Higher Total Bilirubin Levels Research Articles

The medium-fluorescence reticulocyte ratio is an independent predictor of G6PD deficiency neonates.

G6PD deficiency is a potentially life-threatening condition in neonates presenting with hyperbilirubinemia. This study aims to identify clinical and laboratory predictors of G6PD deficiency in neonates presenting with hyperbilirubinemia. This was a retrospective study of 227 term neonates admitted to Heyuan People's Hospital from January 2019 to October 2023. Hematological parameters and bilirubin were compared between those with G6PD deficiency and those with normal G6PD. Term neonates with G6PD deficiency had higher levels of total bilirubin, indirect bilirubin, mean corpuscular volume, mean corpuscular hemoglobin, immature reticulocyte fraction, high-fluorescence reticulocyte ratio, medium-fluorescence reticulocyte ratio, and content of reticulocytes than those with normal G6PD, but lower levels of red blood cells, hemoglobin, hematocrit, and low-fluorescence reticulocyte ratio. Medium-fluorescence ratios (OR = 1.291, P = 0.028) independently predicted G6PD deficiency in neonates. The optimal cut-off value for medium-fluorescence ratios was > 18.55%. The area under the curve for diagnosing G6PD deficiency was 0.924 (95% confidence interval: 0.886-0.962, P < 0.0001), with a sensitivity of 82.6% and specificity of 86.2%. MFR emerged as a potentially valuable predictor for G6PD deficiency in neonates.

Analysis of the efficacy of Percutaneous Transhepatic Cholangiography Drainage (PTCD) and Endoscopic Retrograde Cholangiopancreatography (ERCP) in the treatment of Malignant Obstructive Jaundice (MOJ) in palliative drainage and preoperative biliary drainage: a single-center retrospective study

PurposeThis study aimed to assess the safety and efficacy of percutaneous transhepatic cholangiography drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) in palliative drainage and preoperative biliary drainage for treating malignant obstructive jaundice (MOJ).MethodsA total of 520 patients with MOJ who underwent PTCD or ERCP were enrolled and classified into palliative drainage group and preoperative biliary drainage group. Baseline characteristics, liver function, blood routine, complications were compared among the groups.ResultsThe technical success rates for PTCD and ERCP in palliative group were 97.1% and 85.9%. In palliative drainage group, PTCD had higher levels of total bilirubin (TB) reduction (53.0 (30.0,97.0) vs. 36.8 (17.9,65.0), p < 0.001) and direct bilirubin (DB) reduction (42.0 (22.0,78.5) vs. 28.0 (12.0,50.8), p = 0.001) than ERCP. However, PTCD was associated with higher rates of drainage tube displacement (20 cases, 11.8%), while ERCP had a higher incidence of biliary infection (39 cases, 22.8%) and pancreatitis (7 cases, 4.1%). In preoperative drainage group, PTCD achieved a 50% reduction in total bilirubin faster than ERCP (7.1 days vs. 10.5 days). And the time from palliation of jaundice to surgery was 24.2 days in PTCD group and 35.7 days in ERCP group, a statistically significant difference (Student’s t test, p = 0.017).ConclusionBoth PTCD and ERCP could improve liver function for MOJ patients. PTCD seems to offer better outcomes in jaundice reduction and liver function improvement in palliative drainage, but requires careful postoperative management. In preoperative biliary drainage, PTCD may be a better preoperative bridge to improve liver function and control infection.

A Case-control Study on the Correlation between Serum Bilirubin Levels and Various Types of Appendicitis

