Necroinflammatory Activity Research Articles

6681 Age and Sex Disparity in NASH and the Potential Role of Estradiol Treatment for NASH

Abstract Disclosure: M. Tripathi: None. S. Sakthivel: None. A. Suzuki: None. B.K. Singh: None. P.M. Yen: None. Introduction: NAFLD (nonalcoholic fatty liver disease) and its more severe form, NASH (nonalcoholic steatohepatitis) are sexually dimorphic conditions that exhibit higher prevalence in men than women during reproductive ages but have similar prevalence after menopause. Reproductive age women are protected from hepatic fibrosis relative to men, although they lose this protection after menopause. These sex differences in NASH have been attributed, at least partly, to different circulating estrogen levels. However, the underlying mechanism(s) is not fully understood. We thus conducted animal experiments to investigate: 1) sex differences in the histologic severity of NASH, necroinflammatory and fibrogenic activities, and other relevant pathways in young and old male and female mice and 2) the effects of estradiol administration on these parameters in old male and female mice to evaluate the therapeutic potential of estradiol in NASH. Methodology: Young/reproductive age (12-weeks old) and old/post-reproductive age female and male (48∼50-weeks weeks old) C57BL/6J mice were fed control chow diet (NCD) or high-fat methionine/choline-deficient (MCD) diet for six weeks to induce NASH. The old mice were administered 200nM 17β-estradiol (physiological) in drinking water. We analyzed serum and hepatic NASH parameters, ER stress, and lysosome-autophagy defects. Results and Conclusion: Among reproductive age mice with NASH, females developed less severe histologic inflammation and fibrosis and decreased gene expression of Il1b, Il6, Tgfb, Col1a1, Ccl2, and Ccl5, and lower hepatic collagen than males. Females with NASH also had less inhibition of hepatic autophagy and lysosomal protein expression than males with NASH. Among old mice, post-reproductive age females fed NCD or MCD exhibited more severe hepatic inflammation and fibrosis and had higher gene expression of inflammatory and fibrogenic markers with comparable autophagic inhibition and lysosomal defects as similar age males. Physiological doses of estradiol significantly reduced hepatic gene expression of inflammatory and fibrogenic markers, ER stress and lysosomal-autophagic defects in post-reproductive age females. In conclusion, similar to clinical NASH, we observed marked sex and age-related differences in the severity of NASH. Furthermore, physiological doses of estradiol treatment improved the hepatic histology, lysosome-autophagy, inflammation, and fibrosis in post-reproductive age female mice with NASH and suggests that estradiol supplementation may decrease or reverse NASH progression in post-menopausal women with NASH. Presentation: 6/2/2024

Serum IgG level in autoimmune liver diseases and its significance: Is there a need to revisit existing criteria? Experience from a tertiary care center.

Serum immunoglobulin G (IgG) level is elevated in autoimmune liver diseases (AILDs), especially autoimmune hepatitis (AIH). However, its utility is limited in current practice as different criteria propose different cut-off values leading to considerable ambiguity. A cross-sectional study was conducted among patients with AILD who underwent a liver biopsy over a ten-year period. From 17644 liver biopsies, 630 patients were included and divided into three groups-AIH (455 patients), primary biliary cholangitis (PBC) (97 patients), and overlap (78 patients). Clinical and laboratory details were collected and histological findings were reviewed. Non-cirrhotic non-alcoholic steatohepatitis (NASH) cases were taken as the control group for IgG level comparison. Among AIH patients, IgG values of >2 times the upper limit of normal (ULN) were associated with significant elevation of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, and necroinflammatory activity. IgG level of >1.1 times ULN lacks specificity in differentiating AIH from the control group. The receiver operating characteristic (ROC) curve demonstrates maximum sensitivity and specificity at a cut-off value of >1.3 times ULN. Serum IgG cut-off value for diagnosing AIH, either in isolation or as a component of overlap syndrome, needs revision and uniformity. IgG value of >2 times ULN in AIH is associated with severe AIH. A new cut-off value of >1.3 times ULN is proposed.

