Liver Cirrhosis Patients Research Articles

Non-invasive candidate proteinsignature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response.

A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

Baseline characteristics, grading and mortality in acute on chronic liver failure using CLF-C ACLF CRITERIA.

Objective: To observe baseline characteristics, ACLF (Acute on Chronic Liver Failure) grading and mortality in ACLF patients using EASL CLIF CRITERIA. Study Design: Prospective, Observational study. Setting: Medical unit 111, ward 7, Jinnah Postgraduate Medical Centre, Karachi. Period: January 2022 to June 2022. Material &amp; Methods: We prospectively analysed data of hospitalised liver cirrhosis patients at a tertiary care hospital in Karachi, Pakistan. The data was analysed in SPSS version 25. Results: There were a total of 43 ACLF patients, with the median age of IQR of 56(47-62) years, out of which 20 (46.5%) patients were male and 23 (53.5%) were females. The most common etiology of liver cirrhosis was hepatitis C 26(60.5%) followed by other etiologies nine (20.9%) and hepatitis B eight (18.6%). The most common precipitating factor was infection 19(44.2%) and the most frequent organ failure (OF) was renal failure (60.5%), followed by cerebral failure (46.5%) and other OFs. There were 24 patients in ACLF grade one, 13 in grade two and six in grade three ACLF. All six patients of ACLF grade three belonged to CTP C (Child-turcotte-pugh Cirrhosn) (100%) with 100% mortality. ACLF grade two had nine (69.2%) and ACLF grade one had eight (33.33%) CTP C patients. The in hospital mortality of ACLF was 23%. The median MELD Na of these patients was 28 (23-31), CLIF Consortium Organ Failure score was 9(8-10) and CLIF C ACLF Score was 45 (38-55). Conclusion: Highest mortality was observed in Child Pugh C and ACLF grade three in our patients. Such patients must be closely monitored and referred early for medical management and liver transplantation.

Depression and Anxiety Symptoms in Patients With Cirrhosis: A Prospective Study Before and After Liver Transplantation

Timely identification of possible psychiatric symptoms and/or disorders, such as depression and anxiety, in liver cirrhosis and liver transplant patients is important. This study aimed to determine whether patients with both liver cirrhosis and liver transplantation have depression and anxiety symptoms and, if so, to determine the relationship of these symptoms with the stage of the liver disease and other conditions. Ninety patients with liver cirrhosis and 31 who underwent liver transplantation for liver cirrhosis were included in the study. Patients were divided into 4 groups. Patients with Child-Pugh A cirrhosis were group 1, patients with Child-Pugh B cirrhosis were group 2, patients with Child-Pugh C cirrhosis were group 3, and transplanted patients were group 4. All patient groups answered Beck Depression Inventory and Beck Anxiety Inventory questionnaires. Depression and anxiety scores were similar in patients who underwent liver transplantation and in the Child-Pugh A and Child-Pugh B groups. The lowest depression score was observed in the Child-Pugh A group. This was not statistically different from the patients in the liver transplantation group (3.19 ± 3.487, 7.13 ± 7.822, P > .05). Depression and anxiety scores were statistically higher in the Child-Pugh C group (25.55 ± 8.878, 21.66 ± 11.053, and 25.55 ± 8.878, respectively; P < .001), and depression and anxiety scores increased as the cirrhosis stage increased. In patients with Child-Pugh C liver cirrhosis, evaluation for symptoms of anxiety and depression is strongly recommended.

Bone Marrow Assessment in Liver Cirrhosis Patients with Otherwise Unexplained Peripheral Blood Cytopenia

We performed a retrospective single-center analysis to investigate the diagnostic yield of bone marrow puncture in patients with liver cirrhosis and cytopenia. Liver cirrhosis patients receiving bone marrow aspiration or biopsy for the diagnostic work-up of otherwise unexplained peripheral blood cytopenia at our institution between 2004 and 2020 were enrolled in this study. We evaluated findings from cytologic, histologic and immunologic assessment and final diagnostic outcomes. A total of 118 patients with a median age of 55 years and a median Child–Pugh score of B (8 points) were enrolled. The main etiologies of liver cirrhosis were viral hepatitis (B and C) or chronic alcohol consumption. The majority of patients (60%) exhibited concurrent anemia, leukocytopenia and thrombocytopenia. Bone marrow assessment revealed normal, unspecific or reactive alterations in 117 out of 118 patients (99%). One patient was diagnosed with myelodysplastic syndrome. Our findings suggest that peripheral blood cytopenia in patients with liver cirrhosis is rarely associated with a primary bone marrow pathology.

