Distribution of nitric oxide synthase positive neurons in the substantia nigra of rats with liver cirrhosis

BACKGROUND：Nitrogen monoxide plays an important role in the physiological activity and pathological process of striatum in substantia nigra, and the nitric oxide synthase in substantia nigra may have characteristic changes after liver cirrhosis.OBJECTIYE： To observe the distribution and forms of nitric oxide synthase （NOS） positive neurons and fibers in substantia nigra of rats with liver cirrhosis.DESIGN： A comparative observational experiment.SETTINGS： Beijing Friendship Hospital; Capital Medical University.MATERIALS： Twenty 4-month-old male Wistar rats （120 - 150 g） of clean grade, were maintained in a 12-hour light/dark cycle at a constant temperature with free access to standard diet and water. Cryostat microtome （LEICA, Germany）; All the reagents were purchased from Sigma Company.METHODS： The experiment was carried out in the Department of Anatomy （key laboratory of Beijing city）,Capital Medical University from July 2000 to March 2002. The rats were randomly divided into normal group （n=10） and liver fibrosis group （n=10）. Rats in the liver fibrosis group were subcutaneously injected with 60% CCl4 oil at a dose of 5 mL/kg for the first time, and 3 mL/kg for the next 14 times, twice a week,totally 15 times. Liver fibrosis of grades 5 - 6 was taken as successful models. Whereas rats in the normal group were not given any treatment. Four months after CCl4 treatment, all the rats were anesthetized to remove brain, and frontal frozen serial sections were prepared. The expressions of nitric oxide synthase positive neurons in substantia nigra of rats were observed under inverted microscope. The number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra were detected with NADPH-diaphorase staining.MAIN OUTCOME MEASURES： ①Number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra; ②Expressions of nitric oxide synthase positive neurons in substantia nigra.RESULTS： All the 20 rats were involved in the analysis of results. ①The nitric oxide synthase positive neurons in substantia nigra were obviously fewer in the liver cirrhosis group than in the normal group （P〈0.01）, and the gray scale of the positive cell body was higher in the liver cirrhosis group than in the normal group （P〈0.05）. ② Abundant nitric oxide synthase positive neurons were observed in substantia nigra of neurons in substantia nigra were obviously fewer in the liver cirrhosis group than in the normal group （P〈0.01）, and the gray scale of the positive cell body was higher in the liver cirrhosis group than in the normal normal rats, the cell body of nitric oxide synthase positive neurons was clear and transparent, with short own cloudy processes. In substantia nigra of rats with liver cirrhosis, the body of nitric oxide synthase positive neurons were observed shrink obviously, less fibrin than normal.CONCLUSION： Rats with liver cirrhosis may suffer from the physiological dysfunction of neurons due to lack of fibers. The nitric oxide synthase positive neurons in substantia nigra can shrink and reduce.

Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

AIM:To investigate the inhibitory effect of natural taurine(NTau)on portal hypertension(PHT)in rats with experimentally-induced liver cirrhosis(LC). METHODS:Experimentally-induced LC Wistar rats(20 rats/group)were treated with either oral saline or oral NTau for 6 consecutive weeks.Evaluation parameters included portal venous pressure(PVP),portal venous resistance(PVR),portal venous flow(PVF),splanchnic vascular resistance(SVR)and mean arterial pressure (MAP).Vasoactive substance levels including nitric oxide(NO),nitric oxide synthase(NOS)and cyclic guanosine monophosphate(cGMP)were also measured. Histological investigation of typeⅠandⅢcollagen (COLⅠandⅢ)and transforming growth factor-β1 (TGF-β1)was also performed. RESULTS:Treatment with NTau(1)significantly decreased PVP,PVR and PVF,and increased MAP and SVP;(2)markedly increased the vascular compliance and reduced the zero-stress of the portal vein;(3) markedly decreased the amount of NO and cGMP and activity of NOS;and(4)improved the pathological sta-tus of the liver tissue and reduced the expression of COLⅠ,COLⅢand TGF-β1. CONCLUSION:NTau inhibited the LC-induced PHT by improving hyperdynamic circulation,morphology of liver and biomechanical properties of the portal vein in experimentally-induced LC rats.

Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats

AIM:To examine whether the administration of atorvastatin and rosuvastatin would prevent experimentallyinduced hepatic cirrhosis in rats.METHODS:Liver cirrhosis was induced by injections of thioacetamide(TAA).Rats were treated concurrently with TAA alone or TAA and either atorvastatin(1,10 and 20 mg/kg) or rosuvastatin(1,2.5,5,10 and 20 mg/kg) given daily by nasogastric gavage.RESULTS:Liver fibrosis and hepatic hydroxyproline content,in the TAA-treated group was significantly higher than those of the controls [11.5 ± 3.2 vs 2.6 ± 0.6 mg/g protein(P = 0.02)].There were no differences in serum aminotransferase levels in the TAA controls compared to all the groups treated concomitantly by statins.Both statins used in our study did not prevent liver fibrosis or reduce portal hypertension,and had no effect on hepatic oxidative stress.Accordingly,the hepatic level of malondialdehyde was not lower in those groups treated by TAA + statins compared to TAA only.In vitro studies,using the BrdU method have shown that atorvastatin had no effect of hepatic stellate cells proliferation.Nevertheless,statin treatment was not associated with worsening of liver damage,portal hypertension or survival rate.CONCLUSION:Atorvastatin or rosuvastatin did not inhibit TAA-induced liver cirrhosis or oxidative stress in rats.Whether statins may have therapeutic applications in hepatic fibrosis due to other etiologies deserve further investigation.

Effect of spleen on immune function of rats with liver cancer complicated by liver cirrhosis

OBJECTIVE: To establish a rat model of liver cancer complicated by liver cirrhosis and explore the effects of the spleen on immune function in this model. METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40% CCl_4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver and splenectomy was performed. Two weeks later, the growth and metastasis of tumor were observed and the amount of ascites and the activity of NK cells and CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume were significantly higher in splenectomy group than in controls (P<0.O1). Two weeks after inoculation, the activity of NK cells in both groups was decreased as compared with that before the inoculation (P<0.01). There was no significant difference between the two groups before and after the inoculation (P>0.05). The number of CD25 in both groups was higher than that before the inoculation (P<0.01). However, there was no significant difference between the two groups before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early stage of tumor inoculation can stimulate the tumor growth and metastasis. The activity of NK cells and the number of CD25 are inhibited by tumor itself, not by splenectomy.

Clinical study on the relationship between liver cirrhosis,ascites,and hyponatremia

BACKGROUND Cirrhosis is a common liver disease,and ascites is one of the common clinical conditions.However,the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied.AIM To explore the clinical manifestations,prognostic factors,and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies.METHODS In this study,we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022.Patients were divided into two groups:ascites combined with hyponatremia group and ascites group.We compared the general characteristics,degree of hyponatremia,complications,treatment,and prognosis between the two groups.RESULTS In the study results,patients in the ascites combined with hyponatremia group showed an older average age(58.2±8.9 years),64.4%were male,and had a significantly longer hospitalization time(12.7±5.3 d).Hyponatremia was more severe in this group,with a mean serum sodium concentration of 128.5±4.3 mmol/L,which was significantly different from the ascites group of 137.6±2.1 mmol/L.Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy(56.2%vs 39.0%),renal impairment(45.2%vs 28.6%)and infection(37.0%vs 23.4%).Regarding treatment,this group more frequently used diuretics(80.8%vs 62.3%)and salt supplements(60.3%vs 38.9%).Multiple logistic regression analysis identified older age[Odds ratio(OR)=1.06,P=0.025]and male gender(OR=1.72,P=0.020)as risk factors for hyponatremia combined with ascites.Overall,patients with ascites and hyponatremia present a clear high-risk status,accompanied by severe complications and poor prognosis.CONCLUSION In patients with cirrhosis,ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

Validation of a surgical model for posthepatectomy liver failure in rats

Background:The upper limit for liver resections in rats is approximately 90%.In the early postoperative phase,mortality increases.The aim of the present study was to validate the rat model of 90%partial hepatectomy(PH)as a model of post-hepatectomy liver failure(PHLF).Further,we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.Methods:Sixty-eight rats were randomized to 90%PH,sham operation,or no sur-gery.Further,block randomization was performed based on time of euthanization:12,24,or 48 h after surgery.A general distress score(GDS)≥10 during the day or≥6 at midnight prompted early euthanization and classification as nonsurvivor.Animals euthanized as planned were classified as survivors.During euthanization,blood and liver tissue were collected,and liver-specific biochemistry was evaluated.Results:Based on the biochemical results,all animals subjected to 90%PH expe-rienced PHLF.Seventeen rats were euthanized due to irreversible PHLF.The GDS increased for nonsurvivors within 12–18 h after surgery.The mean time for euthaniza-tion was 27 h after surgery.Conclusion:Based on the GDS and liver-specific biochemistry,we concluded that the model of 90%PH seems to be a proper model for investigating PHLF in rats.As a high GDS is associated with increased mortality,the GDS appears to be valuable in detect-ing lethal outcomes caused by PHLF in rats.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis

BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Endoscopic ultrasound-guided intraportal injection of autologous bone marrow in patients with decompensated liver cirrhosis:A case series

BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis:Evidence and uncertainties

Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.

