Cirrhosis Patients Research Articles

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Comparison of the single-cell and single-nucleus hepatic myeloid landscape within decompensated cirrhosis patients.

A complete understanding of disease pathophysiology in advanced liver disease is hampered by the challenges posed by clinical specimen collection. Notably, in these patients, a transjugular liver biopsy (TJB) is the only safe way to obtain liver tissue. However, it remains unclear whether successful sequencing of this extremely small and fragile tissue can be achieved for downstream characterization of the hepatic landscape. Here we leveraged in-house available single-cell RNA-sequencing (scRNA-seq) and single-nucleus (snRNA-seq) technologies and accompanying tissue processing protocols and performed an in-patient comparison on TJB's from decompensated cirrhosis patients (n = 3). We confirmed a high concordance between nuclear and whole cell transcriptomes and captured 31,410 single nuclei and 6,152 single cells, respectively. The two platforms revealed similar diversity since all 8 major cell types could be identified, albeit with different cellular proportions thereof. Most importantly, hepatocytes were most abundant in snRNA-seq, while lymphocyte frequencies were elevated in scRNA-seq. We next focused our attention on hepatic myeloid cells due to their key role in injury and repair during chronic liver disease. Comparison of their transcriptional signatures indicated that these were largely overlapping between the two platforms. However, the scRNA-seq platform failed to recover sufficient Kupffer cell numbers, and other monocytes/macrophages featured elevated expression of stress-related parameters. Our results indicate that single-nucleus transcriptome sequencing provides an effective means to overcome complications associated with clinical specimen collection and could sufficiently profile all major hepatic cell types including all myeloid cell subsets.

Exploring the Prevalence, Predictors, and Impact of Bacterial Infections to Guide Empiric Antimicrobial Decisions in Cirrhosis (EPIC-AD)

BackgroundThis study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. MethodsWe analyzed acutely decompensated cirrhosis patients (n=971) from North India between 2013-2023 at a tertiary center. Microbiological and clinical features based on infection sites (EASL criteria) and patient outcomes were assessed. ResultsMedian age was 45 years; 87% were males with 47% having alcoholic hepatitis. Of these, 675 (69.5%) had infections; 305 (45%) were culture-confirmed. Notably, 71% of confirmed cases were MDRO-related, chiefly carbapenem-resistant (48%). MDRO prevalence was highest in pulmonary (80.5%) and skin-soft-tissue infections (76.5%). Site-specific distribution and antimicrobials were suggested.Predictive models identified prior hospitalization [OR:2.23 (CI:1.58-3.14)], norfloxacin prophylaxis [OR:2.26 (CI:1.44-3.55)], prior broad-spectrum antibiotic exposure [OR:1.61 (CI:1.12-2.30)], presence of SIRS [OR:1.75 (CI: 1.23-2.47)], procalcitonin [OR:4.64 (CI:3.36-6.40)], and HE grade [OR:1.41 (CI:1.04-1.90)], with an AUC of 0.891 for infection prediction. For MDRO infection prediction, second infection [OR: 7.19 (CI: 4.11-12.56)], norfloxacin prophylaxis [OR: 2.76 (CI: 1.84-4.13)], CLIF-C OF [OR: 1.10 (CI: 1.01-1.20)], prior broad-spectrum antibiotic exposure [OR: 1.66 (CI: 1.07-2.55)], rifaximin [OR: 040 (0.22-0.74)] multisite [OR: 3.67 (CI: 1.07-12.56)], and polymicrobial infection [OR: 4.55 (CI: 1.45-14.17)] yielded an AUC of 0.779 and 93% specificity. Norfloxacin prophylaxis, multisite infection, mechanical ventilation, prior broad-spectrum antibiotic exposure, and infection as acute precipitant predicted carbapenem-resistant infection (AUC: 0.821).Infections (culture-proven or probable), MDROs, carbapenem/pan-drug resistance, and second infections independently linked with mortality (p<0.001), adjusted for age, leucocytosis, and organ failures. A model incorporating age [HR:1.02 (CI: 1.01-1.03), infection [HR:1.52 (CI: 1.05-2.20)], prior hospitalization [HR:5.33 (CI: 3.75-7.57)], norfloxacin [HR:1.29 (CI: 1.01-1.65)], multisite infection [HR:1.47 (CI:1.06-2.04)], and CLIF-C OF [HR:1.17 (CI: 1.11-1.23)] predicted mortality with C-statistics of 0.782 (p<0.05). ConclusionHigh MDRO burden, especially carbapenem-resistant, necessitates urgent control measures in cirrhosis. Site-specific epidemiology and risk models can guide empirical antimicrobial choices in cirrhosis management. Lay summaryOur study delved into infections among hospitalized cirrhosis patients, investigating their occurrence, distribution, risks, and consequences. Notably, infections affected almost 70% of patients, with nearly half of them being confirmed through culture. Most concerning was the identification of multidrug-resistant organisms (MDROs) in 71% of culture-proven cases, particularly carbapenem-resistant bacteria (48%). Pulmonary and skin-soft-tissue infections were the hardest hit. We developed predictive models to foresee infections and particularly drug-resistant and carbapenem-resistant bacterial infections and their mortality. Thus, highlighting the urgent need for measures to counter the substantial impact of MDRO infections in cirrhosis patients. Our findings underscore the importance of targeted antimicrobial therapy guided by site-specific epidemiological insights.

Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects.

Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and Cmax were within 0.5-2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients.

Health-Related Quality of Life Assessment for Liver Cirrhosis Patients at a Tertiary Care Hospital in Karachi, Pakistan.

Background The global health challenge of cirrhosis affects millions of individuals. Still, there is a notable lack of research on the health-related quality of life (HRQOL) of cirrhosis patients, especially in specific regions. This study aims to assess the impact of cirrhosis onHRQOL, including factors influencing it in a tertiary care setting in Pakistan. Methodology A cross-sectional study was conducted on a cohort of 115 patients diagnosed with cirrhosis, confirmed on imaging. HRQOL was measured using the short-form 36 (SF-36) survey. Furthermore, socioeconomic factors and self-rated health perceptions regarding HRQOL were recorded. Factors Influencing HRQOL domains in liver cirrhosis patients were also analyzed. Results Among 115 liver cirrhosis patients, 63.5% (N=73) were aged 40-60 years, and 73.9% (N=85) lived primarily in urban areas. HRQOLassessments highlighted moderate disability in physical functioning (62.6 ± 26.5) and notable impacts on mental health, emotional well-being, and bodily pain. Statistical analysis demonstrated the complexity of factors influencing HRQOL. Physical functioning was significantly associated with a higher Child-Turcotte-Pugh class, diabetes mellitus, hypertension, smoking status, and family monthly income (p-value < 0.05). While the duration of liver cirrhosis showed a significant association with bodily pain (p < 0.05). Additionally, residence status with social well-being (p-value = 0.01), and family monthly income with vitality (p-value < 0.05). Conclusion Our study in Pakistan highlights significant impacts on the HRQOLof liver cirrhosis patients, affecting physical function, mental health, emotional well-being, and bodily pain. Factors influencing HRQOL include liver disease severity, comorbidities, and socio-economic status.Recommendations include educational programs and specialized nursing care to address diverse challenges.The findings stress the importance of a personalized approach to patient care, urging urgent, targeted efforts to improve the health-related standard of life for cirrhotic patients.

Biomarkers of Innate Immunity and Immunological Susceptibility to Viral Infection in Patients with Alcoholic Cirrhosis.

The harmful effect of alcohol on the immune system may be due to both a direct action of the alcohol or its metabolites on immune cells as an indirect action modifying the different mechanisms of intercellular interaction. The interplay between stimulatory (aKIR) and inhibitory (iKIR) natural killer (NK) cell receptors and their corresponding human leukocyte antigen (HLA) ligands influences the outcome of virus infection. The aim was to analyze the influence of the KIR/HLA pair genetic profile in male alcoholic cirrhosis (AC) patients with and without viral infections to find susceptibility biomarkers that can help establish the risks and prevent viral infections. A total of 281 male AC patients were analyzed. The sociodemographic characteristics, viral hepatitis C (HCV), hepatitis B (HBV), and cytomegalovirus (CMV) infections were analyzed. Genomic DNA was extracted, and genetic the KIR/HLA profiles were investigated. A total of 6 KIR genes and their corresponding ligands (HLA-C) were analyzed. Patients were grouped into two groups: with and without associated viral infection. A statistically significant increase in the combination of KIR2DL2+/C1C1 was observed in male AC patients with viral infection compared to those without viral infection (45.9% vs. 24.5%, p = 0.021). The analysis of KIR2DL3+/C1+ showed a high frequency comparing healthy controls and male AC patients without virus infection (85% vs. 76.4%; p = 0.026). The analysis of KIR2DL3+/C2C2 frequency showed a statistically significant increase comparing male AC patients without viral infection and healthy controls (23.6% vs. 15%; p = 0.026). The genetic KIR2DL2+/C2C2 profiles may play a significant role in determining the vulnerability of male AC patients to viral infections, providing valuable insights for future research and potential therapeutic interventions.

