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Background: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. Methods: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. Results: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50–2.87, p = 0.69). Conclusions: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury. [ABSTRACT FROM AUTHOR]

Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury. Synopsis: The liver function in post-cardiac arrest brain injury is not known and was investigated in a pig model of global cerebral ischemia. The frontal lobe infarct area and temporal lobe immune cell adhesion were increased in the ischemic brains in the presence of concurrent hepatic ischemia. Ex vivo, presence of a functioning liver improved neuronal viability, cytoarchitecture, and electrocortical activity post-CA brain injury. Transcriptomics and metabolomics analyses suggest that the liver protects from post-CA brain injury by increased production of ketone bodies. The liver function in post-cardiac arrest brain injury is not known and was investigated in a pig model of global cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background: Early detection of liver dysfunction is crucial for timely intervention and management. Traditional liver function tests (LFTs) have limitations in sensitivity and specificity, necessitating the evaluation of newer diagnostic criteria. Objective: This study aims to compare the efficacy of different diagnostic criteria including Standard LFTs, Enhanced Liver Fibrosis (ELF) Test in detecting early liver dysfunction. Methods: A retrospective analysis was conducted on 125 patients suspected of early liver dysfunction at a tertiary care center. Diagnostic efficacy was assessed through sensitivity, specificity, and odds ratios calculated for each diagnostic criterion. Statistical significance was determined using p-values. [ABSTRACT FROM AUTHOR]

Abstract Background Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. Methods Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. Results Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p

Summary: Context: Hepatic and renal damages manifest in patients with acute or chronic heart failure after the incidence of myocardial infarction (MI). Objective: Our objective in this study was aimed to investigate the protective effects of coenzyme Q10 (CoQ10) and taurine, which are bioactive compounds with protective functions, on liver and kidney toxicity rat exposed to isoprenaline, a popular tool for MI induction. Materials and methods: Following two (2) consecutive days of exposure to isoprenaline (200 mg/kg, i.p.), adult Wistar rats were treated with CoQ10 (10 mg/kg, i.p.) and taurine (100 mg/kg, i.p.) singly and in combination for 19 days. Following 21 days of experimentation, blood, liver and kidney were collected for biochemical and histological studies indicative of hepatic and kidney damage. Results: Our result showed that CoQ10 and taurine significantly decreased serum LDH, AST, ALT, and ALP, indicative of hepatic damage compared to isoprenaline groups. The increased creatinine and urea release suggestive of kidney dysfunction were suppressed by CoQ10 and taurine relative to the isoprenaline group. Additionally, CoQ10 and taurine significantly reversed isoprenaline-mediated oxidative stress-induced liver and kidney damage, which are shown by decreased malondialdehyde and nitrite accompanied by increased antioxidants (SOD, CAT, GST, GSH). Modifications to cellular histoarchitectural and fibrosis of the hepatic and renal tissues were attenuated by CoQ10 and taurine therapy. Discussion and conclusion: The findings from this study suggest that CoQ10 and taurine supplements may prevent isoprenaline-induced hepatorenal dysfunctions, possibly by alleviating oxidative stress and histoarchitectural protective functions of the hepatic and kidney cells.

Abstract Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

Abstract Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert’s syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert’s syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert’s syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert’s syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.

Background and Aim: Abnormal liver biochemistry (ALB) is common among patients with COVID‐19 infection due to various factors. It is uncertain if it persists after the acute infection. We aimed to investigate this. Methods: A multicenter study of adult patients hospitalized for COVID‐19 infection, with at least a single abnormal liver function test, was conducted. Detailed laboratory and imaging tests, including transabdominal ultrasound and FibroScan, were performed at assessment and at 6‐month follow‐up after hospital discharge. Results: From an initial cohort of 1246 patients who were hospitalized, 731 (58.7%) had ALB. A total of 174/731 patients fulfilled the inclusion criteria with the following characteristics: 48.9% patients had severe COVID‐19; 62.1% had chronic liver disease (CLD); and 56.9% had metabolic‐associated fatty liver disease (MAFLD). ALB was predominantly of a mixed pattern (67.8%). Among those (55.2%) who had liver injury (aspartate aminotransferase/alanine aminotransferase >3 times the upper limit of normal, or alkaline phosphatase/γ‐glutamyl transferase/bilirubin >2 times the upper limit of normal), a mixed pattern was similarly predominant. Approximately 52.3% had normalization of the liver lunction test in the 6‐month period post discharge. Patients with persistent ALB had significantly higher mean body mass index (BMI) and serum low‐density lipoprotein (LDL), higher rates of MAFLD and CLD, higher mean liver stiffness measurement and continuous attenuated parameter score on FibroScan, and higher rates of liver injury on univariate analysis. Multivariate analysis was not statistically significant. Conclusions: Approximately 47.7% of COVID‐19 patients were found to have persistent ALB up to 6 months following the acute infection, and it was associated with raised BMI, elevated serum LDL, increased rates of MAFLD and CLD, and higher rates of liver injury on univariate analysis, but not on multivariate analysis. [ABSTRACT FROM AUTHOR]

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert's syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert's syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert's syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert's syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy. [ABSTRACT FROM AUTHOR]

