Liver Cirrhosis Patients Research Articles

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

Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate. To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis. 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. 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. The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.

Metabolomic Analysis of Human Cirrhosis and Hepatocellular Carcinoma: A Pilot Study

BackgroundMolecular changes in HCC development are largely unknown. As the liver plays a fundamental role in the body’s metabolism, metabolic changes are to be expected.AimsWe aimed to identify metabolomic changes in HCC in comparison to liver cirrhosis (LC) patients, which could potentially serve as novel biomarkers for HCC diagnosis and prognosis.MethodsMetabolite expression from 38 HCC from the SORAMIC trial and 32 LC patients were analyzed by mass spectrometry. Metabolites with significant differences between LC and HCC at baseline were analyzed regarding expression over follow-up. In addition, association with overall survival was tested using univariate Cox proportional-hazard analysis.Results41 metabolites showed differential expression between LC and HCC patients. 14 metabolites demonstrated significant changes in HCC patients during follow-up. Campesterol, lysophosphatidylcholine, octadecenoic and octadecadienoic acid, and furoylglycine showed a differential expression in the local ablation vs. palliative care group. High expression of eight metabolites (octadecenoic acid, 2-hydroxybutyrate, myo-inositol, isocitrate, erythronic acid, creatinine, pseudouridine, and erythrol) were associated with poor overall survival. The association between poor OS and octadecenoic acid and creatinine remained statistically significant even after adjusting for tumor burden and LC severity.ConclusionOur findings give promising insides into the metabolic changes during HCC carcinogenesis and provide candidate biomarkers for future studies. Campesterol and furoylglycine in particular were identified as possible biomarkers for HCC progression. Moreover, eight metabolites were detected as predictors for poor overall survival.Graphical

Elevated serum HE4 levels as a novel biomarker of disease severity and hepatic fibrosis in autoimmune hepatitis

BackgroundHuman epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH). MethodsSerum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th–75th percentile). ResultsSerum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15–139.08) vs 73.50 (59.88–82.00) vs 48.75 (43.38–52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child–Pugh class C patients compared with Child–Pugh class B patients and Child–Pugh class A patients [106.50 (83.46–151.25) vs 110.00 (73.83–166.75) vs 77.03 (72.35–83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412–54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146–0.946). ConclusionsSerum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.

Accelerated biological aging mediated associations of ammonium, sulfate in fine particulate matter with liver cirrhosis

BackgroundAlthough both air pollution and aging are related to the development of liver cirrhosis, the role of biological aging in association of the mixture of fine particulate matter (PM2.5) and its constituents with liver cirrhosis was unknown. MethodsThis case-control retrospective study included 100 liver cirrhosis patients and 100 control subjects matched by age and sex. The concentrations of PM2.5 and its constituents were estimated for patients using machine-learning methods. The clinical biomarkers were used to calculate biological age using the Klemera−Doubalmethod (KDM) algorithms. Individual associations of PM2.5 and its constituents or biological age with liver cirrhosis were analyzed by generalized linear models. WQS and BKMR were applied to analyze association of mixture of PM2.5 and its constituents with liver cirrhosis. The mediation effect of biological age on associations of PM2.5 and its constituents with liver cirrhosis was further explored. Resultswe found that each 1-unit increment in NH4+, NO3−, SO42− and biological age were related to 3.618-fold (95%CI: 1.896, 6.904), 1.880-fold (95%CI: 1.319, 2.680), 2.955-fold (95%CI: 1.656, 5.272) and 1.244-fold (95%CI: 1.093, 1.414) increased liver cirrhosis. Both WQS and BKMR models showed that the mixture of PM2.5 and its constituents was related to increased liver cirrhosis. Furthermore, the mediated proportion of biological age on associations of NH4+ and SO42− with liver cirrhosis were 14.7 % and 14.6 %, respectively. ConclusionsBiological aging may partly explain the exposure to PM2.5 and its constituents in association with increased risk for liver cirrhosis, implying that delaying the aging process may be a key step for preventing PM2.5-related liver cirrhosis risk.

Isolation of mucosa-associated microbiota dysbiosis in the ascending colon in hepatitis C virus post-sustained virologic response cirrhotic patients.

Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. In the post-SVR group, the microbial β-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.

Non-invasive predictors to grade esophageal varices in liver cirrhosis patients.

