A Case of Coil-Assisted Retrograde Transvenous Obliteration to Treat Colonic Varices.

Colonic variceal bleeding is a rare cause of lower gastrointestinal (GI) bleeding, which carries a high mortality rate. Due to limited data, the optimal management of colonic variceal bleeding is not known. Coil-assisted retrograde transvenous obliteration (CARTO) has been shown to be very effective in managing non-esophageal variceal bleeding, but only a few cases demonstrate its effectiveness in treating colonic variceal bleeding. Here we present a case of colonic variceal bleeding treated with CARTO in order to expand on the limited body of evidence showing its efficacy in effectively treating this rare cause of life-threatening GI bleeding.

Tobacco is a Leading Risk Factor for Liver and Extrahepatic Cancers in Patients With Liver Cirrhosis: A Prospective Cohort Study.

Background & aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies. Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models. Results: A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer. Conclusions: Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.

Real-World Risk and Outcome of Liver Cirrhosis in Patients with Hyperlipidemia Treated with Red Yeast Rice: A Retrospective Cohort Study.

Objective: Sustained hyperlipidemia contributes to fatty liver and liver cirrhosis. Red yeast rice (RYR) effectively improved the lipid profile; however, the effects of RYR on the risk of incident liver cirrhosis remain to be elucidated. We aimed to evaluate the beneficial effects of RYR use on the risk and outcome of liver cirrhosis. Patients and methods: We identified 156,587 adults who had newly diagnosed hyperlipidemia in 2010-2016 from health insurance data in this retrospective cohort study. Using propensity score matching, we selected 34,367 patients who used RYR and 34,367 patients who used lovastatin. Events of incident liver cirrhosis that occurred in the two cohorts during the follow-up period of 2010-2019 were identified. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (Cis) for liver cirrhosis risk associated with RYR use in the multiple Cox proportional hazard model. Results: Compared with patients who used lovastatin, patients who used RYR had a decreased risk of liver cirrhosis (HR 0.60, 95% CI 0.57-0.63), and this association was significant in various subgroups. A biological gradient relationship between the frequency of RYR use and decreased liver cirrhosis was observed (p for trend < 0.0001). Reduced postcirrhosis jaundice (HR 0.56, 95% CI 0.43-0.72), ascites (HR 0.37, 95% CI 0.28-0.50), hepatic coma (HR 0.36, 95% CI 0.26-0.50), and mortality (HR 0.48, 95% CI 0.38-0.61) were also associated with RYR use. Conclusion: We demonstrated the beneficial effects of RYR use on the risk and outcome of liver cirrhosis; however, the lack of compliance data should be considered. However, our study did not infer causality or claim the superiority of RYR over lovastatin.

Comparison of gastrointestinal bleeding in patients with and without liver cirrhosis.

OBJECTIVES: Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics. METHODS: A retrospective study on cirrhotics hospitalized for GIB 2010-2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included. RESULTS: Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6-32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% (p = 0.002), less commonly gastric ulcer 13% vs. 31% (p < 0.001), duodenal ulcer 9% vs. 29% (p < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls (p < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls (p < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls (p < 0.001). CONCLUSIONS: Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Advances in the management of complications from cirrhosis.

Cirrhosis with complications of liver decompensation and hepatocellular carcinoma (HCC) constitute a leading cause of morbidity and mortality worldwide. Portal hypertension is central to the progression of liver disease and decompensation. The most recent Baveno VII guidance included revision of the nomenclature for chronic liver disease, termed compensated advanced chronic liver disease, and leveraged the use of liver stiffness measurement to categorize the degree of portal hypertension. Additionally, non-selective beta blockers, especially carvedilol, can improve portal hypertension and may even have a survival benefit. Procedural techniques with interventional radiology have become more advanced in the management of refractory ascites and variceal bleeding, leading to improved prognosis in patients with decompensated liver disease. While lactulose and rifaximin are the preferred treatments for hepatic encephalopathy, many alternative treatment options may be used in refractory cases and even procedural interventions such as shunt embolization may be of benefit. The approval of terlipressin for the treatment of hepatorenal syndrome (HRS) in the USA has improved the way in which HRS is managed and will be discussed in detail. Malnutrition, frailty, and sarcopenia lead to poorer outcomes in patients with decompensated liver disease and should be addressed in this patient population. Palliative care interventions can lead to improved quality of life and clinical outcomes. Lastly, the investigation of systemic therapies, in particular immunotherapy, has revolutionized the management of HCC. These topics will be discussed in detail in this review.

Unveiling Renal Lipid Deposition: A Rare Case of Hepatic Glomerulosclerosis Resembling Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency Post Liver Transplantation.