Therapeutic possibilities of gut microbiota modulation in acute decompensation of liver cirrhosis

The formation of liver cirrhosis(LC) is an unfavorable event in the natural history of chronic liver diseases and with the development of portal hypertension and/or impaired liver function can cause a fatal outcome. Decompensation of LC is considered the most important stratification variable for the risk of death. It is currently postulated that decompensation of LC occurs through an acute(including acute-on-chronic liver failure) and non-acute pathway. Acute decompensation of LC is accompanied by the development of life-threatening complications, characterized by an unfavorable prognosis and high mortality.Progress in understanding the underlying molecular mechanisms has led to the search for new interventions, drugs, and biological substances that can affect key links in the pathogenesis of acute decompensation in LC, for example the impaired gut-liver axis and associated systemic inflammation. Given that particular alterations in the composition and function of gut microbiota play a crucial role here, the study of the therapeutic possibilities of its modulation has emerged as one of the top concerns in modern hepatology. This review summarized the investigations that describe the theoretical foundations and therapeutic potential of gut microbiota modulation in acute decompensation of LC. Despite the encouraging preliminary data, the majority of the suggested strategies have only been tested in animal models or in preliminary clinical trials;additional multicenter randomized controlled trials must demonstrate their efficacy in larger patient populations.

Compensated liver cirrhosis:Natural course and disease-modifying strategies

Compensated liver cirrhosis(CLC)is defined as cirrhosis with one or more decompensating events,such as ascites,variceal haemorrhage,or hepatic encephalopathy.Patients with CLC are largely asymptomatic with preserved hepatic function.The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors.The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis,as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years.Furthermore,early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition.With the advent of effective non-invasive tools for detecting hepatic fibrosis,more and more patients with CLC are currently being recognised.This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or,at the very least,prevent its progression.There are numerous emerging approaches for preventing or delaying decompensation in CLC patients.A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression,and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension.Additionally,address-ing various cofactors(such as obesity,diabetes,dyslipidaemia,and alcoholism)and precipitating factors(such as infection,viral hepatitis,and hepatotoxic drugs)that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC.However,high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these diseasemodifying techniques for CLC patients.This article discussed the natural history of CLC,risk factors for its progression,and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.

Study of liver cirrhosis over twenty consecutive years in adults in Southern China

BACKGROUND Liver cirrhosis(LC)is a prevalent and severe disease in China.The burden of LC is changing with widespread vaccination of hepatitis B virus(HBV)and antiviral therapy.However,the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear.AIM To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China.METHODS In this retrospective,cross-sectional study we included LC inpatients admitted between January 2001 and December 2020.Medical data indicating etiological diagnosis and LC complications,and demographic,laboratory,and imaging data were collected from our hospital-based dataset.The etiologies of LC were mainly determined according to the discharge diagnosis,and upper gastrointestinal bleeding,ascites,hepatic encephalopathy,spontaneous bacterial peritonitis,hepatocellular carcinoma(HCC),portal vein thrombosis,hepatorenal syndrome,and acute-on-chronic liver failure(ACLF)were considered LC-related complications in our study.Changing trends in the etiologies and clinical characteristics were investigated using logistic regression,and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test.In-hospital prognosis and risk factors associated with in-hospital mortality were also invest igated.RESULTS A total of 33143 patients were included in the study[mean(SD)age,51.7(11.9)years],and 82.2%were males.The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020(P<0.001),and the proportion of female patients increased from 16.7%in 2001-2010 to 18.2%in 2011-2020(P=0.003).LC patients in the decompensated stage at diagnosis decreased from 68.1%in 2001-2010 to 64.6%in 2011-2020(P<0.001),and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0(P<0.001).HBV remained the major etiology of LC(75.0%)and the dominant cause of viral hepatitis-LC(94.5%)during the study period.However,the proportion of HBV-LC decreased from 82.4%in 2001-2005 to 74.2%in 2016-2020,and the proportion of viral hepatitis-LC decreased from 85.2%in 2001-2005 to 78.1%in 2016-2020(both P for trend<0.001).Meanwhile,the proportions of LC caused by alcoholic liver disease,autoimmune hepatitis and mixed etiology increased by 2.5%,0.8%and 4.5%,respectively(all P for trend<0.001).In-hospital mortality was stable at 1.0%in 2011-2020,whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications(35.8%to 41.0%and 5.7%to 12.4%,respectively)and were associated with 6-fold and 4-fold increased risks of mortality(odds ratios:6.03 and 4.22,respectively).CONCLUSION LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China.HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.

