Severe Liver Disease Research Articles

Self-testing strategy to eliminate Hepatitis C as per WHO's goal: Analysis of disease burden and cost-effectiveness.

The World Health Organization (WHO) aims to eliminate hepatitis C Virus (HCV) by 2030, therefore, widespread HCV screening is required. The WHO recommends HCV self-testing (HCVST) as a new approach. We aimed to evaluate disease burden reduction using the HCVST screening strategy and identify the most cost-effective approach. We developed a dynamic open-cohort Markov model to assess the long-term effects and cost-effectiveness of HCVST in the Republic of Korea from 2024 to 2030. Strategies for comparison included universal, birth cohort, high-risk group screening, and no screening, focusing on the following: (1) incremental cost-effectiveness ratio (ICER) per disability-adjusted life-year (DALY) saved; (2) severe liver disease cases; and (3) liver-related death reduction. Universal HCVST screening is the most effective strategy for achieving the WHO goal by 2030, substantially lowering the incidence of severe liver disease by 71% and preventing liver-related deaths by 69 %, thereby averting 267,942 DALYs. Moreover, with an ICER of $8,078 per DALY and high cost-effectiveness, the sensitivity results prove that cost-effectiveness is robust. Although high-risk group screening offers the lowest cost compared with other strategies, its effectiveness in preventing severe liver disease is minimal, falling short of the current WHO goal. Our study confirms that universal HCVST screening is a cost-effective strategy aligned with the WHO goal to eliminate HCV by 2030. Despite its higher costs compared to risk-based screening, the disease burden can be significantly reduced by providing effective HCVST access to individuals who might otherwise not be tested.

Incidence, In-Hospital and Long-Term Mortality, and Sequelae of Epidermal Necrolysis in Adults

The incidence of epidermal necrolysis (EN), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), varies across studies. While in-hospital mortality rates range from 15% to 20%, contributors to long-term mortality have been rarely evaluated and remain unknown. To assess the incidence of and compare factors associated with in-hospital mortality and postdischarge mortality and sequelae among patients with EN. This cohort study used French Health System data from January 1, 2013, to December 31, 2022, and included all adult patients (aged ≥18 years) with EN identified using International Statistical Classification of Diseases, Tenth Revision codes combined with a validated algorithm. Epidermal necrolysis. Incidence, in-hospital mortality, postdischarge mortality, and sequelae were assessed as main outcomes. Factors associated with mortality were assessed using a multivariable Cox proportional hazards model. A total of 1221 adult patients with EN (median [IQR] age, 66 [49-79] years; 688 females [56.3%]) were included. Incidence was 2.6 (95% CI, 2.5-2.7) cases per million person-years. The in-hospital mortality rate was 19% (95% CI, 17%-21%) and postdischarge mortality rate, 15% (95% CI, 13%-17%) for an overall mortality of 34% (95% CI, 31%-36%). In multivariable analysis, factors associated with in-hospital mortality were age (adjusted hazard ratio [AHR], 1.03 per year of age; 95% CI, 1.02-1.04 per year of age), history of cancer (AHR, 2.04; 95% CI, 1.53-2.72), dementia (AHR, 1.85; 95% CI, 1.12-3.07), liver disease (AHR, 1.81; 95% CI, 1.24-2.64), and EN severity (TEN vs SJS: AHR, 2.14; 95% CI, 1.49-3.07). Cancer, liver disease, and dementia remained associated with postdischarge mortality (AHR, 3.26 [95% CI, 2.35-4.53], 1.86 [95% CI, 1.11-3.13], and 1.95 [95% CI, 1.11-3.43], respectively). Conversely, EN initial severity was not associated with mortality after hospital discharge (TEN vs SJS: AHR, 0.95; 95% CI, 0.60-1.47), but acute complications remained associated (AHR, 2.14 [95% CI, 1.26-3.63] and 2.44 [95% CI, 1.42-4.18] for acute kidney injury and sepsis, respectively). The main sequelae were ophthalmologic and mood disorders. The findings of this cohort study suggest that although EN is a rare condition, it is associated with high rates of in-hospital and postdischarge mortality among patients who are older and have comorbid conditions. However, in contrast with in-hospital mortality, postdischarge mortality is not associated with EN initial severity but with acute in-hospital complications (eg, acute kidney injury and sepsis). Future studies are needed to construct models to estimate long-term outcomes and sequelae in patients with EN.