Studying the effects of stress, mental health and psychological well‐being on wound healing rates after oesophageal varices ligation in liver cirrhosis patients

AbstractIt is of utmost importance to comprehend the impact that psychological factors have on physical rehabilitation, specifically in regards to wound healing following ligation of oesophageal varices in patients with liver cirrhosis. The present study investigated the correlation between wound recovery rates and psychological well‐being, stress and mental health. From January 2022 to September 2023, 148 patients from were evaluated as part of this cross‐sectional observational study. The psychological well‐being of participants was evaluated utilizing the Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS) and Psychological General Well‐Being Index (PGWBI). The rates of wound recovery were assessed following ligation. The mean duration for wound recovery was 28.37 ± 9.65 days. The mean wounds healing time of patients who obtained higher PSS scores (18.55) was marginally longer. On the contrary, there was a moderate reduction in healing time associated with higher HADS scores (mean 14.10). On average (68.88), PGWBI scores indicated a negligible effect on wound healing. The variance in healing durations between Child‐Pugh classifications A, B and C (mean values of 28.65, 26.90 and 29.57 days respectively) suggested that the severity of liver disease has an impact. As a result of ligation of oesophageal varices, the study demonstrated that psychological factors and wound recovery in patients with liver cirrhosis are intricately intertwined. There seems to be the substantial and intricate relationship between stress, mental health and wound recovery. The results of this study supported the notion that psychological evaluation and support should be incorporated into the management of patients with liver cirrhosis.

Portal venous blood flow velocity is a factor associated with portal venous thrombosis after partial splenic artery embolization in hepatic cirrhosis patients

Objective: To investigate risk factors for portal venous thrombosis (PVT) after partial splenic artery embolization (PSE) in hepatic cirrhosis patients. Methods: The authors retrospectively analyzed 151 hepatic cirrhosis patients with hypersplenism who underwent partial splenic artery embolization between January 2020 and December 2021. The patients were divided into a PVT group and a non-PVT group according to whether they had PVT after PSE. Univariate analyses were performed to select risk factors for PVT after PSE, and multivariate analysis was used to analyze variates with a value of P less than 0.1 in univariate analysis. Results: There were 151 patients enroled in the study, with 22 patients in the PVT group and 129 patients in the non-PVT group. There was no significant difference in terms of age, sex, smoking, hypertension, diabetes, Child–Pugh between two groups. White blood cell (WBC) and platelet counts after PSE were significantly higher than those before PSE in both the PVT group and non-PVT group. Univariate analysis showed that portal venous blood flow velocity, ligation of oesophageal varices and WBC after PSE were found to have a P value less than 0.1. Multivariate analysis showed that portal venous blood flow velocity was a factor associated with PVT after PSE. Conclusion: Portal venous blood flow velocity was a factor associated with PVT after PSE. Portal venous blood flow velocity should be considered before patients undergo PSE.

