Pre-treatment with tocilizumab reduces lipopolysaccharide-induced acute lung injury in biliary cirrhotic rats.

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung.

Unraveling the mechanisms of hepatogenous diabetes and its therapeutic perspectives.

The review focused mainly on the pathogenesis of hepatogenous diabetes (HD) in liver cirrhosis (LC). This review reveals parallels between the mechanisms of metabolic dysfunction observed in LC and type II diabetes (T2DM), suggesting a shared pathway leading to HD. It underscores the role of insulin in HD pathogenesis, highlighting key factors such as insulin signaling, glucose metabolism, insulin resistance (IR), and the influence of adipocytes. Furthermore, the impact of adipose tissue accumulation, fatty acid metabolism, and pro-inflammatory cytokines like Tumor necrosis factor-α (TNF-α) on IR are discussed in the context of HD. Altered signaling pathways, disruptions in the endocrine system, liver inflammation, changes in muscle mass and composition, and modifications to the gut microbiota collectively contribute to the complex interplay linking cirrhosis and HD. This study highlights how important it is to identify and treat this complex condition in cirrhotic patients by thoroughly analyzing the link between cirrhosis, IR, and HD. It also emphasizes the vitality of targeted interventions. Cellular and molecular investigations into IR have revealed potential therapeutic targets for managing and preventing HD.

Development of a non-invasive diagnostic model for high-risk esophageal varices based on radiomics of spleen CT.

PURPOSE: To evaluate the diagnostic performance of radiomics models derived from multi-phase spleen CT for high-risk esophageal varices (HREV) in cirrhotic patients. METHODS: We retrospectively selected cirrhotic patients with esophageal varices from two hospitals from September 2019 to September 2023. Patients underwent non-contrast and contrast-enhanced CT scans and were categorized into HREV and non-HREV groups based on endoscopic evaluations. Radiomics features were extracted from spleen CT images in non-contrast, arterial, and portal venous phases, with feature selection via lasso regression and Pearson's correlation. Ten machine learning models were developed to diagnose HREV, evaluated by area under the curve (AUC). The AUC values of the three groups of models were statistically compared by the Kruskal-Wallis H test and Bonferroni-corrected Mann-Whitney U test. A p-value less than 0.05 was considered statistically significant. RESULTS: Among 233 patients, 11, 6, and 11 features were selected from non-contrast, arterial, and portal venous phases, respectively. Significant differences in AUC values were observed across phases (p < 0.05), and the arterial phase models showed the highest AUC values. The best model in arterial phase was the logical regression model, whose AUC value was 0.85, sensitivity was 83.3%, specificity was 80% and F1 score was 0.81. CONCLUSION: Radiomics models based on spleen CT, especially the arterial phase models, demonstrate high diagnostic accuracy for HREV, offering the potential for early detection and intervention.

Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study.

BACKGROUND & AIMS: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.

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.

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.

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.

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. CLINICAL TRIAL REGISTRATION: NCT04662918.

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.

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.

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.

A non-invasive diagnostic nomogram for CHB-related early cirrhosis: a prospective study.

This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis patients with chronic hepatitis B (CHB) which cannot be detected by conventional non-invasive examination methods but can only be diagnosed through invasive liver puncture for pathological examination. 72 patients with CHB were enrolled in this prospective study, and divided into S4 stage of liver cirrhosis and S0-S3 stage of non-liver cirrhosis according to pathological findings. Binary logistic regression analysis was performed to identify independent predictors, and a diagnostic nomogram was constructed for CHB-related early cirrhosis. It was validated and calibrated by bootstrap self-extraction. Binary logistic regression analysis showed that age (OR 1.14, 95% CI (1.04-1.27)), right hepatic vein diameter (OR 0.43, 95% CI 0.23-0.82), presence or absence of nodules (OR 31.98, 95% CI 3.84-266.08), and hepatic parenchymal echogenicity grading (OR 12.82, 95% CI 2.12-77.51) were identified as independent predictive indicators. The nomogram based on the 4 factors above showed good performance, with a sensitivity and specificity of 90.70% and 89.66%, respectively. The area under the curve (AUC) of the prediction model was 0.96, and the predictive model showed better predictive performance than APRI score (AUC 0.57), FIB-4 score (AUC 0.64), INPR score (AUC 0.63), and LSM score (AUC 0.67). The calibration curve of the prediction model fit well with the ideal curve, and the decision curve analysis showed that the net benefit of the model was significant. The nomogram in this study can detect liver cirrhosis in most CHB patients without liver biopsy, providing a direct, fast, and accurate practical diagnostic tool for clinical doctors.

Why are rare diseases underdiagnosed? A clinical management study on detection of primary biliary cholangitis in primary care.

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process. Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines. Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%). Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications.

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, etc., will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Management of extensive portal vein thrombosis via thrombolysis and thrombectomy without underlying liver disease: A case report.

Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.

Clinical Findings, Bacterial Agents, and Antibiotic Resistance in Children with Spontaneous Peritonitis in Southern Iran: An Academic Tertiary Referral Center's Experience.

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP. Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant. Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures. Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities.

In response to Dr. Yue et al's study on prognostic factors for post-hemihepatectomy outcomes in hepatocellular carcinoma (HCC) patients, this critical review identifies methodological limitations and proposes enhancements for future research. While the study identifies liver stiffness measure and standard residual liver volume as potential predictors, concerns regarding small sample size, reliance on biochemical markers for safety assessment, and inadequate adjustment for confounding variables are raised. Recommendations for rigorous methodology, including robust statistical analysis, consideration of confounding factors, and selection of outcome measures with clinical components, are proposed to strengthen prognostic assessments. Furthermore, validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hemihepatectomy.

Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: A retrospective cohort study.

BACKGROUNDS & AIMS: This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis. METHODS: This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively. RESULTS: Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis. CONCLUSIONS: Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.

Antioxidants of commercial interest from Homalium tomentosum attenuates hepatocellular necrosis: Insights from experimental and computational studies.

Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl4)-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-ß; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC-MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski's rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-ß and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biobased materials for the pharmaceutical and food industries.

[New targets for the prevention and treatment of cirrhotic portal vein thrombosis].

Portal vein thrombosis (PVT) is divided into cirrhotic and non-cirrhotic PVTs. The incidence rate of PVT varies greatly among different clinical stages of cirrhosis, with an overall incidence rate of about 13.92%, and the prevalence of cirrhotic PVT following splenectomy is as high as 60%. The pathogenesis of cirrhotic PVT is still unclear. However, the activation of Janus kinase/signal transduction and activator transcription signaling pathways, the rise in the expression of von Willebrand factor, and the gut microbiota along with its metabolite trimethylamine-N-oxide play an important role in the injury of vascular endothelial cells and the formation of PVT in cirrhosis. Therefore, these could be a new target for cirrhotic PVT prevention and treatment.