Metabolic dysfunction-associated steatohepatitis reduces interferon and macrophage liver gene signatures in patients with chronic hepatitis B

Background & AimsChronic HBV patients with concomitant metabolic dysfunction-associated steatohepatitis (MASH) have been shown to develop more advanced fibrosis faster with more severe liver disease as compared to patients with chronic HBV alone. However, our understanding of the underlying mechanisms is limited. Here we study how MASH co-morbidity impact immune activity in the liver of patients with chronic HBV infection. MethodsBulk RNA sequencing was performed on liver biopsies from patients with only MASH (n=10), only HBeAg-negative chronic HBV (ENEG; n=11), combined MASH/ENEG (n=9) and healthy controls (n=9). Biopsies with no or minimal fibrosis (≤F2) were selected to avoid confounding effects of fibrosis. We compared whole transcriptome data from patients with MASH/ENEG to those with ENEG alone to determine the impact of MASH co-morbidity on chronic hepatitis B. ResultsThere is a high degree of overlap of liver gene expression profiles in patients with only ENEG versus those with only MASH compared to healthy controls, suggesting a largely shared mechanism of liver dysfunction and immune activity for these distinct conditions. In patients with ENEG, MASH co-morbidity significantly reduced interferon pathway activity (NES=2.03, p.adj=0.0251), the expression of ISGs (e.g., IFIT2, IFI27, IFITM1, IFI6), and macrophage gene signatures (e.g., MARCO, CD163, CD5L, CD63), when compared to patients with ENEG alone. ConclusionsTranscriptomic profiling of the liver suggests that MASH negatively impacts ISGs expression in the liver of patients with ENEG, which may affect antiviral immune pathways, viral replication and inflammatory responses resulting in an increased risk of advanced fibrosis in patients with chronic hepatitis B. Our study provides valuable insights for guiding future research aimed at developing effective, tailored strategies for managing patients with both conditions. Impact and implicationsIn recent decades, obesity and associated health issues have reached epidemic levels, with steatotic liver disease affecting up to 30% of adults in developed countries, and this trend is also observed among chronic hepatitis B patients. Given the high and rising prevalence of steatotic liver disease and its frequent co-occurrence in chronic hepatitis B patients, it is essential to understand how conditions such as metabolic dysfunction-associated steatohepatitis (MASH) impact immune responses in the liver. This study provides unique insights into the impact of MASH on HBV antiviral immune activity in the liver of patients with chronic hepatitis B. The rising number of patients with both conditions affects treatment outcomes and highlights the urgent need for novel, tailored therapeutic strategies. Our study holds significant relevance for guiding future research on developing treatment strategies for patients with both MASH and chronic hepatitis B.

Current Burden of and Geographic Disparities in Liver Mortality and Access to Liver Transplant

Liver disease is a leading cause of mortality in the US. Liver transplant can be a lifesaving procedure for patients with severe liver disease. To assess temporal trends and geographic variance in liver-related mortality (LRM) and liver transplant in the US. In this cohort study, the frequencies and geographic variance of LRM in 2018 and 2021 were obtained in a cross-sectional analysis of the Underlying Cause of Death data available on the Centers for Disease Control and Prevention's Epidemiologic Research database. The number of livers donated and transplanted according to the state of residence of each donor and recipient were obtained from the United Network for Organ Sharing. Liver-related mortality in 2018 and 2021, overall and by state, as well as the liver transplant rate according to state of residence of recipient and donor. Overall LRM in the US was 93 418 in 2021, with a crude rate of 28.1 per 100 000 individuals, an increase of 19.1% compared with rates seen immediately prior to the COVID-19 pandemic in 2018 (77 282 [23.6 per 100 000 individuals]). Liver-related mortality in 2021 varied several-fold between states, from 18.4 per 100 000 individuals per year in Utah to 65.9 per 100 000 individuals per year in New Mexico. The mean number of liver-related deaths per transplant from all donor sources (in state and out of state) was 7.2 in the lowest LRM quintile compared with 21.5 in the highest (95% CI, 12.1-16.6; SE, 1.1; P < .001). Ten states had no liver transplant center. Paradoxically, residents of states with the highest LRM had a much lower rate of liver transplant (at any location) from organs procured from in-state residents than states with the lowest LRM quintile (13.0% vs 35.2% in-state donors; 95% CI, 14.1%-30.3%; SE, 3.9%; P < .001). This study suggests that rates of LRM have increased dramatically since the COVID-19 pandemic and vary several-fold between states. Rates of liver transplant are paradoxically lowest among residents living in states with the highest LRM. These findings highlight apparent geographic disparities in access to liver transplant that allocation policy cannot address.