Characteristics of liver cirrhosis patients: A literature review

Introduction: Based on data from the World Health Organization (WHO), there is an increase in the number of deaths due to liver cirrhosis from year to year, with the death rate reaching 905,418 in 2000 and soaring to 1,161,914 in 2015. According to a 2016 government public hospital report in Indonesia, The prevalence of liver cirrhosis is estimated at 3.5% of total internal medicine patients, or an average of around 47.4% of all patients treated for cirrhosis. This research using the literature review method aims to describe the characteristics of liver cirrhosis sufferers (gender, etiology of liver cirrhosis, age, child-turcotte-pugh) in Indonesia. Methods: The type of study in this research is a literature review using secondary data in the form of literature that meets the inclusion and exclusion criteria. The inclusion criteria for this research are literature that has been published in the last 10 years, can be accessed in its entirety, literature set in Indonesia, and meets the search keywords. The exclusion criteria in this study were literature with the type of study in the form of a review. Results: A literature search conducted on Google Scholar and Pubmed found eight pieces of literature that met the inclusion and exclusion criteria. Eight pieces of literature are descriptive observational studies. The total samples obtained from the eight pieces of literature were 1010 samples. The time span of the literature obtained was 2015-2023. Before data extraction, each piece of literature was assessed for risk of bias using JBI (Joanna Briggs Institute) critical appraisal. Conclusions: Based on literature review research, cirrhosis sufferers are more likely to suffer from men (685 samples), the elderly age group (&gt;45 years) with hepatitis B etiology (477 samples), and Child-Turcotte-Pugh score category C (397 samples).

High vaccination coverage and infection rate result in a robust SARS-CoV-2-specific immunity in the majority of liver cirrhosis and transplant patients: A single-center cross-sectional study.

In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP). This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023. Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA). On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations. By spring 2023, high vaccination coverage and infection rate have resulted in a robust, mostly hybrid, humoral and cellular immune response in most LTR and LCP. However, booster vaccinations with vaccines covering new variants seem advisable, especially in patients with low immune responses and risk factors for severe disease.

Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield)

Despite the effectiveness of COVID-19 vaccination in reducing the severity of the disease, the demand for booster is increasing in vulnerable populations like elderly and immunocompromised individuals especially with each new wave of COVID-19 in different countries. There is limited data on the sustained immunity against COVID-19 in patients with liver cirrhosis. The study was aimed to compare the T cell and humoral immune response after 1 year of ChAdOx1nCoV-19 Vaccine in patients with liver cirrhosis and healthy health care workers (HCW). This was a prospective observational study including 36 HCW, 19 liver cirrhosis patients and 10 unvaccinated individuals. Anti-SARS-CoV-2S antibody, neutralizing antibody and memory T cell subsets were evaluated by ELISA and flow cytometry, respectively, in all three groups after 1 year of initial vaccination. Compared to HCW and unvaccinated individuals, liver cirrhosis patients had significantly depleted T cells, although CD4:CD8 + T cell ratio was normal. Both cirrhotic patients and HCW developed memory T cell subset [effector memory RA (P = 0.141, P < 0.001), effector memory (P < 0.001, P < 0.001), central memory (P < 0.001, P < 0.01), stem cell memory (P = 0.009, P = 0.08) and naïve (P < 0.001, P = 0.02)] compared to unvaccinated unexposed individuals of CD4 + T and CD8 + T, respectively. However, among HCW and cirrhotic group no difference was noted on central memory and stem cell memory cells on T cells. Patients with liver cirrhosis developed comparable memory T cells after vaccination which can evoke sustainable immune response on reinfection. Therefore, additional vaccine doses may not be necessary for cirrhosis patients.

Patients With Moderate to Severe Liver Cirrhosis Have Significantly Higher Short-Term Complication Rates Following Total Knee Arthroplasty: A Retrospective Cohort Study

BackgroundLiver cirrhosis is associated with increased perioperative morbidity. Our study used the Model for End-Stage Liver Disease (MELD) score to assess the impact of cirrhosis severity on postoperative outcomes following total knee arthroplasty (TKA). MethodsA retrospective review identified 59 patients with liver cirrhosis who underwent primary TKA at a large, urban, academic center from January 2013 to August 2022. Cirrhosis was categorized as mild (MELD < 10; n = 47) or moderate-severe (MELD ≥ 10; n = 12). Modified Clavien-Dindo classification was used to grade complications, where grade 2+ denoted significant intervention. Hospital length of stay, nonhome discharge, and mortality were collected. A 1:1 propensity matching was used to control for demographics and selected comorbidities. ResultsModerate-severe cirrhosis was associated with significantly higher rates of intrahospital overall (58.33 versus 16.67%, P = .036) complications, 30-day overall complications (75 versus 33.33%, P = .042), and 90-day overall complications (75 versus 33.33%, P = .042) when compared to matched mild cirrhosis patients. Compared to matched noncirrhotic controls, mild cirrhosis patients had no significant increase in complication rate or other outcomes (P > .05). ConclusionsPatients with moderate-severe liver cirrhosis are at risk of short-term complications following primary TKA. Patients with mild cirrhosis have comparable outcomes to matched noncirrhotic patients. Surgeons can use MELD score prior to scheduling TKA to determine which patients require optimization or higher levels of perioperative care.