Accuracy of leukocyte esterase reagent strip test and platelet indices for early diagnosis of ascitic fluid infection in liver cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) is one of the serious complexities in patients with cirrhosis and ascites. 30-50% of death may occur if it not treated properly. The leucocyte esterase reagent (LER) strip test is a special apparatus for prior detection of neutrophils in the ascetic fluid. The aim of the study was to investigate the diagnostic accuracy of the LER strip test and platelet indices in the early detection of SBP in cirrhotic patients. Methods: This cross-sectional study was carried out in the department of gastrointestinal hepatobiliary and pancreatic disorders (GHPD), BIRDEM, Dhaka, Bangladesh, from January 2018 to October 2019. A total of 110 indoor patients of liver cirrhosis with ascites were enrolled after fulfilment of the inclusion and exclusion criteria with adequate history taking and clinical examination. Results: Out of 110 cases, 68 were male and 42 were female, and among them 23 (20.9%) patients had SBP. LER strip test at grade 4 set as a cut-off value which showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy was 91.3%, 90.8%, 70%, 97.5%, and 90% respectively. Mean platelet volume (MPV) and platelet distribution width (PDW) were done by complete blood count, where the MPV cut-off value set as 12.5 fl showed sensitivity, specificity, PPV, NPV, and accuracy were 82.6%, 90.8%, 66%, 96.25%, and 88.18% respectively. PDW cut-off value set on 18.10% revealed sensitivity, specificity, PPV, NPV, accuracy was 82.6%, 83.9%, 50%, 95.71% and 79% respectively. ROC curve was plotted to set the cut-off value by examining sensitivity and specificity. Results were considered statistically significant at p&lt;0.05. Conclusions: This study was undertaken to detect LER strip tests that showed significant results in bedside diagnosis of SBP. Apart from this, a significant increase in MPV and PDW was observed in SBP. So, LER strip tests and platelet indices measurement can be economical and reliable appliances for early diagnosis of SBP.

Serum myostatin and irisin as predictive biomarkers of sarcopenia, malnutrition and mortality in patients with decompensated liver cirrhosis

Malnutrition and sarcopenia are nowadays considered the main complications of liver cirrhosis (LC). Myokines are signal peptides synthesized in muscles that regulate muscle strength and mass and mediate crosstalk between skeletal muscles and other organs. It is unknown whether circulating myokines can be used as biomarkers of malnutrition and sarcopenia and have independent prognostic value in LC. The purpose of the study was to assess the relationship of serum levels of myokines myostatin and irisin with nutritional status, skeletal muscle status, and survival in decompensated LC patients. 74 patients (55.30±11.40 years) were involved in the prospective study. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment, and skeletal muscle mass was assessed using the Skeletal Muscle Index. The concentration of serum myostatin and irisin was determined by enzyme immunoassay. Statistical data processing was performed in SPSS22 (© SPSS Inc.). It was established that the concentration of serum myostatin and irisin is not related to the LC severity according to the Child-Turcotte-Pugh, Model For End-Stage Liver Disease, and the grade of ascites. Patients with overt encephalopathy have higher myostatin levels. Patients with severe hypoalbuminemia have higher serum myostatin and lower serum irisin levels. The development of malnutrition and sarcopenia in decompensated LC patients is associated with increased serum myostatin concentration and decreased serum irisin concentration. Serum myostatin level can predict sarcopenia (AUC 0.834 in males and 0.827 in females, p&lt;0.01). Serum irisin level can predict severe malnutrition (AUC 0.830, p&lt;0.001). The mortality of patients with high myostatin levels (above 5.25 ng/ml in males and 3.55 ng/ml in females) and low irisin levels (less than 1.72 ng/ml) is significantly higher. In conclusion, the circulating myokines levels may be useful in the assessment of nutritional and skeletal muscle status, and prediction of mortality in LC patients.

