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Background: We report the case of a patient with melanoma and liver failure with encephalopathy, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. Case presentation: In June 2022, metastatic lesions appeared in the liver associated with melanoma progression under treatment. Liver biopsy was non-diagnostic. The patient developed fever, abdominal distension, and jaundice. Liver function tests (LFTs) began to deteriorate. Hepatic encephalopathy developed in accordance with the worsening liver functions in the patient. Upper abdominal MRI with primovist showed multiple, progressive, metastatic lesions in the liver and mild to moderate dilatation of the intrahepatic biliary tract. Patient was evaluated as acute cholangitis associated with the compression of the biliary tract by progressive liver metastases. In December 2022, the patient was started antibiotherapy for cholangitis and Nivolumab (240 mg flat dose, every 2 weeks) therapy. After the first dose, both LFT and constitutional symptoms began to improve. Subsequently, LFTs almost completely returned to normal, clinical response was achieved. Multiple metastatic lesions in the liver regressed in the radiological evaluation performed at the third month of nivolumab treatment. With partial response, nivolumab treatment is continued. Conclusion: In this case is reported patient with hepatic encephalopathy due to an advanced refractory melanome successfully, and safely, treated with programed cell death-1 (PD-1) inhibitors. Clinical trials to explore the benefits of these immunotherapies in the hepatic failure population with advanced solid tumors should be supported. [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.

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.

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.

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.

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]

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15–37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26–194) vs. 56 (8–292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49–6.35) vs. 2.71 (1.40–4.95) L/min/m2, p = 0.02], central venous pressure [12 (7–19) vs. 9 (5–19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44–65) vs. 65 (45–102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12–3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate the ameliorative effects of Artemisia annua (RA) extract on hepatic toxicity induced by gentamicin injection mice. Sixteen mice were divided into four groups; the control group received saline, the second group received 1% A. annua (RA) extract, third group injected 80 mg/kg gentamicin (GEN) intraperitoneally. The protective group treated with a combination of GEN and A. annua. All mice were treated for consecutive 15 days. Results confirmed that hepatic biomarkers (GPT, GCT, GOT, IL-6 and IL-1β), all were altered after gentamycin injection. The histological analysis confirmed that gentamycin injected mice showed portal vein congestion, micro and macro steatosis, and nuclear pyknosis of hepatocytes. The protective group showed intact central vein with less microsteatosis of some hepatocytes. Immunochemistry analysis confirmed that the immunoreactivity of COX-2 gene showed negative impact in examined groups. Unlike, NF-κB gene exhibited diffuse positive expression in the gentamicin group. TGF-β1 immunoreactivity was mild positive in control and highly upregulated in gentamicin treated mice, all were normalized after RA administration. In conclusion, RA showed a beneficial impact against gentamycin induced hepatic toxicity at cellular and biochemical levels by regulating proteins and inflammatory markers associated with liver activity. [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: Post-hepatectomy liver failure (PHLF) is a common complication in patients with liver cancer. Biomarker-based methods, such as the Fibrosis-4 (FIB-4) index, can potentially reduce PHLF through identification and risk mitigation in high-risk patients. We conducted a systematic review to summarize the literature around the use of the FIB-4 index for predicting PHLF in liver cancer patients. Methods: We searched PubMed and Scopus (1 January 2010 - 31 December 2022) to identify the pertinent literature. We used predefined eligibility criteria to select studies for inclusion in our review. Information on study characteristics, FIB-4 index prognostic utility (sensitivity, specificity, predictive values, Area Under Curve -- AUC), and comparisons with other liver function tests was collected for each included study. Study quality was assessed with the QUIPS checklist. Basic descriptive statistics were used to analyse the data obtained from included studies. Results: We identified 6 published studies for our review. Most studies were from China (5/6, 83.3%), and sample sizes ranged from 140-1353 patients. All studies were assessed to have had a low risk of bias. FIB-4 had a reported sensitivity for PHLF of 65.2-75% and a reported specificity for PHLF of 83.3-93%. The AUCs reported for FIB-4 when used to predict PHLF ranged from 0.647 to 0.758. The prognostic utility of the FIB-4 index was generally comparable to other more complex liver function tests. Conclusion: The FIB-4 index appears to be a promising, non-invasive method for predicting PHLF in patients with liver cancer, warranting further research on this biomarker-based index. [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]