Background. A significant proportion of couples worldwide suffer from infertility associated with polycystic ovary syndrome (PCOS). PCOS is characterized by increased androgen synthesis in the theca cells of the ovaries, hyperandrogenemia and ovarian dysfunction in women. Most of the clinical symptoms and altered levels of blood biomarkers in PCOS patients point to metabolic dysregulation and adaptive changes as key underlying mechanisms of disease development. Since the liver is the metabolic center of the body and participates in steroid-hormonal detoxification, pathological changes in it can contribute to endocrine disorders through the liver-ovary axis. Of particular interest is hyperglycemia, changes in secretory proteins of the liver and insulin sensitivity, which affect the maturation of ovarian follicles and can potentially lead to female infertility. Objective of the review: to provide an understanding of the new metabolic mechanisms underlying PCOS, which lead to the disease and its exacerbation, as well as to summarize therapeutic approaches to the correction of PCOS complications, in particular, liver function disorders using the drug Hepatomunil. Analysis of literary data. This review presents the relationship and underlying mechanistic basis between PCOS and metabolic disorders in women by summarizing the main pathologic features of the disease. Most symptoms of PCOS are associated with insulin resistance, type II diabetes, decreased levels of sex hormone-binding globulin, increased levels of alanine aminotransferase and aspartate aminotransferase, which may indicate liver dysfunction. The metabolic profile and function of the ovaries can be affected by any pathological changes in the levels of systemic metabolism and/or in peripheral organs, in particular the liver, which serves as the metabolic center of the body, mediating its effects through the liver-ovary axis. Conclusions. Despite the lack of a clear protocol for the correction of liver function disorders and non-alcoholic fatty liver disease in PCOS patients, lifestyle modification should be the basis. Drugs that improve metabolism, as well as hepatoprotectors with immunomodulatory properties (the drug Hepatomunil) may have positive prospects for use. [ABSTRACT FROM AUTHOR]

Global pandemic of obesity contributes to increasing the risk of diabetes and non-alcoholic fatty liver disease (NAFLD). To find an alternative approach to lower the risk caused by obesity. Aims: We investigated the antidiabetic and hepatoprotective activity of black rice bran extract (BRE) in obese, insulin-resistant rats induced by a high-fat diet (HFD). Main methods: After HFD feeding, the parameters related to glucose, lipid profiles, and liver injury were determined. Key findings: Rats on a HFD exhibited significantly elevated plasma glucose and lipid levels, as well as increased liver enzyme activities (aspartate transaminase and alanine transaminase), relative to the control group. Interestingly, those parameters in the BRE-treated group were significantly decreased. We investigated the liver histological study, and the BRE-treated group showed to ameliorate the liver injury accompanied by lower inflammatory and apoptotic markers. Significance: Our findings suggest that BRE has the potential to be used as a dietary supplement to lessen metabolic dysregulation and prevent liver impairment.

Ming-Ming Ma,1,&ast; Yao-Yao Xu,2,&ast; Li-Hua Sun,1,&ast; Wen-Jie Cui,1 Miao Fan,3 Su Zhang,4 Lei Liu,5 Ling-Zhi Wu,6 Liu-Cheng Li7 1Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China; 2Department of Pharmacy, The People’s Hospital of Pingyang, Wenzhou, 325400, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 4Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 5Department of Orthopaedics, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, People’s Republic of China; 6Department of Pharmacy, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, 314000, People’s Republic of China; 7Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liu-Cheng Li, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Hangzhou, 310016, People’s Republic of China, Email 3415116@zju.edu.cn Ling-Zhi Wu, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), No. 1882 South Central Road, Jiaxing, 314000, People’s Republic of China, Email wulingzhi1992@163.comAbstract: Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.Keywords: statin, cardiovascular diseases, liver dysfunction, muscle injury, countermeasures

Post-liver transplant (LT) hepatic artery vasospasm is a vascular complication that is not well recognized and its incidence is not known. As a possible sequela to vasospasm, hepatic artery thrombosis is the second major cause of allograft failure after primary nonfunction and its reported incidence is 2.9% in adults and 8.3% in pediatric LT. Lacuna in knowledge regarding early hepatic artery vasospasm post-LT makes it a difficult condition to diagnose and treat, as the initial ischemic insult on graft can have devastating consequences. We report a case of pediatric progressive familial intrahepatic cholestasis type 3-related chronic liver disease who underwent cadaveric orthotopic LT and postoperatively developed fever, worsening hypotension, and elevated liver enzymes with an absence of arterial flow in intrahepatic branches on Doppler ultrasound. Suspecting early hepatic artery thrombosis, the patient was re-explored and the graft hepatic artery was found to be in a state of vasospasm. Following the infusion of intra-arterial papaverine, urokinase, and intravenous nicorandil, there was an improvement in blood flow. The patient responded well and was discharged on postoperative day 23 with normal liver enzymes.

Abstract Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.

ABSTRACTS-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6 ~ 202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

Background: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum total bilirubin at the end of the treatment compared to the baseline value. The secondary endpoint was to evaluate the trend of serum total bilirubin and coagulation parameters up to 72 h after discontinuation of CytoSorb®. The effects of CytoSorb® therapy on the degree of hepatic encephalopathy (HE), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease (MELD) scores as well as the hemodynamic status compared to baseline were also assessed. Methods: Adult patients with a serum total bilirubin level > 10 mg/dL admitted to the Intensive Care Unit were included. Exclusion criteria were hemodynamic instability, postoperative bleeding and platelet count < 20,000/mm3. Results: Seven patients were treated. Serum total bilirubin was significantly reduced at the end of treatment. However, seventy-two hours after the discontinuation of extracorporeal therapy, bilirubin levels returned to baseline levels in four patients. A decrease in platelet count was found during therapy, and platelet transfusion was required in six cases. A significant increase in D-dimer at the end of treatment was detected. HE degree, SOFA and MELD scores remained stable, while a deterioration in hemodynamic status was observed in two cases. Conclusions: Our preliminary findings did not show the possible benefits of CytoSorb® in rebalancing clinical and laboratory parameters in patients with HD after LT or EHR. [ABSTRACT FROM AUTHOR]

