Development Of Hepatorenal Syndrome Research Articles

ЯЗВЕННЫЙ КОЛИТ И ВНУТРИПЕЧЕНОЧНЫЙ ХОЛЕСТАЗ

Background. Ulcerative colitis (UC) is an inflammatory bowel disease with unpredicted clinical course and outcomes. Histology is an important part of UC diagnosis and plays an increasing role in management of patients, since more and more histological signs with prognostic value are being identified and confirmed. Objective. To describe a clinical case of death of a UC patient with intrahepatic cholestasis. Material and methods. The article presents autopsy and pathology findings in UC. Results. A patient admitted to the hospital for unspecified acute hepatitis, nonspecific ulcerative colitis and gastrointestinal bleeding died because of ulcerative colitis complicated by sclerosing cholangitis. The course of ulcerative colitis was complicated by bleeding from ulcerated areas; by intrahepatic and extrahepatic cholestasis as well as necrosis of hepatocytes associated with sclerosing cholangitis; by the development of hepatorenal syndrome and sepsis, that resulted in fatal outcome. Conclusions. Multiple severe disturbances occurring in UC pathogenesis result in mutual aggravation syndrome involving interaction of pathophysiological processes with subsequent patient's condition deterioration as well as increased risk of complications and death.

Elevated D-Dimer levels correlate with the development of hepatorenal syndrome and a poor outcome in patients with cirrhosis

Objectives Whether hemostatic status was correlated with the diverse types of acute kidney injury in cirrhotic patients is unclear. The present study aimed to investigate the relationship between hemostatic markers and the diverse types of acute kidney injury (AKI) in liver cirrhosis. Patients and methods Cirrhotic patients with consecutive treatment at the First Affiliated Hospital of Medicine School, Zhejiang University, were pooled in a cohort. Their demographic and clinical data, biochemistry parameters and hemostatic markers were assessed to identify risk factors for the development and prognosis of AKI. Results A total of 773 cirrhotic patients were included in this cohort. Patients with hepatorenal syndrome (HRS) had significantly higher D-Dimer than those with the other types of AKI. In univariate COX regression, APTT, TT, INR, D-Dimer and Fib were correlated with the development of AKI, HRS and acute tubular necrosis (ATN), however, only D-Dimer remained independently associated with the development of AKI and HRS in multivariate COX regression. The area under the ROC curve of D-Dimer was 0.755 (95%CI, 0.718–0.793) in predicting the development of AKI, 0.879 (95%CI, 0.791–0.967) in predicting the development of HRS, respectively. D-Dimer was used for diagnosis of HRS with a sensitivity of 87.3% and specificity of 72.9% at the cutoff of 3.7 (mg/L FEU). Survival rates differed significantly between groups by D-Dimer level. Conclusions Hemostatic markers were significantly associated with the diverse types of AKI. D-Dimer was an independent risk factor for HRS and correlated with a poor outcome in cirrhotic patients.

Correction of hepatorenal syndrome with the use method of indirect electrochemical detoxification in oncological patients on the background of enteral insufficiency after multi-organic surgeries

Introduction. Enteral insufficiency syndrome accompanies the development of many acute diseases of the abdominal cavity. According to statistics, as a result of advanced and multi-organ surgery in oncosurgery for 2019–2020, enteral insufficiency was a complication in 39 % of all cases, regardless of anatomical and physiological area, and complications such as hepatorenal syndrome – in 50–80 % cases. The aim of the work is to study the effectiveness of correction of hepatorenal syndrome on the background of enteral insufficiency in cancer patients after multiorgan surgery. To do this, we used the method of indirect electrochemical detoxification with a solution of sodium hypochlorite. Materials and methods. 71 patients with oncopathology who underwent multiorgan surgery in different anatomical and physiological areas were examined. Patients were divided into two groups: the main group (n = 36), in which indirect electrochemical detoxification was performed with sodium hypochlorite solution at a concentration of 0.03 ; the comparison group (n = 35) – treatment was carried out according to standard schemes. The groups were compared by age and anatomical and physiological areas that were operated on (surgery was performed on the chest and mediastinum and abdominal organs). Results and discussion. For the treatment of patients with enteral insufficiency used the method of electrochemical detoxification with sodium hypochlorite, which reduces the indicators that reflect blood toxicity and the degree of intoxication. This was evidenced by a decrease in the concentration of bilirubin by 23.1 %, urea by 20.6 %, creatinine by 23.4 %, ALT by 57.2 % alkaline phosphatase by 69.5 %. When using this method for the third day managed to get a detoxifying effect. Conclusions. The expediency of including sodium hypochlorite in the complex postoperative therapy is shown. This is proved by the results of a comprehensive study of cancer patients after multiorgan surgery with the development of hepatorenal syndrome on the background of enteral insufficiency. It was found that the use of infusions of 0.03 % NaClO solution has a detoxifying effect: significantly reduces elevated concentrations of bilirubin by 23.1 %, creatinine by 20.6 %, urea by 23.4 %, improves the rheological properties of the blood. Therefore, given the relatively low effectiveness of conservative and insufficient availability of surgical treatment along with high mortality, prevention of hepatorenal syndrome in patients with enteral insufficiency by indirect electrochemical detoxification can significantly reduce its incidence.

