Liver Disease Research Articles

Comprehensive Analysis of Liver Biopsies in a Tertiary Care Hospital: A Retrospective Histopathological and Clinical Correlation Study

Liver biopsy (LB) served as a vital diagnostic tool for cases with notable alterations in liver function tests and for diagnosing a range of liver diseases, including chronic liver disease, cirrhosis, primary biliary cirrhosis, and hepatic neoplasms. Patients presenting with liver pathology often exhibited nonspecific symptoms, such as abdominal discomfort, nausea, vomiting, fever, indigestion, and flatulence. Based on patients' clinical history and radiological findings that suggested liver disease, a liver biopsy was frequently recommended, as it provided definitive diagnostic insights. Histopathological analysis of liver biopsies offered critical information on disease severity, grading, staging of liver tumors, and the presence of any coexisting hepatic conditions.This study retrospectively examined liver biopsies submitted to the Department of Pathology, correlating histopathological findings with clinical and radiological data. Through this integration, the research contributed to improved diagnosis, management, and follow-up of liver disease cases in a tertiary care setting.

Abstract 4131622: Opportunistic Screening of Chronic Liver Disease With Deep Learning Enhanced Echocardiography

Introduction: Chronic liver disease affects more than 1.5 billion adults worldwide, but the majority of cases are asymptomatic and undiagnosed. Echocardiography is broadly performed and visualizes the liver; however, this information is not diagnostically leveraged. Hypothesis and Aims: We hypothesized that a deep-learning algorithm can detect chronic liver diseases using subcostal echocardiography images that contains hepatic tissue. To develop and evaluate a deep learning algorithm on subcostal echocardiography videos to enable opportunistic screening for chronic liver disease. Methods: We identified adult patients who received echocardiography and abdominal imaging (either abdominal ultrasound or abdominal magnetic resonance imaging) with ≤30 days between tests. A convolutional neural network pipeline was developed to predict the presence of cirrhosis or steatotic liver disease (SLD) using echocardiogram images. The model performance was evaluated in a held-out test dataset, dataset in which diagnosis was made by magnetic resonance imaging, and external dataset. Results: A total of 2,083,932 echocardiography videos (51,608 studies) from Cedars-Sinai Medical Center (CSMC) were used to develop EchoNet-Liver, an automated pipeline that identifies high quality subcostal images from echocardiogram studies and detects presence of cirrhosis or SLD. In a total of 11,419 quality-controlled subcostal videos from 4,849 patients, a chronic liver disease detection model was able to detect the presence of cirrhosis with an AUC of 0.837 (0.789 - 0.880) and SLD with an AUC of 0.799 (0.758 - 0.837). In a separate test cohort with paired abdominal MRIs, cirrhosis was detected with an AUC of 0.726 (0.659-0.790) compared to MR elastography and SLD was detected with an AUC of 0.704 (0.689-0.718). In the external test cohort of 66 patients (n = 130 videos), the model detected cirrhosis with an AUC of 0.830 (0.738 - 0.909) and SLD with an AUC of 0.768 (0.652 – 0.875). Conclusions: Deep learning assessment of clinically indicated echocardiography enables opportunistic screening of SLD and cirrhosis. Application of this algorithm may identify patients who may benefit from further diagnostic testing and treatment for hepatic disease.

Unraveling the Association of Liver Steatosis and Fibrosis with Vitamin B12: A Cross-Sectional Study