Excess adipose tissue, as well as its distribution, correlates strongly with disorders of lipid and liver parameters and chronic inflammation. The pathophysiology of metabolic diseases caused by obesity is associated with the dysfunction of visceral adipose tissue. Effective and alternative interventions such as the Bioenteric Intragastric Balloon and bariatric surgeries such as the Roux-en-Y gastric bypass. The aim of this study was to assess the effect of modifying the recommended standard weight loss diet after bariatric surgery and procedures on reducing chronic inflammation in overweight patients. In the study, bioactive anti-inflammatory dietary components were used supportively. Changes in the concentrations of lipid parameters, liver parameters, antioxidant enzymes, cytokines, and chemokines were demonstrated. The enrichment of the diet, after bariatric surgery, with the addition of n-3 EFAs(Essential Fatty Acids), bioflavonoids, vitamins, and synbiotics resulted in higher weight losses in the patients in the study with a simultaneous reduction in parameters indicating liver dysfunction. [ABSTRACT FROM AUTHOR]

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. [ABSTRACT FROM AUTHOR]

Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPAcaused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction (p = 0.001; p = 0.023, respectively). We also found that the MTHFR A1298C polymorphism was associated with a higher serum Hcy level (p = 0.001) and a lower FA level (p = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = -0.6065, P < 0.001; r = 0.6564, P < 0.001, respectively). Furthermore, logistic analysis indicated that MTHFR A1298C/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from MTHFR A1298C/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction. [ABSTRACT FROM AUTHOR]

Background/Aim: Renal dysfunction necessitates S-1 dose reduction. However, decreased dihydropyrimidine dehydrogenase (DPD) activity may lead to adverse events due to 5-FU. The guidelines provided by pharmaceutical companies state that total bilirubin (T-Bil) should be =upper limit of normal (ULN)×1.5 as a reference value for safely taking S-1. Nevertheless, the relationship between the degree of liver dysfunction and S-1 dose reduction has not been clearly established. Patients and Methods: This study focused on patients who received S-1 monotherapy for various types of cancer. The primary outcome was defined as the variation between blood sampling results on the test day and the subsequent test. The variation data were categorized based on the difference in T-Bil: Low T-Bil group (=2.25) and High T-Bil group (>2.25). Results: The number of patients that underwent S-1 monotherapy was 883 and the running number was 7,511; Low T-Bil group included 7,245 and High T-Bil group included 266. Examination of the effect of the T-Bil Group on clinical outcomes revealed a correlation with red blood cell (RBC) count, platelet (PLT) count, and T-Bil level. When the impact of the interaction between the T-Bil Group and any of the clinical outcomes, such as the RBC count, PLT count, and T-Bil level, was determined, each outcome showed a significant decrease in the High T-Bil group compared with the Low T-Bil group. Conclusion: S-1 administration in patients with liver dysfunction accompanied by elevated T-Bil levels may cause thrombocytopenia. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Abnormal liver biochemistry (ALB) is common among patients with COVID‐19 infection due to various factors. It is uncertain if it persists after the acute infection. We aimed to investigate this. Methods A multicenter study of adult patients hospitalized for COVID‐19 infection, with at least a single abnormal liver function test, was conducted. Detailed laboratory and imaging tests, including transabdominal ultrasound and FibroScan, were performed at assessment and at 6‐month follow‐up after hospital discharge. Results From an initial cohort of 1246 patients who were hospitalized, 731 (58.7%) had ALB. A total of 174/731 patients fulfilled the inclusion criteria with the following characteristics: 48.9% patients had severe COVID‐19; 62.1% had chronic liver disease (CLD); and 56.9% had metabolic‐associated fatty liver disease (MAFLD). ALB was predominantly of a mixed pattern (67.8%). Among those (55.2%) who had liver injury (aspartate aminotransferase/alanine aminotransferase >3 times the upper limit of normal, or alkaline phosphatase/γ‐glutamyl transferase/bilirubin >2 times the upper limit of normal), a mixed pattern was similarly predominant. Approximately 52.3% had normalization of the liver lunction test in the 6‐month period post discharge. Patients with persistent ALB had significantly higher mean body mass index (BMI) and serum low‐density lipoprotein (LDL), higher rates of MAFLD and CLD, higher mean liver stiffness measurement and continuous attenuated parameter score on FibroScan, and higher rates of liver injury on univariate analysis. Multivariate analysis was not statistically significant. Conclusions Approximately 47.7% of COVID‐19 patients were found to have persistent ALB up to 6 months following the acute infection, and it was associated with raised BMI, elevated serum LDL, increased rates of MAFLD and CLD, and higher rates of liver injury on univariate analysis, but not on multivariate analysis.

