Search Results (3,152)

Background/Objectives: To evaluate ocular disease and eye care utilization among adults with vitamin A deficiency (VAD) in a high-resource healthcare setting, with particular emphasis on nutritional etiologies, clinical nutrition oversight, and outcomes associated with severity of deficiency. Methods: A retrospective chart review was conducted at Dartmouth Hitchcock Medical Center (DHMC) from 1 January 2019 through 31 December 2022. Adults (>18 years) with measured serum retinol concentrations were identified, and data were extracted on retinol concentration, diagnosis, referring service, and vital status. Patients with VAD (serum retinol <32.5 µg/dL per our laboratory threshold) underwent detailed chart review, including social determinants of health and documented nutritional risk factors. For patients with VAD who received an ophthalmologic evaluation, slit lamp findings, ocular symptoms, duration of deficiency, and vitamin A treatment were assessed. Results: VAD was identified in 752 of 2725 patients (27.7%) tested for VAD, and 330 patients had concentrations below the World Health Organization (WHO) threshold for VAD (<20 µg/dL). Hepatic, nutritional, and malabsorptive conditions were prominent contributors, including cirrhosis related to alcohol use or hepatitis C virus (30%), malnutrition or malabsorption following bariatric surgery (24%), and pancreatic insufficiency (20.1%). Food insecurity data were incomplete but showed no significant association with vitamin A concentration. Despite biochemical evidence of deficiency, only 72 patients with VAD (9.6%) underwent ophthalmologic evaluation, and only three were referred specifically due to VAD. Clinical signs or symptoms consistent with xerophthalmia were observed in 21% of those evaluated, and 18% demonstrated corneal findings. Vitamin A supplementation was documented in just over half of symptomatic patients, with objective or symptomatic improvement noted in three cases. VAD was explicitly acknowledged in only 9.7% of ophthalmology notes. Increasing severity of VAD was strongly associated with mortality (p < 0.001), independent of food insecurity, which showed no association with serum retinol concentrations. Conclusions: In this high-resource clinical setting, VAD is common in an at-risk population and largely driven by nutrition-related disease states affecting absorption, metabolism, and hepatic storage. Despite clear biochemical deficiency and associated mortality risk, VAD is underrecognized, undertreated, and infrequently linked to ocular evaluation, highlighting a critical gap in nutrition-focused screening, interdisciplinary communication, and proactive vitamin A assessment in medically complex adults. Full article

Background and Objectives: Acute kidney injury (AKI) is a frequent and life-threatening complication in patients with liver cirrhosis (LC). Nephrotic-range proteinuria may reflect underlying structural renal vulnerability; however, its association with AKI severity in cirrhosis remains unclear. Materials and Methods: We conducted a retrospective cohort study of 408 adults with LC admitted to a tertiary referral hospital between January 2016 and December 2025. Nephrotic-range proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g measured within 7 days before or at admission. AKI was staged using serum creatinine-based Kidney Disease: Improving Global Outcomes criteria. Baseline creatinine was defined as the lowest value within 7 days before admission; if unavailable, the lowest stable value within the preceding 3 months was used. Severe AKI was defined as KDIGO stage 2–3. Multivariable logistic regression was performed to evaluate the association between nephrotic-range proteinuria and severe AKI after adjustment for age, sex, diabetes mellitus, hypertension, chronic kidney disease (CKD), sepsis, ICU admission, and Child–Pugh class. Results: Of the 408 patients, 56 (13.7%) had nephrotic-range proteinuria. Severe AKI occurred more frequently in patients with nephrotic-range proteinuria than in those without (39.3% vs. 21.9%), corresponding to an absolute risk difference of 17.4 percentage points (p = 0.008). In the adjusted model, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI (adjusted odds ratio [OR], 2.27; 95% confidence interval [CI], 1.17–4.41; p = 0.015). CKD (adjusted OR, 2.26; 95% CI, 1.33–3.81; p = 0.002), ICU admission (adjusted OR, 2.03; 95% CI, 1.22–3.39; p = 0.007), and Child–Pugh class C versus A (adjusted OR, 3.50; 95% CI, 1.37–8.93; p = 0.009) were also significantly associated with severe AKI. Conclusions: Among hospitalized patients with LC, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI. Quantitative proteinuria assessment may help identify patients at increased risk of advanced renal dysfunction, although causal inference is limited by the retrospective observational design. Full article