Background: There are conflicting studies reporting both an increase and a decrease in vitamin B12 (VB12) levels in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to dissect the effects of steatosis and fibrosis on VB12. Methods: This is a cross-sectional study including all patients with a vibration-controlled transient elastography (VCTE) performed at the Hospital Miguel Servet (Zaragoza, Spain) between 2019 and 2022 for a chronic liver disease and having a recent blood test for VB12 levels. Liver fibrosis was assessed by VCTE and hepatic steatosis by ultrasonography and/or through controlled attenuation parameter (CAP). Results: 1195 patients (NAFLD n = 441, other chronic liver disease n = 754) were included. Median age was 57 years, 53% female. Patients with NAFLD had lower levels of VB12 compared to the rest of chronic liver diseases (289 vs. 313 pg/mL, p < 0.001). A significant negative correlation was observed between VB12 levels and hepatic steatosis measured by CAP (r = −0.13, p < 0.001). A significant positive correlation was observed between VB12 levels and liver stiffness in patients with NAFLD in both sexes (men r = 0.31, p < 0.001 and women r = 0.15, p = 0.016). A significant association between VB12 levels and liver fibrosis in cirrhosis stage was observed in patients with NAFLD (OR 1.06, 95% CI, 1.025–1.098, p = 0.001). Conclusion: VB12 levels were lower with greater hepatic steatosis. In NAFLD, VB12 levels were lower compared to other chronic liver diseases but their levels increased with higher liver stiffness and in cirrhosis stage.

Tobacco use, cirrhosis, and age are predictors of readiness to change and continued drinking following brief alcohol intervention in Veterans.

Alcohol-use disorder (AUD) is prevalent within the Veterans Health System, especially in patients being seen in hepatology clinics, and needs a point-of-care strategy. A brief alcohol intervention based on AUDIT-C (Alcohol Use Disorders Identification Test) may be needed for management of hazardous alcohol intake, but feasibility is unclear. We aimed to define predictors of readiness to cease alcohol intake (0-10, 10 being ready to quit now) and continued drinking after using a brief alcohol intervention in Veterans seen in hepatology clinics cross-sectionally and longitudinally over 6 months. A total of 414 men with liver disease (average age of 61 years old, 48% with cirrhosis, 31% with concomitant psychiatric conditions, 44% with tobacco use, 14% with prior AUD therapy) were approached. 144 patients (35%) had a positive AUDIT-C (8.9±4.0) and were given the brief intervention. 80 of these patients (56%) had a high readiness to change, listing "wanting to improve health" and "prior success at reducing alcohol intake" as their most frequent reasoning. On regression analysis, concomitant tobacco use was associated with a significantly lower readiness to quit alcohol score. On longitudinal follow-up at 6 months, 34 (23%) patients were still drinking. These patients were older, and more likely to have concomitant diagnoses of cirrhosis and anxiety. Overall, we found that in a large cohort of Veterans seen in hepatology clinics that in routine practice,a brief intervention targeted at alcohol use is feasible. Older patients with concomitant tobacco use, cirrhosis, and anxiety may need more longitudinal attention to ensure that the initial interest in reducing problem drinking is sustained.

The Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy

The Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy

Abstract 4144512: Impact of Nutritional Status on Transcatheter Edge-to-Edge Repair Outcomes in Mitral Regurgitation: Insights from a National Database Analysis

Introduction: Transcatheter edge-to-edge repair of the mitral valve with the MitraClip has offered a less invasive percutaneous alternative to surgical repair in select candidates with mitral regurgitation. Various factors impact the outcomes of MitraClip. We investigated the impact of nutritional status on the outcomes of MitraClip. Methods: Utilizing the nationwide inpatient sample data for years from January 1, 2016, and December 31, 2021, patients who underwent MitraClip were identified. They were categorized based on obesity and protein energy malnutrition (PEM). Statistical significance was assigned at p<05. Results: Out of the 8115 patients undergoing MitraClip, 2215 had PEM, and 5900 had obesity—table 1. Patients in the PEM group were older, with a higher prevalence of comorbidities, including anemia, pneumonia, liver disease, and fluid and electrolyte disorders, compared to the obese group. Conversely, the obesity group had a higher prevalence of hypertension, diabetes, and hypertension with complications. Our analysis revealed that PEM subgroups had significantly higher in-hospital mortality, cardiogenic shock, mechanical circulatory support (MCS) requirement, post-procedural worsening heart failure, spontaneous cardiac arrest, and major adverse cardiovascular and cerebrovascular events (MACCE). After adjusting for potential confounders, PEM remained an independent predictor of increased odds of death, cardiac arrest, ECMO, MCS, and MACCE compared to obesity. The propensity score matching analysis confirmed that PEM was associated with significantly higher rates of in-hospital mortality, cardiac arrest, and MACCE compared to obesity. (Figure 1) Conclusion: Our results reveal that PEM is associated with significantly worse outcomes in patients undergoing MitraClip procedures compared to obesity. These findings are consistent across multivariate and propensity score matching analyses.