Background Acute appendicitis is one of the most common types of surgical emergencies. Among laboratory factors, hyperbilirubinemia has recently been identified as a strong predictor of preoperative perforation and gangrene. Aim This study aimed to investigate the correlation between serum bilirubin levels and types of appendicitis. Methods This case-control study was conducted in 2022 using the convenience sampling method on 100 patients who were referred to the emergency department of Imam Khomeini Hospital in Jiroft with abdominal pain. These patients were diagnosed with appendicitis based on the initial clinical examinations. The white blood cells and total bilirubin levels were measured for all the patients. Intraoperative macroscopic findings were recorded by the surgeon, and the pathological results of the specimen were reported. Data was analyzed using SPSS 24, including descriptive and inferential statistics at the significance level of P&lt;0.05. Results Among 100 patients aged between 28.5±14.8, 48% were men, and the rest were women. There was a significant difference between the mean of bilirubin levels in patients with complicated and uncomplicated appendicitis (P &lt;0.01). The results of logistic regression analysis showed that the period of onset of symptoms to hospitalization, leukocytosis level, and preoperative total bilirubin level were significant variables for diagnosing complicated appendicitis (P&lt;0.05). Conclusion In this study, we found that patients with complicated appendicitis had higher total bilirubin levels than patients with uncomplicated appendicitis. Therefore, patients with hyperbilirubinemia and clinical symptoms of appendicitis should be considered as more probable cases of perforation than those with normal bilirubin levels.

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1β, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

Liver iron overload and fat content analyzed by magnetic resonance contribute to evaluatingthe progression of chronic hepatitisB.

Chronic hepatitis B (CHB) and its complications still have a major role in liver-related mortality. It has been indicated that hepatic iron and steatosis may influence liver fibrosis and carcinogenesis. The present study aimed to assess the liver iron and fat in patients with CHB by MRI in order to estimate the associations among liver iron, fat and the severity and progression of liver fibrosis. In the present retrospective study, consecutive patients with CHB examined from August 2018 to August 2020 were analyzed. Liver iron and fat content were assessed by MRI, which was measured as liver iron content (LIC) and proton density fat fraction (PDFF). A total of 340 patients were included in the current study. For LIC, the median value was 1.68 mg/g and elevated LIC was seen in 122 patients (35.9%). For liver fat content, the median value of PDFF was 3.1%, while only 15.0% of patients had liver steatosis (PDFF ≥5%). Age, total bilirubin and sex were independent predictive factors of liver iron overload [odds ratio (OR)=1.036, 1.005 and 8.834, respectively]. A higher platelet count (OR=1.005) and no portal hypertension (OR=0.381) independently predicted liver steatosis. The areas under the receiver operating characteristic curves of PDFF for the identification of liver cirrhosis estimated by different non-invasive tools ranged from 0.629 to 0.704. It was concluded that iron overload was common in patients with CHB, particularly in those with older age, male sex and high total bilirubin level, and liver steatosis was less common in CHB. Liver iron and fat content analyzed by MRI may contribute to the evaluation of the severity and progression of CHB.

Development and evaluation of a model for predicting the risk of healthcare-associated infections in patients admitted to intensive care units.

This retrospective study used 10 machine learning algorithms to predict the risk of healthcare-associated infections (HAIs) in patients admitted to intensive care units (ICUs). A total of 2,517 patients treated in the ICU of a tertiary hospital in China from January 2019 to December 2023 were included, of whom 455 (18.1%) developed an HAI. Data on 32 potential risk factors for infection were considered, of which 18 factors that were statistically significant on single-factor analysis were used to develop a machine learning prediction model using the synthetic minority oversampling technique (SMOTE). The main HAIs were respiratory tract infections (28.7%) and ventilator-associated pneumonia (25.0%), and were predominantly caused by gram-negative bacteria (78.8%). The CatBoost model showed good predictive performance (area under the curve: 0.944, and sensitivity 0.872). The 10 most important predictors of HAIs in this model were the Penetration Aspiration Scale score, Braden score, high total bilirubin level, female, high white blood cell count, Caprini Risk Score, Nutritional Risk Screening 2002 score, low eosinophil count, medium white blood cell count, and the Glasgow Coma Scale score. The CatBoost model accurately predicted the occurrence of HAIs and could be used in clinical practice.

Predictive Value of Interleukin 6 and Interleukin 8 in Response to Treatment of Hepatitis C Virus.