The Correlation between Nutritional Status and Clinical Outcome of Liver Sirosis Patients at RSUD Dr. Saiful Anwar Malang

Introduction: Nutritional status is often associated with mortality and disease morbidity, including liver cirrhosis. Assessment of Tricep Skin Fold (TSF) and mid-arm muscle circumference (MAMC) is an easy parameter of nutritional status.&#x0D; Objective: This study aims to determine the relationship between nutritional status and clinical outcomes in patients with liver cirrhosis.&#x0D; Methods: The study used a retrospective cohort observational design with a sample of 57 patients with liver cirrhosis with various etiologies. The data comes from the results of anthropometric measurements of patients in the poly or inpatient ward and interviews regarding the history of the disease and complications experienced during the last month. Data analysis used the Chi-square test with a 95% Confidence Interval (CI), p &lt; 0.05, to analyze the relationship between nutritional status (TSF and MAMC) with clinical outcomes of liver cirrhosis (hematemesis melena, degree of esophageal varices grade Hepatic encephalopathy (HE) and degree of ascites).&#x0D; Results: Based on the TSF and MAMC values, data on cirrhotic patients who experienced nutritional status with the “low” criteria were 33.3% and 57.89%, respectively. The 'low” TSF value significantly correlates with the HE incidence (p = 0.049) with the RR value of 0.461. The relationship between MAMC and the incidence of ascites was statistically significant (0.004), with an RR value of 0.462.&#x0D; Conclusion: Nutritional status affects the incidence of HE and ascites in liver cirrhosis patients

A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

#4901 THE EFFECT OF CHRONIC KIDNEY DISEASE IN CONTRAST-ENHANCED ULTRASONOGRAPHY WITH ARRIVAL TIME PARAMETRIC IMAGING

Abstract Background and Aims CEUS is a reliable method to diagnose ischemic renal pathologies such as infarction, identify renal abscesses, discriminate between renal tumors and anatomical variants, describe complex cyst lesions, and monitor non-surgical renal lesions. Few studies explore the relationship between CEUS and the diagnosis or progression of CKD. The aim of this study was to evaluate the relationship between contrast-enhanced ultrasonography with arrival time parametric imaging (CEUS-PAT) and CKD. Method We prospectively evaluated 64 subjects (37 liver cirrhosis patients and 27 healthy volunteers) using CEUS-PAT to detect if the presence of CKD influences the arrival time of the contrast in the kidney. CKD was defined according to KDIGO 2021 guidelines. Ultrasonography was performed using the LOGIQ E9 (GE Healthcare, Chalfont St.Giles-UK) system, probe C1-6. CEUS was performed on each subject using SonoVue (Bracco SpA, Milan, Italy) as a contrast agent (1/2 of a vial). A 2.5 mL contrast substance followed by a 5 mL normal saline solution was infused in the cubital vein. A ratio between the arrival time of the substance in the kidney and liver was calculated. Subjects were in fasting conditions for at least 12 h. Laboratory data were extracted from the patient's GP file. The study was conducted between January -December 2018. All patients provided their informed consent for the procedures. Results The study included 64 subjects, mean age of 58.98 ± 8.90 years, predominantly male gender (56.3%). Of the 64 patients, 13 (20.3%) had chronic kidney disease. All patients with chronic kidney disease had liver cirrhosis. When comparing the two groups, with and without CKD, there was a significant difference between the ratio of the arrival time of the contrast agent into the kidney and liver, 0.85 ± 0.09 vs 0.65 ± 0.19, p = 0.0005. The factors associated with kidney disease were liver steatosis (p&amp;lt;0.0001), age over 60 years (p = 0.01) and low albumin (p&amp;lt;0.0001). Conclusion Our study indicated that the presence of CKD influences the contrast agent arrival time in the kidney. Further studies are needed to establish the predictive significance of CEUS-PAT data in CKD patients.

Mammalian cleavage factor 25 targets KLF14 to inhibit hepatic stellate cell activation and liver fibrosis

Liver fibrosis is primarily caused by the activation of hepatic stellate cells (HSCs), which results from chronic liver damage. Understanding the pathogenesis of HSC activation could identify new therapeutic targets to treat liver fibrosis. In this study, we examined the protective role of the mammalian cleavage factor I 25 kD subunit (CFIm25, NUDT21) in inhibiting hepatic stellate cell activation. CFIm25 expression was measured in liver cirrhosis patients and a CCl4-induced mouse model. Adeno-associated viruses and adenoviruses were used to alter hepatic CFIm25 expression in vivo and in vitro to investigate how CFIm25 functions in liver fibrosis. The underlying mechanisms were explored using RNA-seq and co-IP assays. Here, we found that CFIm25 expression was drastically decreased in activated murine HSCs and fibrotic liver tissues. CFIm25 overexpression downregulated the expression of genes involved in liver fibrosis, inhibiting the progression of HSC activation, migration and proliferation. These effects resulted from direct activation of the KLF14/PPARγ signaling axis. KLF14 inhibition abrogated the CFIm25 overexpression-mediated reduction in antifibrotic effects. These data reveal that hepatic CFIm25 regulates HSC activation through the KLF14/PPARγ pathway as liver fibrosis progresses. CFIm25 may be a novel therapeutic target for liver fibrosis.