Hepatic glomerulosclerosis, a renal complication of liver cirrhosis, presents challenges in diagnosis and management. This case report discusses the rarity of kidney biopsy findings resembling lecithin-cholesterol acyltransferase (LCAT) deficiency post liver transplantation. We present the case of a patient with end-stage liver disease (ESLD) from alcohol-related cirrhosis, who underwent orthotopic liver transplantation (OLT) with persistent proteinuria after transplantation. Kidney biopsy revealed features of hepatic glomerulopathy resembling both IgA nephropathy (IgAN) and LCAT deficiency. The histopathological similarities between hepatic glomerulosclerosis and LCAT deficiency suggest a potential link between liver disease and lipid deposition in the kidneys. The clinical course and outcomes of such renal alterations post liver transplantation remain uncertain, highlighting the need for further research in glomerular pathology in the context of liver transplantation. This case underscores the importance of kidney biopsy in ESLD patients and the necessity for more attention to glomerular pathology post liver transplantation, especially in the current era of increasing liver transplantation rates.

Evolution of splenomegaly in liver cirrhosis: simulation using an electronic circuit.

PURPOSE: The evolution of splenomegaly in patients with liver cirrhosis remains largely unknown. In this study, we followed the changes in splenic volume and established the natural course of splenomegaly. We developed an electronic circuit that simulated splenoportal circulation and identified the underlying hemodynamic mechanisms. MATERIALS AND METHODS: This retrospective observational study included 93 patients with cirrhosis. Splenic volumes were measured in imaging studies at 6-month intervals and normalized by the ratio of each patient's maximum volume during follow-up (%Vmax). An electronic simulation model was constructed using software and realized on a breadboard. RESULTS: Overall, the %Vmax increased from 0.77 ± 0.21 to a maximum of 1.00 ± 0.00 (p < 0.001) during a median follow-up of 23 (3 - 162) months and then decreased to 0.84 ± 0.18 (p < 0.001) during the next 9 (3 - 132) months. No interventional radiology procedure was performed to improve hepatic fibrosis and portal hypertension. The evolution of %Vmax showed single-peaked symmetry. An electronic simulation model showed that the upslope of the evolution curve was dependent on the increased intrahepatic vascular resistance and portal hypertension, whereas the downslope was dependent on the decreased portosystemic shunt (PSS) resistance. CONCLUSIONS: Splenomegaly in cirrhotic patients aggravated over a period of 23 months and then regressed spontaneously to its initial volume. Electronic simulation of splenoportal circulation showed that splenic enlargement was due to the advancement of liver cirrhosis and portal hypertension, whereas its regression was due to the development of a PSS.

Prevalence of steatotic liver disease, advanced fibrosis and cirrhosis among community-dwelling overweight and obese individuals in the USA.

BACKGROUND: There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA. METHODS: This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively. RESULTS: The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m2, respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories. CONCLUSIONS: Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered.

Novel Morphological Profiling Assay Connects ex Vivo Endothelial Cell Responses to Disease Severity in Liver Cirrhosis.

Background and Aims: Endothelial cell (EC) dysfunction in response to circulating plasma factors is a known causal factor in many systemic diseases. However, no appropriate assay is available to investigate this causality ex vivo. In liver cirrhosis, systemic inflammation is identified as central mechanism in progression from compensated to decompensated cirrhosis (DC), but the role of ECs therein is unknown. We aimed to develop a novel ex vivo assay for assessing EC responses to patient-derived plasma (PDP) and assess the potential of this assay in a cohort of liver cirrhosis patients. Methods: Image-based morphological profiling was utilized to assess the impact of PDP on cultured ECs. Endothelial cell (EC) monolayers were exposed to 25% stabilized PDP (20 compensated cirrhoses, 20 DCs, and 20 healthy controls (HCs). Single-cell morphological profiles were extracted by automated image-analysis following staining of multiple cellular components and high-content imaging. Patient profiles were created by dimension reduction and cell-to-patient data aggregation, followed by multivariate-analysis to stratify patients and identify discriminating features. Results: Patient-derived plasma (PDP) exposure induced profound changes in EC morphology, displaying clear differences between controls and DC patients. Compensated cirrhosis patients showed overlap with healthy controls and DC patients. Supervised analysis showed Child-Pugh (CP) class could be predicted from EC morphology. Most importantly, CP-C patients displayed distinct EC phenotypes, in which mitochondrial changes were most discriminative. Conclusion: Morphological profiling presents a viable tool to assess the endothelium ex vivo. We demonstrated that the EC phenotype corresponds with disease severity in liver cirrhosis. Moreover, our results suggest the presence of mitochondrial dysfunction in ECs of CP-C patient.

