Liver Cirrhosis Patients Research Articles

Splenectomy ameliorates liver cirrhosis by restoring the gut microbiota balance.

Dysbiosis of gut microbiota is frequent in liver cirrhosis (LC) patients, and splenectomy (SP) has been reported to improve LC. Herein, we report the effects of SP on gut microbiota, especially on Veillonella parvula, a Gram-negative coccus of the gastrointestinal tract, in LC mice, and the underlying mechanism. LC mice models were induced by tail vein injection of concanavalin A (ConA), followed by SP. 16s rRNA sequencing was conducted to analyze the effects of ConA induction and SP on mouse gut microbiota and the gene expression affected by gut microbiota. LC mice receiving SP were gavaged with Veillonella parvula. Likewise, hepatic stellate cells (HSC) and hepatocytes (HC) were induced with conditioned medium (CM) of Veillonella parvula. SP alleviated LC in mice by restoring gut barrier function and maintaining gut microbiota balance, with Veillonella as the key genus. The Veillonella parvula gavage on LC mice reversed the ameliorative effect of SP. The CM of Veillonella parvula promoted the activation of HSC and the release of IL-6, IL-1β, and TNF-α. Also, the CM of Veillonella parvula induced HC pyroptosis and the release of ALT and AST. Veillonella parvula represented an imbalance in the gut microbiota, thus enhancing gut-derived endotoxins in the liver with the main target being Tlr4/Nlrp3. Inhibition of Tlr4 blocked Veillonella parvula-induced HC damage, HSC activation, and subsequent LC progression. SP-mediated gut microbiota regulation ameliorates ConA-related LC progression by inhibiting Tlr4/Nlrp3 in the liver.

A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD.

Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR,1.483;95%CI,1.058-2.079,P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of non-alcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD.

Assessment of the Clinical Value of Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with higher mortality as a result of poor prognosis and unavailability of effective treatment options. This study retrospectively analyzed the clinical value of platelet-to-lymphocyte ratio (PLR) to aid in differentiating early hepatocellular carcinoma from liver cirrhosis patients. Three hundred and nine (309) patients including 155 patients with hepatocellular carcinoma (HCC) and 154 patients with liver cirrhosis were enrolled in this study. General clinical characteristics and blood parameters of each patient were collected, calculated, and retrospectively analyzed. Mann-Whitney U test was calculated to compare the two groups. Receiver operating characteristics (ROC) curve was performed to investigate the diagnostic potential of PLR in the prediction of HCC at a cut-off with high accuracy (area under the curve [AUC]) > 0.80. Hemoglobin (HB) concentration, red blood cell (RBC) count, neutrophil (NEU) count, platelet count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the HCC patients than in the liver cirrhosis patients (p < 0.05). ROC curve analysis showed that the AUC, optimal cut-off value, sensitivity, and specificity of PLR to predict HCC patients were 0.912, 98.7, 81.2%, and 80.6% respectively. The results suggest that PLR is a potential biomarker that can be used to predict early HCC.

Efficacy, immunogenicity, and safety of COVID-19 vaccines in individuals with liver cirrhosis: a rapid review and meta-analysis.

The emergence of coronavirus disease 2019 (COVID-19) vaccines has been a remarkable advancement. However, the efficacy, immunogenicity, and safety of these vaccines in individuals with liver cirrhosis require careful evaluation due to their compromised immune status and potential interactions with underlying liver disease. The present study aimed to evaluate the safety and efficacy of COVID-19 vaccines in liver cirrhosis patients. In the present study, we searched international databases, including Google Scholar, PubMed, Scopus, Embase, and Web of Science. The search strategy was carried out by using keywords and MeSH (Medical Subject Headings) terms. STATA ver. 15.0 (Stata Corp., USA) was used to analyze the data statistically. The analysis was performed using the random-effects model. We also used the chi-square test and I2 index to calculate heterogeneity among studies. For evaluating publication bias, Begg's funnel plots and Egger's tests were used. A total of 4,831 liver cirrhosis patients with COVID-19 were examined from 11 studies. The rate of hospitalization in the patients with liver cirrhosis was 17.6% (95% confidence interval [CI], 9%-44%). The rate of fever in the patients with liver cirrhosis was 4.5% (95% CI, 0.9%-8.1%). The rate of positive neutralizing antibodies in the patients with liver cirrhosis was 82.5% (95% CI, 69.8%-95.1%). Also, the rates of seroconversion after the second vaccination in patients with liver cirrhosis and the control group were 96.6% (95% CI, 92.0%-99.0%), and 99.7% (95% CI, 99.0%-100.0%), respectively. COVID-19 vaccines have demonstrated promising efficacy, immunogenicity, and safety profiles in individuals with liver cirrhosis, providing crucial protection against COVID-19-related complications.