Scoring system for predicting 90-day mortality of in-hospital liver cirrhosis patients at Cipto Mangunkusumo Hospital

BackgroundLiver cirrhosis is the final stage of chronic liver disease. Complications due to progression of liver disease may deteriorate the liver function and worsen prognosis. Previous studies have shown that patients with liver cirrhosis are at increased risk of death within 90-day after hospitalization. It is necessary to identify patients who are at higher risk of early mortality. This study aims to develop a scoring system to predict the 90-day mortality among hospitalized patients with liver cirrhosis that could be used for modification of treatment plan according to the scores that have been obtained. By using this scoring system, crucial care of plans can be taken to reduce the risk of mortality.MethodThis prospective cohort study was conducted on hospitalized cirrhotic patients at Cipto Mangunkusumo National General Hospital, Jakarta. Demographic, clinical, and laboratory data were recorded. Patients were monitored for up to 90-day after hospitalization to determine their condition. Cox regression analysis was performed to obtain predictor factors contributing to mortality in liver cirrhosis patients. The scoring system that resulted from this study categorized patients into low, moderate, and high-risk categories based on their predicted mortality rates. The sensitivity and specificity of the scoring system were evaluated using the AUC (area under the curve) metric.ResultThe study revealed that liver cirrhosis patients who were hospitalized had a 90-day mortality rate of 42.2%, with contributing factors including Child-Pugh, MELD, and leukocyte levels. The combination of these variables had a good discriminative value with an AUC of 0.921 (95% CI: 0.876–0.967). The scoring system resulted in three risk categories: low risk (score of 0–3) with a 4.1-18.4% probability of death, moderate risk (score of 5–6) with a 40.5-54.2% probability of death, and high risk (score of 8–11) with a 78.1-94.9% probability of death.ConclusionThe scoring system has shown great accuracy in predicting 90-day mortality in hospitalized cirrhosis patients, making it a valuable tool for identifying the necessary care and interventions needed for these patients upon admission.

The impact of high body mass index on hepatocellular carcinoma in viral hepatitis and cirrhosis.

10537 Background: The impact of a high body mass index (BMI) on hepatocellular carcinoma (HCC) has been unclear in patients with viral hepatitis and liver cirrhosis (LC). Our aim is to investigate the association between BMI and HCC in patients with viral hepatitis and LC. Methods: We conducted a population-based cohort study. In total, 156,143 Korean adults who underwent routine health examinations during 2003-2006 were followed up until December 2019 via linkage to the national hospital discharge records. Multivariable-adjusted hazard ratios (HRs) per each 5 kg/m2 increase in BMI for HCC risk were calculated using Cox proportional hazard models. Results: BMI was positively associated with HCC in hepatitis B virus (HBV) patients with BMI range of 27.5~29.9 kg/m² and BMI ≥30 kg/m² and LC patients with a BMI range of 27.5~29.9 kg/m². Assuming linear associations, HRs were 1.17 for HBV, 1.08 for hepatitis C virus (HCV), and 1.11 for LC. In the subgroup analysis for the LC, the HR were 1.19 in the HBV-LC, 1.38 in the HCV-LC, 1.36 in the alcoholic LC, and 1.59 in the fatty liver LC. Women showed stronger positive associations between BMI and HCC than men in the HBV (HR, 1.45 vs 1.06) and LC (1.27 vs. 1.02). The positive association seemed to be stronger in younger age ( &lt; 65 years) in HBV (1.17 vs 1.05) and HCV (1.33 vs 0.77) patients compared to older age ( &gt; 65 years). Conclusions: In the BMI range of ≥25 kg/m2, a higher BMI was associated with an increased risk of HCC in LC and HBV. The associations between BMI and HCC risk are different according to liver disease, sex and age.