A Prospective Study of Prevalence and Predictors of Cirrhotic Cardiomyopathy and Its Role in Development of Hepatorenal Syndrome

Cirrhotic cardiomyopathy (CCM) is a term used to collectively describe abnormal structural and functional changes in heart of patients with cirrhosis. The present study was undertaken to find the prevalence of CCM in patients with liver cirrhosis and its predictors. We also followed these patients to evaluate the role of CCM in the development of hepatorenal syndrome (HRS). This was a prospective study carried out in department of Gastroenterology, Sir Ganga Ram hospital, New Delhi. A total of 104 patients with liver cirrhosis were included. Liver cirrhosis was diagnosed on basis of clinical, biochemical, and imaging features. CCM was defined based on echocardiography. Dobutamine stress echocardiographyand hepatic venous pressure gradient (HVPG) were performed in patients who gave consent. HRSwas defined as per standard criteria. Patients with CCM were followed for development of HRS. Fifty (48%) patients were diagnosed with CCM. All patients had diastolic dysfunction, and none had systolic dysfunction. Median age of patients with CCM was significantly higher (59 [31-78y] vs. 52 [24-70y], P<0.05). Severity of liver disease (Child Turcotte Pugh scoreand model for end-stage liver disease score) and portal pressures (HVPG) did not differ in patients with or without CCM. Patients with CCM did not have increased incidence of HRS at the end of 6-month follow-up study. The presence of CCM was not related with the severity of liver dysfunction or portal pressures. Age was a significant determinant of CCM. Diastolic cardiac dysfunction does not influence the occurrence of HRS.

Biglycan: A regulator of hepatorenal inflammation and autophagy

Soluble biglycan, a small leucine-rich proteoglycan, plays a significant role in several pathologies as it has emerged as an extracellular matrix-derived danger-associated molecular pattern. Biglycan is released from the extracellular matrix in response to tissue injury and, as a canonical danger signal, interacts with innate immune receptors, Toll-like receptors 2 and 4, thereby triggering a sustained inflammatory response. Recent evidence indicates that biglycan acts as a molecular switch between inflammation and autophagy by a specific interaction with the Toll-like co-receptor CD14 and CD44, respectively. Biglycan-evoked autophagy further contributes to the anti-inflammatory M2 macrophage polarization, inflammation resolution and tissue repair. These multivalent roles of soluble biglycan have been well characterized in inflammatory kidney diseases. In chronic liver diseases, increased levels of soluble biglycan have been described for years, leading to utilization of biglycan serum levels as a non-invasive biomarker for fibrosis. Hepatorenal dysfunction represents a classic example of inter-organ crosstalk, in which functional and molecular alterations of the cirrhotic liver can promote the development of renal failure. In patients with liver cirrhosis, development of hepatorenal syndrome is associated with high mortality. In this review, we will discuss the crucial role of soluble biglycan in inflammation and autophagy and its possible implications for hepatorenal dysfunction. We propose a novel concept of hepatorenal crosstalk, that is, biglycan produced by the cirrhotic liver could constitute a circulating “messenger” for the kidneys triggering inflammation and/or autophagy ultimately affecting disease outcome.