Background and purposeNutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury.MethodsThis cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA).ResultsThe CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40–0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35–0.64)] in the multivariate logistic model. A positive association between “Organ meat, poultry, and vegetable oil” dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42–6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09–3.05)] was observed.ConclusionIn conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the “Organ meat, poultry, and vegetable oil” dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

The liver and thyroid hormones interact at multiple levels to maintain homoeostasis. The liver requires large adequate amounts of thyroid hormones to execute its metabolic functions optimally, and deficiency of thyroid hormones may lead to liver dysfunction. Hypothyroidism has been associated with abnormal lipid metabolism, non-alcoholic fatty liver disease (NAFLD), hypothyroidism-induced myopathy, hypothyroidism-associated gallstones and occasionally, interferon-induced thyroid dysfunction. NAFLD remain an important association with hypothyroidism and further studies are needed that specifically compare the natural course of NAFLD secondary to hypothyroidism and primary NAFLD. Hepatic dysfunction associated with hypothyroidism is usually reverted by normalizing thyroid status. Large scale studies geared towards finding new and effective therapies, especially for NAFLD are needed. The clinician must be aware that there exists overlapping symptomatology between liver dysfunction and severe hypothyroidism which may make delay the diagnosis and treatment of hypothyroidism; this requires a high index of suspicion. [ABSTRACT FROM AUTHOR]

Introduction: The application of voriconazole in patients with liver dysfunction lacks pharmacokinetic data. In previous study, we proposed to develop voriconazole dosing regimens for these patients according to their total bilirubin, but the regimens are based on Monte Carlo simulation and has not been further verified in clinical practice. Besides, there are few reported factors that significantly affect the efficacy of voriconazole. Methods: We collected the information of patients with liver dysfunction hospitalized in our hospital from January 2018 to May 2022 retrospectively, including their baseline information and laboratory data. We mainly evaluated the efficacy of voriconazole and the target attainment of voriconazole trough concentration. Results: A total of 157 patients with liver dysfunction were included, from whom 145 initial and 139 final voriconazole trough concentrations were measured. 60.5% (95/157) of patients experienced the adjustment of dose or frequency. The initial voriconazole trough concentrations were significantly higher than the final (mean, 4.47 versus 3.90 μg/mL, p = 0.0297). Furthermore, daily dose, direct bilirubin, lymphocyte counts and percentage, platelet, blood urea nitrogen and creatinine seven covariates were identified as the factors significantly affect the voriconazole trough concentration. Binary logistic regression analysis revealed that the lymphocyte percentage significantly affected the efficacy of voriconazole (OR 1.138, 95% CI 1.016–1.273), which was further validated by the receiver operating characteristic curve. Conclusion: The significant variation in voriconazole trough concentrations observed in patients with liver dysfunction necessitates caution when prescribing this drug. Clinicians should consider the identified factors, particularly lymphocyte percentage, when dosing voriconazole in this population. [ABSTRACT FROM AUTHOR]

The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared to the ancestral, Alpha, and Omicron waves. The dataset of 551 hospitalized patients was similar in the Delta/non-Delta waves. At admission and discharge, the median aminotransferase levels were normal or slightly increased. During the Delta wave (172 vs. 379 non-Delta patients), more patients died (OR 1.69, 95%CI 1.09–2.56) or had liver injury at discharge (alanine aminotransferase, ALT ≥ 2 ULN) (OR 1.97, 95%CI 1.08–3.54). In-hospital mortality was associated with age, lung injury, intensive care unit admission, number of and cardiovascular comorbidities, diabetes, chronic kidney disease, and all inflammatory biomarkers. Serious liver injury at admission (ALT ≥ 5 × ULN) was significantly associated with in-hospital mortality (OR = 7.9, 95%CI 2–28.9). At discharge, drug-induced liver injury (DILI) was found in patients treated with remdesivir, ALT ≥ 2 ULN (OR = 2.62, 95%CI 1.22–5.75). Treatment with dexamethasone, remdesivir, and immunomodulators showed improved survival, OR = 0.50 (95%CI 0.33–0.77). Regardless of the variant and treatment options, less than 2% of patients displayed serious liver injury, which was not found to be a death predictor in multivariable analysis. [ABSTRACT FROM AUTHOR]

Background/Aim: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. Patients and Methods: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. Results: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m². Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary. [ABSTRACT FROM AUTHOR]

Critically ill patients are at risk of developing acute liver dysfunction as part of multiorgan failure sequelae. Clearing the blood from toxic liver-related metabolites and cytokines could prevent further organ damage. Despite the increasing use of hemoadsorption for this purpose, evidence of its efficacy is lacking. Therefore, we conducted this systematic review and meta-analysis to assess the evidence on clinical outcomes following hemoadsorption therapy. A systematic search conducted in six electronic databases (PROSPERO registration: CRD42022286213) yielded 30 eligible publications between 2011 and 2023, reporting the use of hemoadsorption for a total of 335 patients presenting with liver dysfunction related to acute critical illness. Of those, 26 are case presentations (n = 84), 3 are observational studies (n = 142), and 1 is a registry analysis (n = 109). Analysis of data from individual cases showed a significant reduction in levels of aspartate transaminase (p = 0.03) and vasopressor need (p = 0.03) and a tendency to lower levels of total bilirubin, alanine transaminase, C-reactive protein, and creatinine. Pooled data showed a significant reduction in total bilirubin (mean difference of −4.79 mg/dL (95% CI: −6.25; −3.33), p = 0.002). The use of hemoadsorption for critically ill patients with acute liver dysfunction or failure seems to be safe and yields a trend towards improved liver function after therapy, but more high-quality evidence is crucially needed. [ABSTRACT FROM AUTHOR]

