End-stage Cirrhosis Research Articles

How improvements in US FDA regulatory process and procedures led to the drug approval for first ever treatment of a common liver disease.

Metabolic-associated liver disease is a growing public health crisis, with phenotypes from fatty liver to steatohepatitis, previously known as NASH (Non-Alcoholic SteatoHepatitis) and currently rebranded as MASH (Metabolic dysfunction-Associated SteatoHepatitis). Dysfunction in liver metabolism can progress to liver fibrosis, end stage cirrhosis and death. MASH (NASH) is associated with an increased risk of cardiovascular disease, elevation in serum lipids and Type 2 Diabetes Mellitus. There is now a US-approved drug to treat patients with NASH (MASH) under the FDA Accelerated Approval Pathway, which requires follow-up outcome studies to confirm clinical benefit or risk drug withdrawal by the agency. Despite extra-hepatic factors that contribute to MASH and complicate clinical trial design, reorganization of the FDA drug premarket review divisions, improvements to agency policies and procedures, as well as updates to the US Food, Drug & Cosmetic Act (FD&C Act) upon which FDA regulation is based, have provided new agency tools that facilitated such a drug approval to address the profound unmet medical need for patients with this metabolic-based liver disease. There is reason for hope that continued evolution of the regulatory process will lead to additional drug approvals, as well as the ability for clinical trial endpoints studying MASH treatments to include both liver-based and traditional metabolic measures, independent of the specific FDA review division. This initial NASH/MASH FDA approval has also opened the door for initiation of Combination Clinical Trials, where the approved drug is paired with an experimental drug with a different mechanism of action, to increase overall efficacy and potentially minimize risks. It is envisioned that future treatment of NASH/MASH will mirror what is currently observed with Type 2 Diabetes Mellitus practice patterns, where multiple drugs with different mechanisms of actions are used to optimize treatment benefit/risk in the selected patient populations.

Therapeutic efficacy and in vivo distribution of human umbilical cord-derived mesenchymal stem cell spheroids transplanted via B-Ultrasound-guided percutaneous portal vein puncture in rhesus monkey models of liver fibrosis

BackgroundLiver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects.MethodsIn the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology.ResultsWe found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver.ConclusionsThis study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19.

Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic lipid accumulation, causes inflammation and oxidative stress accompanied by cell damage and fibrosis. Liver injury (LI) is also frequently reported in patients hospitalised with coronavirus disease 2019 (COVID-19), while pre-existing MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy. Mechanisms of injury at the cellular level remain unclear, but it may be significant that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19, uses angiotensin-converting expression enzyme 2 (ACE2), a key regulator of the 'anti-inflammatory' arm of the renin-angiotensin system, for viral attachment and host cell invasion. To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19. ACE2 protein levels and localisation, and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum (isolated hepatocellular steatosis, metabolic dysfunction-associated steatohepatitis (MASH) +/- fibrosis, end-stage cirrhosis) and in post-mortem tissues from patients who had died with severe COVID-19, using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas, followed by quantification using machine learning-based image pixel classifiers. ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes. Strikingly, ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis. ACE2 protein levels and histological fibrosis are not associated, but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum. Hepatic ACE2 levels are also increased in COVID-19 patients, especially those showing evidence of LI, but are not correlated with the presence of SARS-CoV-2 virus in the liver. However, there is a clear association between the hepatic lipid droplet content and the presence of the virus, suggesting a possible functional link. Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI, while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication, accelerating MASLD progression and COVID-19-mediated liver damage.