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]

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: The advent of direct‐acting antivirals has helped to increase the safe utilization of organs from hepatitis C virus positive (HCV+) donors. However, the outcomes of heart transplantation (HT) using an HCV+ donor are unclear in recipients with underlying liver disease represented by an elevated model for end‐stage liver disease excluding international normalized ratio (MELD‐XI). Methods: The United Network of Organ Sharing database was queried from Jan 2016 to Dec 2021. Post‐transplant outcomes stratified by recipient MELD‐XI score (low <10.37, medium, 10.38–13.39, and high >13.4) was compared between patients with HT from HCV+ (N = 792) and patients with HT from HCV‐negative donors (N = 15,266). Results: The median MELD‐XI score was comparable (HCV+, 12.1, vs. HCV‐negative, 11.8, p =.37). In the HCV+ group, donors were older (33 vs. 31 years, p <.001). Ischemic time of donor hearts (3.48 vs. 3.28 h, p <.001) and travel distance (250 vs. 157 miles, p <.001) were longer in HCV+ group. In the Kaplan Meier analysis with a median follow‐up of 750 days, survival was comparable between the two groups (2‐year survival, MELD‐XI Low: HCV+, 92.4 ± 3.6% vs. HCV‐negative, 91.1 ±.8%, p =.83, Medium: HCV+ 89.2 ± 4.3% vs. HCV‐negative, 88.2 ± 1.0%, p =.68, and High: HCV+, 84.9 ± 4.5% vs. HCV‐negative, 84.6 ± 1.1%, p =.75) In multivariate Cox hazard models, HCV donors were not associated with mortality in each MELD‐XI subgroup (Low: adjusted hazard ratio (aHR), 1.02, p =.94; Medium: aHR,.95, p =.81; and High: aHR,.93, p =.68). Conclusion: Utilization of HCV+ hearts was not associated with an increased risk of adverse outcomes in recipients with an elevated MELD‐ XI score. [ABSTRACT FROM AUTHOR]

The disease sepsis is caused by an infection that damages organs. Liver injury, with ferroptosis playing a key role, is an early sign of sepsis. G protein-coupled receptor 116 (GPR116) is essential in the maintenance of functional homeostasis in various systems of the body and has been proven to play a protective role in septic lung injury. However, it's role in septic liver injury remains unclear. In this study, we found that hepatic ferroptosis during sepsis was accompanied by GPR116 upregulation. Hepatocyte-specific GPR116 gene deletion can prevent hepatic ferroptosis, thereby alleviating sepsis-induced liver dysfunction and improving mouse survival, which was verified in vivo. Mechanistically, GPR116 aggravated mitochondrial damage and lipid peroxidation in hepatocytes by inhibiting system Xc–/GSH/GPX4 in overexpression experiments. In conclusion, we have identified GPR116 as a vital mediator of ferroptosis in sepsis-induced liver injury. It is thus an attractive therapeutic target in sepsis. [ABSTRACT FROM AUTHOR]

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.

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.

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]

Background and Aims: Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population‐based data are scarce. In this population‐based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease. Methods: This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health‐examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase‐alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression. Results: Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04–0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non‐alcoholic fatty liver disease. OCPs, PCBs and perfluoro‐octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05–0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21–2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07–2.68, p < 0.05 respectively). Conclusions: Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease. [ABSTRACT FROM AUTHOR]