The influence of peritumoral parenchyma on local tumor progression of hepatocellular carcinoma after thermal ablation: a retrospective multicenter study.

With the increasing importance of thermal ablation (TA) in hepatocellular carcinoma (HCC) treatment, local tumor progression (LTP) has become a nonignorable recurrence type after ablation. To analyze the influence of peritumoral liver parenchyma on LTP and to explore the possible reasons for this influence. Ablated HCCs with peritumoral parenchymal biopsy and ablation margins greater than 5mm were included from two hospitals. The grade of necroinflammatory activity (G) and stage of fibrosis (S) of the parenchyma were evaluated by Scheuer staging system. Univariate/multivariate Cox model was used to analyze the possible factors influencing LTP. Peritumoral satellite focus rate, ablation energy, ablation volume after treatment, ablation volume after one-month, and volume reduction rate were collected and analyzed to explore the possible reasons for influence. Propensity score matching (PSM) was used to balance baselines across different groups. 346 HCCs (64 with LTP, 282 without LTP) were enrolled from January 2013 to June 2022, with a median follow-up of 27 months. Univariate/multivariate analysis showed fibrosis was a protective factor in LTP (OR = 0.70, 95%CI: 0.55-0.89). The low-fibrosis group exhibited higher satellite focus rate (15.6% vs. 8.4%, p = 0.048), lower ablation energy (22637 ± 9424J vs. 33352 ± 13779J, p < 0.001) and higher volume reduction rate (0.33 ± 0.06 vs. 0.25 ± 0.06, p < 0.001) than the high-fibrosis group. Therefore, we speculated that the protective effect of fibrosis was due to its blocking of tumor invasion and reduction of sublethal zones. Fibrosis of the peritumoral liver parenchyma is a stable protective factor in LTP occurrence.

Role of multiparametric US in the preoperative assessment of hepatic parenchyma in patients with liver tumors.

The aim of this study was to evaluate the diagnostic performance of shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) in assessment of hepatic parenchyma in patients with liver tumors before resection. Patients with liver tumors were prospectively enrolled in this study. All participants underwent SWE, SWD, and ATI examinations. Fibrosis stage, necroinflammatory activity and hepatic steatosis grade were determined histopathologically. We evaluated the stability of ATI, SWE and SWD examinations. Multivariable linear regression analyses were conducted to determine the determinant factors for SWE, SWD, attenuation coefficient (AC) values. A receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance of multiparametric US (ultrasond). A total of 280 participants were enrolled in this study. TG (triglyceride) and steatosis for AC value were significant determinant factors. PLT (platelet), PT (prothrombin time), GGT (glutamyl transpeptidase), and fibrosis stage for SWE value were significant determinant factors. PLT, fibrosis stage and inflammation activity for SWD value were significant determinant factors. AC value was correlated with hepatic steatosis. Both SWE and SWD values were correlated with fibrosis stage, inflammation activity, respectively. The area under the ROC (AUROC) curve of ATI for predicting hepatic steatosis grade were 0.910(≥ S1), 0.927(≥ S2), 0.962(= S3), respectively. The AUROC curve of SWE for predicting fibrosis stage were 0.923(≥ S1), 0.934(≥ S2), 0.930(≥ S3), 0.895(= S4), respectively. The AUROC curve of SWD for predicting fibrosis stage were 0.858(≥ S1), 0.886(≥ S2), 0.866(≥ S1) (≥ S3), 0.825(= S4). The AUROC curve of SWE for predicting inflammation activity were 0.846(≥ G1), 0.724(≥ G2), 0.787 (≥ G3), respectively. The AUROC curve of SWD for predicting inflammation activity were 0.777(≥ G1), 0.727(≥ G2), 0.803 (≥ G3), respectively. For patients with liver tumors, ATI technology showed excellent feasibility and diagnostic performance for detecting and grading hepatic steatosis, SWE was more accurate in detecting fibrosis stage than SWD, SWD was not superior to SWE in detecting inflammation activity.