Evaluation of Factors Affecting Rehospitalization and Survival After Living Donor Liver Transplantation

Complications and comorbidities that may develop after living donor liver transplantation may necessitate rehospitalization after discharge. We aimed to investigate the demographic and clinical factors affecting rehospitalization after discharge. Two hundred seventy patients who underwent living-donor liver transplantation (LDLT) for end-stage liver cirrhosis were included in the study. Patients were divided into two groups as readmission group and others for statistical analysis. Age, gender, body mass index (BMI), model for end-stage liver disease (MELD), Child scores, etiology, blood product transfusion, anhepatic phase, cold ischemia time, operation time, graft-to-recipient weight ratio (GRWR), the type of recipient hepatic artery and hepatic vein utilized in the anastomoses, presence of liver segment 5, segment 8 and inferior accessory hepatic vein, presence of thrombosed, single or reconstructed portal vein, number of bile ducts, use of right, left/left lateral segment graft, postoperative intensive care unit and total hospitalization durations, surgical complications such as leakage/stricture, postoperative portal vein thrombosis, postoperative hepatic vein thrombosis, primary graft dysfunction, intra-abdominal hemorrhage, and postoperative early reoperation were statistically analyzed for readmission. In addition, patients with rehospitalization and others were statistically compared in terms of mortality and survival. There was no statistical difference among etiologic factors, demographic findings, decompensation findings, comorbidities, perioperative findings, hospital durations, mortality, and survival (P > .05). Only patients with bile leakage/stricture had a statistically higher rehospitalization rate (P = .000). Biliary complications are the most frequent cause of hospital rehospitalization following living donor liver transplantation.

Effects of Hepatic Artery Type And Number on Bile Complications in Right Lobe Living Donor Liver Transplant Recipients: Single Center Experience Without Hepatic Artery Thrombosis

Purpose: Hepatic artery provides blood supply to the biliary tract of the graft, one of the causes of the biliary complications that may occur in the post-transplant period may be the problems of the recipient's hepatic artery. We examined the effect of post-transplant biliary complications according to the type and number of recipient hepatic artery. Materials and Methods: One hundred eighty five patients older than 18 years of age who underwent right lobe LDLT for end-stage liver cirrhosis were included in the study. The recipient's right hepatic artery (RHA), left hepatic artery (LHA), propria hepatic artery (PHA) and common hepatic artery (CHA), which were anastomosed to the graft artery and double hepatic artery anastomoses formed of the right and left hepatic arteries, were examined. Biliary complications were analyzed statistically in terms of single or double artery anastomosis and anastomoses with the right or the other hepatic arteries. Results: There was no statistically significant difference between single and dual artery anastomoses in terms of bile duct stricture or leakage (p=0.767). No statistically significant difference was observed between RHA, LHA, PHA, CHA, and between single and dual arteries in the evaluation of artery selection between those with and without biliary tract complications (p=0.445) Conclusion: Hepatic artery type selection and number of the recipient does not change the biliary tract complication.

Effects of comorbid conditions and prescribed chronic medications on the treatment plan for chronic hepatitis C infection: A cross-sectional retrospective study.

Chronic hepatitis C (CHC) infection is a potentially life-threatening condition characterized by various complications, including end-stage liver disease and cirrhosis. The mortality rate associated with CHC has been increasing due to the presence of comorbidities and the use of chronic medications. Therefore, the objective of this study was to investigate the impact of these comorbidities and chronic medications on the treatment plan for CHC. To achieve this objective, a cross-sectional retrospective study was conducted at a tertiary hospital in Jeddah, Saudi Arabia. The study population included patients aged 12 years and above who were diagnosed with CHC between 2016 and 2021. Patients below the age of 12 were excluded from the study. A total of 170 patients with CHC were included in the analysis. The study aimed to evaluate the relationship between CHC complications and the treatment approach. The mean age of the study participants was 66.78 years, with a higher proportion of female patients. The findings revealed a significant association between hypertension (p = 0.042) and cirrhosis (p = 0.007) with changes in the treatment plan for CHC. Moreover, the presence of diabetes mellitus (p = 0.045), renal diseases (p < 0.001), and hypothyroidism (p = 0.004) were significantly associated with HCV clearance after the initiation of therapy. Additionally, the use of proton pump inhibitors (p = 0.033) and levothyroxine (p = 0.025) was found to be associated with a higher rate of CHC clearance. In conclusion, this study highlights the prevalence of comorbid conditions and the use of chronic medications among patients with CHC. The findings emphasize the importance of considering the effects of comorbidities and chronic medications when developing treatment plans for CHC infections. By taking these factors into account, healthcare professionals can optimize the management of CHC and improve patient outcomes.

Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients

IntroductionAcute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.MethodologyIn the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.ResultsOf 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).ConclusionAKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Renal Replacement Therapy During Liver Transplant Surgery

Liver transplant is the treatment available for eligible patients with end-stage liver cirrhosis. Acute kidney injury and electrolyte abnormalities are associated with liver disease and can be exacerbated by surgery. Intraoperative renal replacement therapy has been tried in some large centres. The authors discuss the physiological changes and complications during liver transplant surgery, and review literature on the safety, feasibility, benefits, and drawbacks of intraoperative renal replacement therapy during liver transplant surgery.

Sexual Dimorphism in Decompensated Non Ethanol-related Chronic Liver Disease: A Retrospective Cohort Study

Introduction: Women exhibit a distinct natural history of chronic liver disease compared to men, particularly regarding progression and outcomes. Although liver disease prevalence is generally higher in men, the incidence of non ethanol-related liver disease is increasing among females. Metabolic syndromes and their consequences are less recognised in the female population until they develop end-stage cirrhosis. Limited studies have explored the differences between male and female cirrhosis. The present study aimed to address the knowledge gap in female Decompensated Chronic Liver Disease (DCLD). Aim: To identify the differences in presentation and outcomes between females and males with non ethanol-related cirrhosis. Materials and Methods: The present retrospective cohort study was conducted in the Department of Medical Gastroenterology and Hepatology,Tirunelveli Medical College, Tirunelveli, Tamil Nadu, India, involving 27 males and 33 females with non ethanol-related decompensated cirrhosis. A comparison was made between the aetiologies, presenting symptoms, complications, laboratory values, Model for End-stage Liver Disease (MELD) score, and in-hospital mortality during the first decompensation. Data analysis was performed using Statistical Packages for Social Sciences (SPSS) version 24.0 Quantitative variables were expressed as mean and Standard Deviation, while qualitative variables were expressed as frequency and percentage. The association between categorical variables was analysed using the Chi-square test, and the comparison of continuous variables between the two groups was analysed using independent sample t-test. A p-value of &lt;0.05 was considered statistically significant. Results: The mean age of decompensation was 56.5 years for men and 50.9 years for women. The most common aetiology in men was Non Alcoholic Fatty Liver Disease (NAFLD) (63%), while in females, it was NAFLD (45%) and cryptogenic cirrhosis (45%) (p=0.020). Diabetes Mellitus (DM) was more prevalent in males (55.6% versus 33.3%). Variceal bleed was more common in females (66.7% versus 48.1%). Jaundice was more frequently observed in males (44.4% versus 21.2%) (p=0.05). Ascites was more prominent in males (70.4% versus 45.5%) (p=0.05). Hepatic Encephalopathy (HE) was more prevalent in males (22.2% versus 15.2%). Females had a lower MELD scores compared to males (12.4±6.1 versus 15.2±6.4). Mortality was higher in males (22.2% versus 12.1%). Conclusion: Women with Decompensated Chronic Liver Disease tend to decompensate at a younger age compared to males and have a higher risk of Upper Gastrointestinal (UGI) bleeding. NAFLD was the most common aetiology in both groups. Ascites and HE were more commonly observed in men. Females had lower MELD scores, resulting in a longer waiting period on the transplant list compared to males. Mortality was higher in males.

Tumor Necrosis Factor-Alpha and Adiponectin in Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma.

