Development Of Decompensation Research Articles

Serum Ferritin Levels and Liver-Related Events in Individuals With Steatotic Liver Disease: A Longitudinal Cohort Study.

Serum ferritin has been suggested as a potential biomarker associated with disease progression in metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the association between serum ferritin levels and liver-related events (LREs) in individuals with steatotic liver disease (SLD). This cohort study included 17,560 adults with SLD (MASLD [n = 15,744], MASLD with increased alcohol intake (MetALD) [n = 1103] and cryptogenic SLD [n = 713]) without LRE at baseline. A steatotic liver was diagnosed using ultrasound, and LRE was defined as the development of decompensation (ascites, variceal bleeding and hepatic encephalopathy) or hepatocellular carcinoma. Participants were categorised into high (≥ 300 μg/L for males, ≥ 200 μg/L for females) or normal to low (< 300 μg/L for males, < 200 μg/L for females) ferritin levels. During 211,425 person-years of follow-up (median: 12.3 years), 74 incident LRE cases were identified, with 63 cases in MASLD, 10 in MetALD and 1 in cryptogenic SLD. The multivariable-adjusted hazard ratio (aHR) for LRE comparing individuals with high and normal-to-low ferritin level was 3.13 (95% confidence interval [CI] 1.89-5.18). Increased risk of LRE in individuals with high serum ferritin level compared to those with normal to low serum ferritin level was consistent across SLD subtypes (aHR 2.69, 95% CI 1.55-4.67 for MASLD; aHR 5.73, 95% CI 1.31-25.0 for MetALD), and SLD severity assessed by Fibrosis-4 (FIB-4) index (aHR 2.38, 95% CI 1.34-4.21 for FIB-4 ≥ 1.3; aHR 3.13, 95% CI 1.18-8.29 for FIB-4 < 1.3). Serum ferritin levels correlated with the risk of LRE in patients with SLD.

Insulin-like Growth Factor-1 Levels Reflect Muscle and Bone Health and Determine Complications and Mortality in Decompensated Cirrhosis

The growth hormone-insulin-like growth factor (GH-IGF-1) axis and its impairment with sarcopenia, frailty, bone health, complications, and prognosis are not well characterized in cirrhosis. We investigated the adult decompensated cirrhosis out-patients at a tertiary care institute between 2021 and 2023 for serum GH and IGF-1 levels, and associated them with sarcopenia (CT-SMI in cm2/m2), liver frailty index (LFI), osteodystrophy (DEXA), clinical decompensations (overall, ascites, encephalopathy, infection, and bleed), and survival up to 180 days. One-hundred-seventy-two patients, 95% males, aged 46.5 years (median). logIGF-1 levels were negatively associated with sarcopenia, osteodystrophy, LFI, CTP, and MELD-Na score (P<0.05 each). Patients with low IGF-1 levels had a higher incidence of complications (overall, ascites and encephalopathy) than those with intermediate, and high IGF-1 levels (P<0.05 each). Both logIGF-1 (AUC: 0.686) and MELD (AUC: 0.690) could predict 180-day mortality (P<0.05, each). Adding logIGF-1 with MELDNa further improved discriminative accuracy of MELDNa (AUC: 0.729) P<0.001. The increase in IGF-1 on follow-up was associated with better survival and fewer complications. Reduced IGF-1 levels reflect sarcopenia, frailty, and osteodystrophy in cirrhosis. Low IGF-1 are associated with severity, development of decompensations, and mortality.

Immune Response and Risk of Decompensation following SARS-CoV-2 Infection in Outpatients with Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis.