Portal hypertension commonly occurs due to liver cirrhosis, and esophageal varices (EV) is one of the major complications associated with it. The most common cause of death in liver cirrhosis is EV bleeding. Hence, GE screening for EV is required, which is an invasive procedure. Regular use of endoscopy results in low compliance due to cost and discomfort for patients. Hence, identifying non-invasive markers that could grade EV provides a useful screening tool for family physicians and primary health centers (PHCs) by referring the patient to higher centers for definitive treatment, which could reduce mortality due to variceal bleeding in cirrhotic patients. To assess non-invasive predictors of grade EV in patients diagnosed with liver cirrhosis. Cross-sectional study. A total of 109 patients with liver cirrhosis underwent clinical and biochemical evaluation, USG abdomen with spleen bipolar diameter, ascitic fluid analysis, and upper GE with a grade of EV are recorded. SPSS software with Student t-test, Chi-square t-test, analysis of variance, receiver operator characteristic (ROC) curves, and Spearman correlation with 95% CI is used. P <0.05 is considered significant. Aminotransferase to Platelet count Ratio Index (APRI) score >1.815, PC/SD ≤909, and SAAG >1.1g/dl showed EV in liver cirrhosis (P < 0.05). The order of prediction with ROC curves shows APRI score > PC/SD > SAAG. In grading EV, APRI scores of 1.9-2.5 and >2.5 showed small and large EV, respectively (P < 0.05). APRI score may be used in PHC as an early intervention to grade EV and refer the patient to higher centers for definitive treatment. This would prevent the progression of varices to rupture and reduce mortality due to variceal bleeds in liver cirrhosis patients.

Echocardiographic Assessment of Right Ventricular Function in Patients With Liver Cirrhosis.

In patients with chronic liver disease, the common endpoint of its course is liver cirrhosis which is a cause of cardiovascular morbidity and mortality. These abnormalities in the cardiovascular system, especially the heart, can be detected by echocardiography. Identifying and acting on these abnormalities can have an impact on their management thereby reducing morbidity and mortality of patients with liver cirrhosis. The aim of this study was to determine the prevalence of right ventricular systolic and diastolic dysfunction in liver cirrhosis patients. A hospital-based cross-sectional study was conducted among adult patients of the gastroenterology unit (ward and clinic) diagnosed with liver cirrhosis. A total of 243 patients were recruited and 210 were evaluated for this study. This study was carried out over one year. Cardiology studies, including electrocardiography and echocardiography, were conducted on patients to assess right ventricular function. Among the participants, 44.8% had right ventricular hypertrophy and 3.8% had right ventricular dilatation. Using Tricuspid Annular Plane Systolic Excursion (TAPSE), 17.1% were found to have right ventricular systolic dysfunction and 51.4% had systolic dysfunction using FAC. Diastolic dysfunction was found in 61% of the participants and grade 2 diastolic dysfunction was the commonest. From this study, a high prevalence of right ventricular systolic and diastolic dysfunction was recorded among patients with liver cirrhosis.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

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.

Serum microRNA-16 as a potential biomarker for HCV-induced hepato-cellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80–90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.

Prevalence of Pulmonary Hypertension in Liver Cirrhosis Patients: A Cross-Sectional Analytical Study.

Liver cirrhosis (LC) is a common complication of chronic liver disease. Its prevalence has increased markedly over the last few years. With liver cirrhosis comes cardiovascular morbidity and mortality. It is important that the detection of the abnormalities by echocardiography be given priority, as this can change the clinical outcome of these patients with cardiovascular abnormalities in liver cirrhosis. This study aims to determine the prevalence of pulmonary hypertension in LC patients. A cross-sectional analytical study was carried out at JUTH (Jos University Teaching Hospital) over a period of one year. We recruited 210 adult patients with liver cirrhosis from the gastroenterology clinic and wards for this study. Data from these patients were collected with questionnaires administered by the interviewer and analysed using SPSS 23 statistical software (IBM Corp., Armonk, NY). The data obtained are presented in tables and charts. Categorical variables were expressed as proportions and frequencies, while continuous data were expressed as the median, mean, and standard deviation. Pulmonary hypertension was found in 30.5% of the participants, with mild pulmonary hypertension being the most common. No one had severe pulmonary hypertension. There was an increased risk of developing pulmonary hypertension in patients with coughs, easy fatigability, bilateral leg swelling, abdominal swelling, and ascites (P<0.05). The result showed that there is a high prevalence of pulmonary hypertension in patients with liver cirrhosis.

Beneficial Effects of Traditional Chinese Medicine Fuzheng Huayu on the Occurrence of Hepatocellular Carcinoma in Patients with Compensated Chronic Hepatitis B Cirrhosis Receiving Entecavir: A Multicenter Retrospective Cohort Study.

The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma (HCC) has not been established. Here, we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu (FZHY) on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir (ETV). A multicenter retrospective cohort study was performed. Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment. The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests. Propensity score matching was used for confounding factors. Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation. Out of 910 chronic hepatitis B patients, 458 were in the ETV+FZHY group and 452 were in the ETV group. After propensity score matching, the 5-year cumulative incidence of HCC was 9.8% in the ETV+FZHY group and 21.8% in the ETV group (p<0.01). The adjusted hazard ratio for HCC was 0.216 (0.108, 0.432) when FZHY treatment was >36 months. Age, diabetes, alanine aminotransferase, γ-glutamyl transpeptidase, albumin, hepatitis B e-antigen, and fibrosis 4 score were associated with the occurrence of HCC. FZHY decreased the risk of HCC in patients aged >45 years with a hepatitis B virus DNA level of ≥2,000 IU/l. Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV, possibly due to the antifibrotic properties of FZHY.