Abstract 4137484: Clinical implications of combined midodrine and pulmonary vasodilator therapy in Portopulmonary Hypertension

Introduction: Portopulmonary hypertension (POPH) and associated pulmonary vascular resistance (PVR) elevation is seen in the context of underlying portal hypertension and liver disease. In the systemic circulation, liver cirrhosis can cause inappropriate splanchnic and systemic vasodilation with decreased systemic vascular resistance (SVR). Midodrine is used to maintain blood pressure in the setting of low SVR. Pulmonary vasodilators have systemic vasodilatory effects; the implications of combined midodrine and pulmonary vasodilator use in POPH are unanswered questions. Hypothesis: We hypothesized that SVR would decrease over time in patients with POPH started on pulmonary vasodilators, and that use of midodrine (as a surrogate for depressed SVR), may be associated with increased risk of mortality in patients with POPH starting pulmonary vasodilator therapy. Methods: Patients from the 3 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) diagnosed with POPH from 1988-2020 were included in the database. Patients met hemodynamic criteria for POPH via right heart catheterization (RHC). Hemodynamics were obtained from echocardiography and RHC at initial and subsequent visits. The hazard ratio for risk of death was estimated using Cox proportional hazards method. SVR was calculated using mean arterial pressure and cardiac output. Results: Analysis included 147 POPH patients, 34 (23%) on midodrine and 113 (77%) not requiring midodrine. There were 116 patients with longitudinal SVR data. The mean initial SVR was 1224 Dyne sec cm-5 and decreased 251 Dyne sec cm-5 [95% CI -337 to -165 251 Dyne sec cm-5, p<0.0001] with no difference between midodrine groups (p=0.57). Patients in the midodrine POPH group had an increased risk of mortality compared to those without midodrine use (HR 1.51, 95% CI: 1.02-2.21, p=0.0371). Conclusions: Patients with POPH starting pulmonary vasodilator have a reduction in SVR related to vasodilator therapy. Midodrine use with pulmonary vasodilator therapy is associated with increased mortality in the POPH population. Further study of the safety of combined midodrine and pulmonary vasodilator use in POPH is needed along with exploration of more selective pulmonary vasodilators.

Abstract 4121454: Machine-extractable Markers in Chest Radiograph to Predict Cardiovascular Risk in Screening Population

Introduction: Recent research has shown that AI is able to assess biological aging and cardiovascular disease (CVD) risk using chest radiographs. However, the lack of explainability of such deep learning algorithms hinders clinical utility and adoption. This motivates the current study which searches for and tests the use of machine extractable quantitative features in chest radiographs to predict CVD risk in population screening. Method: Chest radiograph measurements characterizing cardiomediastinal geometry, aortic calcification and tortuosity were handpicked for development of a segmentation-based feature extraction algorithm. The algorithm was applied on the PLCO lung screening dataset for analysis. The association between measurement-based imaging features, clinical characteristics (age, sex, BMI, smoking status, hypertension, diabetes, liver disease) with CVD mortality and 10-year major adverse cardiovascular events (MACE) were analysed by using proportional hazard regression, with feature selection done by LASSO. Result: Of 29,453 eligible subjects, 5693 subjects from a single study centre were used for fitting of all models. The median follow-up time was 19 years. A total of 32 imaging features were extracted and analysed. For both 10-year MACE and CVD mortality, model using imaging features, age, and sex performed similarly to model using conventional risk factors, and a deep learning chest radiograph CVD risk model. Two imaging features, mediastinal width at valve-level [HR 1.36 (1.23-1.50)] and maximal lateral displacement of descending aorta [HR 1.29 (1.18-1.42)] were found to be prognostic. To the best of our knowledge, these features have not been reported previously. Conclusion: Quantitative imaging features can predict CVD risk in chest radiograph similar to deep learning models while providing feature interpretability and explainability. Two novel imaging features prognostic of CVD risk were found and shown to be complementary to conventional risk factors.