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma (HCC), whose prevalence is rising. Although the mechanisms of progression from NAFLD to HCC are not fully elucidated, tumor necrosis factor-α (TNF-α) and adiponectin, as well as their interplay, which seems to be antagonistic, may contribute to the pathophysiology of NAFLD-associated HCC. TNF-α initially aims to protect against hepatocarcinogenesis, but during the progression of NAFLD, TNF-α is increased, thus probably inducing hepatocarcinogenesis in the long-term, when NAFLD is not resolved. On the other hand, adiponectin, which is expected to exert anti-tumorigenic effects, is decreased during the progression of the disease, a trend that may favor hepatocarcinogenesis, but is paradoxically increased at end stage disease, i.e., cirrhosis and HCC. These observations render TNF-α and adiponectin as potentially diagnostic biomarkers and appealing therapeutic targets in the setting of NAFLD-associated HCC, possibly in combination with systematic therapy. In this regard, combination strategy, including immune checkpoint inhibitors (ICIs) with anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin, may warrant investigation against NAFLD-associated HCC. This review aims to summarize evidence on the association between TNF-α and adiponectin with NAFLD-associated HCC, based on experimental and clinical studies, and to discuss relevant potential therapeutic considerations.

Advance care planning in end-stage cirrhosis in a UK district general hospital

Advance care planning in end-stage cirrhosis in a UK district general hospital

Serum wisteria floribunda agglutinin-positive human Mac-2 binding protein is unsuitable as a diagnostic marker of occult hepatocellular carcinoma in end-stage liver cirrhosis.

Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a marker of liver fibrosis and hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the diagnostic ability of WFA+-M2BP for occult HCC, which current diagnostic imaging tests fail to detect. Patients who underwent hepatectomy for liver transplantation (LT) and whose whole liver could be sliced and subjected to histological examination between 2010 and 2018 were eligible for this study (n = 89). WFA+-M2BP levels were measured in samples collected before the LT. Comparison of the postoperative histological test results with the preoperative imaging data grouped the patients into histologically no group (N), histologically detected group (D), histologically increased group (I), and histologically decreased or same group (DS), and the results were compared with the WFA+-M2BP values. In addition, comparisons were made between each data with and without HCC, including occult HCC, and total tumor diameter. Irrespective of underlying hepatic disease conditions, there were 6 patients in the N group, 10 in the D group, 41 in the I group, and 32 in the DS group. The median of the serum WFA+-M2BP level for each group was as follows: N group, 8.05 (1.25-11.9); D group, 11.025 (1.01-18.21); I group, 9.67 (0.29-17.83); and DS group, 9.56 (0.28-19.44) confidence of interval. We found no significant differences between the pairings. Comparison of underlying hepatic diseases revealed that liver cirrhosis due to hepatitis B and C and non-B and -C liver cirrhosis had no significant differences. AFP levels, on the other hand, had significant relationships in comparison between the presence or absence of histological HCC, in correlation between total tumor diameter, and in the ROC analysis for the diagnosis of HCC including occult HCC. Serum WFA+-M2BP cannot help diagnose occult HCC that is already undetected using imaging tests in decompensated liver cirrhosis patients requiring LT.

Black necrosis of the glans penis associated with calciphylaxis: A case report.

Calciphylaxis, known as calcific uremic arteriolopathy, is a rare cause of dry gangrene. Despite an increase in the clinical recognition of demographic characteristics and risk factors associated with calciphylaxis, it remains a poorly understood disease with high mortality. We present a 45-year-old man, who was diagnosed with calciphylaxis disease, with a history of diabetes mellitus, end-stage renal disease and cirrhosis with a half-month evolution of painful dry gangrene on his glans penis and scrotum. The patient also presented with gangrene of fingers. The patient and his family opted for palliative care. However, he died eventually. This case contributed to the current understanding of calciphylaxis. Since no standard treatment is available and the prognosis remained poor, early, and accurate diagnosis of calciphylaxis is important. We here report the current case and provide data for the diagnosis and treatment of this kind of disease.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease: A bibliometric and visualization analysis (2010-2023).