Aims: Polymyxin B (PMB) is widely used to treat infections caused by multidrug‐resistant Gram‐negative pathogens. Currently, the pharmacokinetic data of PMB in patients with liver dysfunction are limited. This study aimed to develop a population pharmacokinetic (PopPK) model of PMB in patients with liver dysfunction and identify the factors affecting PMB pharmacokinetics. Methods: We conducted a retrospective pharmacokinetic study involving 136 adults with different levels of liver function. Nonlinear mixed effects modelling was used to develop a PopPK model of PMB. Monte Carlo simulation was used to design PMB dosage schedules across various liver and renal functions. Results: PMB pharmacokinetic analyses included 401 steady‐state concentrations in 136 adult patients. A one‐compartment pharmacokinetic model with first‐order absorption and elimination was used to describe the data. The typical population value of PMB clearance was 2.43 L/h and the volume of distribution was 23.11 L. This study revealed that creatinine clearance (CrCL) and Child–Pugh class were significantly associated with PMB pharmacokinetic parameters; however, clinically relevant variations of dose‐normalized drug exposure were not significant. For patients with a minimum inhibitory concentration of ≤0.5 mg/L, the appropriate dose was 40–75 mg/12‐h. When the dose exceeded 100 mg/12‐h, the risk of nephrotoxicity increased significantly. Conclusions: This study provided PMB pharmacokinetic information for patients with liver dysfunction. Patients with renal and liver dysfunctions may not require an initial dose adjustment. Rather than PopPK‐guided dose adjustment, therapeutic drug monitoring of PMB plays a more direct role in optimizing dosing regimens based on its therapeutic window. [ABSTRACT FROM AUTHOR]

Background and Objectives: Macronutrients play a vital role in liver dysfunction and affect tuberculosis treatment and prognosis. However, macronutrients intake was inadequate for most tuberculosis patients. This study aimed to clarify the associations between macronutrients intake or energy percentages and liver dysfunction in tuberculosis patients. Methods and Study Design: In this cross-sectional study, 2581 active tuberculosis patients aged =18 years were included from local tuberculosis clinics in Linyi, China. Macronutrients intake and energy percentages were assessed by 24-hour dietary recalls. The concentration of alanine transferase (ALT) or aspartate transaminase (AST) greater than 40 U/L was defined as liver dysfunction. A restricted cubic spline (RCS) was applied to determine the dose-response relationships. Results: Liver dysfunction was assessed for 14.6% (377 patients) of tuberculosis patients. Higher protein (Q2-Q4 in model 1 and 2) or fat intake and fat-to-energy percentages and lower carbohydrate-to-energy percentages (Q4 in model 1) were associated with a decreased incidence of liver dysfunction (p-trend < 0.05). Among those who were male, normal BMI, or consumed energy <1636 kcal/d, inverse associations between protein or fat intake and the risks of liver dysfunction in models were suggested (ptrend < 0.05). Moreover, J-shaped curves in RCS were evident in liver dysfunction tuberculosis patients with protein or fat intake (p-nonlinearity < 0.05). Conclusions: Significant linear associations between macronutrients intake or energy percentages and liver dysfunction prevalence were found only in male, normal BMI, or less energy intake patients. The shapes of liver dysfunction-morbidity differed significantly by macronutrients intake or energy percentage. [ABSTRACT FROM AUTHOR]

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications.A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved promptly post-delivery.Preeclampsia can trigger acute hepatic dysfunction, including hepatic encephalopathy, in the setting of previously compensated preexisting liver disease. Recognizing this association has important implications for management and treatment.

Liver and heart disease are major causes of death worldwide. It is known that metabolic alteration causing type 2 diabetes (T2D) and Nonalcoholic fatty liver (NAFLD) coupled with a derangement in lipid homeostasis, may exacerbate hepatic and cardiovascular diseases. Some pharmacological treatments can mitigate organ dysfunctions but the important side effects limit their efficacy leading often to deterioration of the tissues. It needs to develop new personalized treatment approaches and recent progresses of engineered RNA molecules are becoming increasingly viable as alternative treatments. This review outlines the current use of antisense oligonucleotides (ASOs), RNA interference (RNAi) and RNA genome editing as treatment for rare metabolic disorders. However, the potential for small non-coding RNAs to serve as therapeutic agents for liver and heart diseases is yet to be fully explored. Although miRNAs are recognized as biomarkers for many diseases, they are also capable of serving as drugs for medical intervention; several clinical trials are testing miRNAs as therapeutics for type 2 diabetes, nonalcoholic fatty liver as well as cardiac diseases. Recent advances in RNA-based therapeutics may potentially facilitate a novel application of miRNAs as agents and as druggable targets. In this work, we sought to summarize the advancement and advantages of miRNA selective therapy when compared to conventional drugs. In particular, we sought to emphasise druggable miRNAs, over ASOs or other RNA therapeutics or conventional drugs. Finally, we sought to address research questions related to efficacy, side-effects, and range of use of RNA therapeutics. Additionally, we covered hurdles and examined recent advances in the use of miRNA-based RNA therapy in metabolic disorders such as diabetes, liver, and heart diseases.

