Clinical and experimental substantiation of the use of bentonite suspension in the complex rehabilitation of 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.

ObjectiveConcomitant non-alcoholic fatty liver disease (NAFLD) and coeliac disease (CD) have not been adequately studied. This study investigated the frequency of CD among NAFLD patients and the clinicopathological and immunological...

Reply to: “Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease?”

Introduction: The use of modern drugs with direct antiviral effect allows achieving a stable virologic response (SVR) in patients with chronic hepatitis C (CHC). However, in most cases, after the elimination of HCV infection, the progression of fibrosis continues with the development of its terminal stages and adverse outcomes for patients. The presence of non-alcoholic fatty liver disease (NAFLD) in these patients significantly increases the rate of progression of fibrosis and its complications, even after reaching SVR. Therefore, the search and development of new non-drug treatment technologies for this category of patients is relevant. Aim: to study the effectiveness of mineral water intake (with a high content of bicarbonates, sodium, potassium, and silicon compounds) in the new mode of use in the complex treatment of patients with chronic hepatitis C with concomitant NAFLD. Methods: anamnestic, clinical, general clinical, biochemical (indicators of lipid metabolism, HOMA index), serological (markers of viral hepatitis C, HCV RNA PCR, qualitative and quantitative determination, genotyping), ultrasonographic studies of the digestive system and statistical methods. Results: Patients with chronic hepatitis C (genotype 1b in the phase of replication, minimal and moderate activity) with concomitant NAFLD, which had been divided into two groups, were examined. Patients of group I (control group) received a standard complex of treatment (diet therapy that corresponded to the Mediterranean diet, dosed exercise regimen, antiviral therapy - sofosbuvir (400 mg) and ledipasvir (90 mg) - 3 months). Patients of group II (the main group) additionally received an internal course intake of mineral water (MW) according to our methodology: 3 ml per kg of patient’s body weight 30-40-60 min before meals, depending on the acidity in the stomach, and the same dose after food intake, three times a day (course - 2 months, a break - 2 months, a second course - 2 months). Evaluation of the effectiveness of treatment was carried out after six months from the start of treatment. Conclusion: The results prove the feasibility and effectiveness of using MW in a doubled dosage regimen in the complex treatment of patients with chronic hepatitis C with chronic concomitant NAFLD, which was determined by improving lipid metabolism, reducing signs of insulin resistance, improving ultrasonographic signs and preventing the development of fibrotic changes in the liver.

The paper analyzes modern views on the etiology, epidemiology, pathogenesis, methods of treating patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease (NAFLD), discusses the possibility of using "dry" carbon dioxide baths (DCDB) in this category of patients. Our research was conducted to study the effectiveness of the integrated use of antiviral therapy (AVT) and DCDB procedures in patients with chronic hepatitis C with concomitant NAFLD. The authors of the study were the first to suggest using of DCDB in this category of patients. Based on the results obtained, for the first time, ideas about the specificity of the DCDBʹs effect on the clinical course of the underlying and concomitant diseases, on the functional state of the liver, the dynamics of lipid metabolism, and ultrasonographic parameters of the liver were detailed. It is concluded that DCDB can be successfully used in the complex treatment of patients with chronic hepatitis C with concomitant NAFLD.

589 Background: The proportion of non-alcoholic fatty liver disease (NAFLD) has been increasing as a cause of hepatocellular carcinoma (HCC) worldwide. Natural killer (NK) cells are involved in the first line of immune defense against cancer. NK cell function is regulated by activating and inhibitory NK cell receptors. However, the role of NK cells in the pathogenesis of NAFLD and NAFLD-HCC is still largely unknown. In this study, we aimed to clarify the phenotypic and functional features of NK cells in NAFLD and NAFLD-HCC patients. Methods: We performed mass cytometry (CyTOF) and flow cytometry analysis of NK cells in 33 NAFLD patients (22 chronic hepatitis (CH), 8 liver cirrhosis (LC), 3 with HCC (HCC)) and 9 healthy donors (HDs). We compared surface markers on NK cells in cancerous and non-cancerous intrahepatic lymphocytes (IHLs). We also measured NK cell function in the presence of IL-12 and IL-18. Results: The frequency of NK cells was lower in NAFLD patients compared to HDs. PD-1, CD57, ILT2 were highly expressed, and Siglec-7, NKp30, NKp46 were downregulated on NK cells from NAFLD patients, compared with those of HDs. In NAFLD patients, Siglec-7 levels on NK cells were negatively correlated with PD-1 and CD57, and positively correlated with NKp30 and NKp46. The other inhibitory markers (NKG2A, KIR3DL1 and KIRDL2/L3), activating markers (CD69 and NKG2D) and checkpoint markers (Tim-3 and TIGIT) were comparable between NAFLD patients and HDs. PD-1 and CD57 expression levels on NK cells were also significantly upregulated in NAFLD-HCC patients than those in HDs. CD57 was rarely expressed on NK cells in non-cancerous IHLs, on the other hand, highly expressed in cancerous IHLs. The IFNγ production and CD107a expression on NK cells were also decreased in NAFLD patients. PD-1+CD57+Siglec-7− NK cells were observed in NAFLD patients, rarely in HDs. PD-1+CD57+Siglec-7− NK cells were functionally impaired compared to other NK subsets. Conclusions: In patients with NAFLD, NK cells are reduced and functionally impaired, the reason of which may be the increased proportion of dysfunctional PD-1+CD57+Siglec-7− NK subset, and dysfunctional NK cells might be related to impairment of surveillance for HCC.