Prevalence of Sarcopenia in Liver Cirrhosis Patients and Determinants of Survival in Cirrhotic Population: A Prospective Cohort Study

Introduction: Chronic liver diseases are the leading cause of mortality and are associated with a significant reduction in health-related quality of life, as well as being a major complication in cirrhosis. There is a high risk of reduced muscle mass, muscle strength, or function, known as sarcopenia, in patients with liver cirrhosis. Sarcopenia is a major determinant of survival in cirrhosis patients, along with the Child-Turcotte Pugh (CTP) score and the Model for End-stage Liver Disease (MELD) scores. Aim: To study the prevalence of sarcopenia in patients with liver cirrhosis by assessing skeletal muscle mass using the third lumbar level Skeletal Muscle Index (SMI) through Computed Tomography (CT) and to determine the survival analysis of the cohort using a Cox regression model. Materials and Methods: The present study was a prospective cohort study conducted in the Department of Gastroenterology and Hepatology at Sree Gokulam Medical College and Research Foundation in Thiruvananthapuram, Kerala, India South India, from October 2018 to October 2022. A total of 209 patients with cirrhosis were evaluated. Liver biochemical parameters, CTP score, and the MELD score were studied. Age, gender, and aetiology were noted. All subjects were assessed for sarcopenia using CT at the third lumbar vertebrae level SMI, and all subjects were followed up every six months for survival. Survival curves and survival probability were evaluated for all the subjects recruited in the present study. Cumulative survival rates were estimated by the Kaplan-Meier method for sarcopenia, CTP score, and the MELD scores after categorisation into the aetiology of cirrhosis, and the groups were compared using the Log-rank test. Independent factors associated with mortality were identified using Cox proportional hazards models. A p-value &lt;0.05 was considered statistically significant. Results: The mean age±Standard Deviation of the subjects was 58.24±9.9 years. Among the subjects, males accounted for 161 (77%), while 48 (23%) were females. In subjects with sarcopenia (n=77), the survival rate was 53 (68.8%), and in subjects without sarcopenia (n=132), the survival rate was significantly higher at 110 (83.3%) with a p-value &lt;0.05 (p=0.027). Univariate Cox regression analysis indicated that sarcopenia was a statistically significant predictor of survival. The mortality risk was higher in individuals with sarcopenia, with a Hazard Ratio (HR) of 1.9 and a 95% Confidence Interval (CI) ranging from 1.1-1.4. In the Cox regression model, CTP class B/C had a 2.4 times higher risk for mortality than CTP class A (p&lt;0.05). Individuals with sarcopenia had a 1.76 times higher risk of mortality compared to those without (HR=1.765, 95% CI: 0.983-3.17) in the multivariate Cox regression analysis. Aetiology and CTP class scores were independently associated with mortality (p&lt;0.05) after adjusting for multiple prognostic factors in the multivariate Cox regression analysis. Conclusion: Univariate Cox regression analysis indicated that sarcopenia was a statistically significant predictor of survival, with a higher mortality risk in individuals with sarcopenia. The multivariate Cox regression model for survival concluded that CTP class B/C posed a higher risk for mortality compared to CTP class A.

The Comparison of Serum Interleukin-8 Levels Based on Severity of Liver Cirrhosis.

The molecule known as Interleukin-8 (IL-8), a chemotactic leukocyte, has been found to have a crucial role in the perpetuation of the inflammatory environment that is associated with hepatitis B virus (HBV) infection, as well as in the development of liver cirrhosis and cancer. The aim of this study was to carefully examine the role of IL-8 in the inflammatory reaction and to compare the levels based on the severity of liver cirrhosis. The study was conducted from February 2018 to September 2018 at the Gastroenterohepatology Division, Internal medicine Department, Faculty of Medicine, Universitas Sumatera Utara. The study was designed as an analytic comparative, cross-sectional study. The liver cirrhosis patients who participated in this study met the inclusion criteria and provided informed consent. A total of 70 patients were included in the study, from which we identified 1 individual with child-pugh A, 28 individuals with child-pugh B, and 41 individuals with child-pugh C. The serum level of IL-8 was found to be 98 (11-320) (pg/ml). The IL-8 levels between child-pugh B and C patients did not exhibit any noteworthy differences during our analysis (p = 0.109, p>0.05). There is no notable inequality in the levels of IL-8 across different stages of liver cirrhosis.

