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Background: Etiology of chronic liver disease (CLD) has an impact on the profile of spontaneous bacterial peritonitis (SBP) in terms of infection acquisition, resistance pattern, and treatment outcome. Aims and Objectives: This study aimed to study infection acquisition, antibiotic resistance pattern, and treatment outcome in patients with non-alcoholic fatty liver disease (NAFLD) cirrhosis with SBP. Materials and Methods: This observational prospective study was carried out in Government Medical College; Srinagar: over a period of 2 years from 2017 onward. We did analysis of patients with NAFLDs cirrhosis. We studied infection acquisition, antibiotic resistance pattern, and treatment outcome in this group of patients. Results: Over 2-year period, 246 patients were enrolled. The mean age of patients was 57.09±13.90 years. Hepatitis B virus and NAFLD were the major etiological contributors to the burden of CLD amounting to 51.20% in Kashmir. SBP was present in 33/57 (57.90%) of NAFLD cirrhosis patients. Child-Turcotte-Pugh Class C was 63.60%. Patients with culturepositive SBP (CP-SBP) were 45.45%. In patients of SBP with etiology other than NAFLD, CP-SBP was 61% whereas culture-negative SBP was 38.77%. Conclusion: In our region, NAFLD is one of the leading contributors to CLD. In this study, the trend toward worse treatment outcome and mortality in the patients with NAFLD SBP was observed. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are small, nonreplicating, lipid-encapsulated nanoparticles that carry protein and nucleic acid cargo derived from their tissue of origin. Due to their capacity to provide comparable insights to solid organ biopsy through a minimally invasive collection procedure, EVs provide an attractive biomarker source. This review will provide an insight, how EVs in circulation may provide a novel way to assess cholestasis and will address the possibility of getting a better understanding of the mechanisms of cholestasis of pregnancy through the use of serial hepatic-specific EVs as a window. [ABSTRACT FROM AUTHOR]

Background and aims: Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. Methods: We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. Results: Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. Conclusions: ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic has significantly impacted special populations, including immunocompromised individuals, people living with HIV (PLWHIV), pediatric patients, and those with chronic liver disease (CLD). This scoping review aims to map the clinical outcomes of these vulnerable groups when infected with various SARS-CoV-2 variants. The review identifies trends and patterns, noting that early variants, such as Alpha and Delta, are associated with more severe outcomes, including higher hospitalization and mortality rates. In contrast, the Omicron variant, despite its increased transmissibility, tends to cause milder clinical manifestations. The review highlights the necessity for ongoing surveillance and tailored healthcare interventions due to the heterogeneity of patient populations and the evolving nature of the virus. Continuous monitoring and adaptive healthcare strategies are essential to mitigate the impact of COVID-19 on these high-risk groups. [ABSTRACT FROM AUTHOR]

Objective: To assess economic and social issues faced by cirrhotic patients & its financial burden for developing nations like Pakistan. Method: This cross-sectional study was carried out at the Department of Gastroenterology & Hepatology, Shaikh Zayed Hospital, Lahore, Pakistan during the period between July & December 2019. Patients with liver cirrhosis were recruited and information regarding disease, financial status, treatment expenses & dependency was recorded. Results: A total of 450 patients were recruited, 272 (60%) were males & 178 (40%) were females, with mean age 55.4±6.2 years. HCV was cause of cirrhosis in 86% of cases, 65% were diagnosed incidentally and 39.6% were illiterate. About 82.7% were urban while only 28.7% own their own home. Co-morbid conditions including diabetes, hypertension & ischemic heart disease were present in 54% of cases. Monthly income was

Objectives: Congestive hepatopathy is a significant complication for children suffering from right-sided heart disease (RHD). We hypothesize that hospitalized pediatric patients with ascites will have congestive hepatopathy leading to advanced liver disease if their cardiac condition is RHD versus non-right-sided heart disease (NRHD). Methods: This is a retrospective cohort study of pediatric patients who presented with an ascites diagnosis (ICD-10 R18) and at least one cardiac diagnosis. Patient demographics, past medical history, laboratory values, imaging results, calculated clinical scores (e.g., APRI, FIB-4), treatment, length of stay (LOS), and death at hospital discharge were analyzed. Results: Of the 136 patients with ascites, 21 patients presented with a primary cardiac disease (12 in RHD and 9 in NRHD). Of these patients, eight (38%) were female, and nine (43%) were White, seven (33%) were Black, and five (24%) were unknown. The RHD group had a mean age of 5.1 Y (vs. 9.5 Y in NRHD). The mean APRI score in RHD patients was 2.87, and it was 0.85 in NRDH. Treatments were similar, with most patients requiring diuretics (11 RHD (92%) vs. 8 NRDH (89%)); 5 RHD (42%) vs. 4 NRDH (44%) required inotropic support. RHD patients had a longer LOS, with an average of 92 days vs. 52 days for NRDH patients. Overall, each group had one death at discharge (8% RHD vs. 11% NRDH). Conclusions: In the realm of children with ascites, the subset grappling with congestive heart disease paints a unique picture. In this context, ascites stands as an elusive predictor of liver decompensation, defying conventional diagnostic pathways. [ABSTRACT FROM AUTHOR]