Nonalcoholic fatty liver disease (NAFLD) is chronic, with its progression leading to liver fibrosis and end-stage cirrhosis. Although NAFLD is increasingly common, no treatment guideline has been established. Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD. An up-to-date overview on the knowledge structure of NAFLD through bibliometrics, focusing on research hotspots, is necessary to reveal the rational and timely directions of development in this field. To research the latest literature and determine the current trends in treatment for NAFLD. Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database, from 2010 to 2023. VOSviewers, CiteSpace, and R package "bibliometrix" were used to conduct this bibliometric analysis. The key information was extracted, and the results of the cluster analysis were based on network data for generating and investigating maps for country, institution, journal, and author. Historiography analysis, bursts and cluster analysis, co-occurrence analysis, and trend topic revealed the knowledge structure and research hotspots in this field. GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization. In total, 10829 articles from 120 countries (led by China and the United States) and 8785 institutions were included. The number of publications related to treatment for NAFLD increased annually. While China produced the most publications, the United States was the most cited country, and the United Kingdom collaborated the most from an international standpoint. The University of California-San Diego, Shanghai Jiao Tong University, and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions. The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals, and Hepatology was the most cited and co-cited journal. Sanyal AJ was the most cited author, the most co-cited author was Younossi ZM, and the most influential author was Loomba R. The most studied topics included the epidemiology and mechanism of NAFLD, the development of accurate diagnosis, the precise management of patients with NAFLD, and the associated metabolic comorbidities. The major cluster topics were "emerging drug," "glucagon-like peptide-1 receptor agonist," "metabolic dysfunction-associated fatty liver disease," "gut microbiota," and "glucose metabolism." The bibliometric study identified recent research frontiers and hot directions, which can provide a valuable reference for scholars researching treatments for NAFLD.

The Role of Mesenchymal Stem Cells in Liver Regeneration

Background: Inflammation of the liver caused by cholestasis, viral infection, alcohol, autoimmune reactions, toxins, or metabolism will result in a prolonged immune response. As a result, simultaneous inflammation and tissue remodelling occur, resulting in fibrosis and eventually leading to cirrhosis. The main treatment for end-stage liver cirrhosis is liver transplantation. However, it is often not possible for patients to undergo this life-saving procedure. On the other hand, stem cell transplantation may be a potential strategy to prevent disease progression and improve the degree of fibrosis.&#x0D; Discussion: Inflammation of the liver activates hepatic stellate cells, which are perisinusoidal cells in the Disse cavity that contain vitamin A. Hepatic stellate cells activation results in retinoid storage loss and transformation into myofibroblast-like cells that express α-smooth muscle action (α-SMA) and produce collagen which plays a major role in fibrosis. Liver regeneration due to chronic liver damage is played by mesenchymal cells through the mesenchymal-epithelial or epithelial-mesenchymal transition (MET/EMT) process. Administration by the intrahepatic route is thought to be the ideal route because fewer cells are lost in the circulation and more mesenchymal stem cells differentiates into hepatocytes in the damaged liver area. However, intrasplenic route maybe an alternative with easier administration technique. There are special considerations regarding the risks, including the risk of carcinogenesis and viral transmission.&#x0D; Conclusion: Mesenchymal stem cells transplantation may be a potential therapeutic strategy for patients with end stage liver disease in the future. However, future research is needed regarding the risk of carcinogenesis and viral transmission following the procedure.

Risk factors for hepatic hydrothorax in patients with cirrhosis: a clinical retrospective study.

