Complication Of Liver Cirrhosis Research Articles

Late liver allograft dysfunction: definition, risk factors and outcomes

Introduction. Impaired liver transplant function in the long term often leads to graft loss and the recipient death. There are many causes for the development of a late liver allograft dysfunction and different types of its clinical presentation, but there is no generally accepted definition. This hinders its timely diagnosis, analysis of its prevalence, and also makes it difficult to compare the performance of transplantation programs.Objective. To determine the clinical and prognostic value of late liver allograft dysfunction.Material and methods. The study included 103 cases of cadaveric liver transplantation from donors diagnosed with brain death to 100 recipients, of whom 36% were men, aged 48 years old (40;56) (18–68) at the time of transplant, having MELD score 17 (14;21) (7–41). The follow-up period was 52 months (20;77) (8–180). The cases where the graft loss occurred earlier than 3 months were excluded.The late liver allograft dysfunction was defined as a dysfunction of the transplanted liver, which was manifested by at least one of three following signs and occurred at more than 3 months after transplantation: 1) increased aspartate aminotransferase, alanine aminotransferase and/or gamma glutamyl transferase, alkaline phosphatase, bilirubin; 2) impaired synthetic function (increased international normalized ratio, decreased antithrombin III, cholinesterase); 3) liver cirrhosis complications (signs of portal hypertension, ascites, encephalopathy). The following limits were chosen as a diagnostic threshold for laboratory parameter abnormalities: more than 2 upper limits of normal for total bilirubin, more than 1.5 upper limits of normal for the levels of alanine or aspartic aminotransferases, more than 1.5 upper limits of normal for gamma-glutamyltransferase or alkaline phosphatase, more than 1.6 of normal for international normalized ratio.Results. Late liver allograft dysfunction was diagnosed at least once in 64% of recipients. Through the postoperative course, the proportion of patients with late dysfunction varied from 22% to 40%. The etiology of late liver allograft dysfunction was viral (38%), unknown (25%), biliary (19%), immune (17%), and vascular (1%). Late liver allograft dysfunction was reversible in 75% of cases, persistent in 17%, progressive in 8% of cases. Progressive late liver allograft dysfunction led to a graft loss in all cases observed.Recipients with late liver allograft dysfunction were found to have had a 33% higher incidence of early allograft dysfunction (OR 4.7, 95% CI [1.8–12.3]); the incidence of biliary dysfunction was 3.1 times higher with distant choledochojejunostomy (OR 3.9, 95% CI [1.1–13.9]); in patients with autoimmune and cholestatic disease, the incidence of immune dysfunction was 4.8 times higher (OR 5.8, 95% CI [1.7–20.3]).Conclusion. The progressive nature of late liver allograft dysfunction negatively affects the results of transplantation and therefore should be considered as an indication for retransplantation. Reversible and persistent variants of late liver allograft dysfunction have favorable) prognosis. If the etiology of late dysfunction is not established, the regular surveillance with monitoring for fibrosis and repeated attempts to clarify the diagnosis should be continued.

Letter to the Editor: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis.

Letter to the Editor: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis.

Pay attention to the diagnosis and treatment of "easily neglected" complications in liver cirrhosis

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.

Reply: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis.

Reply: Regarding the use of decision curve analysis in predicting long-term complications of liver cirrhosis.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban

Background and aimsPortal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism.MethodsFirst, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4–10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1).ResultsAfter PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity.ConclusionsA new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

Liver sinusoidal endothelial cells contribute to portal hypertension through collagen type IV-driven sinusoidal remodeling.

Portal hypertension (PHTN) is a severe complication of liver cirrhosis and is associated with intrahepatic sinusoidal remodeling induced by sinusoidal resistance and angiogenesis. Collagen type IV (COL4), a major component of basement membrane, forms in liver sinusoids upon chronic liver injury. However, the role, cellular source, and expression regulation of COL4 in liver diseases are unknown. Here, we examined how COL4 is produced and how it regulates sinusoidal remodeling in fibrosis and PHTN. Human cirrhotic liver sample RNA sequencing showed increased COL4 expression, which was further verified via immunofluorescence staining. Single-cell RNA sequencing identified liver sinusoidal endothelial cells (LSECs) as the predominant source of COL4 upregulation in mouse fibrotic liver. In addition, COL4 was upregulated in a TNF-α/NF-κB-dependent manner through an epigenetic mechanism in LSECs in vitro. Indeed, by utilizing a CRISPRi-dCas9-KRAB epigenome-editing approach, epigenetic repression of the enhancer-promoter interaction showed silencing of COL4 gene expression. LSEC-specific COL4 gene mutation or repression in vivo abrogated sinusoidal resistance and angiogenesis, which thereby alleviated sinusoidal remodeling and PHTN. Our findings reveal that LSECs promote sinusoidal remodeling and PHTN during liver fibrosis through COL4 deposition.

