The gut-liver axis includes the bidirectional communication between the gut and the liver, and thus covers signals from liver-to-gut and from gut-to-liver. Disruptions of the gut-liver axis have been associated with the progression of chronic liver diseases, including alcohol-related and metabolic dysfunction-associated steatotic liver disease and cholangiopathies. Immune cells and their expression of pattern recognition receptors, activation markers or immune checkpoints might play an active role in the communication between gut and liver. Here, we present a 26-color full spectrum flow cytometry panel for human cells to decipher the role of circulating immune cells in gut-liver communication during the progression of chronic liver diseases in a non-invasive manner, which has been optimized to be used on patient-derived whole blood samples, the most abundantly available clinical material. Our panel focuses on changes in pattern recognition receptors, including toll-like receptors (TLRs) or Dectin-1, and also includes other immunomodulatory molecules such as bile acid receptors and checkpoint molecules. Moreover, this panel can be utilized to follow the progression of chronic liver diseases and could be used as a tool to evaluate the efficiency of therapeutic targets directed against microbial mediators or modulating immune cell activation.

Alteration in the gut microbiome in human patients with chronic liver disease is a well-known pathophysiological mechanism. Therefore, it represents both a diagnostic and therapeutical target. Intestinal dysbiosis has also been identified in dogs with chronic liver disease, but clinical trials evaluating the effectiveness of synbiotic administration are lacking. Thirty-two dogs with chronic hepatobiliary disease were equally randomized into two groups: one treated with a synbiotic complex for 4-6 weeks (TG) and one untreated control group (CG). All dogs underwent clinical evaluation, complete anamnesis, bloodwork, abdominal ultrasound, fecal bile acids, and gut microbiome evaluation at T0-T1 (after 4-6 weeks). Treated dogs showed a significant reduction in ALT activity (p = 0.007) and clinical resolution of gastrointestinal signs (p = 0.026) compared to control dogs. The synbiotic treatment resulted in a lower increase in Enterobacteriaceae and Lachnospiraceae compared to the control group but did not affect the overall richness and number of bacterial species. No significant changes in fecal bile acids profile were detected with synbiotic administration. Further studies are needed to better evaluate the effectiveness of synbiotic administration in these patients and the metabolic pathways involved in determining the clinical and biochemical improvement.

BACKGROUND: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time.
METHODS: We utilized the N3C level 3 data set with uncensored dates to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared to infection at the onset of the COVID-19 pandemic.
RESULTS: We identified 117,811 total CLD patients infected with SARS-CoV-2 between 3/2020-11/2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1,016) for CLD patients without cirrhosis and 6.3% (1,732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared to infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95%CI 0.08-0.50) for CLD patients without cirrhosis and 0.35 (95%CI 0.18-0.69) for CLD patients with cirrhosis.
CONCLUSIONS: In this N3C study, we found that the observed 30-day CFR decreased progressively for both CLD patients with and without cirrhosis, consistent with broader trends seen in the general population.

UNASSIGNED: Abnormal liver biochemistry (ALB) is common among patients with COVID-19 infection due to various factors. It is uncertain if it persists after the acute infection. We aimed to investigate this.
UNASSIGNED: A multicenter study of adult patients hospitalized for COVID-19 infection, with at least a single abnormal liver function test, was conducted. Detailed laboratory and imaging tests, including transabdominal ultrasound and FibroScan, were performed at assessment and at 6-month follow-up after hospital discharge.
UNASSIGNED: From an initial cohort of 1246 patients who were hospitalized, 731 (58.7%) had ALB. A total of 174/731 patients fulfilled the inclusion criteria with the following characteristics: 48.9% patients had severe COVID-19; 62.1% had chronic liver disease (CLD); and 56.9% had metabolic-associated fatty liver disease (MAFLD). ALB was predominantly of a mixed pattern (67.8%). Among those (55.2%) who had liver injury (aspartate aminotransferase/alanine aminotransferase >3 times the upper limit of normal, or alkaline phosphatase/γ-glutamyl transferase/bilirubin >2 times the upper limit of normal), a mixed pattern was similarly predominant. Approximately 52.3% had normalization of the liver lunction test in the 6-month period post discharge. Patients with persistent ALB had significantly higher mean body mass index (BMI) and serum low-density lipoprotein (LDL), higher rates of MAFLD and CLD, higher mean liver stiffness measurement and continuous attenuated parameter score on FibroScan, and higher rates of liver injury on univariate analysis. Multivariate analysis was not statistically significant.
UNASSIGNED: Approximately 47.7% of COVID-19 patients were found to have persistent ALB up to 6 months following the acute infection, and it was associated with raised BMI, elevated serum LDL, increased rates of MAFLD and CLD, and higher rates of liver injury on univariate analysis, but not on multivariate analysis.