Abstract 4123530: Disparities in Hypertension Treatment Intensification among Adults in a Large United States Healthcare System

Background: There are racial/ethnic and socioeconomic status (SES) disparities in hypertension control, even in populations with regular care. It is unclear if clinical inertia by clinicians contributes to these disparities. Objectives: To quantify racial/ethnic and SES disparities in treatment intensification (TI) among adults with hypertension. Methods: We performed a retrospective cohort study using electronic health records from Johns Hopkins primary care practices from January 2018 to December 2022. We included non-Hispanic Black (Black) and non-Hispanic White (White) adults with at least 2 elevated blood pressure readings (>=140/90 mm Hg) in the 12 months prior to the index primary care visit and a diagnosis of essential hypertension. We excluded patients with diagnoses of end-stage renal disease, liver disease, dementia, and metastatic solid tumor. Patients could contribute multiple index visits. We measured SES using the national Area Deprivation Index, which comprises 17 neighborhood-level SES indicators, and dichotomized the population into high and low median SES groups. We defined TI as a change in antihypertensive class or dose increase within 14 days of the index visit. We balanced covariates reflecting clinical need at the index visit (age, sex, blood pressure readings, cardiometabolic comorbidities, body mass index) and the index visit’s calendar time across racial/ethnic and SES groups using inverse probability weighting. We estimated annual race/ethnic and SES specific TI rates and risk difference measures of disparity with 95% confidence intervals (CI) using a clustered bootstrap. Results: The cohort included 25,287 patients (11,800 Black, 13,487 White) with 79,898 eligible visits. Black patients were more often younger, female, and residing in low SES areas compared to White patients. In 2018, TI rates for Black patients (37%, 95% CI: 36-38%) were slightly lower than rates for White patients (39%, 95% CI: 38-40%). In 2022, the disparity persisted, with the Black patients’ TI rate lower by 3% (95% CI: -5%, -1%). Similarly, low SES patients had lower TI rates than high SES patients by 2% to 3% over the study period. Conclusion: Black patients and those from low SES consistently had modestly lower rates of TI compared to White patients and those from high SES. It will be important to identify the drivers and clinical implications of these treatment disparities.

Suspected hepatic hydrothorax secondary to cirrhosis in a dog

AbstractAn 8‐year‐old, entire, female labrador retriever presented with a 2‐week history of abdominal distension. Biochemistry identified hepatic dysfunction (elevated hepatobiliary markers, hypocholesterolaemia). Abdominal ultrasonography documented an irregular liver and a large volume of anechoic peritoneal effusion, which laboratory analysis confirmed as a protein‐poor transudate. Thoracic computed tomography identified a moderate volume of pleural effusion with a similar composition to the peritoneal fluid. Hepatic histopathology was consistent with cirrhosis secondary to chronic hepatitis and, in the absence of another cause for the pleural effusion, hydrothorax secondary to the hepatic disease was suspected. The patient was started on ciclosporin for treatment of the underlying liver disease, but developed signs consistent with disseminated intravascular coagulopathy 24 hours later and was humanely euthanased. As reported in humans, hydrothorax may therefore occur secondary to cirrhosis in dogs and should be considered as a differential diagnosis for pleural effusion in patients with advanced hepatic disease and concurrent peritoneal effusion.