Chronological Course and Clinical Features after Denver Peritoneovenous Shunt Placement in Decompensated Liver Cirrhosis.

Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients

IntroductionAcute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.MethodologyIn the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.ResultsOf 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).ConclusionAKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Abstract 985: An effective cfDNA methylation-based assay in discriminating primary liver cancer from cirrhosis or chronic hepatitis virus infection: marker discovery, phase I pilot, and phase II clinical validation

Abstract Background: Early detection of primary liver cancer (PLC) in individuals with liver cirrhosis (LC) or chronic hepatitis virus infection (CHVI) improves survival. Timely, effective, and affordable tools with high sensitivity are urgently needed in clinical practice. Methods: Tissue and/or plasma samples from 159 healthy individuals and 89 PLC, LC, or CHVI patients were sequenced by a targeted methylation panel (~70,000 CpGs) to screen candidate methylated DNA markers (MDMs). In phase I, the performance of each selected MDM was validated in 175 plasma samples (PLC, n=101; LC/CHVI, n=74) by a CO-methylation aMplification rEal-Time PCR (COMET) assay. Logistic models were then trained and validated in phase II with 310 plasma samples (hepatocellular carcinoma [HCC], n=212; combined hepatocellular-cholangiocarcinoma [cHCC-CC], n=12; LC/CHVI, n=106; training vs. validation, 2:1). Results: The methylation levels of eleven selected MDMs with top performance showed a significant increase in PLC compared with LC/CHVI in both tissue and plasma samples (P&amp;lt;0.05). In phase I, eight of the above eleven MDMs with an area under the curve (AUC) over 0.80 to differentiate PLC and LC/CHVI were chosen for further investigation. In phase II, the MDM-based logistic model achieved sensitivity of 87.2% (95% confidence interval [CI], 80.8%-92.4%) and 88.0% (78.4%-94.4%), at respective specificity of 97.1% (90.1%-99.7%) and 100% (90.3%-100%) in the training and validation sets. In the validation set, sensitivity in patients with BCLC stage 0, diameter&amp;lt;3 cm, AFP-negative, and PIVKA-II-negative was 90.0% (55.5%-99.7%), 88.9% (65.3%-98.6%), 80.6% (64.0%-91.8%), and 81.3% (54.4%-96.0%), respectively. The classifier achieved similar sensitivity in patients with or without HBV/HCV infection (88.2% vs 90.0%). Additionally, our model detected 19 of 24 (79.3%, 57.8%-92.9%) intrahepatic cholangiocarcinoma. Combining AFP and PIVKA-II, the model achieved higher sensitivity of 93.3% (85.1%-97.8%) and specificity of 100.0% (90.3%-100%). Conclusion: In conclusion, the present study demonstrated the feasibility of using an easy-to-implement cfDNA methylation assay (COMET) to discriminate early-stage liver cancer from other liver diseases, with superior accuracy over AFP and PIVKA-II. Notably, the combination of the COMET, AFP, and PIVKA-II increased the overall sensitivity, indicating the potential benefit of integrating these approaches in clinical practices. Moving forward, further investigation is needed to validate these findings in larger prospective clinical studies. Keywords: primary liver cancer, early detection, liver cirrhosis, chronic hepatitis virus infection, methylated plasma DNA marker. Citation Format: Yang Tian, Yanan Wang, Mingxin Pan, Lei Zhang, Qiancheng You, Bingsi Li, Shangli Cai, Feng Shen, Guoyue Lv. An effective cfDNA methylation-based assay in discriminating primary liver cancer from cirrhosis or chronic hepatitis virus infection: marker discovery, phase I pilot, and phase II clinical validation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 985.