THU-351 - Single-cell RNA transcriptomics of peripheral blood mononuclear cells revealed altered gene expressions in monocyte and HLA variations in decompensated liver cirrhosis patients with sepsis

THU-351 - Single-cell RNA transcriptomics of peripheral blood mononuclear cells revealed altered gene expressions in monocyte and HLA variations in decompensated liver cirrhosis patients with sepsis

Prediction of acute kidney injury in patients with liver cirrhosis using machine learning models: evidence from the MIMIC-III and MIMIC-IV.

To develop and validate a machine learning (ML)-based prediction model for acute kidney injury (AKI) in patients with liver cirrhosis. Data on liver cirrhosis patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases in this retrospective cohort study. ML algorithms, including random forest (RF), extreme gradient boosting (XGB), light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) were applied to construct prediction models. Predictors were screened via univariate logistic regression, and then the models were developed with all data of the included patients. A bootstrap resampling method was adopted to validate the models. The predictive abilities of our final model were compared with those of the sequential organ failure assessment score (SOFA), simplified acute physiology score II (SAPS II), Model for End-stage Liver Disease (MELD), and MELD Na. This study included 950 patients, of which 429 (45.16%) had AKI. Mechanical ventilation, vasopressor, international normalized ratio (INR), bilirubin, Charlson comorbidity index (CCI), prothrombin time (PT), estimated glomerular filtration rate (EGFR), partial thromboplastin time (PTT), and heart rate served as predictors. In the derivation set, the developed RF [area under curve (AUC) = 0.747], XGB (AUC = 0.832), LGBM (AUC = 0.785), and GBDT (AUC = 0.811) models exhibited significantly greater predictive performance than the logistic regression model (AUC = 0.699) (all P < 0.05). Among the ML-based models, the XGB model had the greatest AUC. In internal validation, the predictive capacity of the XGB model (AUC = 0.833) was significantly superior to that of the logistic regression model (AUC = 0.701) (P = 0.045). Hence, the XGB model was selected as the final model for AKI prediction. In contrast to the XGB model (AUC = 0.832), the SOFA (AUC = 0.609), MELD (AUC = 0.690), MELD Na (AUC = 0.690), and SAPS II (AUC = 0.641) had significantly lower predictive abilities in the derivation set (all P < 0.001). The XGB model was internally validated to have an AUC of 0.833, which was significantly higher than the SOFA (AUC = 0.609), MELD (AUC = 0.690), MELD Na (AUC = 0.688), and SAPS II (AUC = 0.641) (all P < 0.05). The XGB model had a better performance than the logistic regression model, SOFA, MELD, MELD Na, and SAPS II in AKI prediction for cirrhosis patients, which may help identify patients at a risk of AKI, and then provide timely interventions.

Podoplanin-positive dilated lymphatic vessels in duodenum associates with three-month mortality in patients with cirrhosis.

Dilated and dysfunctional gut lymphatic vessels (LVs) have been reported in experimental cirrhosis. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV marker, podoplanin (PDPN), in predicting the mortality of patients with cirrhosis. A prospective, single-center cohort study was performed in liver cirrhosis patients (n = 31) and matched healthy controls (n = 9). D2-biopsies were obtained during endoscopy procedure, immunostained with PDPN, and scored based on 1) intensity and 2) density of positively-stained LVs per high power field. Gut and systemic inflammation were estimated by quantifying duodenal CD3+ intraepithelial lymphocytes (IELs), CD68+ macrophages, and serum TNF-α and IL-6 levels, respectively. Gut permeability and inflammation as assessed by quantifying gene expression of TJP1, OCLN, TNF-α, and IL-6 in D2-biopsies. Gene expression of LV markers, PDPN (8-fold), and LYVE1 (3-fold) was enhanced in D2-biopsies of cirrhosis patients compared to control (p < 0.0001). The mean PDPN score in decompensated cirrhosis patients (6.91 ± 1.26, p < 0.0001) was significantly increased as compared to those with compensated (3.25 ± 1.60). PDPN score positively and significantly correlated with the number of IELs (r = 0.33), serum TNF-α (r = 0.35), and IL-6 (r = 0.48) levels, while inversely correlated with TJP1 expression (r = -0.46, p < 0.05 each). In Cox regression, the PDPN score was a significant and independent 3-month-mortality predictor in patients (HR: 5.61; 1.08-29.109; p = 0.04). The area under the curve for the PDPN score was 84.2, and cutoff value for predicting mortality was ≥6.5 with 100% sensitivity and 75% specificity. Collectively, dilated LVs with high PDPN expression in D2-biopsies is a characteristic feature of patients with decompensated cirrhosis. PDPN score correlates with enhanced gut and systemic inflammation and also associates with 3-month mortality in cirrhosis.