A Case of Acute Upper Gastrointestinal Bleeding in Liver Cirrhosis Complicated by Acute Cerebral Infarction and Acute Myelitis

Background: Acute upper gastrointestinal bleeding in liver cirrhosis combined with acute cerebral infarction is uncommon in clinical work, and then combined with acute myelitis is even rarer and more complex, which poses a greater challenge to clinical diagnosis and treatment. This paper reports a case of acute upper gastrointestinal bleeding in liver cirrhosis complicated by acute cerebral infarction and acute myelitis, which be hoped to provide a reference for clinical work. Methods: We retrospectively evaluated the clinical information of a 68-year-old female admitted to the Digestive Medical Department with acute gastrointestinal bleeding and appeared limb movement disorder on the third day. Results: The patient was eventually diagnosed with acute upper gastrointestinal bleeding in liver cirrhosis complicated by acute cerebral infarction and acute myelitis. Conclusions: When patients with liver cirrhosis have abnormal neurological symptoms, in addition to liver cirrhosis-related complications, doctors need to consider cerebrovascular diseases and myelitis.

Evaluation of the nutritional status of patients with liver cirrhosis

BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation of appropriate nutritional treatment for malnourished patients should be an integral part of the therapeutic process.AIM To evaluate the nutritional status of patients with various severities of advanced liver fibrosis,using various nutritional status parameters.METHODS This study involved 118 patients with liver cirrhosis who were classified into three groups according to their Child-Pugh score.The nutritional status of the patients in each group was assessed using different methods.The average values obtained from the measurements were calculated for each research group.The influence of disease stage on the examined parameters of nutritional status was determined using one-way analysis of variance.To investigate the relationship between the parameters determining nutritional status and the stage of disease advancement,a correlation analysis was performed.RESULTS The Child-Pugh A group had the highest mean body weight(76.42 kg),highest mean body mass index(BMI)(26.72 kg/m²),and largest mean arm circumference(27.64 cm).In the Child-Pugh B group,the mean scores of all examined variables were lower than those of the Child-Pugh A group,whereas the mean body weight and BMI of the Child-Pugh C group were higher than those of the Child-Pugh B group.There was a very strong correlation between the Child-Pugh classification and subjective global assessment score;a very strong correlation between the Child-Pugh classification and arm circumference;a strong correlation between the Child-Pugh classification and body weight,albumin concentration,fat-free mass index,muscle mass index,phase angle,and BMI;and an average correlation between Child-Pugh classification and fat mass index.Notably,these indicators deteriorated with disease progression.CONCLUSION Advanced liver fibrosis leads to the deterioration of many nutritional status parameters.The extent of malnutrition increases with the progression of liver fibrosis.The Child-Pugh score reflects the nutritional status.

Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations:A ten-year United States study

BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions.There are currently no large studies assessing and comparing the prevalence of psy-chiatric illnesses based on patient profiles and the etiology of cirrhosis.AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis.METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis.The outcomes included the prevalence,trends,and associations of psychiatric diagnoses in these hospitalizations.Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized.RESULTS The prevalence of generalized anxiety disorder(GAD)in liver cirrhosis hospitalizations increased from 0.17%in 2009 to 0.92%in 2019(P<0.001).The prevalence of depression increased from 7%in 2009 to 12%in 2019(P<0.001).Attention deficit hyperactivity disorder(ADHD)prevalence increased from 0.06%to 0.24%.The prevalence of schizophrenia increased from 0.59%to 0.87%(P<0.001).Schizoaffective disorder prevalence increased from 0.10%to 0.35%(P<0.001).Posttraumatic stress disorder(PTSD)prevalence displayed increasing trends from 0.36%in 2009 to 0.93%in 2019(P<0.001).The prevalence of suicidal ideation increased from 0.23%to 0.56%in 2019.Cirrhosis related to alcoholic liver disease[adjusted odds ratios(aOR)1.18,95%CI 1.08-1.29,P<0.001]and non-alcoholic fatty liver disease(NAFLD)(aOR 1.14,95%CI 1.01-1.28,P=0.025)was associated with depression more than other causes.Alcohol-and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders.Females had a higher association with GAD(aOR 2.56,95%CI 2.14-3.06,P<0.001),depression(aOR 1.78,95%CI 1.71-1.84,P<0.001),bipolar disorder(aOR 1.64,95%CI 1.52-1.77,P<0.001]and chronic fatigue(aOR 2.31,95%CI 1.31-4.07,P<0.001)when compared to males.Blacks,Hispanics,and Asian/Native Americans had a significantly lower association with GAD,depression,bipolar disorder,PTSD,and ADHD when compared to the white race.CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade.Females had a higher association with psychiatric disorders compared to males.Blacks,Hispanics,and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.