Assessment of single and combined administration of ubiquinone and lactoferrin on histopathology, ultrastructure, oxidative stress, and WNT4 expression gene induced by thioacetamide on hepatorenal system of adult male rats

BackgroundHepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq10) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups (n = 10): control, Coq10, LF, TAA, TAA + Coq10, TAA + LF, and TAA + Coq10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks.ResultsTAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq10 and LF.ConclusionOur data suggested that Coq10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4.

Impact of sarcopenia on variceal rebleeding in patients after endoscopic therapy: a multicenter retrospective cohort study based on propensity score matching

Background Sarcopenia is a common complication of liver cirrhosis and can be used for predicting dismal prognostic outcomes. This study aimed to evaluate the role of sarcopenia in rebleeding and mortality of liver cirrhosis patients after endoscopic therapy. Methods The liver cirrhosis patients who received endoscopic treatment were enrolled. Propensity score matching (PSM) was used to overcome selection bias. Two-year rebleeding episodes and mortality after endoscopic therapy were recorded. Results A total of 109 (32.4%) sarcopenia patients were reported. Before PSM, the frequency of rebleeding was significantly higher in the sarcopenia group relative to the non-sarcopenia group (41.3% vs. 15.9%, p < 0.001). Moreover, the multivariable analysis revealed that sarcopenia (p < 0.001, HR:2.596, 95% CI 1.591–4.237) was independently associated with a 2-year rebleeding episode. After PSM, the sarcopenia group exhibited an increased rebleeding rate as compared with non-sarcopenia group (44.4% vs. 15.3%, p < 0.001). According to multivariable analysis, sarcopenia (p < 0.001, HR:3.490, 95% CI 1.756–6.938) was identified as a significant predictor for 2-year rebleeding. Conclusion Sarcopenia was significantly associated with a high 2-year rebleeding rate in liver cirrhosis patients after endoscopic treatment. Therefore, the precise evaluation of a patient’s nutritional status, including sarcopenia becomes mandatory before endoscopic treatment.

A randomized controlled trial of a postdischarge nursing intervention for patients with decompensated cirrhosis.

Few randomized trials have evaluated the effect of postdischarge interventions for patients with liver cirrhosis. This study assessed the effects of a postdischarge intervention on readmissions and mortality in patients with decompensated liver cirrhosis. We conducted a randomized controlled trial at a specialized liver unit. Adult patients admitted with complications of liver cirrhosis were eligible for inclusion. Participants were allocated 1:1 to standard follow-up or a family-focused nurse-led postdischarge intervention between December 1, 2019, and October 31, 2021. The 6-month intervention consisted of a patient pamphlet, 3 home visits, and 3 follow-up telephone calls by a specialized liver nurse. The primary outcome was the number of readmissions due to liver cirrhosis. Of the 110 included participants, 93% had alcohol as a primary etiology. We found no significant differences in effects in the primary outcomes such as time to first readmission, number of patients readmitted, and duration of readmissions or in the secondary outcomes like health-related quality of life and 6- and 12-month mortality. A post hoc exploratory analysis showed a significant reduction in nonattendance rates in the intervention group (RR: 0.28, 95% CI: 0.13-0.54, p=0.0004) and significantly fewer participants continuing to consume alcohol in the intervention group (p=0.003). After 12 months, the total number of readmissions (RR: 0.76, 95% CI: 0.59-0.96, p=0.02) and liver-related readmissions (RR: 0.55, 95% CI: 0.36-0.82, p=0.003) were reduced in the intervention group. A family-focused postdischarge nursing intervention had no significant effects on any of the primary or secondary outcomes. In a post hoc exploratory analysis, we found reduced 6-month nonattendance and alcohol consumption rates, as well as reduced 12-month readmission rates in the intervention group.