Chronic hepatitis C (CHC) infection is a major public health problem in many low- and middle-income countries. The study aimed to find out how interleukin IL-6 and IL-8 levels in the blood affect the virological response to directacting antivirals (DAAs) and to find useful clinical or immunological markers for the response to HCV treatment. CHC patients from a real Egyptian population (n = 4,300), who were treated during the Egyptian national initiative to eliminate HCV at the Sherbin Central Hospital, Dakahlia Governorate, Ministry of Health, Egypt, were enrolled in our study. They were all patients who did not obtain a sustained virological response (SVR) (n = 75; non-responder; the response rate was 98.26%), and a total of 100 patients were randomly selected from patients who obtained SVR (responder) and were age- and gender-matched (p > 0.05) with non-responder patients. Serum levels of IL-6 and IL-8 were measured by commercial ELISA kits. Non-responder patients were associated with significantly high levels of ALT, AST, ALP, and total bilirubin. Non-responders had significantly (p < 0.05) higher baseline IL-6 (16.7 ± 4.92 pg/mL) and IL-8 (37.81 ± 10.55 pg/mL) levels compared to responders (12.68 ± 2.06, 29.06 ± 5.94 pg/mL, respectively). There was a substantial (p < 0.05) association between the combination of two cytokines and a high likelihood of treatment failure, as indicated by all parameters examined, with the highest correlation values seen. The present study showed that increased IL-6 and IL-8 were associated with HCV treatment failure. Also, IL8 was associated with hepatic fibrosis.

Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment.

To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Correlation between pre-treatment serum total blood bilirubin and unconjugated bilirubin and prognosis in patients with colorectal cancer.

Epidemiological studies have found that unconjugated bilirubin (UCB) levels are positively correlated with the incidence of colorectal cancer (CRC). Therefore, bilirubin may also play an important role in the prognosis of CRC. To investigate the predictive value of total bilirubin (TBIL) and UCB in the prognosis of patients with CRC. A total of 142 CRC patients were selected as the research subjects in Jingxian Hospital, from October 2014 to May 2021. General and tumour-related clinical data at admission and the overall survival at 3 years after surgery were collected. The optimal cut-off values of TBIL and UCB were determined by receiver operating characteristic curve analysis. Univariate and multivariate Cox regression were used to analyse the effect of bilirubin level on the survival of CRC patients. The Kaplan-Meier method was used to assess the survival time. The 3-year overall survival rate of CRC patients was significantly higher in the high TBIL (> 13.45 μmol/L) group than in the low TBIL (≤ 13.45 μmol/L) group (76.4% vs 37.1%; P < 0.05). The 3-year overall survival rate of CRC patients in the high UCB (> 10.75 μmol/L) group was significantly higher than that in the low UCB (≤ 10.75 μmol/L) group (83.3% vs 34.2%; P < 0.05). Multivariate Cox regression analysis showed that higher TBIL levels were an independent predictor of better prognosis in CRC patients (hazard ratio = 0.360, 95% confidence interval: 0.159-0.812, P = 0.014). TBIL levels can be used as a prognostic indicator for CRC patients.

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study

BackgroundWeekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.MethodsThis retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).ResultsAmong 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216–124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052–477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141–137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0–5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8–13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9–15.7 month, P < 0.01 vs RF-2).ConclusionsCareful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis.

Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

STUDY TO KNOW THE EFFECT OF PHOTOTHERAPY ON SERUM CALCIUM LEVEL IN NEONATAL HYPERBILIRUBINEMIA

Background: Phototherapy is the most common method to treat neonatal jaundice. The effect of phototherapy on serum calcium levels is a questionable issue. Objective: To study to know the effect of phototherapy on serum calcium level in neonatal hyperbilirubinemia. Methods: Cohort study compared total serum calcium level before and after phototherapy in neonates with hyperbilirubinemia. Study was conducted on 54 neonates with high total serum bilirubin levels, according to the Bhutani curve and was treated with phototherapy at neonatal intensive care unit in the Department of Pediatrics at Mayo Institute of Medical Sciences from November 2021 to April 2022. Results: Hypocalcaemia was observed in 33.33% of neonates after phototherapy. The difference between pre- and post-phototherapy serum calcium levels was found to be statistically significant (p&lt;0.005). Conclusion: Hypokalcemia has a significant association with phototherapy.

Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation

This research aimed to evaluate the preventing effects of naringin, naringenin, and their combination on liver injury induced by Taxol (paclitaxel) in Wistar rats. Male Wistar rats received 2 mg/kg Taxol intraperitoneal injections twice weekly on the second and fifth days of each week for 6 weeks. During the same period as Taxol administration, rats were given naringin, naringenin, or a combination of the two (10 mg/kg b.wt) every other day. Treatment with naringin and/or naringenin reduced the abnormally high serum levels of total bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase in Taxol-treated rats. It also significantly increased the level of serum albumin, indicating an improvement in the liver. The perturbed histological liver changes were markedly improved due to the naringin and/or naringenin treatment in Taxol-administered rats. Additionally, the treatments reduced high hepatic lipid peroxidation and increased liver glutathione content as well as the activities of superoxide dismutase and glutathione peroxidase. Furthermore, the treatments reduced the levels of alpha-fetoprotein and caspase-3, a pro-apoptotic mediator. The naringin and naringenin mixture appeared more effective in improving organ function and structural integrity. In conclusion, naringin and naringenin are suggested to employ their hepatoprotective benefits via boosting the body’s antioxidant defense system, reducing inflammation, and suppressing apoptosis.Graphical

Efficacy and predictors of immune checkpoint inhibitors in patients with gallbladder cancer.

e16124 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) has shown promising efficacy in multiple cancers including biliary tract cancers (BTCs). However, the data focusing on the efficacy of ICIs in patients with gallbladder cancer (GBC) is still limited. This study aims to assess the efficacy of ICIs in GBC and explore the clinicopathological and molecular markers of ICI benefit. Methods: This was a single center, retrospective study, including 80 GBC patients who had received ICI (anti-PD-1 monoclonal antibody) therapy at Eastern Hepatobiliary Surgery Hospital (Shanghai, China) between January 2016 and December 2020. Tumor samples from 31 of these patients who had previously underwent surgical resection before ICI therapy were obtained and conducted for whole exome sequencing and immunohistochemical analysis. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR) and disease control rate (DCR). The associations between efficacy with clinicopathological factors, genetic variations and PD-L1/CD8 expression were further explored. Results: Of 80 patients with GBC, 36 were male, the median age was 61 years (range, 30-79). The median PFS and OS was 4.5 months (95% CI, 2.99-5.95) and 8.7 months (95% CI, 7.07-10.26) respectively. Multivariate analysis indicated that alcohol intake history (HR, 2.66; 95% CI, 1.31-5.40; p=0.007), extrahepatic metastasis (HR, 2.03; 95% CI, 1.15-3.59; p=0.015), carcinoma embryonic antigen (CEA) level ≥100U/mL (HR, 3.58; 95% CI, 1.65-7.74; p=0.001) and immune-related adverse events (irAEs) (HR, 0.24; 95% CI, 0.10-0.57; p=0.001) were independent prognostic factors for PFS. Extrahepatic metastasis (HR, 2.42; 95% CI, 1.37-4.31; p=0.003), CEA level ≥100U/mL (HR, 2.82; 95% CI, 1.33-5.95; p=0.007) and irAEs (HR, 0.32; 95% CI, 0.14-0.72; p=0.006) were independent prognostic factors for OS. ORR and DCR were 13.75% and 37.5%, respectively. Patients with irAEs (85.7%, OR, 16.00; 95% CI, 3.26-78.61; p&lt;0.001), high CD8+ T-cells-infiltrated GBCs (87.5%, OR, 19.83; 95% CI, 2.00-196.38; p=0.011), immune inflamed phenotype (66.7%, OR, 5.60; 95% CI, 1.16-27.08; p=0.032) had higher DCR, while patients with high level of total bilirubin (TBIL&gt;34.2μmol/L) (8.3%, OR, 0.12; 95% CI, 0.01-0.97; p=0.048) had lower DCR. Patients with high CD8+ T-cells-infiltrated or immune inflamed GBCs also had a notably improved PFS and OS. Conclusions: ICIs were effective in patients with GBC. Alcohol intake history, extrahepatic metastasis, CEA level ≥100U/mL, irAEs, high positivity of CD8+ T-cells and immune inflamed phenotype may be useful for predicting the efficacy of ICIs in GBC.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

The Impact of Patient Age and Corticosteroids in Patients With Sulfonamide Hepatotoxicity.

Sulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity. Between 2004 and 2020, 105 patients with hepatotoxicity attributed to trimethoprim/sulfamethoxazole (TMP-SMZ) (n = 93) or other sulfonamides (n = 12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist. Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). Younger patients were significantly more likely to have rash, fever, eosinophilia, and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared with older patients ( P < 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend toward more rapid normalization of their laboratory abnormalities compared with untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels. Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation, and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury, but further studies are needed.

Association between Serum Total Bilirubin Level and Patients with Primary Open-Angle Glaucoma in China: A Cross-Sectional, Case-Control Study.

To investigate the relationship between peripheral blood total bilirubin (TBIL) levels and the risk of primary open-angle glaucoma (POAG). This study was a cross-sectional, case-control study design. Between April 2021 and January 2022, 198 POAG patients and 205 healthy subjects were recruited from the EENT Hospital of Fudan University. Their clinical information (intraocular pressure, central corneal thickness, vertical cup-disk ratios (VCDR), and axial length) and demographic data were collected. Serum levels of TBIL were measured in enzymes using a Roche C702 biochemical analyzer. The POAG subgroups were classified by gender and VCDR: mild (VCDR ≤ 0.64), moderate (VCDR ≤ 0.85), and severe (VCDR > 0.85). Univariate and multivariate logistic regression analyses were performed. The level of TBIL (11.58 ± 5.16 μmol/L) in the POAG group was higher than that in the control group (10.18 ± 3.38 μmol/L; p < 0.05). In the male subgroup, TBIL was also significantly higher than in the normal control group; TBIL levels were lower in the mild subgroup (10.82 ± 4.48 μmol/L), followed by the moderate subgroup (12.00 ± 5.55 μmol/L) and the severe subgroup (14.47 ± 5.45 μmol/L). The results of the multivariate logistic regression analysis showed that high TBIL levels were a risk factor for male POAG, at 1.126 (95% CI 1.009-1.256). Pearson's analysis revealed that TBIL was positively correlated with intraocular pressure (r = 0.134, p = 0.012), VCDR (r = 0.142, p = 0.046), anterior chamber depth (r = 0.190, p = 0.014), and axial length (r = 0.179, p = 0.019) in the patients. However, no statistical difference (p < 0.05) was observed in the female patients with POAG. The results showed that high levels of TBIL may be related to the pathogenesis of POAG and that the severity of the disease is positively correlated, especially in male patients.

A new, simple marker for predicting complicated appendicitis in patients with normal white blood cell count indicator; LUC.

The aim of this study was to investigate the ability of a new marker that could be easily obtained to differentiate between complicated and uncomplicated appendicitis in a patients with a white blood cell (WBC) count within the normal range. The patients who underwent surgery with histopathologically proven acute appendicitis (AA) between January 2021 and October 2022 were evaluated retrospectively. Patients were classified into two groups as uncomplicated and complicated appendicitis, based on the surgical and histopathological findings. Groups were compared in terms of laboratory parameters at the time of hospital admission. During the study period, 2589 patients underwent an appendectomy, among these 612 patients who had a WBC count within the normal range at the time of admission were analyzed. Uncomplicated appendicitis was detected in 79.6% of the patients and complicated appendicitis in 20.4%. Neutrophil%, neutrophil-to-lymphocyte ratio, C-reactive protein, and total bilirubin levels were significantly higher, whereas lymphocyte%, lymphocyte count, lymphocyte-to-monocyte ratio, sodium levels, and large unstained cells (LUC)% were significantly lower in patients with complicated appendicitis. Multiple logistic regression analysis revealed that lower LUC% (Odds Ratio [OR]: 0.45; 95% Confidence Intervals [CI]: 1.08-2.09; P=0.01) and higher total bilirubin levels (OR: 1.50; 95% CI: 1.08-2.09; P=0.01) were independent risk factors for complicated appendicitis. In patients with a diagnosis of AA with a normal WBC value, LUC% obtained from the complete blood count can be used as a new parameter predicting the diagnosis of complicated appendicitis.