Worse fibro-inflammatory activity on diagnostic liver biopsy adversely impacts biochemical remission in autoimmune hepatitis

BackgroundAutoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. MethodsWe conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). ResultsIncidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. ConclusionsFindings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.

Fatty acid composition of blood serum and erythrocyte membranes in men with steatosis and steatohepatitis with normal transaminase activity

Aim. To study the characteristics of the fatty acid (FA) profi le of blood serum and erythrocyte membranes in patients with two forms of fatty liver disease (metabolic + alcoholic): steatosis and steatohepatitis with normal transaminase activity.Materials and methods. We examined 33 men (50.7 ± 9.6 years) with fatty liver disease (metabolic and alcoholic) with fi brosis F ≤ 1 (FibroTest). According to the ActiTest results, patients were divided into groups of steatosis – with minimal (A0–1) activity (n = 17) and steatohepatitis – with moderate/severe (A2–3) necroinfl ammatory activity (n = 16). The FA composition of blood serum and erythrocyte membranes was studied using gas chromatography/mass spectrometry Agilent 7000B (Agilent Technologies, Inc., USA). Methods of unpaired statistics using volcano plot and discriminant analysis based on orthogonal least squares (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA), ROC analysis were applied.Results. Volcano plot analysis showed that in patients with fatty liver disease (metabolic and alcoholic) with normal transaminase activity, serum levels of stearic C18:0 (p = 0.016), arachidic C20:0 (p = 0.023), ratio saturated / polyunsaturated fatty acids (PUFA) (p = 0.001) were statistically signifi cantly higher in the steatohepatitis group compared with the steatosis group. The total content in the blood serum of all PUFA (p = 0.003), margaric C17:0 (p = 0.011), the sum of two omega-3 PUFA – eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) (p = 0.04), the total content of all omega-3 PUFA (p = 0.042) were statistically signifi cantly lower in patients with steatohepatitis. OPLS-DA demonstrated fairly accurate separation of steatohepatitis and steatosis using individual FA and their ratios. When individual FA and their ratios were included in the analysis, a model was obtained with AUC = 0.827 (95% confi dence interval 0.499–1.0), sensitivity 82.2% and specifi city 80.7%.Conclusion. FA in blood serum and erythrocyte membranes appear to be promising biomarkers of steatohepatitis with normal levels of transaminases.

Evaluation of direct-acting antiviral agents impact on liver biomarkers in patients with type-2 diabetes and hepatitis C virus infection

Objectives. Chronic hepatitis C (CHC) infection still affects a significant portion of the global population. Despite efforts to combat it, the global prevalence remains high. The use of direct antiviral therapy (DAA) has significantly improved cure rates. The study aimed to assess liver parameters and body mass index (BMI dynamics in type 2 diabetes mellitus (T2DM) patients compared to non-diabetics, after obtaining sustained viral response (SVR) under DAA. Material and methods. We conducted a retrospective study on 100 CHC infected patients treated with DAAs between September 2016 and August 2019 at “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, Bucharest (INBI MB). The study group was divided into 2 subgroups according to the presence of diabetes. All patients were evaluated at initiation of treatment and one year after. FibroMax parameters and BMI were monitored. Outcomes. The study found improvements in liver fibrosis, necroinflammatory activity, and steatosis in both groups after treatment. Notably, T2DM patients experienced a more significant decrease in necroinflammatory activity. Moreover, weight gain post-SVR was observed, potentially impacting liver health. Conclusions. Post-SVR, CHC patients showed improvements in liver health markers, emphasizing the importance of early treatment to prevent severe liver complications. Future research should focus on long-term outcomes post-treatment.