Abstract Background Anorexia nervosa (AN) is frequently associated with liver dysfunction, but the precise mechanism remains undefined. Since the nutritional marker albumin has a low correlation with changes in body weight in AN, and patients with AN often have dehydration as a complication, we also examined whether haematocrit (HCT)-adjusted serum albumin could be a better nutritional marker in AN. Case presentation We describe a 15-year-old girl with severe weight loss and liver damage whose liver enzymes normalized after 1.5 months of hospitalization and weight gain. We found a significant correlation between body weight (BW) and HCT-adjusted serum albumin (Spearman’s rank correlation coefficient (rs) = 0.66, P = 5.28 × 10−3) and between BW and alanine aminotransferase (ALT) (rs = -0.825, P = 8.45 × 10−5). After division by HCT, correlations between serum albumin and ALT (rs = -0.835, P = 5.24 × 10−5) and between the iron-storage protein ferritin and the liver enzyme gamma-glutamyl transferase (rs = 1.0, P = 0.017) were also statistically significant. Conclusion These results suggest that improvement of the nutritional status in AN could relieve liver dysfunction and facilitate iron transport. Since a decrease in the iron-transport protein transferrin presumably increases labile non-transferrin-bound iron, resulting in excess reactive oxygen species production, a defect in iron transport due to malnutrition could be one of the causes of liver injury in AN. In addition, HCT-adjusted albumin could be a better marker than its raw data to assess changes in nutritional status in AN.

The global obesity epidemic has led to the increasing popularity of bariatric surgeries. Laparoscopic sleeve gastrectomy is currently the most popular bariatric procedure for obesity. Retracting of the left liver lobe during laparoscopic sleeve gastrectomy is important for achieving an optimal surgical field. Aim. The aim of our study was to evaluate the results of using different methods of retraction of the left liver lobe during laparoscopic sleeve gastrectomy in patients with morbid obesity. Materials and methods. The 86 patients who underwent laparoscopic sleeve gastrectomy were divided into three groups based on the liver retraction method used: group 1 (ENDO RETRACT™ II), group 2 (Nathanson) and group 3 (Clickline Surgical Sponge Holder). All groups were evaluated in terms of demographic characteristics; liver function tests just before surgery and on the 1st and 2nd postoperative day (POD); developing complications and length of hospital stay. Results. The groups did not differ significantly in terms of demographic characteristics (p > 0.05). The Nathanson liver retractor (group 2) caused a significant rise in ALT and AST at POD 1 and POD 2 compared with group 1 and 3 (p < 0.05). The ENDO RETRACT™ II liver retractor (group 1) caused a higher incidence of liver injury than other groups. It led to statistical significance prolonged total operation time (p = 0.003), increased blood loss (p = 0.002) and prolonged postoperative hospital stay (p = 0.001) compared with other groups. Conclusions. The technique of left lobe retraction during laparoscopic sleeve gastrectomy using Clickline Sur- gical Sponge Holder is safe and effective. The use of this technique causes significantly less measurable liver damage and does not lead to an increase in the level of liver enzymes.

Hypertyrosinemia results from abnormality in tyrosine metabolism. Acquired hypertyrosinemia is notably more common than inherited types and typically presents with profile suggestive of secondary aetiology on biochemical testing. Herein, we present an unusual case of a day 16-of-life baby girl who was screened for inborn errors of metabolism (IEM). She presented with jaundice, hypotonia, lethargy and had hepatomegaly on examination. She was treated for sepsis with multiorgan involvement, requiring escalation of intravenous antibiotics and assisted ventilation. Her dried blood spot (DBS) showed moderate elevation of tyrosine (408umol/L, N:10-182) with low Phe:Tyr ratio (0.15mmol/L, N:0.32-3.45). Plasma amino acid showed isolated hypertyrosinemia at 807mmol/L (N:5-167) with mild, non-significant elevations of other liver metabolites. No succinylacetone peak seen with urine organic acids, making the diagnosis of inherited Tyrosinemia type I less likely despite the characteristic findings from DBS, plasma amino acids, and presenting clinical signs. Repeated IEM screening two weeks later revealed a non-diagnostic profile across both DBS and plasma amino acids in light of resolving sepsis and clinical improvement. This case highlights the challenges associated with incompatible biochemical testing in a child with a high index of suspicion for inherited Tyrosinemia. In our case, repeated screening ruled out inherited Tyrosinemia, suggesting the initial picture of hypertyrosinemia to be likely due to liver dysfunction and impaired activity of liver enzymes that are responsible for tyrosine catabolism.

Current study examined the protective impact of Rhodiola rosea (R. rosea) extract on hepatic toxicity markers caused by MSG. MSG induced significant increases in hepatic stress biomarkers. There were significant declines in GSH, catalase and SOD levels, which were accompanied by substantial elevations in IL-1β, IL-6, and TNF-α. There was hepatic cellular damage, and upregulation of caspase-3 and a decrease in Bcl-2 expression. The hepatotoxic impacts of MSG were normalized by Rhodiola supplementation. R. rosea downregulated caspase-3 and upregulated HO-1 and Nrf2 mRNA expression. R. rosea regulated the immunoreactivity of COX-2, TGF-β1, and NFkB genes associated with hepatic toxicity. R. rosea extract normalized histopathological changes induced by MSG and restored hepatic architecture. R. rosea extract exhibited anti-apoptotic, antioxidant, and anti-inflammatory properties. In conclusion, R. rosea extract is a promising medication against hepatic toxicity induced by MSG, which works by regulating the different signaling pathways of inflammation-, oxidative-stress-, and apoptosis-associated markers.