Insulin-like growth factor 1 (IGF-1), which is primarily produced in hepatocytes and is associated with liver functional reserve, plays a crucial role in the pathological condition of cirrhosis. This study aimed to investigate the usefulness of serum IGF-1 levels for predicting the long-term prognosis and decompensation development in patients with cirrhosis. We retrospectively evaluated 148 patients with cirrhosis and divided them into three groups according to baseline IGF-1 levels: low (L)-, intermediate (I)-, and high (H)-IGF-1 groups. The cumulative survival rates were compared among these groups in compensated and decompensated cirrhosis, respectively. Significant and independent factors associated with mortality and decompensation development were identified using Cox proportional hazards regression analysis. The median observation period was 57.1 (41.7-63.2) months. Thirty (20.3%) patients died of liver disease-related events and 21 (22.3%) patients with compensated cirrhosis developed decompensation. Multivariate analysis identified low serum IGF-1 levels as a significant and independent factor associated with mortality (all patients: hazard ratio [HR], 0.967; p = 0.004; patients with compensated cirrhosis: HR, 0.927; p = 0.002). The cumulative survival rates were significantly lower in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (all patients: p < 0.001 and = 0.009; patients with compensated cirrhosis: p = 0.012 and 0.003, respectively). However, in decompensated cirrhosis, the cumulative survival rates demonstrated no significant differences among the three groups. The cumulative decompensation incidence rates were significantly higher in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (p < 0.001 and = 0.009, respectively). Low serum IGF-1 levels were significantly and independently associated with decompensation development (HR, 0.939; p < 0.001). Low serum IGF-1 levels were significantly and independently associated with decompensation development and poor long-term prognosis in patients with compensated cirrhosis. Therefore, IGF-1 may be useful for predicting decompensation-related events and should be regularly monitored in the management of compensated phase.

A prospective study on the differential association of sarcopenia and frailty with health outcomes in cirrhotic patients

BackgroundTo investigate the joint impact of sarcopenia and frailty on mortality and the development of decompensation in cirrhosis. MethodsSarcopenia was assessed using the skeletal muscle mass index (SMI) by computed tomography, whereas frailty was measured using the Fried Frailty Phenotype (FFP). Cox proportional hazard regression and competing risks analysis were used to evaluate their association with adverse outcomes. ResultsThe prevalence of sarcopenia and frailty was 29.6% and 37.2%, respectively. Sarcopenia and frailty separately increased more than two times higher risk of all-cause mortality after adjustment for age, gender, Child-Turcotte-Pugh, and comorbidities. Co-occurrence of sarcopenia and frailty was associated with a higher incremental risk of mortality in patients with cirrhosis (HR = 4.16, 95% CI: 1.64–10.58, P = 0.003), but these two conditions didn't have significant interaction. Frailty, but not sarcopenia, was significantly associated with an increased cumulative incidence of liver-related mortality and decompensation after adjusting covariates. Subgroup analysis revealed that frailty shortened the liver-related survival of cirrhosis patients with male or higher liver severity based on MELD. ConclusionsCo-occurrence of sarcopenia and frailty increased the risk of death in cirrhosis, but these two conditions didn't have a significant interaction association. Frailty, but not sarcopenia, was associated with more adverse outcomes in cirrhotic patients.

Natural History of Hepatosplenic Schistosomiasis (HSS) Non-Cirrhotic Portal Hypertension (NCPH): Influence of Gastrointestinal Bleeding and Decompensation in Prognosis.

Hepatosplenic schistosomiasis (HSS) is a peculiar form of non-cirrhotic portal hypertension (NCPH). Although HSS patients present normal hepatic function, some evolve signs of hepatocellular failure and features of decompensated cirrhosis. The natural history of HSS-NCPH is unknown. A retrospective study was conducted that evaluated patients who fulfilled clinical-laboratorial criteria for HSS. A total of 105 patients were included. Eleven patients already presented with decompensated disease and had lower transplant-free survival at 5 years than those without (61% vs. 95%, p = 0.015). Among 94 patients without prior decompensation, the median follow-up was 62 months and 44% of them had varicose bleeding (two or more episodes in 27%). Twenty-one patients presented at least one episode of decompensation (10-year probability 38%). Upon multivariate analysis, varicose bleeding and higher bilirubin levels were associated with decompensation. The 10-year probability of survival was 87%. Development of decompensation and age were predictive of mortality. HSS is characterized by multiple episodes of GI bleeding, a high probability of decompensation and reduced survival at the end of the first decade. Decompensation is more common in patients with varicose esophageal bleeding and is associated with lower survival.