Evaluation of direct-acting antiviral agents impact on liver biomarkers in patients with type-2 diabetes and hepatitis C virus infection

Objectives. Chronic hepatitis C (CHC) infection still affects a significant portion of the global population. Despite efforts to combat it, the global prevalence remains high. The use of direct antiviral therapy (DAA) has significantly improved cure rates. The study aimed to assess liver parameters and body mass index (BMI dynamics in type 2 diabetes mellitus (T2DM) patients compared to non-diabetics, after obtaining sustained viral response (SVR) under DAA. Material and methods. We conducted a retrospective study on 100 CHC infected patients treated with DAAs between September 2016 and August 2019 at “Prof. Dr. Matei Bals” National Institute for Infectious Diseases, Bucharest (INBI MB). The study group was divided into 2 subgroups according to the presence of diabetes. All patients were evaluated at initiation of treatment and one year after. FibroMax parameters and BMI were monitored. Outcomes. The study found improvements in liver fibrosis, necroinflammatory activity, and steatosis in both groups after treatment. Notably, T2DM patients experienced a more significant decrease in necroinflammatory activity. Moreover, weight gain post-SVR was observed, potentially impacting liver health. Conclusions. Post-SVR, CHC patients showed improvements in liver health markers, emphasizing the importance of early treatment to prevent severe liver complications. Future research should focus on long-term outcomes post-treatment.

Non-alcoholic fatty liver disease in patients with morbid obesity: the gut microbiota axis as a potential pathophysiology mechanism

Background/aimAlterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy.Subjects/methods110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis.ResultsGut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity.ConclusionsWe established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.

Protocol of quantitative ultrasound techniques for noninvasive assessing of hepatic steatosis after bariatric surgery.

Roux-en-Y gastric bypass surgery can effectively improve steatosis, necroinflammatory activity, and hepatic fibrosis in individuals diagnosed with morbid obesity or nonalcoholic steatohepatitis (NASH). Common methods such as body mass index (BMI) to evaluate the postoperative effect of clinical bariatric surgery cannot differentiate subcutaneous fats from visceral fats and muscles. Several Quantitative ultrasound (QUS)-based approaches have been developed to quantify hepatic steatosis. QUS techniques (tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI)) from radio frequency (RF) data analysis as a means for the detection and grading of hepatic steatosis has been posited as an objective and noninvasive approach. The implementation and standardization of QUS techniques (TAI, TSI) in assessing hepatic steatosis quantitatively after bariatric surgery is of high-priority. Our study is aimed to assess hepatic steatosis with QUS techniques (TAI, TSI) in morbidly obese individuals before and after bariatric surgery, and to compare with anthropometric measurements, laboratory assessments and other imaging methods. The present investigation, a self-discipline examination of navigational capacity devoid of visual cues, is designed as a single-site, forward-looking evaluation of efficacy with the imprimatur of the institutional review board. The duration of the study has been provisionally determined to span from 1 January 2023 through 31 December 2025. Our cohort shall encompass one hundred participants, who was scheduled to undergo Roux-en-Y gastric bypass (RYGB) at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All patients will undergo anthropometric measurements, blood-based biochemical analyses, ultrasonic examination and magnetic resonance imaging proton density fat fraction (MRI-PDFF). The primary endpoint is the analysis of evaluating the efficacy of QUS techniques assessing hepatic steatosis compared to other methods before and after bariatric surgery. Prior to the fomal study, we recruited 21 obese Chinese participants who received ultrasonic examination (TAI, TSI) and MRI-PDFF. AC-TAI showed moderate correlations with MRI-PDFF (adjusted r = 0.632; P < 0.05). For MRI-PDFF ≥10%, SC-TSI showed moderate correlations with MRI-PDFF (adjusted r = 0.677; P < 0.05). Our pre-experiment results signified that using QUS techniques for postoperative evaluation of bariatric surgery is promising. QUS techniques will be signed a widespread availability, real-time functionality, and low-cost approach for assessing hepatic steatosis before and after bariatric surgery in obese individuals, thus is capable for subsequent scale-up liver fat quantification. The present research endeavor has been bestowed with the imprimatur of the Ethics Committee of the Hospital, as indicated by its Approval Number: 2023-KY-015. In due course, upon completion of the study, we intend to disseminate our findings by publishing them in a suitable academic journal, thereby facilitating their widespread utilization. The trial is duly registered with the Chinese Clinical Trial Registry, and with a unique Trial Registration Number, ChiCTR2300069892, approved on March 28, 2023.