The purpose of this study was to investigate the correlation between the severity of fatty liver and factors such as gender, lifestyle, and the risks of metabolic abnormalities, inflammation, and liver dysfunction in the working population. This cross-sectional study included 2936 workers aged 21–64 years. The severity of fatty liver was assessed using ultrasound. A self-administered survey was used to evaluate lifestyle habits. Data on anthropometric measurements, blood pressure, blood tests, and biochemical evaluations was collected. The 45.5% of workers had fatty liver. Males had a higher prevalence of fatty liver and health risks and several unhealthy lifestyle habits compared to females. The health behavior score related to exercise showed notable declines as the severity of fatty liver increased (p < 0.001). Percentages of current alcohol drinkers differed among different levels of fatty liver, with rates of 43.1, 48.4, 44.8, and 63.4% (p = 0.005) observed in the absence, mild, moderate, and severe fatty liver, respectively. Workers with fatty liver showed increased risks related to metabolic anomalies, especially in severe cases. The risk of inflammation and liver dysfunction also significantly increased with elevated fatty liver severity. Overall, fatty liver presents significant health risks, with nearly half of the workers diagnosed with the condition. To improve liver health, it is crucial to have customized strategies for promoting health, taking into account the different levels of severity in fatty liver. [ABSTRACT FROM AUTHOR]

Background: Anorexia nervosa (AN) is frequently associated with liver dysfunction, but the precise mechanism remains undefined. Since the nutritional marker albumin has a low correlation with changes in body weight in AN, and patients with AN often have dehydration as a complication, we also examined whether haematocrit (HCT)-adjusted serum albumin could be a better nutritional marker in AN. Case presentation: We describe a 15-year-old girl with severe weight loss and liver damage whose liver enzymes normalized after 1.5 months of hospitalization and weight gain. We found a significant correlation between body weight (BW) and HCT-adjusted serum albumin (Spearman's rank correlation coefficient (rs) = 0.66, P = 5.28 × 10−3) and between BW and alanine aminotransferase (ALT) (rs = -0.825, P = 8.45 × 10−5). After division by HCT, correlations between serum albumin and ALT (rs = -0.835, P = 5.24 × 10−5) and between the iron-storage protein ferritin and the liver enzyme gamma-glutamyl transferase (rs = 1.0, P = 0.017) were also statistically significant. Conclusion: These results suggest that improvement of the nutritional status in AN could relieve liver dysfunction and facilitate iron transport. Since a decrease in the iron-transport protein transferrin presumably increases labile non-transferrin-bound iron, resulting in excess reactive oxygen species production, a defect in iron transport due to malnutrition could be one of the causes of liver injury in AN. In addition, HCT-adjusted albumin could be a better marker than its raw data to assess changes in nutritional status in AN. [ABSTRACT FROM AUTHOR]

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. Methods We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I–IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. Results Forty-eight (13.3%) colorectal cancer patients (Stages I–IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P

According to the World Health Organization (2022), severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is liable for more than 572 million cases worldwide and more than six million deaths globally. It has been reported that pregnancy can change the disease manifestations such that gastrointestinal symptoms, which are common in pregnant women, are difficult to distinguish from COVID-19 related complications. Hence, in isolated cases of gastrointestinal or liver forms of COVID-19, diagnosis might be delayed. Previous studies have suggested that serious complications of COVID-19 in pregnancy are associated with a higher body mass index (BMI), gestational diabetes, and older age; thus, this population should be considered as high risk. In this article, we summarized previously published evidence about pregnant women with COVID‐19 and liver dysfunction.

Abstract Background We previously reported a case that led us to hypothesize that decreased production of thrombopoietin (TPO) leads to thrombocytopenia in patients with anorexia nervosa (AN) with severe liver dysfunction and that prolonged prothrombin time-international normalized ratio (PT-INR) predicts thrombocytopenia in such cases. To validate this hypothesis, we report another case in which TPO levels were measured. In addition, we examined the association between prolonged PT-INR and thrombocytopenia in such patients. Main body Similar to the previously reported patient, a patient with AN with severe liver dysfunction showed that TPO levels increased after improvements in liver enzyme levels and PT-INR, followed by recovery of platelet count. In addition, a retrospective study was also conducted to review patients with AN whose liver enzyme levels were > 3 × the upper limit of normal (aspartate aminotransferase > 120 U/L or alanine aminotransferase > 135 U/L). The study included 58 patients and showed a correlation coefficient of -0.486 (95% confidence interval [CI], -0.661 to -0.260; P

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

Excess adipose tissue, as well as its distribution, correlates strongly with disorders of lipid and liver parameters and chronic inflammation. The pathophysiology of metabolic diseases caused by obesity is associated with the dysfunction of visceral adipose tissue. Effective and alternative interventions such as the Bioenteric Intragastric Balloon and bariatric surgeries such as the Roux-en-Y gastric bypass. The aim of this study was to assess the effect of modifying the recommended standard weight loss diet after bariatric surgery and procedures on reducing chronic inflammation in overweight patients. In the study, bioactive anti-inflammatory dietary components were used supportively. Changes in the concentrations of lipid parameters, liver parameters, antioxidant enzymes, cytokines, and chemokines were demonstrated. The enrichment of the diet, after bariatric surgery, with the addition of n-3 EFAs(Essential Fatty Acids), bioflavonoids, vitamins, and synbiotics resulted in higher weight losses in the patients in the study with a simultaneous reduction in parameters indicating liver dysfunction.