A phage is a virus that targets bacteria with high precision. While phage therapy provides a targeted alternative to broad-spectrum antibiotics, it is not completely free from the challenges of antimicrobial resistance, as phages can facilitate the horizontal transfer of resistance genes through transduction and promote the growth of phage-resistant strains. Nonetheless, within the One Health framework, the strategic use of phages remains a vital and promising tool for addressing the global antimicrobial resistance crisis. This paper reviews current research on phage therapy for gastrointestinal diseases such as cirrhosis, enteritis, and Helicobacter pylori infection. It also details how phages help regulate gut microecological balance and discusses how phage dysbiosis can lead to innate immune dysfunction and worsen conditions like inflammatory bowel disease. The review summarizes both the therapeutic potential and limitations observed in clinical trials and fundamental studies. Transitioning from laboratory research to clinical practice is hindered by multiple complex challenges, including the stomach’s extreme acidity, physical entrapment by the intestinal mucus layer, the rapid co-evolution of bacterial resistance, and ecological risks associated with temperate phages. To overcome challenges like gastrointestinal barrier tolerance and address ethical, technical, and practical hurdles for clinical use, the paper outlines treatment strategies for specific conditions and highlights future directions, providing guidance for employing phages in digestive system disease management. These future innovations focus on integrating artificial intelligence-driven precision matching, advanced bioengineering for durable delivery systems, and multimodal combination therapies to safely modulate the intestinal microecology. Full article

Background: Direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) in hepatitis C virus (HCV) patients with cirrhosis, yet the risk of hepatic decompensation or hepatocellular carcinoma (HCC) persists. Fibrosis-4 (FIB-4), a pre-treatment index that predicts advanced fibrosis, is linked to HCC risk post SVR. We compared post-SVR outcomes and care engagement, and determined the optimal pre-treatment FIB-4 index to predict the risk of HCC or decompensation in HCV patients with cirrhosis treated at the Department of Corrections (DOC) and non-DOC clinics. Methods: HCV patients with cirrhosis treated with DAAs since 2014 in the HCV Treatment Registry were included. Cirrhosis was defined by elastography, imaging, or clinical criteria. Patients with prior decompensation or HCC were excluded. Outcomes (HCC, decompensation) were collected from records. The FIB-4 index was compared between DOC and non-DOC groups. Results: Among 2104 cirrhotic patients (mean age 54; 76% male), 53% were treated in DOC via telemedicine and 47% in non-DOC clinics. HCC developed in 4.8% and decompensation in 8.1%. DOC patients had lower FIB-4 scores and SVR, partly from higher loss to follow-up (9% vs. 1%). Of 1581 with follow-up, surveillance was more common in non-DOC, which also had higher HCC and decompensation. A higher baseline FIB-4 index independently predicted HCC and decompensation (cutoffs: 3.24, 3.7; AUROC 0.79, 0.75, respectively). Conclusions: Despite SVR, cirrhotic patients—especially with a high FIB-4 index—remain at risk for HCC and decompensation. Outcomes differ by care setting, highlighting the need for continued AASLD-recommended surveillance post-SVR. Full article

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder that, without treatment, can advance to fibrosis and cirrhosis. Although standard regimens with corticosteroids and thiopurines have significantly improved survival, many patients still experience relapses and drug-related toxicity, highlighting the urgent need for alternative strategies. Recent studies underscore AIH’s multifactorial nature, revealing intricate interactions among genetic susceptibility, environmental triggers, and dysregulated immune responses. Next-generation diagnostics, ranging from novel biomarkers to high-resolution imaging, are enhancing early detection and more precise disease classification. At the same time, multi-omics analyses and artificial-intelligence-based models are refining predictions of disease trajectory and therapeutic response. On the treatment horizon, investigational options such as targeted immunomodulators, B-cell–depleting therapies, and cell-based interventions aim to achieve durable remission while minimizing adverse effects. This review critically appraises these advances and explores how integrating epidemiological insights with cutting-edge research in pathogenesis, diagnostics, and therapy could pave the way for more personalized and effective management of AIH. Full article