SURGICAL MANAGEMENT FOR BLEEDING FROM ESOPHAGUS VARICOSE VEINS

Portal hypertension and bleeding from varicose veins of the esophagus and stomach due to portal hypertension are the most dangerous and threatening complications of liver cirrhosis (6,7). The mortality rate from ongoing bleeding is about 4-8% (6,8,11). 20% of patients with acute bleeding die within 6 weeks compared with other complications (6,8,11). Mortality from rebleeding in patients with decompensated stages of liver cirrhosis reaches up to 78% (7). Currently, there are a number of different methods for the treatment of portal hypertension complicated by bleeding from varices of the esophagus and stomach (VES), including both endovascular interventions and endoscopic treatment. Many surgical methods have been developed to reduce pressure in the portal vein and prevent re-bleeding. But these operations have their limitations. Minimally invasive methods for bleeding from VES include endoscopic sclerotherapy, endoscopic ligation, endovascular transjugular intrahepatic portosystemic shunt, endovascular percutaneous transhepatic embolization of gastroesophageal varices and other combined methods. Surgical practice has proven that treatment results and patient survival are much better with delayed and especially with planned surgical interventions. At the same time, in the last decade, preference has been given to indirect portocaval anastomoses, and recently many adherents of the Sugiura operation have appeared (3,10,13). Thanks to the joint efforts of gastroenterologists, radiologists and surgeons in the treatment of bleeding from the esophagus with portal hypertension, gastrointestinal endoscopy and invasive diagnostic and therapeutic radiographic methods have acquired significant importance. Transendoscopic sclerotherapy of VRV has become particularly widespread. Recurrence of hemorrhages is possible in approximately 10% of cases, which is not much higher than the best results of surgical treatment (1,6,11), and complications (mediastenitis, pyothorax, bleeding, stenosis) develop in only 2% of patients (3).

Awareness of Atherosclerosis and Cardiovascular Events Among Undergraduate Healthcare Professionals

The word atherosclerosis consists of two parts: atherosis (accumulation of fats accompanied by several macrophages) and sclerosis (fibrosis layer comprising smooth muscle cells. The presence of hyperlipaemia is the major risk issue factor for coronary artery disease. In 2016 advances in atherosclerosis research were focused on the discovery and validation of newly targeted genetics and mechanistic connection to atherothrombotic heart diseases. The Survey on awareness about the risk factors and complications of liver cirrhosis among college students was conducted using a Google form link. We have distributed our survey among 100 college students. Pie charts and Bar diagrams were used to represent output variables. Results showed that the knowledge of cardiovascular 54.00 % said No and 46.00 % said yes. Stroke caused due to lack of blood supply to 44.00 % said heart, 50.00 % said brain, and 6.00 % said I don’t know. These findings conclude that the majority of the population is unaware of the risk factors such as obesity, LDL, and family history, which lead to the development of atherosclerosis, but only a few populations are aware of stress, smoking, coronary heart attack, cholesterol, sleep apnea, HDL, work pressure, physical activity, heart disease, and coronary disease that leads to atherosclerosis.

Transplantace jater pro deficit alfa-1-antitrypsinu

Summary: Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant genetic condition which manifests with lung emphysema at young age and with liver disease. A point mutation in the SERPINA1 gene, which encodes 1-antitrypsin (AAT), causes a defective secondary structure of the protein, which subsequently accumulates in the endoplasmic reticulum of hepatocytes and is not transported into the blood and body fluids. Deficiency of AAT, which inhibits neutrophil elastase in the lung, thus allows proteolytic damage to the connective tissue of the lung, leading to the development of emphysema. Liver disease is caused by the accumulation of the mutant AAT in liver cells, contributing to proteotoxic liver injury that can lead to liver cirrhosis. Liver transplantation (LT) is the only curative method; after LT, the recipient has the phenotype of the donor organ and normal serum AAT concentrations. The indication for LT should be considered in all patients with AATD and end-stage liver disease. The patients should be referred to the transplant centre when severe complications of liver cirrhosis, such as variceal bleeding, ascites, encephalopathy, and hepatorenal syndrome. In patients with hepatocellular carcinoma, LT represents an optimal treatment modality in the case of an early, unresectable tumour. The timing of LT is crucial; LT should be performed before the patient develops life-threatening complications of end-stage liver disease. LT should be considered in patients of Child-Pugh classification B and C and MELD score of 15 points or higher. Survival of patients after LT for AADT is excellent. Key words: 1-antitrypsin – 1-antitrypsin deficiency – liver cirrhosis – end-stage liver disease – hepatocellular carcinoma – live transplantation

Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

Machine-learning-based plasma metabolomic profiles for predicting long-term complications of cirrhosis.