Assessment of the influence of vitamin D level on the course of chronic hepatitis C in comorbidity with chronic pancreatitis

Background. Chronic hepatitis C (СHC) is often complicated by the presence of concomitant gastrointestinal diseases, one of which is chronic pancreatitis (CP). This has a negative impact on the clinical course of both diseases, contributes to nutrient deficiencies, in particular vitamin D, and worsens the quality of life of patients. The aim of the research was to study the features of the clinical course of CHC in comorbidity with CP and to evaluate the quality of life in patients with different levels of vitamin D in blood serum. Materials and methods. The study included 120 patients who were divided into 2 groups: group 1 — 72 patients with CHC and CP and group 2 — 48 patients with CHC. In turn, patients of group 1, depending on the enzymatic activity of the pancreas, were divided into group 1a (n = 52), which included patients with CHC and CP with exocrine insufficiency (EI), and group 1b (n = 20) — patients with CHC and CP with preserved exocrine function of the pancreas. In all patients, fecal coproscopy was performed, the level of fecal elastase (FE-1), vitamin D, viral load was determined, and the degree of fibrosis and necroinflammatory activity was evaluated using FibroTest and ActiTest. Situational anxiety was assessed according to the Spielberger-Hanin method, and quality of life using the SF-12 questionnaire. The analysis and processing of the results of the examination of patients was carried out using the computer program Jamovi 2.3.2.1, Microsoft Office Excel for Windows 2016 using the Kruskal-Wallis method, the Mann-Whitney-Wilcoxon criterion and the Pearson correlation coefficient. The difference was considered to be statistically significant at p &lt; 0.05. Results. A significantly lower level of vitamin D was found in patients of group 1a than in patients of groups 1b and 2. Patients of group 1 with higher stages of fibrosis (F2–3 and F3–4), a higher degree of necroinflammatory activity in the liver (&gt; A2) and a high viral load have lower levels of vitamin D than those with initial stages of fibrosis and less severe necroinflammatory process in the liver. Patients with CHC, CP and exocrine insufficiency complained of mood changes, increased anxiety, rapid fatigue, and muscle weakness significantly more often than those with preserved exocrine function and patients with CHC. The level of vitamin D in people with CHC, CP and exocrine insufficiency positively correlates with the level of FE-1. In all patients with CHC in comorbidity with CP, a negative effect of low levels of vitamin D on indicators of quality of life and anxiety was found. Conclusions. A reduced level of vitamin D in the blood of patients with CHC and CP worsens the course of the disease and is associated with a decrease in quality of life.

Prediction of Early-stage Liver Fibrosis Using FDG-PET/CT.

18F-fluorodeoxyglucose (FDG) is known to accumulate in the liver. We investigated whether accumulation of FDG was correlated with the degree of liver fibrosis and the grade of necro-inflammatory activity. This retrospective study included 35 patients who underwent FDG-positron emission tomography (PET)/computed tomography (CT) before liver surgery. On fusion images of CT and PET, by placing regions of interest on the lateral, anterior and posterior segments of the liver and the aorta, the standardized uptake value (SUV) mean, and SUV normalized by lean body mass (SUL) mean of the liver were measured, and the ratio SUVmean liver/SUVmean aorta was calculated. According to the New Inuyama Classification, subjects were classified into three groups based on the grade of liver-fibrosis degree, i.e., F0, F1+F2 and F3+F4, and into three groups based on the grade of necro-inflammatory activity, i.e., A0, A1 and A2. Each of the above parameters was then compared among the groups using a Tukey test. Average SULmean liver values of the F0, F1+F2 and F3+F4 groups were 1.573±0.211, 1.845±0.220 and 1.716±0.119, respectively. The SULmean liver of the F1+F2 group was significantly higher than that of the F0 group (p=0.0296). No significant difference was observed for the other two parameters. None of the parameters exhibited significant difference among the A0, A1, and A2 groups. FDG accumulation in the liver may be increased in the early stage of liver fibrosis. SULmean liver could be used to determine the necessity for therapeutic intervention in chronic liver disease.