Introduction Chronic liver disease progression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6% and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health problem. Dietary intervention plays an important role in patients with MAFLD.
OBJECTIVE: We aimed to provide a reference for dietary patterns in patients with MAFLD.
METHODS: The presence of MAFLD was determined in the United Kingdom Biobank cohort. Nine dietary pattern scores were derived from the dietary records. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The contrast test was employed to calculate the heterogeneity across MAFLD statuses.
RESULTS: We identified 175,300 patients with MAFLD at baseline. Compared with non-MAFLD, MAFLD was significantly associated with chronic liver disease (CLD) (HR: 3.48; 95% CI: 3.15, 3.84), severe liver disease (SLD) (HR: 2.87; 95% CI: 2.63, 3.14), liver cancer (HR: 1.93; 95% CI: 1.67, 2.23), and liver-related death (LRD) (HR: 1.93; 95% CI: 1.67, 2.23). In the overall cohort, the alternate Mediterranean diet (aMED) (HRCLD: 0.53; 95% CI: 0.37, 0.76; HRSLD: 0.52; 95% CI: 0.37, 0.72), planetary health diet (PHD) (HRCLD: 0.62; 95% CI: 0.47, 0.81; HRSLD: 0.65; 95% CI: 0.51, 0.83), plant-based low-carbohydrate diet (pLCD) (HRCLD: 0.65; 95% CI: 0.49, 0.86; HRSLD: 0.66; 95% CI: 0.51, 0.85), and healthful plant-based diet index (hPDI) (HRCLD: 0.63; 95% CI: 0.47, 0.84; HRSLD: 0.61; 95% CI: 0.47, 0.78) were associated with a lower risk of CLD and SLD. Additionally, unhealthful plant-based diet index (uPDI) was associated with increased risk of CLD (HR: 1.42; 95% CI: 1.09,1.85), SLD (HR: 1.50; 95% CI: 1.19, 1.90), and LRD (HR: 1.88; 95% CI: 1.28-2.78). The aforementioned associations remained consistently strong within the MAFLD subgroup while exhibiting less pronounced in the non-MAFLD group. However, no significant heterogeneity was observed across different MAFLD statuses.
CONCLUSIONS: These findings highlight the detrimental effects of MAFLD on the development of subsequent liver diseases and the importance of dietary patterns in managing MAFLD.

BACKGROUND: The World Health Organization (WHO) reports that Asia and Africa have the highest Chronic Liver Disease (CLD) mortality rate. Cirrhosis, responsible for 22.2 fatalities per 100,000 people, is India\'s 10th most common cause of mortality. The increasing prevalence of chronic liver disease necessitates a study to identify predictive factors for patients who visit the emergency department. Identifying elements that enhance the predictive value of mortality in unstable patients with CLD complications is important in emergency departments. This study aims to determine Clinical and Laboratory Parameters as mortality predictors in adult chronic liver disease patients.
METHODS: The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with chronic liver disease above 18 years of age who satisfied the inclusion criteria were clinically evaluated. Clinical and demographic details were collected, and data was analyzed.
RESULTS: Two hundred thirty-six patients were enrolled. The mean age was 50.77 ± 14.26 years. 78.4% of the participants were men. Abdominal distension, affecting 59.7% of patients, was the most common presenting ailment, followed by melena and hematemesis, affecting 41.9% and 32.6%, respectively. The mean stay in the emergency department was 10.29 ± 8.10 h. Refractory septic shock, the leading cause of mortality, accounts for 69.2% of all deaths, alongside grade 4 hepatic encephalopathy and massive Upper Gastrointestinal (UGI) bleeding, as identified in our study. Factors such as altered mental sensorium, high respiratory rate, low SpO2, increased heart rate, low systolic blood pressure, low diastolic blood pressure, and low Glasgow Coma Scale (GCS) on Emergency Department (ED) arrival are significantly associated with mortality.
CONCLUSIONS: Chronic liver disease, a prevalent condition in India, most commonly seen in middle aged men and lower socioeconomic groups. The parameters independently associated with mortality in our study were presence of altered mental sensorium, Glasgow coma scale, Child Pugh class and need for ICU admission. Understanding the presentation pattern, and mortality predictors can help ED physicians in managing acute events and follow-ups.