Seropositivity and coinfection of hepatitis B and hepatitis C viruses in Central India: A hospital-based study

ABSTRACT Background: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) show similarity in the transmission, distribution, hepatotropism, and leading to chronic asymptomatic infection. Coinfection of HBV and HCV can lead to more severe liver disease and an increased risk for progression to hepatocellular carcinoma (HCC). Most of the people with chronic infection are unaware of their HBV and HCV infections, hence facilitating these to go undiagnosed until these viruses have caused serious liver damage and they act as a potential source of infection for the community at large. Therefore, the present study aimed to find the prevalence of HBV and HCV along with incidences of coinfection of HBV and HCV in patients seeking hospital care in central India. Methods: A five-year hospital-based study was carried out at the tertiary care hospital in Central India from 2018 to 2022. A total of 72402 patients attending the outdoor patients and admitted indoor patients who were advised for HBV and HCV for screening before any invasive/surgical procedure and patients who presented with symptoms of acute or chronic liver disease were included in this study. Screening was done by immunochromatography-based card test followed by the confirmation of all samples by enzyme immunoassay. Results: Seroprevalence of HBV and HCV was found to be 3.71% and 1.91%, respectively. Coinfection with HBV/HCV was seen in 0.13% of the individuals. The overall prevalence of HBV, HCV, and HBV-HCV coinfection was significantly higher in the male population as compared to females. Conclusion: The study findings of seroprevalence of HBV and HCV among the hospital-based population will help to get a baseline understanding of the disease burden in central India. The HBV/HCV coinfection rate also raises serious concerns owing to its high prevalence rate among the younger age.

A non randomised pilot study to investigate the acceptability and feasibility of LivR Well: a multifaceted 28-day home based liver optimisation program for acute-on-chronic liver failure.

Background and AimsAcute-on-chronic liver failure (ACLF) has a 22-74% 28-day mortality rate and 30-40% 30-day re-admission rate. We investigated the acceptability and feasibility of a multimodal community intervention for ACLF. MethodsA single-arm, non-randomized pilot study of consecutive participants with ACLF was conducted in a tertiary health service. Participants received weekly medical and nursing reviews, dietetics, physiotherapy, pharmacy, social work, addiction medicine, and/or neuropsychiatry. A digital platform included remote weight monitoring, and online surveys. The primary outcome was acceptability/feasibility. Secondary outcomes included safety, mortality, re-admission, liver disease severity, and costs. ResultsFifty-nine patients were enrolled with median age 51 years (IQR: 45-59); majority alcohol etiology (74%),and median Model for End-Stage Liver Disease Sodium (MELD-Na) score 16 (IQR: 12-21). LivR Well was acceptable with low attrition (8/59), adherence to the program including home visits (mean 8.4±4.2) and consultations (mean 2.4±1.5) per patient. This was supported by positive feedback and themes identified through a qualitative sub-analysis. Feasibility was demonstrated by recruitment rate of 4.94 patients/month and 86% completion. Mortality was lower than expected at 3%, 30-day readmission rate was 15%, and median MELD-Na score reduced to 15 (p = 0.01). Median 6-month costs reduced from $30,454 (IQR: 21953-$65657) to $17, 657 ($4249-42876) (p=0.009). The total 6-month healthcare cost was $1,868,859 (95% CI 1,081,821-2,655,897) compared to $2,518,227 (95% CI 1,959,610-3,076,844). ConclusionLivR Well was acceptable, feasible and safe with low short-term mortality and readmission rates. Healthcare costs were reduced by 26% driven by a 40% reduction in 30-day re-admission. Further evaluation includes a randomized, controlled trial of LivR Well compared to standard care.