The Contemporary Role of Speckle Tracking Echocardiography in Cirrhotic Cardiomyopathy.

Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association-in the majority of studies-with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis.

Statin use in cirrhosis and its association with incidence of portal vein thrombosis.

Statin use has shown a reduction in hepatic decompensation and portal hypertension. Its association with portal vein thrombosis (PVT) incidence is unknown. We aim to compare the incidence of PVT in patients with and without statin use. We excluded patients with a history of hepatocellular cancer, liver transplants, Budd-Chiari syndrome, and intra-abdominal malignancies. Patients with cirrhosis were followed from their first hepatologist clinical encounter (January 1, 2016, to January 31, 2021) for 180days to determine PVT incidence. We tested the association of statin use with PVT using 1:1 propensity score (PS) matching and Cox proportional hazard regression. We analyzed 2785 patients with cirrhosis (mean age:61.0±12.3years, 44.3% female, 63.8% White, mean MELD-Na score:11.7±6.1, and statin use:23.1%). A total of 89 patients developed PVT during the follow-up, which was lower in patients with statin use as compared to no statin use (1.3% vs 3.8%, P=0.001, unadjusted HR:0.28, 95% CI: 0.13-0.62, P=0.001). After matching for demographics, comorbidities, and hepatic decompensation events, patients with statin use had a lower risk of developing PVT in 180-day follow-up as compared to those without statin use (HR:0.24, 95% CI: 0.10-0.55, P=0.001). Subgroup analysis showed that statin use was associated with lower PVT incidence in non-NASH (HR: 0.20, 95% CI: 0.07-0.54, P=0.002) and decompensated cirrhosis (HR: 0.12, 95% CI:0.03-0.53, P=0.005) than no statin use. PVT incidence was lower in decompensated cirrhosis patients with statin use than in those with no statin use. However, this finding needs to be further tested in randomized control trials.

Evaluation of brain age changes in patients with liver cirrhosis and hepatic encephalopathy with deep learning models based on structural magnetic resonance imaging

Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

Importance of 1H-MR spectroscopy of the brain to identify the minimal hepatic encephalopathy in different patients with liver cirrhosis: A prospective study.

Liver cirrhosis patients commonly progress to minimal hepatic encephalopathy (MHE) with cognitive impairment and raised blood ammonia and proinflammatory cytokines levels. This study aims to identify the subjects of MHE in patients with liver cirrhosis by hydrogen 1 magnetic resonance (1H-MR) spectroscopy of the brain, serum proinflammatory cytokines, and neuropsychiatric tests. This prospective was carried out on 100 patients of liver cirrhosis without overt hepatic encephalopathy (HE) and compared with 100 healthy controls in a tertiary care hospital in Northeast India between September 2017 and October 2019. The psychometric hepatic encephalopathy score (PHES) neuropsychological tests, cranial MRIwith 1H-MR spectroscopy, and estimation of serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were done. The PHES scores and serum proinflammatory markers levels were correlated with the conventional and 1H-MR spectroscopy findings of the brain. The mean PHES score in the case group was -7.58±3.43 (standard deviation [SD]) and the control group was -3.41 ± 3.87 (SD). Patients with Child-Pugh class A (n = 8) had a PHES score of -8.7 ± 2.5 (SD), class B (n = 42) -7.62 ± 3.7 (SD), and class C (n = 50) had a score of -7.36 ± 3.3 (SD). The mean value of IL-6 and TNF-α in the case group was 219 ± 180 (SD) pg/mL and 99 ± 118 (SD) pg/mL and the control group was 67.4 ± 77 (SD) pg/mL and 57.5 ± 76 (SD) pg/mL. Globus pallidus T1-weighted hyperintensities on the visibility scale with a visibility score of 0 were observed in 39 cases, a score of 1 in 38 cases, and a score of 2 in 23 cases. Increased glutamate/glutamine/creatine (Glx/Cr) ratio was identified in the case group on MR spectroscopy as compared to the control (0.95 ± 0.24 vs. 0.31 ± 0.19, P < 0.0005), a decrease of myoinositol/creatine (mI/Cr) ratio (0.11 ± 0.13 vs. 0.30 ± 0.12, P < 0.0005), and increase choline/creatine (Cho/Cr) ratio (0.69 ± 0.26 vs. 0.61 ± 0.20, P < 0.0005). There was a statistically significant difference in Glx/Cr, mI/Cr and Cho/Cr ratio between the case and control groups with P < 0.0005. Predicting the development of MHE in established cases of liver cirrhosis using non-invasive modalities like PHES, IL-6, TNF-α levels, and 1H-MR spectroscopy plays an important role in further progression to overt HE and coma.