Impact of Physical Activity on Overall Survival and Liver Cirrhosis Incidence in Steatotic Liver Disease: Insights from a Large Cohort Study Using Inverse Probability of Treatment Weighting.

Physical activity is a cornerstone of a healthy lifestyle, with benefits in managing chronic diseases. This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD). The primary outcomes of interest were overall survival in the entire population, individuals without steatotic liver disease, patients with MASLD, and those with MetALD. The secondary outcomes included the incidence of liver cirrhosis. Participants were categorized based on physical activity frequency and Kaplan-Meier survival curves and Cox proportional hazards models were used for analysis. Higher physical activity was associated with significantly better survival in the overall cohort and MASLD cohort before and after inverse probability of treatment weighting (IPTW). In participants without steatotic liver disease and the MetALD cohort, higher physical activity showed significant survival improvement after IPTW. For the incidence of liver cirrhosis, higher physical activity showed significant associations before IPTW in the overall cohort and MASLD cohort, but these associations were not significant after IPTW. Marginal significance was observed in the MetALD cohort before and after IPTW. In conclusion. promoting physical activity may be key in improving liver-related outcomes.

Alterations in Intestinal Mucosal Barrier Visualized by Confocal Laser Endomicroscopy in Liver Cirrhosis: A Pilot Trial (AMBIC).

BACKGROUND: Chronic liver disease occurs throughout the world irrespective of region, age, sex, or race, and it is caused by a variety of liver conditions. One of the most frequent infectious complications in liver cirrhosis that severely reduces the median survival is spontaneous bacterial peritonitis. Current guidelines recommend a paracentesis before starting an antibiotic prophylaxis for this complication. METHODS: Selective intestinal decontamination significantly lowers the rate of first or recurrent SBP in cirrhotic patients, so in this study we aimed to investigate and quantify the intestinal integrity of patients with liver cirrhosis and correlate a pathologically increased permeability with the incidence of SPB. We included 14 patients who met the inclusion criteria. No patient was excluded. For the CLE investigation, we use probe based confocal laser endomicroscopy techniques from Mauna Kea (Cellvizio), enabling in vivo surface imaging. The images (optical biopsies) were analyzed for functional and structural barrier defects after the procedure using Mauna Kea software (version 1.0.09). RESULTS: Because of the small number of included patients and healthy controls, most results are lacking statistical relevance. We found that the CLE investigation showed an increased intestinal permeability in patients with liver cirrhosis, in concordance with previous published data, based on other assessment methods. CONCLUSIONS: This study confirms that previously published permeability scores can be applied for patients with liver cirrhosis and is, to our knowledge, the first to investigate the intestinal permeability in vivo in patients with liver cirrhosis. Further data are needed to identify patients at risk and help develop new and less invasive diagnostic criteria for cirrhotic patients who may profit from a prophylactic antibiotic treatment.

Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.

Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance.

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.

Bilirubin Molecular Species Play an Important Role in the Pathophysiology of Acute-on-Chronic Liver Failure.

Bilirubin plays a key role in early diagnosis, prognosis, and prevention of liver diseases. Unconjugated bilirubin (UCB) requires conversion to a water-soluble form through liver glucuronidation, producing monoglucuronide (BMG) or diglucuronide bilirubin (BDG) for bile excretion. This study aimed to assess the roles of bilirubin's molecular species-UCB, BMG, and BDG-in diagnosing and understanding the pathogenesis of liver cirrhosis in patients with acute-on-chronic liver failure (ACLF), compensated liver cirrhosis (LC) patients, and healthy individuals. The study included patients with ACLF and compensated LC of diverse etiologies, along with healthy controls. We collected laboratory and clinical data to determine the severity and assess mortality. We extracted bilirubin from serum samples to measure UCB, BMG, and BDG using liquid chromatography-mass spectrometry (LC-MS). The quantification of bilirubin was performed by monitoring the mass charge (m/z) ratio. Of the 74 patients assessed, 45 had ACLF, 11 had LC, and 18 were healthy individuals. Among ACLF patients, the levels of molecular species of bilirubin were UCB 19.69 µmol/L, BMG 47.71 µmol/L, and BDG 2.120 µmol/L. For compensated cirrhosis patients, the levels were UCB 11.29 µmol/L, BMG 1.49 µmol/L, and BDG 0.055 µmol/L, and in healthy individuals, the levels were UCB 6.42 µmol/L, BMG 0.52 µmol/L, and BDG 0.028 µmol/L. The study revealed marked elevations in the bilirubin species in individuals with ACLF compared to those with compensated cirrhosis and healthy controls, underscoring the progression of liver dysfunction. The correlation of BMG and BDG levels with commonly used inflammatory markers suggests a relationship between bilirubin metabolism and systemic inflammation in ACLF.