The dichotomous roles of microbial-modified bile acids 7-oxo-DCA and isoDCA in intestinal tumorigenesis

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear. We found that although high-fat diet treatment in mice elevated both 7-oxo-DCA and isoDCA levels, during intestinal tumorigenesis, 7-oxo-DCA levels rise while isoDCA levels decrease. Interestingly, 7-oxo-DCA promotes cancer cell growth, while isoDCA suppresses it. Moreover, 7-oxo-DCA promotes whereas isoDCA inhibits the proliferation of intestinal stem cells in organoids derived from WT and APCMin/+ mice, as well as in patient-derived colon cancer organoids. The APCMin/+ mice administered with 7-oxo-DCA heightened gut permeability and increased tumor burden, whereas isoDCA protected gut barrier and reduced tumor loads. Both BAs reshape the BA pool and shifted gut microbiome. Mechanistically, we identified 7-oxo-DCA as a natural antagonist of Farnesoid X Receptor (FXR) to downregulate FXR signaling, as opposed to isoDCA, which is a potent FXR agonist to upregulate FXR signaling. In conclusion, we unveiled the opposing roles of 7-oxo-DCA and isoDCA to promote or inhibit intestinal tumorigenesis, respectively. Manipulating the BA-FXR axis during tumor initiation and progression holds great promise for developing innovative diagnostic and therapeutic approaches for the treatment of colorectal cancer.

Acetylcorynoline alleviates acute liver injury via inhibiting TLR4/JNK/NF-ĸB pathway Based on RNA-seq and molecular docking in vivo and in vitro

Acute liver injury is characterized by massive inflammatory cell infiltration, destruction of liver structure and abnormalities in liver function. Acetylcorynoline (AC) is one of the main chemical components of Corydalis bungeana Turcz. which has been shown to have a protective effect against acute liver injury. However, Whether AC is protective against acute liver injury remains unclear. This study aimed to explore the protective mechanism of AC against acute liver injury from in vivo as well as experiments in vitro. In experimental in vivo studies, AC pretreatment reduced the serum levels of ALT and AST and inhibited the expression of inflammatory factors in the liver of LPS/D-GalN-induced mice and alcohol liver disease mice. RNA-sequencing and molecular docking were used to predict that AC exerts its anti-inflammatory effects through the Toll-like receptor signaling pathway. Using RT-qPCR and Western blotting to detect expression levels of key genes and nodal proteins of the Toll-like receptor signaling pathway, AC was found to inhibit the phosphorylation of nuclear factor-kappaB (NF-ĸB) and c-Jun amino-terminal kinase (JNK). This finding was validated in cellular experiments. In conclusion, AC exerts its anti-hepatic injury effect by suppressing inflammation through inhibition of the TLR4/JNK/NF-ĸB pathway.

Abstract 4122301: The Role of Hepatic CDS2 in Phosphatidylinositol Homeostasis and Lipid Metabolism

Background: Recent studies in both human genetics and mouse models have highlighted the significance of phosphatidylinositol (PI) in the progression of fatty liver disease (FLD). Despite this, the precise mechanisms underlying PI's role remain elusive. Aims: This study aimed to elucidate the involvement of PI in FLD by disrupting hepatic PI biosynthesis through modulation of CDP-diacylglycerol synthase 2 (CDS2) expression, the primary enzyme in PI biosynthesis (A). Methods: We generated liver-specific knockouts of CDS2 and SCAP (SREBP cleavage-activating protein) using adeno-associated virus (AAV) expressing sgRNA against each gene. Phospholipid species were analyzed and quantified by LC/MS. Results: CDS2 liver-specific knockout mice (B, C) exhibited a pronounced development of fatty liver, characterized by elevated triglyceride and cholesterol levels (C). Notably, liver PI levels were significantly reduced in CDS2 knockout mice (E), accompanied by dysregulated activation of sterol regulatory element-binding protein (SREBP) even during fasting conditions (F), leading to increased de novo lipogenesis. Intraperitoneal administration of exogenous PI effectively normalized SREBP cleavage (G), highlighting PI's critical role in SREBP regulation. Furthermore, simultaneous knockout of SCAP with CDS2 restored the normal liver phenotype, implicating SREBP activation as a central mechanism underlying fatty liver development in CDS2 knockout mice (H, I). Conclusion: Deletion of CDS2 in the liver reduced PI levels, subsequently inducing significant fatty liver due to dysregulated SREBP activation. This study underscores the importance of CDS2 in maintaining PI homeostasis, which in turn regulates SREBP activity and lipid metabolism. Our findings provide valuable insights into the pathogenesis of metabolic disorders and offer potential therapeutic strategies for targeting FLD.