Objectives: The objective of this study was to investigate metabolic dysfunction-associated steatotic liver disease (MASLD)-related awareness, health literacy (HL), and illness perception among patients at risk of MASLD in European primary care settings. Methods: Participants aged ≥50 years with either obesity, metabolic syndrome (MetS), or type 2 diabetes mellitus (T2DM), and attending general practices (GPs) in Greece, Spain, or The Netherlands were included in the study. The participants completed surveys to collect data on their socio-demographic characteristics and health habits, including the European Health Literacy Survey (HLS-E-Q16), the Brief Illness Perception Questionnaire [B-IPQ], and the Public Awareness of NAFLD Questionnaire. Results: Overall, 234 patients participated in the study (mean age: 66.5 ± 9.5 years; 45.7% were male). Among the participants, 64.5%, 66.2%, and 59.8% had a diagnosis of diabetes, obesity, and MetS, respectively. Almost one-third (27.9%) had never heard about MASLD or discussed MASLD with their GP. Twelve percent (12.1%) had never heard about cirrhosis, and 20.5% were unaware that liver disorders may cause serious health problems. Overall, 43.6% of the patients had a sufficient level of HL (score >13) with a mean score of 11.5 ± 3.3. Illness perception (B-IPQ score) was low at 41.6 ± 11.6. Significantly higher B-IPQ scores were documented for female compared to male respondents (43.1 vs. 39.8; p < 0.01). Multivariate analysis found that knowledge about MASLD was associated with higher HLS-E-Q16 (p = 0.017) and B-IPQ (p = 0.028) scores. Conclusions: Despite being at risk, a significant proportion of the study participants were unaware of MASLD, its risk factors, and their personal susceptibility. This study underscores the importance of enhancing patient HL and promoting prevention and risk reduction, particularly among high-risk patient populations. Full article

Liver diseases, ranging from chronic hepatitis and metabolic dysfunction to cirrhosis and hepatocellular carcinoma, represent a major global public health burden. As an immune-privileged organ, the liver harbors a unique and intricate immune microenvironment, which plays a dual role in pathogen clearance and chronicity. Kupffer cells (KCs), the primary resident macrophages in the liver, constitute the first line of defense in liver innate immunity and play complex and important roles in pathogen recognition, phagocytosis, and the regulation of liver inflammation and immune responses. The complement receptor of the immunoglobulin superfamily (CRIg) is a membrane receptor that is specifically expressed on KCs. It serves not only as a sentinel for the liver against pathogen invasion but also as a sophisticated regulator for maintaining immune homeostasis. As a key component of the liver’s immune system, CRIg can efficiently mediate the clearance of complement-opsonized particles, thereby playing multidimensional roles in pathogen clearance, antigen cross-presentation, and the establishment of immune tolerance, functioning as both a “pathogen catcher” and an “immune brake.” This review focuses on the CRIg molecule, detailing its mechanisms in the recognition and phagocytic clearance by KCs, and its subsequent impact on hepatic immune responses. Furthermore, we explored the potential involvement of CRIg in the pathological progression of diverse liver diseases, including persistent inflammation, fibrosis, and hepatocarcinogenesis. This synthesis provides novel insights into the immunopathology of liver diseases and establishes a theoretical foundation for developing CRIg-targeted therapeutic strategies. Full article

Liver diseases, including fatty liver, hepatitis, and cirrhosis, remain major global health challenges due to their disruption of metabolic homeostasis and detoxification processes. Redox imbalance plays a central role in liver disease progression by promoting inflammation, hepatic stellate cell activation, mitochondrial dysfunction, and fibrogenesis. Although flavonoids have historically been considered direct reactive oxygen species (ROS) scavengers, emerging evidence indicates that their biological effect at physiological concentrations are primarily mediated through modulation of intracellular redox signalling rather than simple radical neutralisation. This review highlights flavonoids as redox-modulating agents capable of restoring hepatic redox homeostasis through coordinated regulation of molecular pathways. Mechanistically, flavonoids activate the Nrf2-Keap1 axis to enhance endogenous antioxidant defences, including heme oxygenase-1 and glutathione biosynthesis enzyme, while suppressing NF-κB-mediated pro-inflammatory signalling and modulating MAPK and PI3K/Akt pathways. They also regulate mitochondrial redox balance, supporting mitophagy, metabolic adaptation, and cellular resilience to oxidative stress. In addition, flavonoid biotransformation by the gut microbiome improves intestinal barrier integrity, reduces endotoxin-driven hepatic inflammation, and contributes to gut–liver crosstalk. Collectively, these mechanisms position dietary flavonoids as multi-target redox modulators with promising therapeutic potential in chronic liver disease, although further studies are needed to improve their bioavailability and clinical translation. Full article

Hepatitis C virus (HCV) infection is a global health concern, chronically affecting over 71 million people. It primarily targets the liver but also causes systemic complications through inflammation, oxidative stress, and metabolic dysregulation. HCV is a highly variable RNA virus with six major genotypes that are mainly transmitted via blood. Often asymptomatic, the infection progresses silently to chronic hepatitis C (CHC), which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have revolutionized treatment, achieving cure rates above 95%, improving liver function, reversing fibrosis, and normalizing metabolism. HCV disrupts iron metabolism by suppressing hepcidin, causing iron overload and oxidative stress. It also alters lipid metabolism, inducing steatosis, and affects glucose metabolism, contributing to insulin resistance and type 2 diabetes. DAAs improve these metabolic outcomes. HCV promotes oxidative stress via viral proteins, damaging liver cells and DNA and triggering inflammation and fibrogenesis. Even post-cure, oxidative stress and iron overload may continue to drive disease progression. Genetic and epigenetic factors influence fibrosis progression and HCC risk. Despite a sustained virologic response (SVR), patients with advanced liver damage remain at risk for HCC and metabolic diseases, highlighting the need for continued monitoring and personalized post-treatment care. Full article