Prevalence and Severity of Polycystic Liver Disease (PLD) in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Prevalence and Severity of Polycystic Liver Disease (PLD) in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Severe acute liver disease in adults: Contemporary role of histopathology.

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first-line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so-called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug-induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up-to-date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug-induced, autoimmune-like hepatitis (DI-AIH).

Missed and Delayed Diagnoses of Chronic Liver Disease in Primary Care Patients with Cirrhosis.

Chronic liver diseases (CLD), cirrhosis, and hepatocellular carcinoma (HCC) cause significant morbidity and mortality. Unfortunately, patients with CLD often go undiagnosed until progression to cirrhosis and HCC. We aimed to determine the proportion of primary care patients with severe liver disease outcomes that had missed or delayed CLD diagnoses. This retrospective cohort study evaluated primary care patients with a diagnosis of cirrhosis, HCC, or other severe liver disease outcome between 2012 and 2021. The outcomes of interest were missed and delayed diagnoses of CLD, defined as the absence of a CLD diagnosis (missed) or first appearance of CLD on the same day as the cirrhosis diagnosis (delayed). Univariate analyses were performed to describe the cohort. Multivariable logistic regression models analyzed the association of aminotransferase elevations with the outcomes of interest. Of 667 patients with cirrhosis or HCC, 133 (20%) had a missed CLD diagnosis, and 243 (36%) had a delayed CLD diagnosis. Alcohol-related liver disease was the most common etiology among patients with missed/delayed diagnoses. A lower proportion of patients with missed/delayed diagnoses had an elevation in ALT or AST compared to patients with timely diagnoses (61% vs. 77%, p < 0.001). Elevated aminotransferase values were associated with lower odds of a missed/delayed diagnosis (OR 0.47; 95%CI 0.34-0.66). Most patients with cirrhosis or HCC had missed or delayed diagnoses of CLD in the context of probable overreliance on aminotransferase elevation for CLD detection. Enhanced screening for high prevalence CLD, especially alcohol, in primary care is needed.

Structural and functional neural correlates of sensorimotor deficits in progression of hepatic encephalopathy

Hepatic encephalopathy (HE) is a neurological condition that occurs as a complication of liver dysfunction that involves sensorimotor symptoms in addition to cognitive and behavioral changes, particularly in cases of severe liver disease or cirrhosis. Previous studies have reported spatially distributed structural and functional abnormalities related to HE, but the exact relationship between the structural and functional alterations with respect to disease progression remains unclear. In this study, we performed surface-based cortical thickness comparisons and functional connectivity (FC) analyses between three cross-sectional groups: healthy controls (HC, N=51), patients with minimal hepatic encephalopathy (MHE, N=50), patients with overt hepatic encephalopathy (OHE, N=51). In addition to the distributed cortical thinning that is extensively thought to be associated with cognitive decline in HE, we found significant cortical thickening in the left parahippocampal gyrus cortex in the OHE group (p<0.001, p=0.009) as compared to the HC and MHE group respectively, which is further corroborated by the significant correlation between the cortical thickness and digit symbol test (DST) scores. Furthermore, the decreased FC between the right postcentral gyrus and several sensory regions (bilateral somatosensory and visual cortices) was found to be significant in MHE patients as compared to the HC group. Our results revealed cross-sectional structural and functional variations concerning disease progression across different subsystems (e.g., visual, motor and sensory), providing evidence that can potentially explain the mechanisms underlying the sensorimotor and cognitive deficits related to HE.

Effect of comorbidities on mortality in patients with nontuberculous mycobacterial infection in Korea: National Health Insurance Service-National Sample Cohort data