Hepatic hydrothorax, which presents as an unexplained pleural effusion, is one of the important complications in patients with end-stage cirrhosis. It has a significant correlation with prognosis and mortality. The aim of this clinical study was to detect the risk factors for hepatic hydrothorax in patients with cirrhosis and to better understand potentially life-threatening complications. Retrospectively, 978 cirrhotic patients who were hospitalized at the Shandong Public Health Clinical Center from 2013 to 2021 were involved in this study. They were divided into the observation group and the control group based on the presence of hepatic hydrothorax. The epidemiological, clinical, laboratory, and radiological characteristics of the patients were collected and analyzed. ROC curves were used to evaluate the forecasting ability of the candidate model. Furthermore, 487 cases in the experimental group were divided into left, right, and bilateral groups, and the data were analyzed. The patients in the observation group had a higher proportion of upper gastrointestinal bleeding (UGIB), a history of spleen surgery, and a higher model for end-stage liver disease (MELD) scores compared with the control group. The width of the portal vein (PVW) (P = 0.022), prothrombin activity (PTA) (P = 0.012), D-dimer (P = 0.010), immunoglobulin G (IgG) (P = 0.007), high-density lipoprotein cholesterol (HDL) (P = 0.022), and the MELD score were significantly associated with the occurrence of the hepatic hydrothorax. The AUC of the candidate model was 0.805 (P < 0.001, 95% CI = 0.758-0.851). Portal vein thrombosis was more common in bilateral pleural effusion compared with the left and right sides (P = 0.018). The occurrence of hepatic hydrothorax has a close relationship with lower HDL, PTA, and higher PVW, D-dimer, IgG, and MELD scores. Portal vein thrombosis is more common in cirrhotic patients with bilateral pleural effusion compared to those with unilateral pleural effusion.

Streptococcus cristatus bacteremia in a patient with poor oral hygiene: a case report

BackgroundStreptococcus cristatus is a member of the Mitis streptococcus group. Like other members of this group, it resides on mucosal surfaces of the oral cavity. However, little is known about its ability to cause disease as there are only a handful of cases in the literature. Two of these cases involved infective endocarditis with significant complications. However, these cases involved additional microbes, limiting the inferences about the pathogenicity of Streptococcus cristatus.Case presentationA 59-year-old African American male with end-stage cryptogenic cirrhosis and ascites presented with fatigue and confusion. A paracentesis was negative for spontaneous bacterial peritonitis, but two separate blood cultures grew Streptococcus cristatus. Our patient had a history of dental caries and poor oral hygiene, which were likely the source of the infection. Echocardiograms revealed new aortic regurgitation, indicating “possible endocarditis” per the Modified Duke Criteria. However, since his clinical picture and cardiac function were reassuring, we elected against treatment for infective endocarditis. He was treated for bacteremia with a 2-week course of cephalosporins consisting of 8 days of ceftriaxone, transitioning to cefpodoxime after discharge. Despite having end-stage liver disease, our patient did not experience any significant complications from the infection.ConclusionA patient with end-stage cirrhosis and poor oral hygiene developed bacteremia with an oral bacterium called Streptococcus cristatus. Unlike previous cases in literature, our patient did not meet criteria for a definitive diagnosis of infective endocarditis, and he experienced no other complications from the infection. This suggests coinfectants may have been primarily responsible for the severe cardiac sequelae in prior cases, whereas isolated Streptococcus cristatus infection may be relatively mild.

A Single-Center's Early Surgical Outcomes of Living Donor Liver Transplantation

Living donor liver transplantation (LDLT) has become an increasingly common surgical option because the number of cadaveric donors is insufficient to fulfill the organ needs of patients facing end-stage cirrhosis. Many centers are investigating different surgical techniques to achieve lower complication rates. We aimed to examine our complication rates in light of demographic data, graft data, and perioperative findings as a single-center experience. The study included one hundred and three patients who underwent LDLT for end-stage liver cirrhosis. Demographic data; sex; age; blood group; Model for End-Stage Liver Disease score; Child score; etiology; liver side; graft-to-recipient weight ratio; hepatic artery, portal vein, and bile anastomosis type rates; anhepatic phase; cold ischemia time; operation time; and blood product transfusion rates were analyzed. Biliary complications in patients with single or multiple biliary anastomoses, right or left liver transplants, and with or without hepatic artery thrombosis were analyzed statistically. There was no significant difference in biliary complications between patients who underwent single or multiple bile anastomosis (P=.231) or patients receiving right lobe and left lobe transplants (P=.315). Although there was no statistically significant difference in the rate of portal vein thrombosis between the regular and reconstructed portal vein anastomosis groups (P=.693), the postoperative portal vein thrombosis rate was statistically higher in patients with left lobe transplants (P=.044). Vascular and biliary complication rates can be reduced with increasing experience.