Simple Summary: Intestinal microbiome dysbiosis in human patients with chronic liver disease is known to influence disease progression. Several studies show benefits from administering probiotics/prebiotics. Similar intestinal dysbiosis was identified in dogs with chronic liver disease, but clinical trials evaluating the benefits of gut microbiome modulation in these patients are lacking. In the study, 32 dogs with chronic hepatobiliary disease were divided into two groups: one treated with a probiotics/prebiotics complex for 4–6 weeks and untreated control group. All dogs underwent clinical evaluation, complete anamnesis, bloodwork, abdominal ultrasound, fecal bile acids, and gut microbiome evaluation. Treated dogs showed a significant reduction in biochemical markers of liver injury and resolution of gastrointestinal signs compared to the control group. Some qualitative modifications of the gut microbiome were observed, but no significant changes in the fecal bile acids profile were detected in association with the probiotics/prebiotics administration. 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. [ABSTRACT FROM AUTHOR]

Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post‐abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random‐effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I2, τ2 statistics, and P‐value. Eight studies were included for review. Six studies reported incident events of post‐abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15–0.69%). The mean values for pre‐procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0–0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure‐related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements. [ABSTRACT FROM AUTHOR]

Background and Aim: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationships between peripheral blood uric acid, thyroid hormone levels and the risk of non-alcoholic fatty liver disease (NAFLD) . Methods Totally 139 NAFLD patients (NAFLD group) and 54 healthy adults who underwent physical examinations (healthy control group) were selected. General information and lab‑ oratory test results were collected and compared between patients of the two groups, including gender, age, fasting blood glucose (FBS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) ，γ-glutamyltransferase (γ-GT) ，tri‑ glycerides (TC), total cholesterol (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), serum uric acid, creatinine (Cr), thyroid stimulating hormone (TSH), and total T3 (TT3 ), total thyroxine (TT4 ), free T3 (FT3 ), and free thyroxine (FT4 ) . Logistic regression method was used to analyze the influencing factors of NAFLD. Logistic regression method was used to analyze the influencing factors of NAFLD with normal and elevated serum uric acid levels by using serum uric acid level of 416 μmol/L as the judgment standard. Results The NAFLD group had higher levels of age, ALT, AST，γ-GT, TG, HDL, and uric acid in comparison with those of the healthy control group, while the FT4 level was lower (all P<0. 05) . ALT and HDL levels were independent influencing factors for NAFLD. The age, FBS, ALT, AST，γ-GT, TG, and uric acid levels were higher in the NAFLD group with normal serum uric acid level than in the healthy control group, while TT3, FT4, and HDL levels were lower (all P<0. 05) . There were no statistically significant dif‑ ferences in general data or laboratory test results between the NAFLD group with elevated serum uric acid levels and the healthy control group (all P>0. 05) . The γ-GT, HDL, TT3, and FT4 levels were independent risk factors for NAFLD in pa‑ tients with normal serum uric acid levels. Conclusions The correlation between the incidence of NAFLD and thyroid hormone level is influenced by the peripheral blood uric acid level. When the peripheral blood uric acid level is within the normal range, TT3 and FT4 are independent risk factors for the onset of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Liver cirrhosis presents significant challenges in the pediatric population due to a complex interplay of etiological factors, clinical manifestations, and limited therapeutic options. The leading contributors to cirrhosis among pediatric patients are chronic cholestasis, metabolic disorders present from birth, and long-term hepatitis. Materials and method: Our narrative review aimed to synthesize literature data on the etiology, clinical picture, diagnostic techniques, optimal management of complications, and timely transplantation. Results: The epidemiology of liver cirrhosis in pediatric patients is evolving. The introduction of a universal vaccination and effective long-term viral suppression in viral hepatitis have significantly decreased complications rates. Liver transplantation programs worldwide have also improved the management of cirrhosis complications. Conclusions: Early diagnosis, comprehensive management strategies, and advancements in treatment modalities are critical for improving outcomes. Understanding these differences is crucial in providing age-appropriate care and support for those affected by cirrhosis. [ABSTRACT FROM AUTHOR]