Patients with nontuberculous mycobacteria (NTM) infection have multiple comorbidities, but the impact of comorbidities on mortality are not well known. We aimed to compare the mortality between people with and without NTM infection and associated comorbidities and their prognostic value on mortality using National Health Insurance Service-National Sample Cohort data from 2006 to 2019. In this matched cohort study, people with and without NTM infection aged 20–89 years were matched 1:4 by sex, age, region, and income. The hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality in patients with NTM infection were estimated using a Cox proportional hazard regression model. In total, 2421 patients with NTM infection (mean age, 54.8 years) and 9684 controls were included. NTM-infected patients had a significantly increased risk of mortality than matched controls in the multivariable model adjusted for age, sex, region, income, and Charlson comorbidity index (aHR = 1.88, 95% CI 1.65–2.14). Among patients with NTM infection, respiratory comorbidities including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and moderate to severe liver disease and malignancy were positively associated with mortality. NTM infection was independently associated with an increased risk of mortality, and mortality risk in patients with NTM infection may be increased by coexisting comorbidities.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

STUDY OF SERUM SODIUM LEVELS AND ITS CLINICAL SIGNIFICANCE IN DECOMPENSATED CHRONIC LIVER DISEASE PATIENTS ADMITTED IN A TERTIARY CARE CENTRE OF NORTH EASTERN STATE, TRIPURA

Introduction: Chronic Liver Disease is a major source of death and morbidity globally. Hyponatremia is one of the most common electrolyte abnormalities in chronic liver disease patients. Various studies have established a correlation between serum sodium levels and survival in these patients. Hyponatremia is a marker of severity in CLD patients and studies have shown its relationship with MELD score and Child Pugh score. The complications of DCLD and mortality also increases with hyponatremia. The aim of this study was to study the serum sodium levels in patients with DCLD and to establish its significance. Materials And Methods: Data was collected from 100 patients admitted in medical wards. Patients were divided into 3 groups based on serum sodium levels and the relevant parameters analyzed among the groups. OBSERVATIONS: Among 100 patients, 45 had serum sodium levels ≥136 mEq/L, while 32 had serum sodium levels between 131 and 135 mEq/L and 23 patients had serum sodium level ≤130. No patients had serum sodium levels greater than 145. Serum sodium levels were associated strongly with the severity of liver disease as assessed by Child Pugh and MELD scores. Serum sodium ≤130 indicated the existence of Hepatic Encephalopathy, Hepatorenal Syndrome and Spontaneous Bacterial Peritonitis. Patients with serum sodium less than 130 mEq/L had increased frequency of complications than those with ≥136 mEq/L. Patient with serum sodium levels ≤130 had increased mortality. Conclusion: Hyponatremia is more common in DCLD and low serum sodium levels are associated with increased frequency of complications such as hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis and GI bleeding. Lower serum sodium levels were associated with increased MELD and Child Pugh score and mortality indicating the inverse relationship between serum sodium levels and severity of the disease.

Validation of EncephalApp Stroop Test for Diagnosing Minimal Hepatic Encephalopathy in the Romanian Population.

Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. MHE has been associated with impairment of quality of life and job performance, and is a major cause of premature retiring in cirrhotic patients. However, MHE is usually overlooked by most physicians, due to its asymptomatic nature. We aim to present our experience with the EncephalApp Stroop Test for diagnosing MHE in cirrhotic patients. We also want to establish if Stroop test performance correlates with age, educational level, liver disease severity (as assessed by the MELD and Child-Pugh scores), duration of disease, previous episodes of overt hepatic encephalopathy, and other relevant clinical or laboratory parameters. A cross-sectional observational single-center study, in which 100 adult patients diagnosed with liver cirrhosis were evaluated for the presence of MHE by using the EncephalApp Stroop Test. In parallel, 45 healthy adult controls without liver cirrhosis were recruited and tested under the same conditions as the patients. There were no age-related differences between the two groups (p=0.6). Stroop test performance of the controls (143.1 ± 20.8 seconds) was significantly better than that of the patients (171.9 ± 33.3 seconds) (p<0.0001). Stroop test results correlated with the MELD (R=0.28, p=0.005) and Child-Pugh scores (R=0.2, p=0.04). There was a positive correlation between Stroop test results and age in patients (R=0.45, p<0.0001) and controls (R=0.75, p<0.0001). Stroop test performance was not influenced by the duration of liver disease (p=0.4) or prior episodes of overt hepatic encephalopathy (p=0.25). Gender and level of education did not have an impact on Stroop test results. Alcoholic liver disease, diabetes mellitus, hyperglycemia, anemia and hyponatremia were associated with poorer performances. EncephalApp Stroop Test proved to be a quick and simple method for diagnosing minimal hepatic encephalopathy in the hospital setting. Test performance was influenced primarily by age, but also by liver disease severity, anemia, hyponatremia and hyperglycemia.