Hepatic steatosis is an important parameter to assess in chronic liver disease patients. The controlled attenuation parameter (CAP) assesses liver steatosis using transient elastography. To determine the accuracy of CAP for evaluation of hepatic steatosis in chronic hepatitis B virus (CHBV)-infected, chronic hepatitis C virus (CHCV)-infected, and non-alcoholic fatty liver disease (NAFLD) patients and to determine the influence of etiology on the diagnostic accuracy of CAP. One hundred forty-six CHBV patients, 108 CHCV-infected patients and 63 patients with NAFLD, who underwent both liver biopsy and successful CAP measurements within the study period, were assessed. Area under the receiver operating characteristics was used to evaluate performance of CAP for diagnosing steatosis compared with biopsy. Multivariate analysis found that CAP correlated with body mass index (odds ratio, 95% confidence interval = 4.09 [1.2-6.8] for CHBV; 4.7 [1.1-8.4] for CHCV, and 16.2 [9.1-24.5] for NAFLD patients respectively) and hepatic steatosis score on biopsy (odds ratio, 95% confidence interval = 30.7 [19.2-42.2] for CHBV; 24.2 [11.5-37.3] for CHCV, and 21.8 [10.1-45.0] for NAFLD patients respectively). Area under the receiver operating characteristics for CAP was 0.683 (0.601-0.757) for steatosis (S) ≥ 6%, 0.793 (0.718-0.856) for S > 33%, and 0.841 (0.771-0.896) for S > 66% respectively for CHBV-infected patients. There was no difference in accuracy of CAP for assessing liver fat among CHBV, CHCV, and NAFLD patients. CAP is a novel, non-invasive tool that can detect and quantify steatosis accurately among CHBV, CHCV, and NAFLD patients, the accuracy being similar for all the three groups of patients.

Relevance. Platelet activation and platelet aggregation are central processes in the pathophysiology of coronary heart disease and thrombosis. The relationship between cardiovascular morbidity and mortality varies with the presence of other concomitant cardiovascular risk factors. Objective. To determine the state of platelet hemostasis in patients with essential hypertension (HT), with concomitant non-alcoholic fatty liver disease (NAFLD). Materials and methods. 152 patients were examined: 72 men and 80 women. Three groups were identified: I - 46 patients with stage II HT without concomitant NAFLD, II - 54 patients with NAFLD without HT, group III - 52 patients with HT and concomitant NAFLD. A study of total platelet count, mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PCT) and spontaneous platelet aggregation was performed. Results. The level of mean platelet volume (MPV) in both groups of patients with hepatic steatosis exceeded control values equally - by 6%, both in patients with NAFLD (p<0.001) and in NAFLD with concomitant hypertension (p<0.01). In patients of the NAFLD group and hypertension, the relative width of the platelet distribution by volume (PDW) had high values - 2% (p<0.05) higher than in the control cohort, and 2.4% (p<0.05) than in patients with isolated HT. An increase in the degree of spontaneous aggregation in patients of all surveyed groups compared to controls. So in patients with HT II stage. spontaneous aggregation increased 2.2 times (p<0.001), while in both groups of patients with hepatic steatosis, the increase in spontaneous platelet activity was twice as high: in patients with NAFLD - 4.3 times (p<0.001), in patients with HT II stage. and concomitant NAFLD - 4.1 times (p<0.001). Conclusion. NAFLD is accompanied by an increased in MPV, the size of which correlates with their functional activity. In patients with isolated NAFLD, a statistically significant increase in spontaneous platelet aggregation is also observed, which allows considering NAFLD as one of the risk factors for thrombophilic changes in the primary hemostasis.