IL-15-induced CD38+HLA-DR+CD8+ T cells correlate with liver injury via NKG2D in chronic hepatitis B cirrhosis.

CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA-DR+CD8+ T cells, or bystander-activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA-DR+CD8+ T cell-mediated pathogenesis during liver cirrhosis. The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity-related indicators of CD38+HLA-DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA-DR+CD8+ T-cell killing was detected using cytotoxicity and antibody-blocking assays. The proportion of CD38+HLA-DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate-like functional characteristics. This CD8+ T-cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity-related cytokines, granzyme B and perforin. IL-15 promoted CD38+HLA-DR+CD8+ T-cell activation and proliferation, inducing significant TCR-independent cytotoxicity mediated through NKG2D. CD38+HLA-DR+CD8+ T cells correlated with cirrhosis-related liver injury and contributed to liver damage by signalling through NKG2D in a TCR-independent manner.

Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study.

Extracellular vesicles (EVs) represent an attractive source of biomarkers due to their biomolecular cargo. The aim of this study was to identify candidate protein biomarkers from plasma-derived EVs of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Plasma-derived EVs from healthy participants (HP), LC, and HCC patients (eight samples each) were subjected to label-free quantitative proteomic analysis using LC-MS/MS. A total of 248 proteins were identified, and differentially expressed proteins (DEPs) were obtained after pairwise comparison. We found that DEPs mainly involve complement cascade activation, coagulation pathways, cholesterol metabolism, and extracellular matrix components. By choosing a panel of up- and down-regulated proteins involved in cirrhotic and carcinogenesis processes, TGFBI, LGALS3BP, C7, SERPIND1, and APOC3 were found to be relevant for LC patients, while LRG1, TUBA1C, TUBB2B, ACTG1, C9, HP, FGA, FGG, FN1, PLG, APOB and ITIH2 were associated with HCC patients, which could discriminate both diseases. In addition, we identified the top shared proteins in both diseases, which included LCAT, SERPINF2, A2M, CRP, and VWF. Thus, our exploratory proteomic study revealed that these proteins might play an important role in the disease progression and represent a panel of candidate biomarkers for the prognosis and diagnosis of LC and HCC.

Detection of a Prethrombotic State in Patients with Hepatocellular Carcinoma, Using a Clot Waveform Analysis.

Background: Although hepatocellular carcinoma (HCC) is frequently associated with thrombosis, it is also associated with liver cirrhosis (LC) which causes hemostatic abnormalities. Therefore, hemostatic abnormalities in patients with HCC were examined using a clot waveform analysis (CWA). Methods: Hemostatic abnormalities in 88 samples from HCC patients, 48 samples from LC patients and 153 samples from patients with chronic liver diseases (CH) were examined using a CWA-activated partial thromboplastin time (APTT) and small amount of tissue factor induced FIX activation (sTF/FIXa) assay. Results: There were no significant differences in the peak time on CWA-APTT among HCC, LC, and CH, and the peak heights of CWA-APTT were significantly higher in HCC and CH than in HVs and LC. The peak heights of the CWA-sTF/FIXa were significantly higher in HCC than in LC. The peak times of the CWA-APTT were significantly longer in stages B, C, and D than in stage A or cases of response. In the receiver operating characteristic (ROC) curve, the fibrin formation height (FFH) of the CWA-APTT and CWA-sTF/FIXa showed the highest diagnostic ability for HCC and LC, respectively. Thrombosis was observed in 13 HCC patients, and arterial thrombosis and portal vein thrombosis were frequently associated with HCC without LC and HCC with LC, respectively. In ROC, the peak time×peak height of the first derivative on the CWA-sTF/FIXa showed the highest diagnostic ability for thrombosis. Conclusion: The CWA-APTT and CWA-sTF/FIXa can increase the evaluability of HCC including the association with LC and thrombotic complications.

Portal vein thrombosis in patients with liver cirrhosis

Background/Aim. Portal vein thrombosis (PVT) in patients with liver cirrhosis (LC) has a prevalence of 0.6- 26%. It is most commonly discovered incidentally as part of the evaluation of LC or in the context of acute decompensation of LC due to portal hypertension. The aim of the study was to determine the prevalence of PVT in patients with LC in relation to the severity of the disease and individual elements of portal hypertension. Methods. A total of 326 patients treated for LC decompensation were included in a retrospective study. Standard laboratory analyses, abdominal ultrasonography and/or computed tomography, and esophagogastroduodenoscopy were performed. Results. The diameter of the portal vein (PV) differed between patients without esophageal varices (12.2 mm) and those with large varices (13.6 mm), p = 0.026. PVT was identified in 6.1% of patients with LC. The patients were classified according to the Child-Pugh scoring system, which has the A, B, and C categories used to assess the severity of liver disease. PVT was present in 3.0% of patients in class C and 12.0% in class B, while none of the patients in class A had PVT (p = 0.005). PVT was present in 4.4% of patients with small varices and 16.7% with large varices (p &lt; 0.001). There was no difference in the presence of PVT between the groups of patients with and without variceal bleeding nor between groups with different degrees of ascites. A fatal outcome occurred in 29.4% of patients, but there was no difference between patients with and without PVT. Conclusion. PVT is present in more advanced stages of LC and predominantly in patients with large esophageal varices. There was no higher prevalence of PVT observed with the occurrence of variceal bleeding or with the death outcome in patients with LC.