Ultrastructural reorganization of the constituent components of the rat periodontium under conditions of chronic opioid exposure

Opioid addiction has acquired the characteristics of an epidemic in recent years and is a serious problem in modern medicine. In users of narcotic substances, a significant prevalence of diseases of the oral cavity and periodontal tissues is noted in comparison with the general population. The aim of the work was to investigate the ultrastructural organization of the periodontal tissues of rats at the end of the fourteenth week of the experimental opioid effect. The animals were administered intramuscularly, daily, once, the opioid analgesic nalbuphine (pharmacotherapeutic group: analgesics, opioids, morphinan derivatives) in increasing doses for 14 weeks: 1-2 weeks – 0.212 mg/kg, 3-4 weeks – 0.225 mg/kg, 5-6 weeks – 0.252 mg/kg, 7-8 weeks – 0.260 mg/kg, 9-10 weeks – 0.283 mg/kg; 11-12 – 0.300 mg/kg, 13-14 weeks – 0.450 mg/kg. At the end of the fourteenth week of opioid exposure, ultrastructural changes in the epithelium of the mucous membrane of the gums, periodontium, and hemomicrovessels with the development of decompensation and pronounced dystrophic-destructive changes were established. With the long-term effect of an opioid analgesic, signs of karyorrhexis, segregation of nucleoli, spongiosis, apoptosis, violation of the integrity of intercellular contacts, as well as vacuole-like formations, which were a manifestation of focal necrosis of epitheliocytes, were revealed. The development of necrotic changes was caused by significant damage and destruction of organelles, as well as fragmentation or lysis of bundles of tonofilaments. The intercellular spaces were mostly expanded and uneven, which was caused by edematous phenomena. Fragmentation and destruction of periodontal collagen fibers, destructive changes in fibrocytes and fibroblasts were found in the periodontium. The translucency of the amorphous component of the intercellular substance of the connective tissue was determined. The ultrastructural reorganization of the cellular components of the periodontium was caused by vascular disorders of a systemic nature, which were manifested by the phenomena of dilatation, hemoptysis, sludge phenomenon, dystrophic changes in the endotheliocytes of hemocapillaries and venules, and the progression of sclerotic changes, which significantly disturbed the trophism of the periodontal tissues of rats.

Long-Term Outcomes of Endoscopic Management of Patients with Symptomatic Portal Cavernoma Cholangiopathy with No Shuntable Veins for Surgery or Failed Surgery

Shunt surgery is the definitive treatment for symptomatic patients with portal cavernoma cholangiopathy (PCC), but few patients are non-surgical candidates or fail to improve even after surgery. This study aims to analyze the long-term outcomes of endoscopic therapy in these patients. Retrospective review of a prospectively maintained database of all patients with symptomatic PCC managed with endoscopic retrograde cholangiography (ERC) followed by stent placement. Outcomes studied included number of biliary interventions, complications, resolution of stricture, development of decompensation and mortality. Thirty-five patients (68.6% males, median age = 35 years) with a median follow-up duration of 46 months (12-112) were included in the analysis. Presentation was only jaundice in 51.4% cases while one-third (37.1%) of the patients presented with cholangitis. Patients underwent a total of 363 endoscopic sessions with a median of 9 procedures (3-29) per patient. Hemobilia was the most common complication of the procedure (6.06%). Ten (28.5%) patients required frequent stent exchanges. Patients who required frequent stent exchanges had higher number of cholangitis episodes and hospitalization. Secondary biliary cirrhosis developed in 4 (11.4%) patients and 2 (5.7%) patients had mortality. Of the 5 (14.3%) patients who were given a stent free trial, 3 patients required restenting due to redevelopment of symptoms. Patients with PCC without shuntable veins for surgery or those who failed to improve after surgery can be managed long-term with repeated endoscopic intervention with a slightly increased risk of non-fatal hemobilia.