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.

Pre-hospital symptom clusters and symptom network analysis in decompensated cirrhotic patients: A cross-sectional study.

To generate pre-hospital symptom networks, explore core, bridge and sentinel symptoms, identify pre-hospital symptom clusters and analyse relationship between influencing factors and symptom clusters in decompensated cirrhosis patients. A cross-sectional study design using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Demographical, physiological, psychological and sociological characteristics and the pre-hospital symptoms of 292 decompensated cirrhotic patients were collected from October 2021 to March 2023 in China. Frequencies, percentages, means, standard deviations, independent samples t-tests, one-way analysis of variance, exploratory factor analysis, multiple stepwise regression analysis and network analysis were used for data analysis. 'I don't look like myself' and itching were core and bridge symptoms, while bloating and lack of energy were sentinel symptoms in decompensated cirrhotic patients. Monthly family income, anxiety, depression, social support and disease duration influenced the neuropsychological symptom cluster, with worrying as the strongest predictor symptom. Influential factors for cirrhosis-specific symptom cluster included Child-Pugh class, monthly family income, disease duration, anxiety and depression, with itching being the strongest predictor symptom. Monthly family income, disease duration and depression were influential factors for gastrointestinal symptom cluster, with loss of appetite as the strongest predictor symptom. Neuropsychological, cirrhosis-specific and gastrointestinal symptom clusters were formed in decompensated cirrhotic patients. Through network analysis, direct connections between symptoms, symptom clusters and their influencing factors were revealed, thereby offering clinicians a foundation for effectively managing patients' pre-hospital symptoms. Decompensated cirrhosis patients commonly have multiple symptoms, while the management of pre-hospital symptoms is often suboptimal. This study identified neuropsychological, cirrhosis-specific, gastrointestinal symptom clusters and recognized core, bridge and sentinel symptoms in these patients. It also revealed the most prominent symptoms within each cluster. This provides insight into the hierarchy of symptoms, improving symptom management in decompensated cirrhosis. There was no patient or public involvement.

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.

ONBLR: An effective optimized ensemble ML approach for classifying liver cirrhosis disease

Liver cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. Early diagnosis and management can help slow the progression of the disease and improve quality of life. Developing more accurate and non-invasive methods for the early detection of liver cirrhosis to enhance timely intervention and improve patient outcomes. Effective prediction reduces overall cirrhosis patients' mortality due to various bleeding, making further study in this field a significant task. Therefore, we propose a novel ensemble machine learning based approach for classification. Label encoding and data normalization using the min-max approach are performed in preprocessing. Then, characteristics such as age, gender, Liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and Medical history and comorbidities are retrieved using the ConvNeXt approach. Using the Improved Grasshopper optimization algorithm (IGOA), the essential features that increase the accuracy even more were selected. Finally, the optimized ensemble machine learning approach naïve Bayes and logistic regression (ONBLR) is employed to classify the liver cirrhosis disease. Harris Hawks optimization algorithm is employed to optimize the hyperparameters. The proposed approach is compared with the existing state-of-the-art machine learning approaches. While compared with existing approaches, the proposed model yields 99.18 % accuracy, 99.12 % of Sensitivity and 98.92 % of specificity which is greater among other approaches.