Objectives: Liver fibrosis is independently associated with pulmonary arterial hypertension (PAH). Investigating the relationship between liver fibrosis and PAH may provide mechanistic insight into this relationship. In this study, we aimed to elucidate the relationship between the fibrosis-4 (Fib-4) index and PAH. Materials and Methods: In this retrospective, single-center cohort study, 61 patients diagnosed with PAH were included. During a median follow-up period of 27 months, Fib-4 indexes calculated from alanine aminotransferase, partate aminotransferase, and platelet values at the time of PAH diagnosis were evaluated in patients who experienced mortality and survived. Results: During the subsequent evaluation of the study cohort, 20 patients were found to have experienced mortality. The group with mortality had higher Fib-4 scores (1.6±0.22 vs. 0.69±0.4, p=0.003). Independent predictors of mortality and the diagnostic performance of the Fib-4 index were analyzed by ROC curve analysis. Accordingly, the predictive value of the Fib-4 index for mortality was >1.02, with a sensitivity of 77% and specificity of 72% (area under the curve: 0.824, 95% confidence interval: 0.740-0.880). Conclusion: The Fib-4 index, a straightforward and valuable metric, can be used as a prognostic marker for mortality in patients with PAH. [ABSTRACT FROM AUTHOR]

Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended for patients with chronic liver diseases as the vaccine can prevent and/or reduce the severity of SARS-CoV-2 infection. However, we have little information on the often-reported liver-related adverse events (LrAEs) caused by the mRNA vaccine. Methods: We retrospectively investigated the frequency and details of severe LrAEs and changes in liver function tests in patients with chronic liver diseases. Results: Among 431 patients with chronic liver diseases, 416 (96.5%) had received the SARS-CoV-2 vaccine ≥ 2 times. Among the 345 patients included in the analysis, 6 (1.7%) had severe LrAEs; 3 ascites, 2 increases in transaminases, and 1 an increase in total bilirubin. Multivariate analysis demonstrated that cirrhosis and autoimmune disease were risk factors for severe LrAEs. In contrast, the liver function reserve assessed by the Child–Pugh and ALBI scores did not markedly change after vaccination in patients with cirrhosis and/or autoimmune diseases despite a small increase in transaminase levels. Conclusion: SARS-CoV-2 mRNA vaccines, which were used in most of our patients, are safe in patients with chronic liver diseases, but the frequency of severe LrAEs is slightly increased in patients with cirrhosis and/or autoimmune diseases.

Background/Aims Gastric varices (GV) are present in 25% of cirrhotic patients with high rates of rebleeding and mortality. Data on endoscopic ultrasound (EUS)-guided treatment in severe liver disease (model for end stage liver disease sodium [MELD-Na] >18 and Child-Turcotte-Pugh [CTP] C with GV) are scarce. Thus, we performed a retrospective comparison of endoscopic glue injection with EUS-guided therapy in cirrhotic patients with large GV. Methods A retrospective study was performed in the tertiary hospitals of India. A total of 80 patients were recruited. The inclusion criteria were gastroesophageal varices type 2, isolated gastric varices type 1, bleeding within 6 weeks, size of GV >10 mm, and a MELD-Na >18. Treatment outcomes and complications of endoscopic glue injection and EUS-guided GV therapy were compared. Results In this study, the patients’ age, sex, liver disease severity (CTP, MELD-Na) and clinical parameters were comparable. The median number of procedures, injected glue volume, complications, and GV obturation were better in the EUS group, respectively. On subgroup analysis of the EUS method (e.g., direct gastric fundus vs. paragastric collateral [PGC] coil placement), PGC coil placement showed decreased coil requirement, less injected glue volume, decreased luminal coil extrusion, and increased successful GV obturation. Conclusions EUS-guided treatment is more efficient and safer, and requires a smaller number of treatment sessions, as compared to endoscopic treatment in severe liver disease patients with large GV. Furthermore, PGC coil placement increases the complete obliteration of GV.

AimsEpisodes of acute heart failure (AHF) may lead to end-organ dysfunction. In this post hoc analysis of the Relaxin in Acute Heart Failure trial, we used the MELD-XI (Model of End-Stage Liver Dysfunction) score to examine hepatorenal dysfunction in patients with AHF.Methods and resultsOn admission, the MELD-XI score was elevated (abnormal) in 918 (82%) patients, with 638 (57%) having isolated renal dysfunction (creatinine > 1 mg/dL), 73 (6.5%) isolated liver dysfunction (bilirubin > 1 mg/dL), and 207 (18.5%) coexisting dysfunction of the kidneys and the liver (both creatinine and bilirubin > 1 mg/dL). The percentage of patients with elevated MELD-XI score remained constant through a 60 day follow-up, as we observed a gradual decrease of liver dysfunction prevalence, counterbalanced by an increase in renal dysfunction. Serelaxin treatment was associated with a lower MELD-XI score on Day 2 and Day 5 (both P

Abstract Liver dysfunction is a common complication of Graves’ disease (GD) that may be caused by excessive thyroid hormone (TH) or anti-thyroid drugs (ATDs). Radioactive iodine (RAI) therapy is one of the first-line treatments for GD, but it is unclear whether it is safe and effective in patients with liver dysfunction. 510 consecutive patients with GD receiving first RAI were enrolled in the study, and followed up at 3-, 6- and 12-month. Liver dysfunction was recorded in 222 (43.5%) patients. GD patients with liver dysfunction had higher serum levels of free triiodothyronine (FT3) (median 27.6 vs. 20.6 pmol/L, p

We aimed on evaluating the effect of liver dysfunction on retinal nerve fiber layer (RNFL), GCL++ (ganglion cell layer + RNFL + inner plexiform layer), central macular thickness (CMT) and subfoveal choroidal thickness (CT) measurements.