Дикарбонільний стрес: гіпотеза клітинного пошкодження в умовах гіпоксії. Пусковий механізм розвитку мультиорганної дисфункції

Актуальність. Різноманітні критичні стани організму часто асоційовані з розвитком гіпоксії, у результаті чого активуються механізми гліколізу, під впливом звільнення стресових гормонів розвивається гіперглікемія. Показано, що в умовах анаеробного гліколізу на тлі гіперглікемії в клітинах продукуються токсичні речовини, що викликають гліколізування протеїнів та нуклеїнових кислот. Разом із порушенням функції клітинних білків виникає мітохондріальна дисфункція, що призводить до енергетичного дефіциту та порушення функціонування органів. Мета дослідження: виявити провідні механізми дикарбонільного стресу, їх значення для формування критичних станів організму та визначити найбільш перспективні способи корекції для фахівців у галузі інтенсивної терапії. Матеріали та методи. Детальне вивчення результатів сучасних наукових досліджень процесів вуглеводного обміну при патологічних станах на підставі інформації, поданої в Інтернеті. Результати. Провідна роль у пошкодженні клітинних структур організму при дикарбонільному стресі належить гліоксалю та метилгліоксалю. Ці хімічні сполуки утворюються як побічні продукти анаеробного гліколізу. Збільшенню їх синтезу сприяють активація анаеробного гліколізу та гіперглікемія. Дикарбонільні сполуки вступають у хімічні реакції з амінними групами протеїнів, нуклеїнових кислот та інших біологічно активних сполук, порушуючи їх функціонування. Природна детоксикація здійснюється гліоксалазною системою за участю відновленого глутатіону, що є основним компонентом антиоксидантної системи. Прогресування окислювального стресу та поява антиоксидантного дефіциту зумовлюють збільшення тяжкості пошкоджень, що викликає підвищене утворення гліоксалю та метилгліоксалю. Профілактика дикарбонільного стресу здійснюється за допомогою збільшення потужності антиоксидантної системи, насамперед за рахунок зростання утворення відновленого глутатіону. Для нейтралізації токсичних дикарбонільних метаболітів можуть бути використані препарати, що виконують функцію «пасток». Перспективне застосування терапії, що спрямована на усунення мітохондріальної дисфункції. Висновки. Нова проблема пошкодження організму в умовах дикарбонільного стресу диктує необхідність аналізу та переоцінки численної кількості заходів інтенсивної терапії. Докладне вивчення особливостей вуглеводного обміну при різних критичних станах, включаючи визначення концентрації гліоксалю та метилгліоксалю, моніторинг рівня глікемії та кліренсу лактату в поєднанні з поверненням до оцінювання стану компенсації функції прооксидантної/антиоксидантної системи організму, є одним із перспективних напрямів наукових досліджень у клініці, що має розпочатися. Фахівці з інтенсивної терапії щоденно стикаються із ситуаціями, коли дикарбонільний стрес може виступати як один із дійсних механізмів формування органної та мультиорганної дисфункції й визначає розвиток декомпенсації життєво важливих функцій. Навчитися протистояти йому є актуальною найближчою задачею.

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development

There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n= 421) and was validated in an independent NAFLD cohort (n= 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic exvivo cultures of clinical fibrotic liver tissues (n= 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n= 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n= 122). A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic exvivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in exvivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.

Health-related quality of life improves after entecavir treatment in patients with compensated HBV cirrhosis.

Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5years of antiviral therapy (all p < 0.001), with all dimensions improved more than five points except for physical functioning. Proportion of patients reporting no problems in all five dimensions in EQ-5D increased from 57.8 to 72.0%; visual analogue scale (VAS) and utility index (UI) increased significantly (VAS 79.8 ± 16.4 to 84.4 ± 13.2, UI 0.91 ± 0.13 to 0.95 ± 0.10, both p < 0.001). HRQoL improved or kept stable in the majority of patients who had LRE during follow-up, even stratified by Baveno VI criteria for clinically significant portal hypertension. After 5years of ETV treatment, HRQoL significantly improved in patients with compensated HBV cirrhosis. (NCT01943617, NCT02849132).