Background and goals: The outcomes of patients with primary sclerosing cholangitis (PSC) in central Missouri are unknown. The University of Missouri–Columbia services 600,000 individuals in central Missouri. Our aims were (a) to examine the outcomes of PSC patients receiving care at our academic institution, and (b) to identify the predictors of PSC-related serious adverse events. Methods: A retrospective study of patients with PSC in a non-transplant center. The primary outcome was the development of ≥1 of PSC-related serious adverse event for (1) progression to cirrhosis, or (2) development of cholangiocarcinoma. Results: From 2000 to 2018, 42 patients fulfilled the criteria for the diagnosis of PSC. A total of 55% of the patients were male, and 79% had associated inflammatory bowel disease (IBD). The median follow-up from time of diagnosis of PSC until the last follow-up or death was 5.5 years. A total of 57% of the patients developed ≥ 1 PSC-related adverse event; 36% (8/22) of those who progressed to decompensation underwent liver transplantation. The median time from diagnosis of PSC until progression to decompensation was 6.3 years; the median time from decompensation to transplantation was 10.8 years. A total of 12% of the patients developed ≥ 1 cancer (cholangiocarcinoma = 2; gallbladder cancer = 2; colon cancer = 1; and hepatocellular carcinoma = 1). The overall mortality was 9.5%. The median time from PSC diagnosis until death was 10.2 years. A Cox hazards regression analysis showed only age (HR = 1.16; p = 0.032; 95% CI, 1.01–1.13) and serum bilirubin (HR = 1.42; p = 0.036; 95% CI, 1.03–2.69) at the time of PSC diagnosis were independently associated with PSC-related serious events. Conclusions: Age and bilirubin are important predictors of PSC-related outcomes. Full article

Metabolic dysfunction-associated (non-alcoholic) steatotic liver disease (MASLD) is a chronic inflammatory liver disorder characterized by excessive hepatic lipid accumulation. Its progressive subtype, metabolic dysfunction-associated (non-alcoholic) steatohepatitis (MASH), is featured by enhanced inflammation and liver injury. Some MASH cases are accompanied by hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). MASLD is also associated with comorbidities such as cardiovascular disease and chronic kidney disease. To date, only Resmetirom has been approved by the FDA for MASH treatment, highlighting the urgency of investigating MASH pathogenesis and developing effective therapeutic agents. Establishment of experimental animal models which can mimic the clinical symptom of MASLD are fundamental to explore therapeutic targets and advance clinical drugs development. Therefore, this review focus on the pathological features of MASLD/MASH and comprehensively summarizes the current MASH-related mouse models, which can be useful for researchers to select appropriate models in order to explore the underlying mechanisms and dig novel targets for MASH treatment. Full article

Cirrhosis is no longer viewed solely as an isolated hepatic disorder but rather as a complex multisystemic disease that affects cardiovascular, renal, pulmonary, metabolic, and immune systems. One of its most clinically relevant but under-recognized consequences is cardiac dysfunction, manifesting as cirrhotic cardiomyopathy, portopulmonary hypertension, right ventricular (RV) failure, and impaired myocardial strain. Oxidative stress (OS) has recently emerged as a fundamental mechanistic link between hepatic fibrogenesis and myocardial remodeling, acting through mitochondrial injury, NADPH oxidase activation, nitric oxide dysregulation, iron-mediated ferroptosis, and inflammatory cytokines. These alterations lead to diastolic dysfunction, autonomic imbalance, myocardial fibrosis, electrophysiological abnormalities (including QTc prolongation), and impaired RV–pulmonary artery coupling. Redox biomarkers such as malondialdehyde (MDA), NOX2-derived peptides, GSH/GSSG ratio, sST2, NT-proBNP, and 8-isoprostanes hold promise in detecting early subclinical cardiac involvement in cirrhosis. Novel antioxidant therapies, including mitochondrial-targeted molecules, NOX inhibitors, and ferroptosis blockers, may improve myocardial remodeling and hemodynamic stability. This review explores the central role of redox imbalance in the cardiohepatic syndrome and its potential utility in diagnosis, monitoring, and therapy. Full article