The complications of liver cirrhosis occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic-based score tool to predict these events. We enrolled 64,005 UK biobank participants with metabolomic profiles. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with HCC. An interpretable machine-learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created 3 groups: low-risk, middle-risk, and high-risk through selected cutoffs of the nomogram. The predictive performance was validated through the area under a time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict the 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC: 0.84 [95% CI: 0.82-0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference: 0.06 [0.03-0.10]) and polygenic risk score (0.25 [0.21-0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The HR in the high-risk group was 43.58 (95% CI: 27.08-70.12) compared with the low-risk group. We developed a metabolomic state-integrated nomogram, which enables risk stratification and personalized administration of liver-related events.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers.

Portal vein thrombosis (PVT), a complication of liver cirrhosis, is a major public health concern. PVT prediction is the most effective method for PVT diagnosis and treatment. To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis. Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved. Following a 1:1 propensity score matching 572 patients with cirrhosis were screened, and relevant clinical data were collected. PVT risk factors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables. A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT, and its predictive performance was verified using a receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Finally, a network calculator was constructed based on the nomograms. This study enrolled 286 cirrhosis patients with PVT and 286 without PVT. LASSO analysis revealed 13 variables as strongly associated with PVT occurrence. Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors, including etiology, ascites, gastroesophageal varices, platelet count, D-dimer, portal vein diameter, portal vein velocity, aspartate transaminase to neutrophil ratio index, and platelet-to-lymphocyte ratio. LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables. A nomogram was constructed based on the screened independent risk factors. The nomogram had excellent predictive performance, with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups, respectively. Calibration curves and DCA revealed its good clinical performance. Finally, the optimal cutoff value for the total nomogram score was 0.513. The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706, respectively. A nomogram for predicting PVT occurrence was successfully developed and validated, and a network calculator was constructed. This can enable clinicians to rapidly and easily identify high PVT risk groups.

The relationship between the active cell mass index and complications of liver cirrhosis: ascites and hepatic encephalopathy

Changes in body composition, in particular sarcopenia and sarcopenic obesity, are complications of liver cirrhosis affected by unfavorable parent substances. The selection of diet and exercise for at least 8 weeks allows you to get the best results when taken by patients with cirrhosis of the liver. The correlate of motor activity in the bioimpedance analysis of the active fraction of the active cell mass in the lean mass of the human body. Aim of the study. To assess the relationship between increased cell mass and the severity of ascites and hepatic encephalopathy in liver cirrhosis. Material and methods. 46 patients with liver cirrhosis were examined. The component composition of the body is felt with the help of ABC-01 "Medass" devices (STC Medass, Russia). Ascites was assessed during the clinical examination, as well as the results of the examination of the abdominal cavity and retroperitoneal space. Diagnosis of hepatic encephalopathy impact test on the speed of cognitive reaction: "Number connection test". Results. A significant relationship was found between the proportion of active cell mass and the severity of ascites (r = –0.312, p-value = 0.034), indicating that a decrease in active cell mass is a prognostically unfavorable disease for the progression of ascites in patients with liver cirrhosis. Correlation analysis showed the presence of a negative correlation average strength between the values of the share of AKM in TMT and high body weight of PE: r = –0.229 (p value = 0.125), which requires research on studies between the values of the relationship between active cell mass and body weight. hepatic encephalopathy. Conclusion. Sensitive relationships have been found between active cell mass and the severity of liver cirrhosis. Determination of body composition products, in particular the absolute and relative indicators of active cell mass, in patients with liver cirrhosis can be of practical use in compiling promising mathematical models of prognosis.

Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis

IntroductionHepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore,...

Correlation of non-invasive parameters with upper gastrointestinal endoscopy findings for presence and grading of gastroesophageal varices in liver cirrhosis patients.

