liver function (increased activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase, thymol levels, alkaline phosphatase and total bilirubin). After treatment, the majority of patients in subgroup 2 had a statistically significant increase in SABF and a quantitative improvement in protein fractions and functional state of the liver. In subgroup 2-b, where hepatoprotective treatment was not performed, significant changes in most indicators did not occur. The results may be related to the positive effect of the drug on the liver, which leads to improved functional status of hepatocytes and their protein-synthesizing ability. In subgroup 2 b, where hepatoprotective treatment was not performed, significant changes in most indicators did not occur. The results may be related to the positive effect of the drug on the liver leading to improved functional status of hepatocytes and their protein-synthesizing ability. Conclusions. Changes of the functional state of the liver are observed when HT without concomitant pathology. HT with NAFLD is accompanied by a significant decrease in SABF, changes in protein metabolism and the functional state of the liver. Prescribing Antral to such patients helps to increase SABF, normalize protein metabolism and improve the functional state of the liver.

DYNAMICS OF FIBROTIC CHANGES IN THE LIVER AFTER THE SUCCESSFUL ERADICATION OF HEPATITIS C VIRUS IN PATIENTS WITH NAFLD.

The aim: To assess the dynamics of serum levels of angiopoietin-2 and transforming growth factor-β1 in patients with chronic hepatitis C (CHC) with concomitant nonalcoholic fatty liver disease (NAFLD) after successful DAAs. Materials and methods: 82 patients with CHC were examined, of which 56 were diagnosed with NAFLD and increased body weight. Ang-2, TGF-β1, leptin, adiponectin, and the degree of liver fibrosis were determined for all participants. The patients were divided into groups: 1 gr. (n=23) - CHС + increased body weight + hepatic steatosis, 2 gr. (n=33) - СНС + increased body weight + nonalcoholic steatohepatitis, 3rd gr. (n=26) - CHC. All patients received DAAs for 12 weeks. Results: From 82 patients F3-4 had 31 people, F1-2 - 25, F0-1 - 11, F0 -15 patients. F3-4 and steatosis S2-3 (p<0.05) was more common in patients of 2 gr.. Serum Ang-2 levels were higher (p<0.05) in patients of 2 gr. with F3-4, than in patients with F0-2. Fibrosis regression occurred more often in patients with 1 and 3 gr. with F1-2 than in patients 2 gr. and F3-4 and was accompanied by a decrease in Ang-2 and TGF-β1 levels. Conclusions: High levels of Ang-2 and TGF-β1 are registered in patients with CHC+NAFLD, which correlate with the degree of liver fibrosis and significantly decrease after successful DAAs in patients with low initial stages of liver fibrosis and normal body weight.