Hypothyroidism is affecting the normal structure and functions of the liver. The elevation of transaminase enzymes in patients with hypothyroidism is exactly not cleared. The present study is aimed to determine the status of serum aspartate amino transaminase (AST) and alanine amino transaminase (ALT) levels in patients with hypothyroidism. In casecontrol study, 30 diagnosed hypothyroid patients and 30 age-matched healthy controls were enrolled. Levels of ALT and AST along with thyroid stimulating hormone (TSH), thyroxine (T4 ) and triiodothyronine (T3) were analyzed by using commercially available kit. A p-value of <0.05 was considered statistically significant. Mean of ALT, AST, and TSH were found significantly elevated in case than control (p=0.001). Mean of T4 and T3 was found significantly low in cases than controls (p<0.001). A significant positive correlation was found between ALT and AST among cases (r= 0.843, p<0.01). Serum ALT and AST have shown a negative correlation with T³ . In conclusion, the mean of ALT, AST and TSH were found significantly elevated in cases than controls. A significant positive correlation was found between ALT and AST among cases. Therefore, regular screening of liver functions should be done in patients with hypothyroidism to reduce the further disease complications. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the contribution of Type 2 Diabetes Mellitus (T2DM) and hypertension (HT) as comorbidity-enhancing factors on survival in patients with malignant solid tumors who have developed hepatic dysfunction. Methods: Patients who had received treatment in the medical oncology inpatient service between January 01, 2019, and January 01, 2023, and had developed organ insufficiency.. Grading was performe dusing National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Patients requiring hospitalisation of Grade 3 or higher were included in the evaluation. Results: 66 patients (22%) had T2DM, and 75 patients (25%) had been diagnosed with HT and were undergoing antihypertensive treatment. T2DM patients exhibited a Median Overall Survival (OS) of 7.81 months compared to 16.72 months for non-diabetic patients (p=0.002). Patients with HT had a median OS of 7.85 months compared to 17.41 months for those without HT (p=0.001), indicating significantly higher survival outcomes in those without a diagnosis of HT. Conclusion: It has been demonstrated that T2DM and HT have vital importance in cancer patients, and the regulation of blood sugar levels and blood pressure control play a significant role in survival outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study is to investigate the impact of the timing of chemotherapy (CT) initiation and CT protocol on overall survival (OS) in patients with hepatic visceral crisis (HVC). Methods: The study evaluated the timing of starting CT and the contribution of the initiated CT protocol to OS in patients with hepatic visceral crisis (HVC) who have clinical symptoms due to tumor burden characterized by liver metastasis and hyperbilirubinemia ≥1.5 times the upper limit, along with elevated at least one of ALT/AST values. Results: Between November 2007 and July 2021, analyzed 233 patients in HVC. 60 individuals were able to receive CT and divided into two groups based on the timing of initiating CT during HVC. CT initiated patients within 7 days were observed to have longer median OS (mOS) compared to patients initiated CT after 7 days (3.88 vs 2.99 months; p=0.04). Furthermore single-agent CT exhibited a significantly mOS compared to patients unable to undergo CT (1.70 months vs 1.08 months; p=0.03) Additionally patients who received combination CT had longer mOS compared to those who received monotherapy (4.27 months vs 1.70 months; p=0.03). Conclusion: Initiating early CT during HVC in eligible patients has a positive impact on OS. [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

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

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.

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.

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.

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

Background and Aims: Although transhepatic arterial chemo-embolization (TACE) is beneficial for the survival of intermediate stage hepatocellular carcinoma (HCC) patients, its cost is the damage of liver reserve. Liver dysfunction is one of factors associated with TACE refractory status and poor prognosis. The study aims to determine the prevalence and predictors of liver dysfunction in HCC patients after TACE.. Methods: Using the ASUS EMR search 3.0 system, the patients with discharge codes "HCC (C22.0)" plus "TACE" were collected since 2016 till 2021 in Taipei Tzu Chi Hospital. Liver reserve was determined by modified albumin-bilirubin (mALBI) grade. The liver dysfunction was defined as mALBI grade migration within 1–3 months after TACE.. Results: A total of 220 HCC patients with 314 TACE were found in 5-year duration. Those with TACE-experienced tumors, incomplete laboratory data for mALBI grade and incorrect diagnosis coding were excluded. 91 HCC patients (62 male; mean age 65.86 ± 11.61 year-old) were recruited for final analysis. 10 (11%) patients with baseline mALBI grade 3 were excluded. The percentage of mALBI grade migration was 27.2% (22/81) after TACE. Binary logistic regression discovered "up-to-seven out" and "up-to-eleven out" were associated with mALBI grade migration after TACE. Conclusion: In this retrospective study, liver dysfunction occurred in 27.2% of HCC patients after TACE. "Up-to-seven out" and "up-to-eleven out" were predictors for liver dysfunction after TACE, suggesting early switch to systemic therapy to reduce the risk of liver dysfunction for HCC patients with high tumor burden. [ABSTRACT FROM AUTHOR]