Effect of branched-chain amino acid supplementation and exercise on quadriceps muscle quantity and quality in patients with cirrhosis as assessed by ultrasonography: A randomized controlled trial

Background/aimSarcopenia and myosteatosis are common in patients with cirrhosis. The study aimed to evaluate efficacy of ultrasound to monitor muscle status during branched-chain amino acid (BCAA) supplementation and/or muscle exercise interventional approaches. Patients & MethodsA randomized controlled study, included 220 liver cirrhosis patients with Child- Pugh B & C, randomized into a control group (55 patients) received only the standard care, and interventional groups (165 patients) equally distributed into three subgroups, in addition to standard care, they received BCAA, programmed exercise, or BCAA and programmed exercise. At baseline and after 28 days, all participants were subjected to ultrasound-measured quadriceps muscle thickness and echo-intensity, muscle strength using handgrip, performance using short physical performance battery (SPPB), MELD score and nutritional assessment using 7- subjective global assessment score (SGA) and laboratory assessment. ResultsAll interventional groups showed a significant improvement in the ultrasound detected quadriceps muscle thickness (p = 0.001) & echo intensity, in addition to muscle strength, muscle performance, and SGA. Hematological parameters (hemoglobin & platelet count), biochemical parameters (ALT, AST, bilirubin, creatinine, urea and INR) & MELD score were also improved in the interventional groups. In Child-Pugh B patients BCAA combined with exercise showed an add-on effect. ConclusionBCAA supplements, programed muscle exercise and both are useful interventional methods in improving muscle quality and quantity in cirrhosis patients, which can be monitored by ultrasound. The best results can be achieved by combined intervention in Child-Pugh B, while in Child-Pugh C single intervention may lead to an acceptable improvement. The trial was registered retrospectively in the Clinical Trials RegistryRegistration number NCT06088550).

Evaluation of D-dimer and prothrombin time in alcohol related liver cirrhosis with comparison of machine learning analyses

ObjectivesLiver cirrhosis (LC) can be caused by obesity, alcohol consumption, viral infection, and autoimmune disease. Early diagnosis and management of LC is important for patient quality of life. Non-invasive diagnostic methods are useful for predicting the current status and mortality risk of LC. The purpose of this study is to identify relevant diagnostic factors measured in routine laboratory test of alcohol-related liver cirrhosis (ALC) patients. MethodsThis study analyzed data from 127 patients with ALC, including their laboratory test results and clinical information, including coagulation parameters, hematologic parameters, and biochemical parameters. These data were used to compare the performance of the prediction models from three machine learning algorithms including K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF). ResultsHigher Model for End-stage Liver Disease (MELD) score were associated with prothrombin time (PT) and D-dimer. Logistic and multiple linear regression analyses revealed significant factors predicting mortality in the MELD group. Machine learning approaches were used to predict death in ALC patients using some laboratory parameters associated with mortality. The prediction model based on SVM exhibited better prediction performance than others. ConclusionPT and D-dimer were the factors that were most strongly associated with 90-day mortality, and machine learning methods can create prediction models with good predictive power.

Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.

Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with routine laboratory tests for accurate detection of HCC. Epithelial cell adhesion molecule (EpCAM), α-fetoprotein, albumin, and platelets count were assayed in HCC patients (98), liver cirrhosis patients (77). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named EpCAM-HCC = AFP (U/L) × 0.11 - Albumin (g/dl) × 1.5 + EpCAM % × 2.9 - Platelets count (×109)/L× 0.75 - 93. EpCAM-HCC score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.7 (i.e., less than 1.7 the case is considered cirrhotic, whereas above 1.7 it is considered HCC. EpCAM-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Hepatic Decompensation in Patients with Chronic Liver Disease: Exploring the Role of Vitamin D Deficiency as a Prognostic Marker.

Although the function of vitamin D as a regulator of calcium and bone metabolism is well recognized, its role as an immunomodulator, regulator of cellular differentiation, and anti-inflammatory and antifibrotic actions is being increasingly noted. It is estimated that one-third of liver cirrhosis patients are vitamin D deficient. It has been reported that as liver disease progresses, the incidence of vitamin D deficiency rises. Several clinical implications of vitamin D levels have been proposed, including as a prognostic marker for the assessment of mortality in liver cirrhosis. To analyze the link between levels of vitamin D and decompensation of liver cirrhosis. This observational, cross-sectional study was conducted on 100 patients with liver cirrhosis admitted at Goa Medical College, a tertiary care government hospital in Goa, from March 2020 to February 2022. Demographic profile, history, and examination findings were recorded, and biochemical analysis included vitamin D levels. Child-Pugh (CP) and Model for End-Stage Liver Disease (MELD) scores were calculated, and based on these, patients were grouped into classes of disease severity. Data was interpreted using Statistical Package for the Social Sciences (SPSS) version 22. Mean age of the study population was 50 ± 9 years, with a 96% male predominance. Mean levels of vitamin D were 12.13, with a standard deviation (SD) of 7.38. Significant differences were noted between different classes of CP score (CPS). A vitamin D deficient state was noted in 93.3% CP class C group and 0% of class A group. A statistically significant association was demonstrated between low levels of vitamin D and CP class severity of liver dysfunction as well as MELD scores. This study confirms a high prevalence of vitamin D deficiency among patients with liver cirrhosis concurrent with the results of similar studies done earlier. More importantly, with increasing severity of hepatic decompensation as measured by CPS and MELD, vitamin D concentrations reduce.