IMMUNE MECHANISMS FOR THE DEVELOPMENT OF HEPATORENAL SYNDROME IN LIVER CIRRHOSIS

Hepatorenal syndrome is a life-threatening complication of liver cirrhosis. 90% of patients with liver cirrhosis die within 2 months since the onset of hepatorenal syndrome development. For many years the hypothesis of the hemodynamic mechanism of hepatorenal syndrome development was accepted as the only true one, according to this hypothesis compensatory systemic vasodilation in response to portal hypertension causes renal ischemia and the development of functional specific acute kidney damage, the so-called “hepatorenal syndrome – acute kidney damage”. In recent years some works were published that substantiate the role of a systemic inflammatory reaction in the development of hepatorenal syndrome; this inflammatory reaction being associated with activation of innate immunity cells in response to a bacterial infection, including that to the microflora of the intestine which is adjacent to the liver. Data has been obtained which indicated that Toll-like receptors (TLRs), in particular TLR4 and TLR9 are involved in the development of hepatorenal syndrome.

Clinical, morphological and biochemical signs of polymycotoxicosis in highly productive cows

Mycotoxicological monitoring of forages shows that the problem of mycotoxicosis has been relevant for several decades. Minimal doses of mycotoxins in feed lead to a decrease in milk productivity, increased sensitivity to infectious and non-infectious diseases. When several mycotoxins enter the body simultaneously, a synergistic effect develops, causing a significant increase in toxicity. Feed contaminated with several types of fungi and their toxins is dangerous for dairy cattle. It was found that the feed mixture contained the types of associations of Aspergillus spp. fungi + Fusarium; Aspergillus spp. + Penicillium spp. + Mucor spp; Fusarium + Penicillium; Mucor spp. + Fusarium + Ustilaginales. Pathogenetic features of metabolic and morphological changes in highly productive cows with polymycotoxicosis were studied. Feeding food contaminated with various metabolites of mold fungi leads to the development of signs of chronic toxemia in animals. Clinical manifestations are the development of diarrhea and dehydration, with a decrease in milk productivity. Metabolic disorders feature the development of an inflammatory process, metabolic acidosis, hyperfermentonemia, with an increase in the amount of creatinine and urea in the blood serum. Metabolic signs indicate the development of hepatorenal syndrome due to structural disorders of the liver and kidneys. Histological signs of polymicotoxicosis are intracapillary and hemorrhagic glomerulonephritis, hepatocyte micronecrosis, and proliferation of connective tissue stroma cells, which leads to the development of atrophic cirrhosis in the interstitial and circular phases.

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury.

Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear. Here, we aim to map the morphological, metabolomic and transcriptomic changes systematically after acute liver injury and search for the potential crosstalk between the liver and the extra-liver organs. Significant changes of transcriptome were observed in multiple extra-liver organs after different types of acute liver injury despite dramatic morphological damage only occurred in lung tissues of the ConA/BDL models and spleen tissues in the ConA model. Liver transcriptomic changes initiated the serum metabolomic alterations which correlated to transcriptomic variation in lung, kidney, and brain tissues of BDL and LR models. The potential crosstalk might lead to pulmonary damage and development of hepatorenal syndrome (HRS) and hepatic encephalopathy (HE) during liver injury. Serum derived from acute liver injury mice damaged alveolar epithelial cells and human podocytes in vitro. Our data indicated that different types of acute liver injury led to different transcriptomic changes within extra-liver organs. Integration of serum metabolomics and transcriptomics from multiple tissues can improve our understanding of acute liver injury and its effect on the other organs.

980 Renal Resistive Index at the Level of Renal Arcuate Artery as a Predictor of Natriuresis in Cirrhotic Patients

INTRODUCTION: It has been postulated that the vasoconstriction at the level of renal arcuate artery plays a key role in the development of Hepatorenal syndrome(HRS). However, the measure of renal resistive index at the level of renal arcuate artery can provide a direct measure of renal hemodynamics among cirrhotics. The aim of this study is to determine the difference in the renal resistive index amongst both compensated as well as decompensated cirrhotics and to evaluate its association with natriuresis. METHODS: This prospective study included all consecutive cirrhotic patients visited gastroenterology clinic of our hospital from May 2018 to May 2019. After obtaining informed consent, the demographic parameters were noted along with a detailed drug history (Dose and duration of diuretics and beta blocker). Later on an ultrasound abdomen was also performed for documenting the features of chronic liver disease and the renal resistive index was noted. These patients were then stratified into two groups i.e. compensated cirrhosis and decompensated cirrhosis. Chi square test was applied and P value was calculated. RESULTS: A total of 60 patients were included in the study. The mean age of the patients was 40.3 ± 18.1, and were predominantly males 31(51.7%). Hepatitis C was the most common etiology for liver disease seen in 22 patients (36.7%).The mean CTP score, MELD and MELD sodium score were as follows: 7.9 ± 1.93, 15.2 ± 6.6 and 13.3 ± 4.2 respectively. Compensated liver disease was present in 16(26.7%) patients, while decompensated liver disease was present in 44(73.3%) patients. Mean renal resistive index of patient with compensated cirrhosis was 0.59 ± 0.04, while with decompensated cirrhosis was 0.62 ± 0.04. Patients with a higher RI had poor natriuresis as manifested by low urinary sodium potassium ratio &lt; 1.0 and AROC is 0.775. At the cut off value of RI = 0.615 sensitivity, specificity, positive predictive value and negative predictive value for nartriuresis was 65.0%, 70.0%, 73.3% and 60.1% respectively. Patient with higher RI value were having decompensated cirrhosis (P = 0.06, 0.62 vs 0.59) CONCLUSION: The renal resistive index at the level of arcuate artery were found to be higher among patients with decompensated cirrhosis. At a higher RI value ( &gt;0.615) patients had poor natriuresis. Therefore, RI can be used to predictor of natriuresis among cirrhotic patients. Key words:

The role of differences of metabolism in the formation of disorder of function of the liver and the kidney in tetrachloride carbon intoxication

Currently, there is a steady tendency for the growth of diseases of the hepatobiliary system, which is caused by a complex of endogenous and exogenous influences. Therefore, treatment of chronic hepatitis remains one of the important and complex problems in the general medicine clinic. The purpose of the study is to evaluate the role of some regulatory mechanisms in the formation of liver and kidney disorders in carbon tetrachloride intoxication. The experimental studies were performed on 54 white Wistar rats of the autohybrid breeding line, which were divided into control and experimental groups. Within 7 days, the experimental group of animals was subjected to carbon tetrachloride intoxication by administering 0.5 ml CCl₄ subcutaneously. Kidney function status was assessed by changes in diuretic diuresis, glomerular filtration function, percent tubular reabsorption, serum creatinine and urea content, chloride excretion and urine pH. Liver function was assessed by ALT and AST activity, bilirubin in the blood, serum creatinine and urea content, total serum protein. The status of other aspects of metabolism was evaluated by MDA composition and catalase activity; NO content, uric acid, Na⁺/K⁺ and Ca⁺²/Mg⁺² activity — ATP-az. Changes in the overall blood count as well as the state of the regulatory components of the immune response by the content of circulating immune complexes and the content of heterogeneous antibodies were evaluated. The data obtained were subjected to standard statistical processing using a coefficient of authenticity. As a result, changes in kidney and liver function, characteristic of the development of hepatorenal syndrome, have been established. According to the results of the study, it is concluded that the systemic metabolism of the animal body changes due to the violation of the properties of cell membranes, slowing the flow of intracellular processes of life, which disrupts the elimination of xenobiotics and plays a negative role in the pathogenesis of hepatorenal insufficiency.

Hepatorenal Syndrome.

Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver-kidney transplantation.

PS-088-Impaired cardiac contractile reserve on dobutamine stress echocardiography predicts development of hepatorenal syndrome

PS-088-Impaired cardiac contractile reserve on dobutamine stress echocardiography predicts development of hepatorenal syndrome

Impact of diastolic dysfunction (LVDD) on clinical response and prognosis after transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites

Introduction: Left ventricular diastolic dysfunction (LVDD) in patients with liver cirrhosis is associated with circulatory dysfunction, hepatorenal syndrome development and heart failure in stressfull conditions.

Случай развития гепаторенального синдрома у ребенка с муковисцидоз-ассоциированным циррозом печени

Случай развития гепаторенального синдрома у ребенка с муковисцидоз-ассоциированным циррозом печени

Clinical and microbiological characteristics associated with mortality in spontaneous bacterial peritonitis: a multicenter cohort study.