Frailty as tested by the Liver Frailty Index is associated with decompensation and unplanned hospitalization in patients with compensated cirrhosis

Background and Aims Frailty is associated with morbidity and mortality in advanced cirrhosis. However, the information on the association between frailty and outcome in compensated cirrhosis is scarce. We aimed to explore the prognostic impact of frailty in compensated cirrhosis. Methods Compensated cirrhotic patients were prospectively enrolled. Frailty was defined by the Liver Frailty Index (LFI). Development of new hepatic decompensation (worsening ascites, portal hypertension-related bleeding, hepatic encephalopathy, or acute kidney injury), unplanned hospitalization, and decompensation-free survival were recorded. Quality of life (QoL) was assessed by SF-36 questionnaire. Results 152 patients were included (MELD 9.2 ± 3.4, Child-Pugh A/B 84.9%/15.1%), and 24.3% were frail. By multivariable logistic regression analysis, age > 65 years, MELD score > 10, and Child-Pugh B were associated with frailty. Compared to the robust group, pre-frail and frail patients had significantly higher cumulative 1-year probabilities of developing decompensation (0% vs. 8.5% vs. 18.4%, p = .009), and unplanned hospitalization (0% vs. 13.5% vs. 34.2%, p < .001), and lower 1-year decompensation-free survival (100% vs. 90.8% vs. 80.4%, p = .014). Two models of multivariable Cox regression analysis were done adjusted with MELD-Na and Child-Pugh B, frailty was associated with developing decompensation (HR 3.01, p = .04; and 2.98, p = .04, respectively) and unplanned hospitalization (HR 2.46, p = .02; and 2.39, p = .03, respectively), but not the decompensation-free survival. By multivariable linear regression analysis, Child-Pugh B and frailty significantly decreased both physical and mental component scores of the SF-36 questionnaire. Conclusion Frailty is prevalent in compensated cirrhosis. The LFI provides additional prognostic values to recognized risk scores regarding the development of decompensation, hospitalization, and impaired QoL.

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

Background/AimsThe development of decompensation in cirrhosis demarcates a marked change in the natural history of chronic liver disease. HMG-CoA reductase inhibitors (statins) exert pleiotropic effects that reduce inflammation and fibrosis as well as improve vascular reactivity. Retrospective studies uniformly have associated statin utilization with improved outcomes for patients with cirrhosis. Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage when added to standard therapy with an acceptable safety profile. This proposal aims to extend these findings to demonstrate that simvastatin reduces incident hepatic decompensation events among cirrhotic patients at high risk for hepatic decompensation. MethodsWe will perform the SACRED Trial (NCT03654053), a phase III, prospective, multi-center, double-blind, randomized clinical trial at 11 VA Medical Centers. Patients with compensated cirrhosis with clinically significant portal hypertension will be stratified based upon the concomitant use of nonselective beta-blockers and randomized to simvastatin 40 mg/day versus placebo for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Ancillary studies will evaluate patient-reported outcomes and pharmacogenetic corollaries of safety and/or efficacy. ConclusionStatins have a long track-record of safety and tolerability. This class of medications is generic and inexpensive, and thus, if the hypothesis is proven, there will be few barriers to widespread acceptance of the role of statins to prevent decompensation in patients with compensated cirrhosis.ClinicalTrials.gov Identifier: NCT03654053

Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy.

Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6months. LRE was defined as development of decompensation, HCC or death. Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%. Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.