Systemic Inflammatory Molecules Are Associated with Advanced Fibrosis in Patients from Brazil Infected with Hepatitis Delta Virus Genotype 3 (HDV-3).

Hepatitis Delta virus (HDV) genotype 3 is responsible for outbreaks of fulminant hepatitis in Northeastern South America. This study investigates if systemic inflammatory molecules are differentially expressed in patients with advanced fibrosis chronically infected with Hepatitis Delta virusgenotype 3(HDV-3). Sixty-one patients from the north of Brazil coinfected with hepatitis B virus (HBV)/HDV-3 were analyzed. HDV quantification and genotyping were performed by semi-nested real-time polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) methodologies. Ninety-two systemic inflammatory molecules (SIMs) were measured by Proximity Extension Assay (PEA) technology. The Shapiro-Wilk, Student's t-test, Mann-Whitney tests, and logistic regression analysis were used when appropriate. The median age was 41 years, and all patients were HBeAg negative. Advanced fibrosis or cirrhosis was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Established non-invasive fibrosis scores (APRI, FIB-4, and AST/ALT ratio) revealed low sensitivities and positive predictive values (PPVs) with an AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP.4, CCL19, EN.RAGE, SCF, and IL18 showed a positive correlation with fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an odds ratio of 2.202 for advanced fibrosis. Standard non-invasive fibrosis scores showed poor performance in HDV-3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV-3 infection.

The correlation between Body Mass Index and histological features of Nonalcoholic Fatty Liver Disease.

Introduction: NAFLD is strongly associated with metabolic syndrome, and for many years, fatty liver was an exclusive feature of obese patients. The study tries to assess whether the body mass index (BMI) and body circumference is correlated to steatosis, fibrosis, or inflammatory activity of the liver. Methods: 81 patients with recent hepatic biopsy were included in the study and were weighed and measured. The biopsy results were compared to the measurements. Results: The average BMI overall for the whole lot was 30.16. There was a significant difference in BMI across the inflammatory activity categories (p=0.009): groups with higher necro inflammatory activity tended to have higher BMI values (average values per grade: 0 - 28, 1 - 29, 2 - 33, 3 - 32, 4 - 29). There was no significant difference for grades of steatosis (p=0.871). With regards to waist circumference, the overall average was 90.70cm/35.70in. There was a significant difference across the steatosis categories (p<0.001): groups with higher steatosis scores had higher waist circumferences (average values per grade: 1 - 77cm / 30 in, 2 - 95 cm / 37 in, 3 - 94 cm / 37 in). There was no significant difference for grades of activity (p=0.058). Conclusion: BMI and waist circumference are easy to measure, non-invasive parameters, which could be useful in screening patients at higher risk for necro inflammatory activity or severe steatosis.

Autoantibody Positivity Has No Impact on Histological Parameters in Nonalcoholic Fatty Liver Diseases

Previous reports on association of autoantibodies with histological severity in nonalcoholic fatty liver disease (NAFLD) have revealed inconsistent results. Therefore, this study was undertaken to find the impact of autoantibodies on histological severity of NAFLD. All cases with histological diagnosis of NAFLD during January 2016 to January 2021 were included in the study. Laboratory parameters were recorded, and histological assessment was done. The positivity of autoimmune markers was defined as presence of either antinuclear antibody (ANA; titer >1:80), anti-smooth muscle antibodies (ASMA), or anti-liver-kidney-microsomal antibodies (LKM-1; titer >1:40). Serum levels of CK18 - M30 and PIIINP were evaluated to assess the subtle changes in necroinflammatory activity and fibrosis in the liver. Autoantibodies were present in 281/683 (41.1%, 95% CI 37.4-44.9) patients. ANA, ASMA, ANA+ASMA was seen in 20.9% (95% CI 17.9-24.2); 14.5% (95% CI 11.9-17.4); and 5.7% (95% CI 4.1-7.7) cases, respectively. No significant difference was noted between the two groups in terms of age and metabolic tests. No significant difference was noted in the histological parameters between groups with autoantibodies positivity and no-positivity. Mean value of CK18-M30 between cases with negative autoantibody; ANA positivity; ASMA positivity; and combined positivity of autoantibody were 178.2±81.8, 161.6±63.7, 153.2±70.3 and 169.8±42.9, respectively (P= 0.57). However, CK18-M30 and PIIINP showed a rising trend with NAFL, NASH, NASH+AIH (P < 0.001). Autoantibodies noted in 41% NAFLD cases. No significant necroinflammatory activity or fibrosis associated with presence of antibodies in NAFLD cases. However, CK-18-M30 showed a rising trend from NAFL to NASH to NASH+AIH.

Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

The Hepatoprotective Effect of Curcuma longa Extract on Dengue Virus Serotype-2 infected BALB/c Mice

BACKGROUND: Dengue infection has a wide clinical spectrum ranging from asymptomatic infection to severe form with organ damage. Liver is among the common organ affected. Curcuma longa is a widely used herb that exhibits a hepatoprotective effect. AIM: This study aimed to investigate effect of C. longa on liver necroinflammatory activity and alanine aminotransferase (ALT) levels in dengue virus serotype-2 (DENV-2) infected BALB/c mice. MATERIALS AND METHODS: BALB/c mice were assigned into Group 1 (healthy mice), Group 2 (without C. longa administration), and Group 3 (C. longa administered). DENV-2 was inoculated intraperitoneally in Groups 2 and 3. C. longa extract was given at dose of 0.147 mg/mL intraorally in the 1st to 7th day. Liver histopathology and ALT level were assessed on the 7th day. Necroinflammatory activity was assessed with a Knodell histology activity index (HAI) score. RESULTS: The median Knodell HAI score in Group 1, Group 2, and Group 3 were 1.0 (0–5), 7.0 (4–10), and 3.5 (0–8), respectively. The mean difference of Knodell HAI score between Group 2 and Group 3 is 4.1 (95% CI 1.75–6.45, p = 0.002). The mean ALT in Groups 1, 2, and 3 were 58.22 ± 18.31 IU/L, 58.26 ± 18.31 IU/L, and 57.00 ± 10.71 IU/L, respectively. One-way analysis of variance test showed no significant differences in ALT level levels among the three groups (F = 0.26, p = 0.974). CONCLUSION: This study showed the hepatoprotective effect of C. longa that might decrease the liver necroinflammatory activity in dengue infection.

Возможности использования электрических и вязкоупругих параметров эритроцитов для диагностики стеатогепатита у пациентов с жировой болезнью печени

Aim: to study the possibilities of using electrical and viscoelastic parameters of erythrocytes to differentiate steatohepatitis from liver steatosis. Patients and Methods: 84 men (48.9±2.5 years) with fatty liver disease diagnosed by abdominal ultrasound were examined. Liver fibrosis severity, which did not exceed grade 1, was determined by indirect elastometry on the FibroScan® 502 Echosens device (France), with confirmation using the FibroTest–ActiTest test system (BioPredictive, France). Patients were divided into 2 groups according to the severity of hepatic necroinflammatory activity, assessed using the same test system. Group 1 (n=44) included patients with hepatic steatosis with minimal histologic disease activity (A 0–1); group 2 (n=40) included patients with steatohepatitis with significant necro-inflammatory activity (A 2–3). The electrical and viscoelastic parameters of erythrocytes were determined by dielectrophoresis at 4 frequencies of an inhomogeneous alternating electric field. Results and Discussion: the most significant electrical and viscoelastic indicators allowing to differentiate steatohepatitis from fatty liver disease were reduced values of strain amplitude at a frequency of 1 MHz (p=0.0003), dipole moment (p=0.009), capacity (p=0.014) and cell polarizability at a frequency of 1 MHz (p=0.03) and more high summarized viscosity (p=0.006), rigidity (p=0.005) and electrical conductivity (p=0.008). Diagnostic panel, including a set of electrical and viscoelastic parameters of erythrocytes, for the differentiation of steatohepatitis from steatosis demonstrated the following: AUC 0.904, sensitivity 0.9, specificity 0.83. Correlations of erythrocyte parameters with indicators of cytolysis syndrome (transaminase activity, serum iron levels, direct bilirubin) and serum inflammatory markers (fibrinogen, C-reactive protein, ferritin) were established. Conclusion: the electrical and viscoelastic parameters of erythrocytes studied using the dielectrophoresis should be considered as a new promising method in determining the severity of fatty liver disease. KEYWORDS: fatty liver disease, steatohepatitis, steatosis, electrical and viscoelastic parameters, erythrocytes, dielectrophoresis, diagnostic model. FOR CITATION: Kruchinina M.V., Parulikova M.V., Belkovets A.V., Gromov A.A. Possibilities of using electrical and viscoelastic parameters of erythrocytes for the diagnosis of steatohepatitis in patients with fatty liver disease. Russian Medical Inquiry. 2023;7(5):249–257 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-2.