Introduction: Vitamin D deficiency is common among patients with chronic viral hepatitis and nonalcoholic fatty liver disease (NAFLD). There is no published data on vitamin D levels in Pakistani patients with chronic viral hepatitis or NAFLD. Objective: To determine the prevalence of vitamin D deficiency in Pakistani patients with chronic viral hepatitis B and C and NAFLD. Methods: Patients with chronic viral hepatitis B and C but not cirrhosis were prospectively tested for vitamin D levels. 25- hydroxyvitamin D levels were measured using a direct competitive immunoluminometric assay. Results: Of the 400 patients enrolled in the study, 110 (27%) had chronic hepatitis B and 190 (48%) had chronic hepatitis C and 100 (25%) had NAFLD. 224 (56%) patients were male and the average age was 52 years. Overall, 154 (39%) had vitamin D deficiency (<10 ng/ml), 212 (53%) had vitamin D insufficiency (10-30 ng/ml), and 34 (8%) were vitamin D sufficient (>30 ng/ml). Among chronic hepatitis C patients, 59 (31%) were vitamin D deficient and 112 (59%) were vitamin D insufficient. Of chronic hepatitis B patients, 52 (47%) were vitamin D deficient and 51 (46%) were vitamin D insufficient. Among NAFLD patients, 43 (43%) were vitamin D deficient, 49 (49%) were vitamin D insufficient. Conclusion: Vitamin D deficiency or insufficiency affects greater than 90% of non-cirrhotic, chronic viral hepatitis and NAFLD patients in Pakistan. Further studies are needed to assess this problem in a larger cohort of patients and in cirrhotic patients, and to determine its impact on treatment outcomes in Pakistani patients.

Patients with Nonalcoholic Fatty Liver Disease (NAFLD) have Higher Oxidative Stress in Comparison to Chronic Viral Hepatitis

Background According to modern concepts of hypertension (HT) and obesity, the hemostatic system in these diseases is characterized by prothrombogenic changes. Since the liver is the site of the formation of many factors of hemostasis, the concomitant non-alcoholic fatty liver disease (NAFLD), which often accompanies the course of both of these diseases, is an actual problem. Purpose To improve the efficiency of early diagnosis of thrombophilic blood changes in hypertensive patients with concomitant obesity and NAFLD by determining the state of platelets and their functional activity. Materials and methods We examined 167 patients (80 men and 87 women). The average patient age 55.5 [47.0; 61.0] years. Patients were divided into three groups: I - 46 patients with hypertension without NAFLD, II - 54 patients with NAFLD without hypertension, III group - 52 hypertensive patients with NAFLD. The control group consisted of 15 healthy subjects matched for age and sex. Platelet count and mean platelet volume (MPV) was performed on an automated analyzer, spontaneous and induced platelet aggregation was evaluated by laser aggregometer. Results A significant increase in the degree of spontaneous aggregation of platelet has been found in patients in all groups compared to the control group: I group - 2.2-fold increasing in aggregation (p&amp;lt;0.05), II group to 4.2-fold (p&amp;lt;0.05), III group had increasing by 4.1-fold (p&amp;lt;0.05). ADP-induced platelet aggregation was the same in I group and control, but it was 39% higher (p&amp;lt;0.001) in II cohort and by 22.6% (p&amp;lt;0.01) in III group. Adrenalin-induced platelet activity increased in all groups versus control: I group – 2.1-fold (p&amp;lt;0.001), II group – 2.3-fold (p&amp;lt;0.001), III group – 1.6-fold (p&amp;lt;0.01) elevation. Arachidonic acid-induced aggregation elevated by 64,2% (p&amp;lt;0.001) in I group and decreased by 56.3% (p&amp;lt;0.01) in II and by 43% (p&amp;lt;0.05) III cohorts. Collagen-induced activity had not significant difference between groups. MPV was increased in both groups with NAFLD by 5.9, but in II group significance level was higher - p&amp;lt;0.01 than in group III - p&amp;lt;0.001. MPV had not significant changes in I group versus control. Conclusion Spontaneous platelet aggregation is increased in hypertensive patients and it is significantly enhanced in combination with NAFLD. Thus in patients with isolated NAFLD also observed a statistically significant increase in spontaneous aggregation of platelets. That is possibly explained by an increase in MPV which can be considered as one of the NAFLD risk factors thrombophilic changes in primary hemostasis. An analysis of induced platelet aggregation showed that patients with NAFLD may have a lower sensitivity to acetylsalicylic acid therapy. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Bogomolets National Medical University