Evaluating aspartate–platelet ratio index: A potential non-invasive tool for liver cirrhosis and esophageal varices detection

Background: The global health challenge posed by liver cirrhosis, notably its progression to complications such as esophageal varices, necessitates advancements in diagnostic techniques. Aims and Objectives: This study probes the aspartate–platelet ratio index (APRI) capability, a non-invasive diagnostic approach, in effectively managing liver cirrhosis and foreseeing the development of esophageal varices. Materials and Methods: The research at MES Medical College in Perinthalmanna included a cohort of 114 ultrasonographically diagnosed liver cirrhosis patients. Utilizing established formulae, the APRI score was computed and juxtaposed with the incidence and gravity of esophageal varices, ascertained through endoscopic examinations. The analysis encompassed receiver operating characteristic (ROC) curve evaluation alongside descriptive and inferential statistical methodologies. Results: Within the participant group, the average age was 59.35 years, with males constituting 64.04% of the sample. Notably, 83.33% of the subjects were found to have esophageal varices varying in severity. The APRI score’s predictive capability was moderate (ROC curve area=0.655), indicating limitations in its sole use for diagnosing esophageal varices. Conclusion: While user-friendly and non-intrusive, the APRI score exhibits limited effectiveness in the specific diagnosis of liver cirrhosis and in forecasting the emergence of esophageal varices. Its utility, primarily in signaling liver fibrosis, does not extend robustly as an independent diagnostic tool in clinical scenarios. This study underscores an urgent need for extended research to affirm APRI’s accuracy in diverse liver disease stages and anticipate associated complications.

Assessment of Glu504 Lys Genotype and Single Nucleotide Polymorphisms in Exon 12 and 13 of ALDH2 Gene in Alcoholic Liver Cirrhosis patients in Northern Karnataka,India: A Cross-sectional Study

Assessment of Glu504 Lys Genotype and Single Nucleotide Polymorphisms in Exon 12 and 13 of ALDH2 Gene in Alcoholic Liver Cirrhosis patients in Northern Karnataka,India: A Cross-sectional Study

Forgettable in the care of liver cirrhosis: the unseen culprits of progression from bad to worse.

Patients with liver cirrhosis constitute a critically ill and unique population, and their stability relies on a well-coordinated multidisciplinary team with a carefully structured plan. Overlooking any aspect of this plan can expedite disease progression, leading to severe complications. The lack of disease-specific nutritional guidance, the prevalent sedentary lifestyle among patients, and insufficient screening for hepatocellular carcinoma, oesophageal varices, sarcopaenia, minimal hepatic encephalopathy, and diabetes mellitus, along with fibrosis progression and cirrhosis decompensation, can add further complexities. Additionally, devaluing the impact of obesity in triggering liver cirrhosis can be disadvantageous. Prolonged and inappropriate use of proton pump inhibitors also poses a significant challenge with a wide range of complications. These often-unheeded aspects in the care of liver cirrhosis patients represents the unseen culprits of progression from bad to worse and warrant serious consideration.

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

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

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. To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China. 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 investigated. 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). 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.

Assessment of Left Ventricular Systolic and Diastolic Functions on Echocardiography in Cirrhotic Patients