Comorbidities associated with dysphagia after acute ischemic stroke

BackgroundPre-existing comorbidities increase the likelihood of post-stroke dysphagia. This study investigates comorbidity prevalence in patients with dysphagia after ischemic stroke.MethodsThe data of patients with acute ischemic stroke from two large representative cohorts (STROKE-CARD trial 2014–2019 and STROKE-CARD registry 2020–2022 – both study center Innsbruck, Austria) were analyzed for the presence of dysphagia at hospital admission (clinical swallowing examination). Comorbidities were assessed using the Charlson Comorbidity Index (CCI).ResultsOf 2054 patients with ischemic stroke, 17.2% showed dysphagia at hospital admission. Patients with dysphagia were older (77.8 ± 11.9 vs. 73.6 ± 14.3 years, p < 0.001), had more severe strokes (NIHSS 7(4–12) vs. 2(1–4), p < 0.001) and had higher CCI scores (4.7 ± 2.1 vs. 3.8 ± 2.0, p < 0.001) than those without swallowing impairment. Dysphagia correlated with hypertension (p = 0.034), atrial fibrillation (p < 0.001), diabetes (p = 0.002), non-smoking status (p = 0.014), myocardial infarction (p = 0.002), heart failure (p = 0.002), peripheral arterial disease (p < 0.001), severe chronic liver disease (p = 0.002) and kidney disease (p = 0.010). After adjusting for relevant factors, the associations with dysphagia remained significant for diabetes (p = 0.005), peripheral arterial disease (p = 0.007), kidney disease (p = 0.014), liver disease (p = 0.003) and overall CCI (p < 0.001).ConclusionsPatients with multiple comorbidities have a higher risk of developing post-stroke dysphagia. Therefore, early and thorough screening for swallowing impairment after acute ischemic stroke is crucial especially in those with multiple concomitant diseases.Trial registrationStroke Card Registry (NCT04582825), Stroke Card Trial (NCT02156778).

Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease

The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH. We revealed a crucial role for the Notch-Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) signaling pathway in controlling the monocyte-to-macrophage transition, with Rbpj deficiency blunting inflammatory macrophages and monocyte-derived KC differentiation and conversely promoting the emergence of protective Ly6Clo monocytes. Mechanistically, Rbpj deficiency promoted lipid uptake driven by elevated CD36 expression in Ly6Clo monocytes, enhancing their protective interactions with endothelial cells. Our findings uncover the crucial role of Notch-RBPJ signaling in monocyte-to-macrophage transition and will aid in the design of therapeutic strategies for MASH treatment.

Hepatitis B

Hepatitis B is a viral infection caused by the Hepatitis B virus (HBV), primarily affecting the liver and leading to both acute and chronic disease. With over 250 million individuals suffering from chronic Hepatitis B, it poses a significant global health challenge, being a leading cause of liver cirrhosis, liver failure, and hepatocellular carcinoma. This study aims to elucidate the transmission pathways, treatment options, and necessary public health strategies for Hepatitis B. We analyze the modes of transmission, which include contact with infectious body fluids—primarily through perinatal transmission, unprotected sexual contact, and sharing contaminated needles. Despite the availability of an effective vaccine since the 1980s, Hepatitis B remains endemic in many parts of Asia and Africa due to limited immunization coverage. The pathogenesis of HBV involves complex interactions between the virus and the host immune system, potentially leading to liver inflammation and fibrosis. Clinical presentations vary widely, ranging from asymptomatic infections to severe liver disease. Current treatment options for chronic Hepatitis B include antiviral medications such as tenofovir and entecavir, which suppress viral replication but do not cure the infection. Recent advancements in therapeutic strategies, including novel antivirals and immune modulators, show promise for more effective management and potential cures in the future. Comprehensive public health strategies—such as vaccination, screening, and education—are crucial for controlling the spread of HBV and reducing the global burden of Hepatitis B-related complications.