Introduction: Nonalcoholic fatty liver disease (NAFLD) is strongly linked to insulin resistance. As a result, type 2 diabetes mellitus (T2DM) is commonly comorbid in NAFLD and can increase morbidity and reduce weight loss treatment efficacy. We studied weight loss in adult NAFLD patients without and with T2DM (NAFLD-DM) receiving care in the Yale Fatty Liver Disease Program (YFLDP), which focuses on the integration of medical weight management treatments and hepatology care. Methods: We analyzed retrospective data for adult patients with diagnostic codes for NAFLD and T2DM with complete data on body weight and at least one clinic visit between 5/23/2018 and 5/02/2022. Patients were categorized as NAFLD or NAFLD-DM. Total body weight loss (WL) was quantified using 0%, 5%, and 10% thresholds. Between NAFLD and NAFLD-DM groups, we compared total body weight loss (WL) and across WL threshold groups, we also compared initial weights, follow-up time, medical interventions received, and results of non-invasive liver fibrosis tests. Results: There were 933 patients with NAFLD, of whom 463 (49.6%) had NAFLD-DM. After a median follow-up of 7.7 months, 632 (67.7%) of all patients achieved any weight loss. Significantly more patients with NAFLD-DM lost weight compared to NAFLD alone (73.9 vs 61.7%, p< 0.0001). Weight loss between NAFLD and NAFLD-DM groups varied, respectively: 0-5% WL: 34.7% vs. 34.8% (p=0.98); 5-10% WL: 13.2% vs. 19.2% (p=0.01), >10% WL: 13.8% vs. 19.9% (p=0.01). Compared to those not losing weight, NAFLD and NAFLD-DM patients with >10% WL had significantly greater proportion of participation in a complete meal replacement program (Optifast®) or treatment with GLP-1 agonist semaglutide. For NAFLD and NAFLD-DM groups, there was no significant difference between initial Fibroscan stiffness or FIB-4 index and subsequent WL percentages (Table). Conclusion: The majority of NAFLD and NAFLD-DM patients receiving care in a specialty clinic incorporating medical weight management with liver care successfully achieved weight loss in a relatively short period. Patients with NAFLD-DM did not have significantly worse outcomes with weight loss, and NAFLD-T2DM patients lost more weight than NAFLD patients. These findings suggest that an integrative care liver clinic with concurrent weight management care can help patients improve metabolic diseases associated with NAFLD, particularly T2DM, and in turn improve liver-related outcomes.Figure 1.: Comparison of Clinic Interventions between No Weight Loss (WL) versus >10% WL patients with NAFLD (top panel, a) and NAFLD-DM (bottom panel, b). *Statistically significant p-values using chi-square analysis, which can be found in Table Table 1. - Characteristics of and Clinical Interventions for NAFLD and NAFLD-DM Patients in the Yale Fatty Liver Disease Program (YFLDP). There was a significantly lower proportion of patients with NAFLD compared to NAFLD-DM who were able to achieve > 10% Weight Loss (13.8 vs. 19.9, p=0.014), and significantly more NAFLD patients compared to NAFLD-DM who did not achieve any weight loss (38.3 vs. 26.1, p<0.001) NAFLD (n=470 patients) NAFLD-DM (n=463 patients) Patient Categories n (%) No WL180 (38.3) >10% WL65 (13.8) p No WL121 (26.1) >10% WL92 (19.9) p Clinic Interventions n (%) Nutrition Consultation 80 (44.4) 31 (47.7) 0.652 58 (47.9) 40 (43.5) 0.518 OPTIFAST® Program 4 (2.2) 5 (7.7) 0.045 2 (1.7) 8 (8.7) 0.016 Naltrexone/Buproprion 6 (3.3) 5 (7.7) 0.146 16 (13.2) 6 (6.5) 0.111 Semaglutide 15 (8.3) 17 (26.2) < 0.001 30 (24.8) 37 (40.2) 0.016 Liraglutide 11 (6.1) 7 (10.8) 0.217 21 (17.4) 7 (7.6) 0.037 Phentermine 9 (5.0) 10 (15.4) 0.007 15 (12.4) 17 (18.5) 0.219 Bariatric Surgery Referral 13 (7.2) 5 (7.7) 0.901 21 (17.4) 31 (33.7) 0.006 Health Outcomes mean (SD) Follow-Up Time, days 256 (276.5) 422 (296.8) < 0.001 271 (280.2) 403 (297.3) 0.001 Initial FibroScan® Stiffness, kPa 8.63 (6.72) 13.18 (14.01) 0.663 13.18 (14.01) 12.48 (12.49) 0.701 Initial FIB-4 Score 1.32 (1.13) 1.70 (1.98) 0.068 1.70 (1.98) 1.83 (2.11) 0.648 Initial Weight, kg 93.82 (25.45) 102.20 (24.90) 0.015 102.20 (24.90) 109.61 (25.07) 0.056 *Denotes statistical significance p<0.05. WL = Weight Loss.

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

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&lt;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.

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.