Most studies have indicated that the sex hormone estrogen is hepatoprotective, but little attention has been paid to investigating the effect of testosterone on hepatic ischemia/reperfusion (I/R) injury. Our study aimed to the evaluation of the effect of testosterone on the liver's functional and structural responses to hepatic I/R. To achieve this, 65 male Wistar albino-rats were divided into 5 groups: sham-operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone-treated hepatic ischemia/reperfusion group (T+I/R) and orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. The data obtained demonstrated that hepatic I/R significantly increased serum ALT, AST, hepatic tissue MDA, TNF-α, and NF-κB, and significantly decreased serum testosterone, estradiol, hepatic tissue SOD and Nrf2. Histopathological examination revealed cytoplasmic vacuolization, sinusoidal dilatation, inflammatory cell infiltration, and increased collagen fibers with a significant increase in apoptotic cell death (increased caspase-3). Orchidectomy worsened the effect of hepatic I/R while testosterone treatment improved the hepatic I/R-induced functional and morphological disruption in both intact and testosterone-depleted rats, owing to its antioxidant, anti-inflammatory, and anti-apoptotic properties, which were exerted partly via its direct action, and via being converted to estradiol. [ABSTRACT FROM AUTHOR]

Patients with heart failure (HF) often exhibit signs of liver dysfunction such as high bilirubin concentrations, leading to physical dysfunction and poor prognosis. Nevertheless, the relationship between direct bilirubin (DB), a fractionated form of total bilirubin, and dynapenia remains unclear, as does their effect on prognosis. This study investigated the association between DB concentrations and dynapenia in patients with HF. This retrospective study included patients with HF who underwent assessments for DB concentration, and handgrip and leg strengths to evaluate dynapenia and muscle weakness, respectively. Multiple logistic regression analyses examined the associations of DB with muscle strength and dynapenia. Additionally, we examined the prognostic value of comorbid high DB concentrations (≥0.5 mg/dL) and dynapenia. The endpoint was all-cause mortality. Of 853 inpatients, high DB was identified in 147 and dynapenia in 377 (44.2%). Multiple regression analysis revealed that high DB was independently associated with decreased muscle strength (handgrip strength, P = 0.027; leg strength, P = 0.002). After adjusting for covariates, the high DB group (odds ratio: 1.800, 95% confidence interval [CI]: 1.203–2.695, P = 0.004) had a significantly higher risk of dynapenia than the low DB group. During the follow-up period, 189 patients died (median, 1.77 years; interquartile range, 0.64–3.81 years). The risk of death was significantly higher in the high DB and dynapenia group, even after adjusting for HF severity (hazard ratio: 2.610, 95% CI: 1.680–4.051, P <0.001). High DB is associated with muscle weakness, and when combined with dynapenia, DB predicts a poorer prognosis in patients with HF. [Display omitted] [ABSTRACT FROM AUTHOR]

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]

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.

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 Therapeutic experiments are commonly performed on laboratory animals to investigate the possible mechanism(s) of action of toxic agents as well as drugs or substances under consideration. The use of toxins in laboratory animal models, including rats, is intended to cause toxicity. This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals. The current narrative review used databases such as Medline, Web of Science, Scopus, and Embase and appropriate keywords until June 2021. Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin, acetaminophen, doxorubicin, some anticancer drugs, and other materials through various signaling pathways are investigated. To understand the models of renal or hepatotoxicity in laboratory animals, we have provided a list of toxic agents and their toxicity procedures in this review.

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.

Peripartum cardiomyopathy (PPCM) is a rare pregnancy-associated dilated cardiomyopathy occurring in the last month of pregnancy and five months postdelivery, which presents with features of cardiac failure. Diagnosis is based on characteristic echocardiographic findings and elevated cardiac biomarkers and has significant mortality and morbidity when undiagnosed and untreated. Atypical presentations in earlier gestations are rare and associated with risk factors. Here we present a case of PPCM diagnosed in the second trimester in a post in vitro fertilization (IVF) twin pregnancy to emphasize the importance of considering the diagnosis of PPCM in all cases of unexplained cardiac failures during pregnancy in previously healthy patients, especially in the presence of risk factors. [ABSTRACT FROM AUTHOR]