Background: The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology. Methods: We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation. Results: In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001). Conclusions: The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (AH) affect a large part of the general population worldwide. Dysregulation of lipid metabolism and alcohol toxicity drive disease progression by the activation of hepatic stellate cells and the capillarization of liver sinusoidal endothelial cells. Collagen deposition, along with sinusoidal remodeling, alters sinusoid structure, resulting in hepatic inflammation, portal hypertension, liver failure, and other complications. Efforts were made to develop treatments for NASH and AH. However, the success of such treatments is limited and unpredictable. We report a strategy for NASH and AH treatment involving the induction of integrin αvβ3-mediated cell apoptosis using a rationally designed protein (ProAgio). Integrin αvβ3 is highly expressed in activated hepatic stellate cells (αHSCs), the angiogenic endothelium, and capillarized liver sinusoidal endothelial cells (caLSECs). ProAgio induces the apoptosis of these disease-driving cells, therefore decreasing collagen fibril, reversing sinusoid remodeling, and reducing immune cell infiltration. The reversal of sinusoid remodeling reduces the expression of leukocyte adhesion molecules on LSECs, thus decreasing leukocyte infiltration/activation in the diseased liver. Our studies present a novel and effective approach for NASH and AH treatment. [ABSTRACT FROM AUTHOR]

Background: Pirfenidone has demonstrated significant anti‐inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti‐inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro‐inflammatory cytokines, apoptosis, and fibroblast activation. Objective: To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. Findings: Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. Conclusion: Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions. [ABSTRACT FROM AUTHOR]

Serum phosphatidylethanol (PEth) testing has emerged as a promising biomarker for assessing recent alcohol consumption, surpassing the limitations of self-reported data. Limited clinical data exists comparing PEth levels and patients' reported alcohol intake. Compare PEth testing results with self-reported alcohol intake and assesses variables associated with underreporting. Single-center retrospective cohort of patients with a diagnosis of chronic liver disease and serum PEth. A patient's first positive PEth (>/=10 ng/mL) and self-reported alcohol consumption was used. PEth results were categorized as mild (10–20), moderate (20–200), or heavy (>200). Severity measures between self-report and PEth were assessed using Bhapkar's test and Bonferroni-adjusted McNemar's tests. Demographic data was analyzed using Chi-Square tests. 279 patients were included. 94 (33.7%) patients had consistency with self-report, and 185 patients had inconsistencies in their report (66.3%, p < 0.001). Of 279 patients, 161 (57.7%) underreported their alcohol consumption, and 55 (19.7%) heavy PEth patients underreported alcohol consumption as light. 58% of alcohol-related and 56.4% of non-alcohol-related cirrhotic patients underreported their alcohol use. In our cohort, only one third of self-reported alcohol consumption was consistent with the PEth level. Notably, 57.7% underreported alcohol intake. Our study reinforces the clinical importance of PEth testing as an objective clinical measure. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease. [ABSTRACT FROM AUTHOR]

ObjectiveWe aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10.DesignThis was a retrospective database review.SettingAll centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included.Patients/participantsPatients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included.InterventionOpen reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment.Main outcome measurementsThirty-day complications, mortality, readmission, and reoperation rates were measured.ResultsOf the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications.ConclusionsA MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty.Level of evidencePrognostic Level III.

Lucy Gracen,1 Melanie Aikebuse,2,3 Babak Sarraf,2– 4 Steven M McPhail,5 Anthony W Russell,6 James O’Beirne,7 Katharine M Irvine,8 Suzanne Williams,9 Patricia C Valery,4,&ast; Elizabeth E Powell2– 4,&ast; 1Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; 3Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Australian Centre for Health Services Innovation School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia; 6Endocrinology and Diabetes, the Alfred Hospital, Melbourne, VIC, Australia; 7Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, Australia; 8Mater Research, Translational Research Institute, Brisbane, QLD, Australia; 9Inala Primary Care General Practice, Inala, QLD, Australia&ast;These authors contributed equally to this workCorrespondence: Elizabeth E Powell, Centre for Liver Disease Research, Faculty of Medicine, Translational, Research Institute, The University of Queensland, Level 5, West Wing, 37, Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia, Tel +61 412 014 337, Email e.powell@uq.edu.auBackground: Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear.Methods: Sequential adults with T2D attending selected community clinics during 2021– 2023 were invited to receive a “liver health check” (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. “Template” letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants’ GPs.Results: Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥ 8), 15 participants with ‘red flags’ (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the “template” letters favourably on a Likert rating scale.Conclusion: The low rate of participation in the “liver health check” and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.Keywords: NAFLD, primary care, chronic liver disease, FibroScan