A predicted epithelial-to-mesenchymal transition-associated mRNA/miRNA axis contributes to the progression of diabetic liver disease.

Despite public health measures, type 2 diabetes (T2D) is still a significant concern worldwide, given its associated complications, including hepatic alterations. The role of epithelial-to-mesenchymal transition (EMT) in liver fibrosis is well established. However, its effects on the progression of diabetic liver diseases are not well understood. Therefore, this study aims to investigate the mRNA/miRNA axes involved in this process. Bioinformatic analysis revealed new EMT-associated genes (CDH2, ITGB1, COL4A1, COL1A1, TNC, CCN2, and JUN), which showed higher expression in obese T2D and hepatocellular carcinoma (HCC) patients. In addition, six miRNAs (miR-21-5p, miR-26a-5p, miR-34a-5p, miR-106a-5p, miR-320a-3p and miR-424-5p) have been found as potential targets. Among them, miR-26a-5p and miR-424-5p were significantly downregulated in nonalcoholic steatohepatitis (NASH) and HCC (p < 0.05), being considered potential negative regulators of the EMT process. In our hepatic mesenchymal culture model, miR-26a-5p negatively regulated cadherin 2 (also known as N-cadherin, CDH2) and promoted the cadherin 1 (also known as E-cadherin, CDH1) expression. Our results reveal potential molecules involved in liver tumor development. Moreover, we observe that miR-26a-5p impairs EMT in the initial stages of diabetic liver disease by inhibiting CDH2 and could be a valuable target in this pathology.

Clinical and Biochemical Outcomes in Transgender Individuals Undergoing Hormone Therapy: Protocol for a Systematic Review.

Monitoring of various clinical outcomes and parameters, such as lipid levels, is recommended in transgender individuals undergoing hormone therapies. However, comprehensive data to inform these recommendations is scarce. This study aims to conduct a systematic review and meta-analysis to synthesize evidence from existing literature on the effect of exogenous hormone therapy on clinical and biochemical outcomes for transgender adolescents and adults. We will search multiple electronic databases and will include prospective and retrospective observational studies with and without a control group. The study population will include transgender individuals undergoing hormone therapy with testosterone or estrogen. Comparisons will include age-matched, cisgender individuals and changes from baseline. Primary outcomes include changes in or the development of abnormal lipid parameters. Secondary outcomes include BMI, weight, height, and blood pressure for age, serum testosterone or estrogen levels, and development of disease including hypertension, diabetes, fatty liver disease, obesity, adverse cardiac events, as well as all-cause mortality. The meta-analysis will pool the studies where applicable, and meta-regressions will be conducted to evaluate effect modifiers. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach will be used to evaluate the overall certainty of evidence. We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. Data collection is ongoing, and the paper is expected to be published in Spring 2025. This systematic review will summarize and evaluate the evidence of the clinical and biochemical outcomes associated with hormone therapies for transgender individuals. PROSPERO CRD42024483138; https://tinyurl.com/yc4sfvnb. PRR1-10.2196/57931.