BACKGROUND: While low muscle mass is considered a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), whether the relationship is independent of fat mass remains unclear.
OBJECTIVE: This study aims to clarify the association between the sex-specific height-adjusted low skeletal muscle mass index (LSMI) and MASLD.
METHODS: Data from the 2008-2010 Korean National Health and Nutrition Examination Survey were analyzed. LSMI was defined using the 2019 Asian Working Group for Sarcopenia. The non-alcoholic fatty liver disease-liver fat score was used to assess MASLD. Gender-specific 1:1 propensity score matching (PSM) was performed to mitigate the confounding effects of anthropometric variables and lifestyles. Conditional logistic analysis was used on the dataset after PSM to estimate the odds ratio (OR) with a 95% confidence interval (CI).
RESULTS: After PSM, the prevalence of MASLD was significantly higher in men with LSMI than in those without LSMI (37.4% vs. 29.6%). No significant difference was observed in the prevalence of MASLD between groups after PSM in women (20.4% vs. 20.3%). Conditional logistic analysis revealed that the odds of having MASLD were significantly higher in men with LSMI compared to those without LSMI (OR = 1.38, 95% CI: 1.09-1.75), while no significant association was found in women with LSMI (OR = 1.10, 95% CI: 0.87-1.40).
CONCLUSIONS: Height-adjusted LSMI is an independent factor associated with MASLD in the condition of the same level of fat mass in men. Further prospective studies in diverse populations are needed to confirm our findings.

UNASSIGNED: Presarcopenia is a common complication of chronic liver disease. However, the relationship between serum zinc concentration and presarcopenia in patients with chronic liver disease remains unclear. Herein, we examined whether serum zinc concentration could predict presarcopenia in patients with chronic liver disease.
UNASSIGNED: Between October 2015 and December 2019, 278 patients with chronic liver disease (median age, 68 years; women/men, 133/145; hepatitis B virus/hepatitis C virus/negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody, 55/124/99) who underwent abdominal computed tomography (CT) and simultaneous measurement of serum zinc concentration were included. Zinc deficiency and subclinical zinc deficiency were classified using serum zinc concentration cutoff values of <60 and <80 μg/dL [based on the Japanese Society of Clinical Nutrition (JSCN) guidelines], respectively. Additionally, presarcopenia was evaluated based on the skeletal muscle mass as per the Japan Society of Hepatology (JSH)\'s sarcopenia criteria.
UNASSIGNED: Univariate analysis revealed that the following factors were significantly associated with the presence of presarcopenia in patients with chronic liver disease: age (P<0.001), male sex (P<0.001), body mass index (BMI) (P<0.001), serum zinc concentration (P=0.005), fibrosis-4 index (P<0.001), and serum albumin concentration (P=0.03). Additionally, the median L3 skeletal muscle indices were as follows: men, non-presarcopenia group/presarcopenia group, 47.56/37.91 cm2/m2 (P<0.001); women, non-presarcopenia group/presarcopenia group, 41.64/32.88 cm2/m2 (P<0.001). Multivariate analysis using logistic regression analysis revealed that male sex [odds ratio (OR), 0.194; 95% confidence interval (CI): 0.089-0.419; P<0.001], BMI (OR, 0.666; 95% CI: 0.582-0.761; P<0.001), and serum zinc concentration <60 μg/dL (OR, 5.930; 95% CI: 1.480-23.80; P=0.01) were factors associated with presarcopenia. The OR for serum zinc concentration between 60 and 80 μg/dL was 1.910 (95% CI: 0.824-4.420; P=0.13).
UNASSIGNED: Low serum zinc levels may be an independent predictor of presarcopenia in patients with chronic liver disease.

Although the effectiveness and safety of ticagrelor versus clopidogrel may differ in patients with chronic liver disease, there is a scarcity of evidence comparing ticagrelor and clopidogrel in patients with chronic liver disease. We aimed to evaluate the risk of major adverse cardiovascular events (MACE) and major bleeding associated with ticagrelor versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome by chronic liver disease status.
Using the Korean healthcare claim database, we included adult patients who underwent PCI and initiated ticagrelor or clopidogrel treatment within 7 days of an acute coronary syndrome diagnosis. Patients were classified into 2 mutually exclusive groups: patients with chronic liver disease and patients without chronic liver disease. Within each group, the hazard ratios (HRs) with 95% confidence intervals (CIs) of MACE and major bleeding associated with ticagrelor versus clopidogrel were calculated using a Cox proportional hazards model within a 1:1 propensity score (PS) matched cohort.
The final cohort included 14,261 and 148,535 patients with and without chronic liver disease, respectively. After PS matching, the risk of MACE (with chronic liver disease, HR: 1.01, 95% CI: 0.91-1.13; without chronic liver disease, HR: 1.02, 95% CI: 0.98-1.05; P for homogeneity: 0.865) and major bleeding (with chronic liver disease, HR: 1.07, 95% CI: 0.71-1.61; without chronic liver disease, HR: 1.32, 95% CI: 1.15-1.53; P for homogeneity: 0.342) for ticagrelor versus clopidogrel do not vary with chronic liver disease status.
Among acute coronary syndrome patients undergoing PCI, the use of ticagrelor versus clopidogrel was associated with a similar risk of MACE and an increased risk of major bleeding, but these risks did not vary with chronic liver disease status.