Objective: To assess the prevalence of left ventricular (LV) systolic and diastolic function on Echocardiography (ECHO) in patients presented with liver cirrhosis. Study Design: Analytical Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Diseases Rawalpindi,Pakistan, from Apr 2023 to May 2023. Methodology: Total of n=131 liver cirrhotic patients were recruited by non-probability consecutive sampling technique. All these patients presented and diagnosed with liver cirrhosis on ultrasound, were selected. Their echocardiographic assessment was done by an experienced operator. Gathered data specially the LV diastolic and systolic function, was entered and analyzed in SPSS version-24:00. Chi-square and analysis of variance was applied to find the p-values for study variables in relation with severity of liver cirrhosis. p-value &lt;0.05 was taken statistically significant. Results: Out of 131 Patients, 85(64.9%) patients had liver cirrhosis for less than 5-years, 32(24.4%) had for 5-10 years and 14(10.68%) for more than 10-years. There was almost similar frequency of males and females [67(51.1%) and 64(48.9%)respectively] with mean age of 57.14±9.84 years. Statistically significant association of demographics and clinical parameters with liver cirrhosis was found (p&lt;0.05) except left ventricular systolic diameter (p&gt;0.05). LV diastolic dysfunction was reported in 94(71.8%) while systolic function was normal in all participants. LV diastolic dysfunction was found in 56(42.7%) as grade-I, 31(23.7%) as grade-II and 7(5.3%) cases as grade-III which was statistically significant (p&lt;0.001). Conclusion: Diastolic dysfunction is relatively more common in liver cirrhosis patients as compared to systolic function. There was significant ...

A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol

BackgroundLiver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.MethodsIn this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DiscussionThe anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.Trial registrationClinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic.clinicaltrials.gov/ct2/show/NCT05502198.

Portal Vein Thrombosis in Patients With Cirrhosis of the Liver: Prevalence and Risk Factors.

Chronic liver disease very often culminates into cirrhosis and its associated complications. One of the serious complications is portal venous thrombosis, which can occur due to a variety of risk factors. One significant factor contributing to portal hypertension is portal vein thrombosis (PVT).In this study, we aimed to investigate the prevalence of PVT among patients with liver cirrhosis in a tertiary hospital and identify the factors associated with this complication. This was a cross-sectional observational study of 93 diagnosed liver cirrhosis patients treated at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) hospital in southern India between June 2020 and January 2021.A thorough evaluation of the clinical condition of the patients and associated comorbidities was done. The patients then underwent Doppler ultrasound/CECT/MRI to look for PVT and its extent. The collected data were analyzed using Statistical Product and Service Solutions (SPSS, version 24) (IBM SPSS Statistics for Windows, Armonk, NY). Comparison between two proportions was done using two two-tailed Z-test/Fisher's exact tests. Our study found a PVT prevalence of 17.2% in cirrhotic patients, with a higher prevalence of acute PVT than chronic PVT. Ascitic fluid infection, longer duration of cirrhosis, and increased cirrhosis severity were significantly associated with PVT development. We found no significant associations between PVT and gender, hypertension, smoking, diabetes, or the duration of alcohol intake. This study highlights the importance of early screening for PVT using Doppler USG in all patients diagnosed with cirrhosis. Additionally, anticoagulation therapy for acute PVT may be considered in patients without bleeding risks.

A Physiologically Based Pharmacokinetic Model to Predict Systemic Ondansetron Concentration in Liver Cirrhosis Patients.

Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events. A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populations. The developed model successfully described the pharmacokinetics of ondansetron in healthy and liver cirrhosis populations. The predicted area under the curve, maximum systemic concentration, and clearance were within the allowed twofold range. The exposure of ondansetron in the population of Child-Pugh class C has doubled in comparison to Child-Pugh class A. The dose has to be adjusted for liver cirrhosis patients to ensure comparable exposure to a healthy population. In this study, the developed PBPK model has described the pharmacokinetics of ondansetron successfully. The PBPK model has been successfully evaluated to be used as a tool for dose adjustments in liver cirrhosis patients.

Non-targeted metabolomics study for discovery of hepatocellular carcinoma serum diagnostic biomarker

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Due to the asymptomatic features of HCC at early stages, patients are often diagnosed at advanced stages and missed effective treatment. Thus, there is an urgent need to identify sensitive and specific biomarkers for HCC early diagnosis. In the present study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was used to profile serum metabolites from HCC patients, liver cirrhosis (LC) patients, and normal controls (NC). Univariate and multivariate statistical analyses were performed to obtain the metabolomic differences of the three groups and select significantly changed metabolites that can be used as diagnostic biomarkers. In total, 757 differential metabolites were quantified among the three groups, and pathway enrichment analysis of these metabolites indicated that glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism were the most altered pathways involved in HCC development. Receiver operating characteristic (ROC) curve analysis was performed to select and evaluate the diagnostic biomarker performance. Seven metabolites were identified as potential biomarkers that can differentiate HCC from LC and NC, and LC from NC with the good diagnostic performance of area under the curve (AUC) from 0.890 to 0.990. In summary, our findings provide highly effective biomarker candidates to differentiate HCC from LC and NC, LC, and NC, which shed insight into HCC pathological mechanisms and will be helpful in better understanding and managing HCC.