Background: Etiology of chronic liver disease (CLD) has an impact on the profile of spontaneous bacterial peritonitis (SBP) in terms of infection acquisition, resistance pattern, and treatment outcome. Aims and Objectives: This study aimed to study infection acquisition, antibiotic resistance pattern, and treatment outcome in patients with non-alcoholic fatty liver disease (NAFLD) cirrhosis with SBP. Materials and Methods: This observational prospective study was carried out in Government Medical College; Srinagar: over a period of 2 years from 2017 onward. We did analysis of patients with NAFLDs cirrhosis. We studied infection acquisition, antibiotic resistance pattern, and treatment outcome in this group of patients. Results: Over 2-year period, 246 patients were enrolled. The mean age of patients was 57.09±13.90 years. Hepatitis B virus and NAFLD were the major etiological contributors to the burden of CLD amounting to 51.20% in Kashmir. SBP was present in 33/57 (57.90%) of NAFLD cirrhosis patients. Child-Turcotte-Pugh Class C was 63.60%. Patients with culture-positive SBP (CP-SBP) were 45.45%. In patients of SBP with etiology other than NAFLD, CP-SBP was 61% whereas culture-negative SBP was 38.77%. Conclusion: In our region, NAFLD is one of the leading contributors to CLD. In this study, the trend toward worse treatment outcome and mortality in the patients with NAFLD SBP was observed.

Abstract A combined model was developed using contrast-enhanced CT-based radiomics features and clinical characteristics to predict liver fibrosis stages in patients with chronic liver disease (CLD). We retrospectively analyzed multiphase CT scans and biopsy-confirmed liver fibrosis. 160 CLD patients were randomly divided into 7:3 training/validation ratio. Clinical laboratory indicators associated with liver fibrosis were identified using Spearman's correlation and multivariate logistic regression correlation. Radiomic features were extracted after segmenting the entire liver from multiphase CT images. Feature dimensionality reduction was performed using RF-RFE, LASSO, and mRMR methods. Six radiomics-based models were developed in the training cohort of 112 patients. Internal validation was conducted on 48 randomly assigned patients. Receptor Operating Characteristic (ROC) curves and confusion matrices were constructed to evaluate model performance. The radiomics model exhibited robust performance, with AUC values of 0.810 to 1.000 for significant fibrosis, advanced fibrosis, and cirrhosis. The integrated clinical-radiomics model had superior diagnostic efficacy in the validation cohort, with AUC values of 0.836 to 0.997. Moreover, these models outperformed established biomarkers such as the aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis 4 score (FIB-4), as well as the gamma glutamyl transpeptidase to platelet ratio (GPR), in predicting the fibrotic stages. The clinical-radiomics model holds considerable promise as a non-invasive diagnostic tool for the assessment and staging of liver fibrosis in the patients with CLD, potentially leading to better patient management and outcomes.

Background: Chronic liver disease (CLD) significantly impacts global health, affecting nearly 1.5 billion individuals. Sodium disturbances are common in CLD and can lead to severe systemic effects. However, the relationship between these disturbances and CLD-related complications such as diarrhea and dehydration is complex and not fully understood. Objective: To assess the sodium disturbances in chronic liver disease patients suffering from diarrhea with dehydration presenting at a tertiary care hospital, in Karachi, Pakistan. Methodology: A cross-sectional study was conducted from October 2022 to July 2023, including individuals aged >18 years diagnosed with CLD, experiencing diarrhea and dehydration, and on diuretic therapy. The blood sample was collected from all of the participants and sent to a laboratory for analysis. The blood is then tested to measure the concentration of sodium in milliequivalents per liter (meq/L). The normal range for sodium levels in the blood typically falls between 135 to 145 meq/L. Levels below or above this range can indicate sodium imbalances. Descriptive statistics and inferential statistics were performed on SPSS. Results: The mean age of the participants was 33.35 years, with a standard deviation of 8.01. Of 126 patients, 38.1% were male, 27% had hypertension, and 15.1% had diabetes. The mean sodium concentration was found as 132.17±14.23 meq/L, with 42.9% of CLD patients experiencing diarrhea and dehydration having sodium levels

Abstract Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients’ stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. Critical relevance statement This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. Key Points Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice. Graphical Abstract

Abstract 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. Methodology 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.