Clinical-diagnostic and prognostic significance of impairment of the fatty tissue biomarker in patients with obesity and disturbance of carbohydrate

Type 2 diabetes mellitus (DM) is a heterogeneous disease characterized by a complex of metabolic disorders, the main features of which are insulin resistance and insufficient of pancreatic cell function of varying severity. Objective — to study the clinical, diagnostic and prognostic value of the level of omentin in type 2 diabetes mellitus in combination with excess body weight (EBW) and obesity. Material and methods. 98 people with diabetes mellitus were examined, the first group consisted of 64 people with EBW and obesity (body mass index > 25). The second group consisted of 34 people with type 2 diabetes mellitus and normal body weight (body mass index ≤ 25). As a control, a group of 28 practically healthy individuals were examined, which were comparable to the first and second groups by gender and age. Results. The presence of type 2 diabetes, EBW and obesity in patients leads to a decrease in the marker of compensation for impaired metabolism of carbohydrates, lipids and a decrease in insulin resistance — omentine by 127.48% relative to patients with type 2 diabetes without EBW and obesity. Patients with glycated hemoglobin HbA1c values of more than 8% showed a decrease in omentin values compared with patients with compensated diabetes, the difference was more pronounced in patients with EBW and obesity (28.29%, p<0.05), in the absence of EBW and obesity the difference was 13.66%. An increase in the duration of type 2 DM led to a depression of the studied marker of omentin in patients with obesity by 39.24% (p<0.05), in the absence of obesity — by 25.95%. The development of the complicated course of type 2 DM in patients with obesity led to a decrease in the values of omentin by 51.09% (p<0.05), in the absence of obesity — by 13.39%. A high and very high cardiovascular risk in patients with type 2 DM with obesity led to a difference in omentine values by 39.48% (p <0.05) in favor of high risk, and in patients without obesity — by 25.66%. Conclusion. Omentin levels in type 2 diabetes mellitus depend on the presence of excess body weight and obesity in patients and on the characteristics of the clinical course of comorbidity, decreasing with the development of decompensation and complications.

СОВРЕМЕННЫЕ АСПЕКТЫ МЕДИКАМЕНТОЗНОЙ ТЕРАПИИ СИНДРОМА ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Chronic heart failure (CHF) is an important problem for the country, which has both medical and socio-economic aspects. The presence of the syndrome not only significantly increases the risks of an unfavorable course of diseases underlying its etiological basis, but in itself, through the development of decompensation, causes a high frequency of deaths. Despite all the advances in pharmacotherapy, the prognosis of heart failure remains poor. More than 40% of patients die within 4 years after the diagnosis of heart failure, and the one-year mortality rate for patients with severe CHF (NYHA class IV) exceeds 50%. The foregoing determines the need and importance of using all possible drug and non-drug therapy technologies aimed at reducing mortality, increasing the duration and quality of life of patients with CHF, as well as reducing the number and likelihood of decompensation and related hospitalizations, and makes this direction one of the priorities in medicine. The article describes current approaches to the treatment of patients with CHF syndrome from the perspective of evidence-based medicine and taking into account the recommendations of leading international organizations for the treatment and prevention of cardiovascular diseases. The drugs used were analyzed in terms of their influence on clinical symptoms, quality of life of patients, the risk of hospitalization due to decompensation of CHF, and mortality rates. The emphasis is made on the possibilities, mechanism of action and further prospects for the use of a new class of drugs in the treatment of CHF, acting at the level of the renin-angiotensin-aldosterone system and the system of neutral endopeptidases - inhibitors of angiotensin-neprilisin receptors.

P4509The cardiopulmonary vicious cycle in patients with heart failure, a mechanism for accelerated decompensation