S100A8/A9-activated IFNγ+ NK cells trigger ß-cell necroptosis in hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIMS: Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear. METHODS: Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet ß cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation. RESULTS: Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated ß cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased ß cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE. CONCLUSION: Together, the data indicate that IFN-γ produced by NK cells induces ß cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.

[Ethical aspects regarding the management of patients with liver disease in the intensive care unit]. / Ethische Aspekte beim Management von Patienten mit Leberkrankung auf der Intensivstation.

BACKGROUND: Especially in terms of alcohol-related liver cirrhosis, discussions quickly arise in times of scarce resources about the justification for carrying out (prolonged) intensive care measures. AIMS, MATERIALS, AND METHODS: The following review aims to address ethical aspects specifically in patients with liver cirrhosis in the intensive care unit. A possible structured approach is presented. CONCLUSION: A general recommendation is not possible. Ultimately, decisions remain on a case-by-case basis and have to take a wide variety of perspectives into account.

Association between serum vitamin D status and severity of liver cirrhosis: implications for therapeutic targeting in Nigerian patients.

BACKGROUND: Liver cirrhosis is a chronic and progressive liver disease with significant global health implications. Recent evidence suggests an association between serum vitamin D levels and the severity of liver cirrhosis, potentially serving as a therapeutic target. This study aimed to investigate the relationship between serum vitamin D status and the severity of liver cirrhosis in a population of Nigerian patients. METHODS: This analytical, cross-sectional study involved 201 participants, including 103 with liver cirrhosis and 98 age- and sex-matched controls. Serum vitamin D was measured using ELISA, with deficiency defined as < 20 ng/ml. Cirrhosis severity was assessed using Child-Pugh and MELD scores. Spearman's correlation was used to assess the relationship between vitamin D and severity of liver cirrhosis while ordinal regression analysis assessed its performance as an indicator of the disease severity. RESULT: Among cirrhotic patients, 36.9% were deficient, 31.1% insufficient, and 32.0% had sufficient vitamin D levels. Serum vitamin D showed strong negative correlations with Child-Pugh and MELD scores (r = -0.696, p < 0.001; r = -0.734, p < 0.001, respectively). Ordinal regression showed that higher vitamin D levels were associated with lower severity scores (Child-Pugh: OR = 0.856, 95% CI: 0.815-0.900, p < 0.001; MELD: OR = 0.875, 95% CI: 0.837-0.915, p < 0.001). CONCLUSION: Lower serum vitamin D levels correlated with increased liver cirrhosis severity, suggesting its potential as both a prognostic marker and therapeutic target. Further studies should investigate the efficacy of vitamin D supplementation in improving cirrhosis outcomes.

Therapeutic potential of rifaximin in liver diseases.

Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin.

Resmetirom and Metabolic Dysfunction-Associated Steatohepatitis: Perspectives on Multidisciplinary Management from Global Healthcare Professionals.

PURPOSE OF REVIEW: The approval of resmetirom brings great hope to patients with metabolic dysfunction-associated steatohepatitis (MASH). The purpose of this review is to explore its impact on the global health environment. The implementation of multidisciplinary management MASH is proposed. RECENT FINDINGS: Resmetirom has benefits in the treatment of MASH, and its safety and effectiveness have been studied. The adverse events (AEs) need to be noticed. To improve patient outcomes, a multimodal approach with medication such as resmetirom, combined with metabolic and bariatric surgery (MBS) and lifestyle interventions can be conducted. MASH, a liver disease linked with obesity, is a challenging global healthcare burden compounded by the absence of any approved pharmacotherapy. The recent conditional approval by the Food and Drug Administration (FDA) in the United States of resmetirom, an oral, liver-directed, thyroid hormone receptor beta-selective agonist, marks a significant milestone, offering a treatment option for adults with non-cirrhotic MASH and who have moderate to advanced liver fibrosis. This narrative review discusses the efficacy and safety of resmetirom and its role in the therapeutic landscape of MASH treatment. Despite the promising hepatoprotective effect of resmetirom on histological liver endpoints, its use need further research, particularly regarding ethnic differences, effectiveness and cost-effectiveness, production scalability, social acceptance and accessibility. In addition, integrating resmetirom with other multidisciplinary therapeutic approaches, including lifestyle changes and MBS, might further improve clinical liver-related and cardiometabolic outcomes of individuals with MASH. This review highlights the importance of a comprehensive treatment strategy, supporting continued innovation and collaborative research to refine treatment guidelines and consensus for managing MASH, thereby improving clinical patient outcomes in the growing global epidemic of MASH. Studies done to date have been relatively short and ongoing, the course of the disease is highly variable, the conditions of various patients vary, and given this complex clinical phenotype, it may take many years of clinical trials to show long-term benefits.

Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.