Spontaneous bacterial peritonitis (SBP) is a prevalent and high mortality complication of cirrhosis. We aimed to describe these patients' clinical and microbiological characteristics and evaluate their impact on outcomes. This was a retrospective cohort study including 139 consecutive patients with positive culture SBP from three Portuguese centers diagnosed between 2009 and 2014. Multivariate logistic regression was used to study associations with 30-day mortality. The mean age of the patients was 62 years and 81% of patients were men. The mean model for end-stage liver disease score was 19. Hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding developed in 47, 30, and 21% of patients, respectively. Gram-positive bacteria were isolated in the ascitic fluid of 42% of patients. Resistance to quinolones and multiresistance were found in 33 and 17% of patients, respectively. C-reactive protein level (adjusted odds ratio, 1.16 per 1 mg/l increment) and development of hepatorenal syndrome (adjusted odds ratio, 2.86) were associated independently with 30-day mortality (model's area under the curve, 0.78). In this cohort, SBP portended high early mortality. Gram-positive bacteria, bacteria resistant to quinolones, and multiresistant bacteria were identified in considerable proportions of patients. In the setting of the high early mortality and changing microbiological profile, SBP management strategies need to be improved.

Cell death biomarkers are associated with development of hepatorenal syndrome as well as response to terlipressin therapy

Background and aim: Hepatorenal syndrome (HRS) is a severe complication of patients with liver cirrhosis and associated with high mortality rates if left untreated. Levels of cell death parameters are significantly elevated in patients with acute and chronic liver diseases. However, the role of these markers in patients with HRS is unknown. Aim of the study was to investigate if serum levels of M30 and M65 correlate with the risk of HRS development in cirrhotic patients and clinical outcome of HRS.

Severity of hepatic dysfunction and its correction in the complex treatment of acute intestinal obstruction

The article describes the role that could play a hepatoprotective therapy in the treatment of patients with acute intestinal obstruction. The study involved 128 patients with mechanical acute intestinal obstruction, accompanied by the syndrome of enteral insufficiency. Hepatoprotective drugs have been added in the scheme of treatment. It has been proven beneficial therapeutic effect of this measure on the dynamics of the development of hepatorenal syndrome, syndrome of enteral insufficiency.

Diagnostik und Therapie des hepatorenalen Syndroms

Portal hypertension occurs frequently in advanced liver cirrhosis and accounts for the majority of lethal complications. Compensatory splanchnic vasodilation and counter regulatory mechanisms (e.g. activation of the renin-angiotensin-aldosterone system) increase renal vascular resistance, which may facilitate acute kidney injury and the development of hepatorenal syndrome (HRS). HRS represents a functional, yet reversible renal impairment with elevated serum creatinine levels. Establishing the diagnosis, fluid challenge test and several investigations are needed to exclude acute kidney injury and other causes of renal failure. Early treatment with albumin and vasoconstrictors improves the prognosis of HRS patients. The only curative treatment of HRS so far is improvement of liver function implying liver transplantation in many cases. TIPS placement may be useful as a bridging tool to transplantation unless hepatic encephalopathy is present. Spontaneous bacterial peritonitis (SBP) is a relevant, independent risk factor for HRS. In patients with liver cirrhosis and SBP in addition to antibiotics, preventive albumin treatment is recommended.

The challenges and excitement of liver transplantation.

The challenges and excitement of liver transplantation.

Post‐paracentesis circulatory derangements are related to monocyte activation

Post-paracentesis circulatory dysfunction is associated with development of hepatorenal syndrome and increased mortality. The impact of large volume paracentesis (LVP) on the 24-h blood pressure (BP) profile is unknown, and the relationship to Na+-retentive and pro-inflammatory cytokines also remains unknown. The aims of this study were to (i) define the effects of LVP with albumin administration on 24-h BP profiles, and (ii) relate changes in BP over time to changes in Na+-retentive hormones, clinical factors and inflammatory cytokines. Ten patients undergoing LVP had 24-h ambulatory BP monitoring performed pre- and post-paracentesis. Markers of the innate immune system, bacterial translocation and Na+-retentive hormones were drawn pre- and post-LVP. Mean arterial pressure (MAP) dropped in nine of the 10 patients in the 24 h following a paracentesis compared to 24 h preceding the procedure (mean drop of 5.5 mmHg, P<0.005). A mixed effects model was used to define time-covariate interactions in predicting changes in BP profile. Monocyte chemotactic protein-1 (MCP1) was associated with Δsystolic BP (β=-0.011, P<0.05), Δdiastolic BP (β=-0.012, P<0.05) and ΔMAP (β=-0.012, P<0.05). Plasma renin activity was also significantly associated with Δsystolic BP (β=-0.21, P<0.05). Renal function was also significantly reduced following LVP. Systolic, diastolic and MAP decreased over 24 h after LVP compared to the 24 h pre-LVP. This drop is related to increases in MCP-1 after LVP. Increased MCP-1, a marker of monocyte activation, was strongly related to changes in BP.