Walking exercise through smartphone application plus branched-chain amino acid supplementation benefits skeletal muscle mass and strength in liver cirrhosis: A prospective control trial.

Whether a combination of exercise and branched-chain amino acid (BCAA) supplementation was more beneficial than those given alone in sarcopenia related to liver cirrhosis (LC) is unknown. Widely used smartphone applications provide continuous and easily expandable management of chronic liver disease (CLD). This study is to investigate the effects of unsupervised walking exercise using WeChat combined with BCAA supplementation on skeletal muscle mass and strength in LC. The 127 LC patients of Child-Pugh A/B were assigned to group A (BCAA supplements, n=42), group B (walking exercise, n=43) and group C (walking exercise plus BCAA supplements, n=42). Laboratory data, average daily steps, serum BCAA, skeletal muscle mass index (SMI) and grip strength were analyzed pre- and 3 months after interventions. Of the 124 patients who completed interventions, albumin and daily steps were significantly increased in all groups (p=0.0001). Post-intervention BCAA were significantly elevated in group A (A vs B, p=0.001) and C (C vs B, p=0.012;). While post-intervention daily steps in group B (B vs A, p=0.0001) and C (C vs A, p=0.0001) were higher. Grip strength (C vs A, p=0.020; C vs B, p=0.036) and SMI (C vs A, p=0.035; C vs B, p=0.012) were increased in group C. Prevalence of sarcopenia was significantly decreased in group C (p=0.015). A combination of unsupervised walking exercise using smartphone applications and BCAA supplementation might be an effective and safe treatment for cirrhosis patients with Child-Pugh A/B to improve skeletal muscle mass and strength or to prevent progress of sarcopenia.

Model for End Stage Liver Disease (MELD) Score: A Tool for Prognosis and Prediction of Mortality in Patients With Decompensated Liver Cirrhosis.

Decompensated liver disease has become a common occurrence inmedical wards. It has become the third most common cause of death in medical wards. This high mortality rate has become a matter of concern. It is important that a reliable scoring system helps to stratify patients with liver cirrhosis who will require liver transplantation. To determine the value of the Model for End-Stage Liver Disease (MELD) score in assessing the mortality of patients with decompensated liver cirrhosis over one month period (30 days). A longitudinal study was conducted. A total of 110 patients diagnosed with decompensated liver cirrhosis wererecruited from the gastroenterology clinic and medical wards of the University of Benin Teaching Hospital (UBTH), Benin City. The patients were recruited consecutively and met the inclusion criteria for the study. Demographic data, history, clinical, biochemical, ultrasonographic, and liver biopsy findings were evaluated in the patients who participated in this study. Results: The mean age of the patients was 57 ± 11.06 years. Out of the 110 study participants, a 2.9:1 male-to-female ratio was appreciated in the patient population, with a total of 82 males and 28 females. Multiple logistic regression analysis identified MELD scores as an independent predictorof mortality in the studied patients. Predictive values of the MELD score for 1-month mortality which was analyzed using the receiver operating characteristic (ROC) curves showed that the MELD score had a sensitivity of 72.2% and positive predictive value of 93.6% with an area under the curve of 0.926 for all-cause mortality among decompensated liver cirrhosis patients. MELD score is a good predictor of mortality among patients with decompensated liver cirrhosis over a 1-month (30 days) period.

In-Depth Serum Proteomics Reveals the Trajectory of Hallmarks of Cancer in Hepatitis B Virus–Related Liver Diseases