Development of esophageal varices is one of the major complications of liver cirrhosis, and endoscopy is used to see the presence, grading, and long-term monitoring of esophageal varices which is an invasive and unpleasant procedure. There is no adequate data available showing noninvasive methods can be used for the same. Seventy patients with liver cirrhosis participated in the study. Factors like portal vein diameter, spleen size, platelet count, serum bilirubin, Child-Pugh score, prothrombin time (PT), and PT INR were observed and correlated endoscopically with the presence and grading of esophageal varices in all patients. The platelet count, portal vein diameter, serum bilirubin, spleen bipolar diameter, and PT had statistically significant correlations with the presence of varices. Among them, platelet count, portal vein diameter, and serum bilirubin also had statistically significant correlations with the grading of varices. Monitoring of these noninvasive parameters can help in monitoring variceal growth. Noninvasive parameters can be used effectively to predict the presence and grading of esophageal varices and at the same time keep the rate of undiagnosed varices acceptably low. By using noninvasive parameters, patients can be benefited by decreasing the requirement of repeated endoscopic evaluation which is an unpleasant procedure and availability is also limited.

Primary sarcopenia is associated with elevated spontaneous NET formation.

Introduction: Sarcopenia is a frequent complication of liver cirrhosis, but it can also occur independently as a result of any underlying cause. The immune system plays an important role in the pathogenesis of both liver cirrhosis and sarcopenia. Neutrophil function, including neutrophil extracellular trap (NET) formation, is linked to chronic inflammation; however, it has not been extensively studied in patients with sarcopenia. Here, we aim to study if main neutrophil functions, such as phagocytosis, reactive oxygen species (ROS) production, and NET formation, are altered in patients with sarcopenia with or without liver cirrhosis. Methods: Neutrophils from 92 patients (52 patients with liver cirrhosis and sarcopenia, 25 patients with liver cirrhosis without sarcopenia, and 15 patients with sarcopenia without liver cirrhosis) and 10 healthy controls were isolated and stimulated with heat-inactivated E. coli (250 bacteria/cell), phorbol 12-myristate 13-acetate (PMA) (100nM), or incubation medium in duplicates for 2h at 37°C. Cells were fixed with paraformaldehyde and stained with 4',6-diamidino-2-phenylindole (DAPI). Pictures of 10 random fields of vision per slide were taken with an Olympus BX51 fluorescence microscope (Olympus, Shinjuku, Tokyo, Japan) at 600x total magnification. The DNA Area and NETosis Analysis (DANA) algorithm was used to quantify the percentage of NET formation per patient. Phagocytosis and ROS production were assessed with the PhagotestTM kit and PhagoburstTM kit (Glycotope, Heidelberg, Germany) in 92 patients and 21 healthy controls, respectively. Results: Spontaneous NET formation was significantly elevated in patients with only sarcopenia compared to patients with cirrhosis and sarcopenia (p = 0.008) and healthy controls (p = 0.039). NET formation in response to PMA was significantly decreased in patients with cirrhosis (p = 0.007), cirrhosis and sarcopenia (p < 0.001), and sarcopenia (p = 0.002) compared to healthy controls. There was no significant difference in NET formation in response to E. coli between the groups. The DANA algorithm was successfully optimized and validated for assessment of clinical samples. There were no significant changes in neutrophil phagocytosis between patients' groups compared to healthy controls. A significantly lower percentage of neutrophils produced ROS in response to N-formylmethionine-leucyl-phenylalanine (fMLF) in patients compared to healthy controls. Discussion: Spontaneous NET formation might contribute to chronic inflammation and sarcopenia pathogenesis. This, however, does not result in the impairment of the NET formation function of neutrophils in response to a bacterial stimulus and, therefore, cannot be not linked with the increased risk of bacterial infections neither in sarcopenia nor in cirrhosis. The semi-automated NET formation analysis can be successfully implemented to analyze the vast amount of data generated within clinical studies. This approach opens up the possibilities to develop an NET formation-based biomarker in different diseases including sarcopenia and implement NET formation analysis into clinical settings. Phagocytosis and ROS production were not affected in patients with sarcopenia. Further research is needed to explore the mechanism of NET formation in patients with sarcopenia and its potential as a biomarker in sarcopenia.

SERPINB3 in fibrogenic chronic liver diseases and primary liver cancers

Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to the development of primary liver cancers, represent a major burden for human health on a worldwide basis. Although the present knowledge on the pathogenesis of CLDs progression and primary liver cancers development has remarkably increased in the last decades, critical molecular mediators remain incompletely understood, and approved antifibrotic therapies to efficiently counteract CLDs progression and liver cancer are lacking. In the present review, this study will specifically analyse the putative contribution of SERPINB3, a member of the superfamily of serine-protease inhibitors (SERPINs), which has been shown to exert significant pro-inflammatory and pro-fibrogenic roles in progressive CLDs as well as to be involved in the development of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and hepatoblastoma.