Liver transplantation and comprehensive rehabilitation in the reversal of hepatic myelopathy: a case report

Hepatic myelopathy (HM) is a rare complication of end-stage chronic liver disease, primarily presenting as symmetrical lower limb weakness that progresses to spastic paralysis without sensory or sphincter dysfunction. We report a case of decompensated cirrhosis associated with hepatitis B virus and HM. The patient showed significant recovery after liver transplantation (LT) and comprehensive rehabilitation training. We summarize the patient’s clinical characteristics post-diagnosis and the assessment outcomes following integrated treatment.

Relationship between breastfeeding and hepatic steatosis in women with previous gestational diabetes mellitus.

Non-alcoholic fatty liver disease (NAFLD), characterized by excess liver fat, is common in women with a history of gestational diabetes mellitus (GDM). While breastfeeding improves postpartum lipid levels, its impact on NAFLD in these women is not well studied. We aimed to investigate the relationship between the duration and intensity of breastfeeding and the amount of liver fat and prevalence of NAFLD in women with previous GDM at approximately 1 year postpartum. This prospective cohort study was conducted at a university hospital in Bangkok, Thailand between November 2021 and February 2024. Overall, 130 women who had experienced GDM in their most recent pregnancy were followed up for 1 year postpartum. We collected data on breastfeeding practices and quantified liver fat using controlled attenuation parameters (CAPs) during transient elastography. NAFLD was defined as a CAP of ≥ 302 dB/m. Women were divided into three groups according to the duration and intensity of breastfeeding: group 1 (breastfeeding for < 6 months), group 2 (breastfeeding for ≥ 6 months and exclusive breastfeeding [EBF] for < 6 months), and group 3 (breastfeeding for ≥ 6 months and EBF for 6 months). Overall, 57 (43.8%), 26 (20.0%), and 47 (36.2%) participants were categorized into groups 1, 2, and 3, respectively. Group 3 had the lowest CAPs, followed by groups 2 and 1. The median values (interquartile ranges) of the CAPs were 219.0 (189.0-271.0) dB/m, 257.5 (205.3-317.3) dB/m, and 279.0 (191.5-324.0) dB/m for groups 3, 2, and 1, respectively (p = 0.034). NAFLD prevalence was significantly lower in group 3 compared to groups 2 and 1 (19.1% vs. 38.5% vs. 43.9%, respectively; p = 0.026). Multivariate analysis showed that breastfeeding for ≥ 6 months and EBF for 6 months reduced the risk of NAFLD, with an adjusted odds ratio of 0.34 (95% confidence interval 0.14, 0.95). Breastfeeding for ≥ 6 months, particularly EBF for the first 6 months, may offer a practical strategy to reduce the risk of NAFLD in women with prior GDM. Thai Clinical Trials Registry: Registration no. TCTR20211027008. Date of registration: October 27, 2021. Date of initial participant enrollment: November 1, 2021.

A Novel Preoperative Classification System for Selecting Suitable Surgeries in Liver Transplant Patients with Portal Vein Cavernous Transformation

Background To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT). Methods This retrospective observational study analyzed data from allograft LTs performed for various liver diseases Results The study included 22 males and 4 females with LT indications comprising cirrhosis (n = 9), hepatocellular carcinoma (n = 12), PVCT (n = 2), liver failure from fulminant hepatitis B (n = 1), dysfunction of transplanted liver (n = 1), and chronic rejection of transplanted liver (n = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1–C5). In total 16 simple operations were performed on C1–C3 cases and 9 complex operations on C4–C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively (p = 0.526). Conclusion The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.

Cell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding. In contrast, MLKL, divergent to RIPK3, contributes to both obesity and MAFLD in a manner largely independent of inflammation. We also uncover that MLKL regulates the expression of molecules involved in lipid uptake, transport, and metabolism, and congruent with this, we discover a shift in the hepatic lipidome upon MLKL deletion. Collectively, these findings highlight MLKL as an attractive therapeutic target to combat the growing obesity pandemic and metabolic disease.

Multiple-response logistic regression modeling with application to an analysis of cirrhosis liver disease data

Multiple-response logistic regression modeling with application to an analysis of cirrhosis liver disease data