Hepatocellular carcinoma (HCC) is a prevalent cancer in China, with chronic hepatitis B (CHB) and liver cirrhosis (LC) being high-risk factors for developing HCC. Here, we determined the serum proteomes (762 proteins) of 125 healthy controls and Hepatitis B virus–infected CHB, LC, and HCC patients and constructed the first cancerous trajectory of liver diseases. The results not only reveal that the majority of altered biological processes were involved in the hallmarks of cancer (inflammation, metastasis, metabolism, vasculature, and coagulation) but also identify potential therapeutic targets in cancerous pathways (i.e., IL17 signaling pathway). Notably, the biomarker panels for detecting HCC in CHB and LC high-risk populations were further developed using machine learning in two cohorts comprised of 200 samples (discovery cohort = 125 and validation cohort = 75). The protein signatures significantly improved the area under the receiver operating characteristic curve of HCC (CHB discovery and validation cohort = 0.953 and 0.891, respectively; LC discovery and validation cohort = 0.966 and 0.818, respectively) compared to using the traditional biomarker, alpha-fetoprotein, alone. Finally, selected biomarkers were validated with parallel reaction monitoring mass spectrometry in an additional cohort (n = 120). Altogether, our results provide fundamental insights into the continuous changes of cancer biology processes in liver diseases and identify candidate protein targets for early detection and intervention.

Impact of Liver Cirrhosis on the Occurrence of Diabetes Mellitus and Glucose Intolerance among Liver Cirrhosis Patients in European Gaza Hospital: A Retroactive Study

Background: Third of liver cirrhosis patients have diabetes mellitus. In addition, most of patients with cirrhosis may be glucose intolerant. This study aimed to shed light on the impact of liver cirrhosis on the occurrence of diabetes mellitus among liver cirrhosis patients. Materials and Methods: This study is a retrospective analytical study design. The study was a descriptive study. The study was conducted at the gastroenterology outpatient clinic in European Gaza Hospital. Data were collected retrospectively from patients records and from patients themselves when attending at the clinic. The study was conducted during the period from September 2022 to February 2023. The study tool is a self-designed questionnaire based on most recent published literature. The questionnaire included basic information about the patients, data related to liver cirrhosis and some laboratory work done for the patients. Results: A total of 70 patients were included in the study, with more than half being male (60%). The mean age of participants was 61.97 ± 11.54 years. The most frequent cause of liver cirrhosis among participants was cryptogenic (54.3%), and two-thirds of the participants had comorbid conditions besides liver cirrhosis, with diabetes mellitus being the most frequent (54.3%). The majority of participants were overweight or obese, with a mean body mass index of 31.15 kg/m2. Ultrasound imaging showed that most participants had severe steatosis (88.6%) and a shrunken liver (72.9%). The laboratory findings showed raised mean alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, with high levels of triglycerides and cholesterol. Conclusion: Most participants were overweight or obese. More than half of the participants had comorbidities, including diabetes mellitus, and cryptogenic liver cirrhosis was the most prevalent etiology. Most liver ultrasounds indicated significant steatosis. Participants had increased alanine transaminase, aspartate aminotransferase, triglycerides, and total bilirubin.

Study of 43 SLE patients with autoimmune liver cirrhosis: emphasis on clinical features and differences from lupus without cirrhosis.

To investigate the clinical characteristics of systemic lupus erythematosus accompanied by autoimmune liver cirrhosis (SLE-ALC) patients and differences from the non-cirrhosis group. Forty-three patients with SLE-ALC were enrolled in this study from 2653 patients with SLE in Peking University People's Hospital. A descriptive case-control study was performed between SLE-ALC patients and the entry time-matched non-cirrhosis group. Among the 43 SLE-ALC patients, 41 (95.3%) were female. Eight patients (18.6%) were first found to have cirrhosis and then diagnosed with SLE. Eighteen patients (41.9%) had jaundice and 27 (62.8%) had esophageal and gastric varices. The age of SLE-ALC patients was 51.1 ± 17.2 years, which was significantly older than the non-cirrhosis group (P < 0.001). Lung involvement was more common as initial manifestations in SLE-ALC patients during the SLE course (P=0.027). Compared with the non-cirrhosis group, SLE-ALC patients had worse liver function. A significantly higher rate of hematological system involvement (anemia, leucopenia, and thrombocytopenia) and a higher level of immunoglobulins were observed in SLE-ALC patients (P<0.05). Moreover, SLE-ALC patients displayed a lower positive rate of anti-double-stranded DNA and anti-ribosomal P protein (P<0.05). The most common radiologic manifestations are ascitic fluid (72.1%) and splenomegaly (71.4%) in SLE-ALC patients. Six SLE-ALC patients underwent liver biopsy, and interface hepatitis was present in all patients. Cirrhosis is rare in SLE patients but is manifested as a unique pattern of clinical features characterized by late-onset age, lung involvement, high immunoglobulins, and impaired liver function.