APRI and FIB-4 indices as diagnostic noninvasive scores for prediction of severe fibrosis in patients with biliary atresia.

Biliary atresia (BA) is a blockage in the tubes (ducts) that carry bile from the liver to the gallbladder. The aspartate aminotransferase to platelet ratio (APRI), and Fibrosis-4 (FIB-4) scores are commonly used compound surrogates for advanced fibrosis. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. So, we determined the optimal cutoff values of the APRI and FIB-4 indices in prediction of fibrosis in BA patients. The aim of the study was to evaluate the validity of the APRI and FIB-4 indices in prediction of fibrosis in patients with BA. A cross sectional hospital-based study was conducted on 121 children complaining of BA attending the National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt, during the period from January 2022 to February 2023. The APRI score was significantly higher among neglected BA than BA type II a, BA type III, type II b and type I (p = 0.001). Also FIB-4 was significantly higher among neglected BA than BA type II a, BA type II b, type III and type I (p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that the cutoff point of the APRI score in prediction of fibrosis in patients with BA was 1.29, with sensitivity of 88.6% and specificity of 76.0%, while the cutoff point of FIB-4 in prediction of fibrosis in patients with BA was 9.82 with sensitivity of 89.0% and specificity of 70.0%. Our study confirms that FIB-4 and APRI scores are both able to predict severe fibrosis. APRI score and FIB-4 are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis and its extent in patients with BA.

PECULIARITIES OF THE FUNCTIONAL STATE OF THE LIVER IN PATIENTS WITH CHRONIC HEPATITIS C IN THE PRESENCE OF CHRONIC PANCREATITIS.

The aim: To study the features of the functional state of the liver in patients with chronic hepatitis C (CHC) in the presence of CP, depending on the enzymatic activity of the pancreas. Materials and methods: 72 patients were under observation: 52 with CHC and CP with exocrine secretory insufficiency (EI) of the pancreas and 20 - with CHC and CP without EI. In all patients, the degree of liver fibrosis, levels of aminotransferases, total bilirubin, gamma-glutamyltransferase, albumin, stool coproscopy and pancreatic fecal elastase-1 (FE-1) were determined. Results: It was revealed that in patients with CHC combined with CP+EI of the pancreas, higher activity of the necroinflammatory process and deeper stages of liver fibrosis is more often noted than in patients with preserved exocrine function of the pancreas. A statistically significant association was established between the degree of liver fibrosis and the presence of EI of the pancreas (p=0.03), namely, in patients with CHC and CP with EI of the pancreas, the degree of fibrosis F2-4 was 2.8 times more frequent. Also, higher levels of aminotransferases and lower levels of albumin were noted in this group of patients than in patients with CHC and CP with preserved exocrine function of the pancreatic gland. Conclusions: In patients with CHC combined with CP+EI of the pancreas, higher levels of fibrosis and necroinflammatory activity of the liver are more often detected, as well as a tendency to lower albumin levels, than in patients with CHC and CP without EI.