Abstract Background Hemodynamic congestion appears days prior to the development of clinical congestion. Lung congestion is associated with increased respiratory effort and dyspnoea. The effects of increased respiratory effort on pulmonary circulation were not well-defined. Purpose The study investigates the cardiopulmonary interactions and the role of the respiratory effort in the development of decompensation. It is well-accepted that lung congestion affects the lung mechanics and increases the respiratory effort. On the other hand, changes in the intrathoracic and alveolar pressures, due to the increase in the respiratory effort, may have detrimental effects on the pulmonary circulation and the workloads of the heart. Methods We have simultaneously measured the hemodynamic indices and the respiratory mechanics in patients undergoing right heart catheterization (n=56) for the diagnosis of dyspnoea. The patients were classified either as heart failure (HF) or lung disease, according to their clinical history, symptoms and signs. The pulmonary capillary wedge pressure (PCWP) was decomposed into cardiac and respiratory waves. The respiratory effort (Presp) was defined as the respiratory wave amplitude that modulates the PCWP. Lung compliance was calculated as the ratio of the tidal volume to Presp. Results and discussion The HF patients (n=35) exhibited huge Presp of 9.6±3.7 mmHg [2.6–16.7], ∼4 fold the normal Presp, of about 2–3 mmHg (figure below). Their lung compliance decreased with increasing PCWP (2.0±0.4%/mmHg of PCWP). Both PCWP and pulmonary artery pressure (PAP) rose with Presp, by 0.92±0.36 mmHg and 1.68±0.47 mmHg, for 1 mmHg of Presp, respectively (Figure below). Interestingly, PCWP always exceeded Presp, leading to the stipulation of a novel fundamental constraint/law: the continuous pulmonary flow throughout the respiratory cycle requires that PCWP &gt; Presp (above the identity line in figure A), otherwise the capillary pressure will decrease below the surrounding alveolar pressure and the pulmonary circulation will collapse, especially during inspiration. This constraint imposes a positive feedback of Presp on the pulmonary circulatory pressures. It is also supported by the increase in PWCP with Presp in the patients with lung diseases (Figure A). The bigger rise in PAP than in PWCP is attributed to the increase in the pulmonary vascular resistance (PVR) with Presp (0.3±0.06 wood units for 1mmHg Presp). The latter constructs additional positive feedback of Presp on the cardiac workload. A decrease in the intrathoracic pressure that surrounds the heart increases the LV apparent afterload. The increase in PAP and PVR elevates the right ventricle afterload. PCWP (A) and PAP (B) vs. Presp Conclusions The respiratory effort is not just a hallmark of HF but plays a pivotal role in the cardiopulmonary vicious cycle. An increase in the respiratory effort increases the PWCP, PAP, PVR, and the afterloads of both ventricles, and thereby may accelerate cardiac decompensation.

Sarcopenia Is Associated With Development of Acute-on-Chronic Liver Failure in Decompensated Liver Cirrhosis Receiving Transjugular Intrahepatic Portosystemic Shunt.

INTRODUCTION:Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height.METHODS:One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS.RESULTS:The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients.CONCLUSIONS:This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.

Prognostic Role of Liver Stiffness Measurements Using Magnetic Resonance Elastography in Patients with Compensated Chronic Liver Disease.

To retrospectively evaluate the prognostic role of liver stiffness (LS) measurement using magnetic resonance elastography (MRE) in patients with compensated chronic liver disease (cCLD). We enrolled 217 patients with cCLD who underwent MRE. After mean follow-up of 45.0 ± 17.6 months, cumulative incidence (CI) of hepatocellular carcinoma (HCC) occurrence, development of decompensation and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazard regression model. During the follow-up period, HCC occurred in 33 patients, and 1-, 3- and 5-year CIs of HCC occurrence were 3.8%, 14.8% and 18.9%, respectively. The LS value was a significant predictive factor for HCC occurrence [p < 0.001, hazard ratio (HR) = 1.59 per unit (1.25-2.03)]. Eighteen patients experienced hepatic decompensation, and 1-, 3- and 5-year CIs of decompensation were 2.8%, 7.3% and 11.3%, respectively. The LS value was also significantly associated with decompensation development [p < 0.001, HR = 2.02 per unit (1.37-2.98)]. Fourteen patients died, and 1-, 3- and 5-year OSs were 99.1%, 98.0% and 89.8%, respectively. The LS value was demonstrated to be a significant affecting factor for OS [p = 0.008, HR = 1.39 per unit (1.10-1.78)]. LS obtained from MRE was a significant predictive factor for the development of decompensation, HCC occurrence and OS in cCLD patients. • Liver stiffness (LS) values obtained from MRE can provide prognostic information. • The LS value was a significant predictive factor for occurrence of hepatocellular carcinoma. • The LS value was significantly associated with development of hepatic decompensation. • Survival of compensated chronic liver disease patients was affected by the LS value.