Background: Pregnancy in women with liver cirrhosis is considered a rare clinical condition due to the decreased fertility commonly associated with chronic liver disease. Hormonal disturbances, anovulation and impaired hepatic function contribute to the lower conception rates observed in this population. However, when pregnancy occurs, it is associated with a significantly increased risk of maternal and fetal complications. Maternal risks include hepatic decompensation, variceal bleeding, ascites, coagulopathy and a higher rate of hypertensive disorders during pregnancy and related complications. Fetal complications involve prematurity, intrauterine growth restriction, and increased perinatal mortality. Methods: We present the clinical case of a woman with idiopathic liver cirrhosis who experienced four consecutive pregnancies with different clinical courses and outcomes. Results: The case highlights the complexity of managing pregnancy in patients with chronic liver disease and underscores the importance of individualized clinical assessment and multidisciplinary management. This report also reviews current management strategies and discusses key considerations for optimizing care in pregnant women with liver cirrhosis. Conclusions: Advances in multidisciplinary care and improved management strategies have contributed to better pregnancy outcomes in recent years. Careful monitoring during pregnancy, appropriate management of portal hypertension, and coordinated care between obstetricians, hepatologists, and neonatologists are essential to minimizing potential complications, ensuring favorable maternal and fetal outcomes. Full article

Background: Alcohol-related liver disease is frequently associated with systemic vascular dysfunction and increased arterial stiffness. This may contribute to adverse clinical outcomes. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy in liver cirrhosis, but its influence on vascular stiffness in humans remains insufficiently characterized. Methods: This prospective study evaluated arterial stiffness in patients with alcohol-related liver cirrhosis undergoing FMT. A control group received standard care. Vascular stiffness was assessed non-invasively using an oscillometric arteriograph based on pulse wave analysis. Measurements were performed at baseline and at one and three months after FMT under standardized conditions. The main indices assessed included aortic pulse wave velocity, augmentation index, ejection duration and return time. Direct microbiome sequencing and metabolomic profiling were not performed. Results: At baseline, the study and control groups had comparable vascular stiffness profiles. Only minor differences in selected hemodynamic parameters were observed. At one month after intervention, no statistically significant differences in arterial stiffness indices were observed between groups. Longitudinal analysis within the FMT group also showed no significant changes in direct markers of arterial stiffness across the three-month follow-up period. A non-significant tendency toward reduced ejection duration was noted. Conclusions: In patients with advanced alcohol-related liver cirrhosis, FMT did not produce measurable short-term improvements in arterial stiffness. These findings suggest that short-term vascular effects of microbiota modulation may be difficult to detect in patients with advanced alcohol-related liver cirrhosis. Larger studies including earlier-stage patients, longer follow-up and direct microbiome and metabolomic assessment are needed to clarify potential vascular effects of FMT. Full article

Background and Objectives: Ascites is associated with substantial symptom burden and increased healthcare utilization, and it is observed in patients with advanced disease across multiple etiologies. However, because ascites is a clinical sign rather than a diagnosis category, it can be challenging to study using routine health reporting. In routinely collected hospital administrative data, ascites is commonly captured using International Classification of Diseases, Tenth Revision (ICD-10) code R18, an etiologically non-specific classification whose outcome implications are less documented. We aimed to evaluate the incremental association of R18-coded ascites with length of stay (LOS), readmission burden, and in-hospital mortality in the Gastroenterology and Internal Medicine inpatient department, beyond comorbidity burden and other coded decompensation proxies. Materials and Methods: We conducted a single-center retrospective study using routinely collected administrative discharge data from adult inpatient admissions (2015–2023) in the Gastroenterology and Internal Medicine department of a Romanian tertiary-care hospital. Admissions were classified by the presence of ICD-10 R18-coded ascites. Outcomes were LOS, readmission burden (count of subsequent admissions), and in-hospital mortality. Multivariable models adjusted for age, sex, and comorbidity burden (Charlson Comorbidity Index), with additional models incorporating ICD-10-derived decompensation proxies to assess overlap in administrative severity signal. LOS was further examined within Charlson strata to evaluate incremental stratification. Results: Coded ascites was associated with higher hospital burden, including longer LOS and greater readmission burden, and with higher in-hospital mortality in partially adjusted models. Within each CCI stratum, LOS remained higher among admissions with R18-coded ascites, supporting incremental stratification beyond comorbidity alone. Furthermore, mobility impairment was an important predictor of LOS. Age-stratified analyses suggested a high-burden phenotype among younger patients and infrequent R18 coding among the very elderly in this cohort. Conclusions: These findings support the potential utility of R18-coded ascites as a pragmatic administrative marker for risk adjustment and service planning. Full article