Risk Factors of Liver Cirrhosis in Chad: Large Proportion of Cases without Clear Etiology

Background: In comparison to other forms of chronic liver diseases, cirrhosis is generally poorly studied in sub Saharan Africa. In Chad, more particularly, no data are available despite the burden of liver diseases considered as the first cause of hospitalizations in the country. Methods: We conducted a retrospective analysis of 268 patients with liver cirrhosis attending care at the University Reference Hospital between 2007 and 2016. Results: This series of liver cirrhoses was characterized by a weak mal predominance (M:F = 1.7). The age of onset occurs significantly earlier in women than in men (40.6 ± 12.0 vs. 44.4 ± 13.4, p = 0.0171). The principal risk factor was persistent infection with hepatitis B virus (49% of cases) followed distantly by infection with hepatitis C virus (13%) and excessive alcohol consumption (10%). Men were more frequently carrying HBV surface antigen than women (65.6% vs 35.9% p = 0.0019). HBV-associated liver cirrhosis was overall more severe than diseases from other causes. A large proportion of cirrhosis (30%), observed primarily in women (48.1% vs 24.1%, p = 0.0036), was considered are cryptogenic. Conclusions: The etiological spectrum of liver cirrhosis remains to be properly defined in Chad. This lack of knowledge prevents the implementation of an efficient policy of prevention. A significant effort should be secured to characterize hitherto neglected infectious, lifestyle or genetic risk factors responsible of this form of terminal disease and improve subsequently liver health of local populations.

Molecular Mechanism of Zhizi Ganjiang Decoction in Regulating Liver Cirrhosis Based on BATMAN-TCM Platform

[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction in the treatment of liver cirrhosis based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of Zhizi Ganjiang Decoction,and the GeneCards database searched for targets related to liver cirrhosis;Cytoscape 3.5.1 software was used to construct compound-cirrhosis target interaction network and protein interaction network;then gene ontology(GO)enrichment analysis,Reactome pathway enrichment analysis,and KEGG-based biological pathway enrichment analysis were performed.[Results]The compound-disease-target network of Zhizi Ganjiang Decoction was constructed.The PPI network of Zhizi Ganjiang Decoction targets constructed based on String contained 130 nodes and 689 interaction relationships.The key nodes mainly involved nuclear hormone receptor-like domain superfamily and ligand binding domain,serpentine type 7TM GPCR chemoreceptor and chemoreceptor Srx,rhodopsin family transmembrane receptors,zinc finger NHR/GATA type nuclear hormone receptors and ligand binding domains,PI3-kinase family p85 binding domain,phosphoinositide(PI)3-kinase catalytic domain and other categories.GO enrichment analysis pathway related entries mainly involved steroid hormone receptor activity,nuclear receptor activity,transcription factor activity,direct ligands regulation sequence-specific DNA binding,G protein-coupled amine receptor activity,steroid binding,catecholamine binding,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,and oxidoreductase activity,etc.KEGG channel analysis mainly involved neuroactive ligand-receptor interaction,aldosterone regulates sodium reabsorption,regulates lipolysis in adipocytes,regulates inflammatory mediators of TRP channels,tyrosine metabolism,calcium signaling pathway,cAMP signaling pathway,and nonalcoholic fatty liver diseases.[Conclusions]The research results suggest that Zhizi Ganjiang Decoction regulates the process of liver cirrhosis mainly through aldosterone regulation of sodium reabsorption,regulation of lipolysis in adipocytes,regulation of inflammatory mediators of TRP channels,calcium signaling pathways,and nonalcoholic fatty liver diseases.This reflects the multi-target and holistic action characteristics of the Chinese herbal compounds,and is expected to provide new ideas for further research on the molecular mechanism of Zhizi Ganjiang Decoction.