Myeloid beta-arrestin 2 depletion attenuates metabolic dysfunction-associated steatohepatitis via the metabolic reprogramming of macrophages

Macrophage-mediated inflammation has been implicated in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH); however, the immunometabolic program underlying the regulation of macrophage activation remains unclear. Beta-arrestin 2, a multifunctional adaptor protein, is highly expressed in bone marrow tissues and macrophages and is involved in metabolism disorders. Here, we observed that β-arrestin 2 expression was significantly increased in the liver macrophages and circulating monocytes of patients with MASH compared with healthy controls and positively correlated with the severity of metabolic dysfunction-associated steatotic liver disease (MASLD). Global or myeloid Arrb2 deficiency prevented the development of MASH in mice. Further study showed that β-arrestin 2 acted as an adaptor protein and promoted ubiquitination of immune responsive gene 1 (IRG1) to prevent increased itaconate production in macrophages, which resulted in enhanced succinate dehydrogenase activity, thereby promoting the release of mitochondrial reactive oxygen species and M1 polarization. Myeloid β-arrestin 2 depletion may be a potential approach for MASH.

Impact of non-selective beta blockers on further decompensation and death in decompensated cirrhosis: Benefit and risk stratification by MELD score.

Non-selective beta blockers (NSBBs) can reduce the risk of decompensation, but their impact on further decompensation has been rarely investigated. The aim is to evaluate the impact of NSBBs on further decompensation and death in decompensated cirrhosis stratified by the severity of liver disease. Overall, 332 decompensated cirrhotic patients were retrospectively included, of whom 149 used NSBBs. Kaplan-Meier and Nelson-Aalen cumulative risk curves as well as Cox regression and competing risk analyses were used to estimate the associations of NSBBs with further decompensation and death, if appropriate. Hazard ratio (HR) and sub-distribution HR (sHR) were calculated. Subgroup analyses were performed based on the model for end-stage liver disease (MELD) score at admission. In the overall analysis, the use of NSBBs was not significantly associated with further decompensation in multivariate competing risk analysis (sHR = 1.09, p = 0.580). In the subgroup analysis of patients with a MELD score of ≤9, the use of NSBBs was significantly associated with decreased risk of further decompensation in multivariate competing risk analysis (sHR = 0.57, p = 0.021). In the subgroup analysis of patients with a MELD score of >9, the use of NSBBs was associated with increased risk of further decompensation in multivariate competing risk analysis (sHR = 1.45, p = 0.044). Regardless of overall and subgroup analyses, the use of NSBBs was not significantly associated with death in multivariate Cox regression analyses. NSBBs may be beneficial for the prevention of further decompensation in cirrhotic patients with a MELD score of ≤9, but deleterious in those with a MELD score of >9.

Fetal hemochromatosis: rare case of hepatic and extrahepatic siderosis involving thyroid on fetal MRI

BackgroundNeonatal hemochromatosis (NH) is a rare condition that is characterized by severe neonatal liver disease in association with hepatic and extrahepatic excess iron deposition (siderosis), while sparing the reticuloendothelial system. The most common cause of fetal liver injury leading to the NH phenotype (accounting for over 95% of cases) is gestational alloimmune liver disease. This condition is caused by the transfer of maternal IgG antibodies through the placenta, targeting a fetal hepatocyte antigen. Prenatal diagnosis, particularly the identification of iron overload involving both liver and thyroid, is of significant importance and can have a profound impact on patient care. To our knowledge, no case has been reported on prenatal diagnosis of iron overload involving both liver and thyroid.Case presentationWe present an exceptionally rare case of fetal hemochromatosis in a primigravida, a case that significantly contributes to our understanding of this condition. The diagnosis was made with the presence of hepatic and extrahepatic siderosis involving the thyroid using Ultrasonography (USG) and fetal Magnetic Resonance Imaging (MRI) findings. A 23-year-old primigravida was referred to our center in view of oligohydramnios, Intrauterine Growth Restriction (IUGR) and echogenic bowel at 29 weeks of gestation. USG and fetal MRI showed features of coarse liver echotexture and iron overload involving the liver and thyroid; this is the first case describing iron accumulation in the fetal thyroid gland diagnosed in utero.ConclusionThis case underscores the critical importance of performing MRI in suspected cases of fetal hemochromatosis for early diagnosis and intervention, emphasizing the potential to significantly improve patient outcomes.