Abstract Background Mitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored. Methods We extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality. Results 96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value

Abstract Background Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. Methods Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). Results Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (β = 0.24, p

Abstract The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p

Introduction: Chronic liver disease is a progressive deterioration of liver functions for duration of more than six months, associated with features of inflammation, destruction and regeneration of the liver parenchyma, resulting in fibrosis or cirrhosis. Liver enzyme elevations are the mainstay for diagnoses. However, variations in sodium, potassium and chloride profiles are often seen in patients presenting with chronic liver disease and its associated complications such as hepatic encephalopathy and advanced cirrhosis. In our study, we hope to better understand the importance of dyselectrolytemia in liver dysfunction and the necessity of routine electrolyte tests performed in the clinical setting. Materials and methods: We analyzed sodium, potassium, chloride and creatinine levels with respect to three time points in hospitalization, that is ‘at the time of admission’, ‘during hospitalization’ and ‘at the time of discharge’ and the amount of variability of each electrolyte parameter with respect to these time points. Results: During the course of hospitalization, sodium and chloride showed no deviation from normalcy. Creatinine showed a decreasing trend towards normalcy and Potassium showed a mild variation in the initial stages of hospitalization but remained within normal limits. Conclusion: The routine testing of sodium and chloride in those with chronic liver disease may be rendered unnecessary in future and that the analysis of potassium and creatinine trends may help prognosticate the status of liver disease through the status of renal function. Nevertheless, further research is essential to better understand the association of these electrolyte parameters with chronic liver disease.

Abstract Background Imaging-based assessment of sarcopenia is a well-validated prognostic tool for patients with chronic liver disease. However, little is known about its value in patients with primary sclerosing cholangitis (PSC). This cross-sectional study aimed to investigate the predictive value of the cross-sectional imaging-based skeletal muscle index (SMI) for transplant-free survival (TFS) in patients with PSC. Methods A total of 95 patients with PSC who underwent abdominal cross-sectional imaging between 2008 and 2022 were included in this retrospective study. SMI was measured at the third lumbar vertebra level (L3-SMI). The cut-off values to define sarcopenia were 10% at 12 months, which is used as MELD standard exception (SE) criterion in Eurotransplant (in Germany only until September 2023), was not significantly associated with TFS in the multivariate Cox regression analysis (HR = 1.417; p = 0.330). Substitution of BMI reduction with L3-SMI in the German SE criteria improved the predictive accuracy of TFS compared to the established SE criteria (multivariable Cox regression analysis: HR = 4.007, p

Background: Cirrhosis is one of the major causes of morbidity and mortality worldwide and the second leading cause of digestive disease mortality. Portal hypertension is the main driver of cirrhosis-related complications such as ascites and variceal bleeding. Portal hypertension is defined as a hepatic venous pressure gradient >5 mm Hg, although it is clinically significant and associated with clinical complications when >10 mm Hg. Summary: Therefore, detection of clinically significant portal hypertension (CSPH) in chronic advanced liver disease or compensated cirrhosis is of paramount importance to guide the management of these patients. Key Messages: This study aimed at revising the non-invasive and invasive tools for assessment of portal hypertension and risk stratification for CSPH in patients with chronic liver disease.

Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients' stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. Critical relevance statement: This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. Key Points: Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice. [ABSTRACT FROM AUTHOR]

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. Methodology: 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. [ABSTRACT FROM AUTHOR]

Background: Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. Methods: Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). Results: Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (β = 0.24, p < 0.001), coping strategies (β=-0.51, p < 0.001), and doctor communication (β=-0.35, p < 0.001) predict mental health. Quality of life is associated with the severity of symptoms (β=-0.36, p < 0.001), coping strategies (β = 0.26, p < 0.05), and doctor communication (β = 0.09, p < 0.05). Conclusions: A 'bio-psycho-social-spiritual' model is recommended for Pakistan's CLD patients which includes the integration of social officers to provide support in four key areas to secure mental health and quality of life of patients. [ABSTRACT FROM AUTHOR]

The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis. [ABSTRACT FROM AUTHOR]