Abstract 4847: Investigating the transcriptional regulation by estrogen-related receptor alpha (ERRα) under different metabolic conditions

Abstract Estrogen-related receptors (ERRs) are orphan nuclear receptors identified based on their high sequence similarity to estrogen receptors (ERs), but ERRs do not have a known endogenous ligand. ERRs play a primary role in regulating the transcription of genes involved in mitochondrial and lipid metabolism and are abundantly expressed across tissues. Because of ERR’s role in metabolism, it is suggested that they may also play a role in tumor metabolism, where dysfunction in lipid metabolism promotes tumor cell growth. The ERR subfamily is comprised of three isoforms: ERRα, ERRβ, and ERRγ. Studies targeting the ERR isoforms found that the absence of ERRα presents obesity and insulin resistance with an increase in bone mass, deletion of ERRβ causes placental abnormalities and embryonic lethality, and deletion of ERRγ leads to mitochondrial dysfunction. Together, these studies strongly suggest that ERRs, particularly ERR α and γ, function primarily as metabolic regulators, with ERRα being the predominant isoform expressed in the liver. In addition, the mechanisms leading to lipid accumulation vary under different feeding conditions. Previous studies from our lab showed that PTEN and PI3K/AKT signaling regulates ERRa expression and its function. Furthermore, we demonstrated that inhibiting ERRα blocks liver steatosis and steatohepatitis developed in a mouse model where loss of tumor suppressor PTEN drives both steatosis and cancer development. In addition, we found that ERR-PA, a small molecule inhibitor for ERR, attenuated cancer cell growth and proliferation in both mouse hepatocytes and human cancer cell lines. Here, we report transcriptome network regulated by ERRα under different metabolic conditions and further explored its regulation by the PI3K/AKT pathway. A better understanding of the role ERRα plays in physiology will allow further development of ERR-PA as a potential therapy for liver steatohepatitis, which progresses to end stage cirrhosis and ultimately liver cancer. Citation Format: Brittney A. Hua, Chien-yu Chen, Yang Li, Lina He, Bangyan Stiles, Ielyzaveta Slarve. Investigating the transcriptional regulation by estrogen-related receptor alpha (ERRα) under different metabolic conditions. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4847.

Left-Sided Prosthetic Valve Dysfunction and Gastrointestinal Bleeding.

Introduction We sought to investigate the association between left-sided prosthetic valve dysfunction and gastrointestinal (GI) bleeding. Methods In a retrospective cohort of patients with left-sided prostheses, we identified those who experienced one or more GI bleeds. The latest or chronologically closest echocardiogram to the GI bleed was analyzed by a blinded investigator for prosthetic valve dysfunction. Results Among 334 unique patients, 166 had aortic prostheses, 127 had mitral prostheses, and 41 had both. A total of 58 (17.4%) subjects had GI bleeding events. Patients in the "GI Bleed" group had higher mean ejection fraction (56±14% vs. 49±15%; P = 0.003) and higher prevalence of hypertension, end-stage renal disease, and liver cirrhosis compared to the "No GI Bleed" group. There was a higher prevalence of moderate or severe prosthetic valve regurgitation in the GI Bleed vs. No GI Bleed group (8.6% vs. 2.2%; P = 0.027). Moderate or severe prosthetic valve regurgitation was independently associated with GI bleeding (odds ratio, 6.18; 95% confidence interval, 1.27-30.05; P = 0.024), after adjusting for ejection fraction, hypertension, end-stage renal disease and liver cirrhosis. Paravalvular regurgitation was associated with a higher incidence of GI bleeding compared to transvalvular regurgitation (35.7% vs. 11.9%; P = 0.044). The prevalence of prosthetic valve stenosis was similar between the GI Bleed and No GI Bleed groups (6.9% vs. 5.8%; P = 0.761). Conclusion In a cohort of patients with predominantly surgically placed prosthetic valves, moderate to severe left-sided prosthetic valve regurgitation was independently associated with GI bleeding.