Increase In Total Bilirubin Research Articles

Hyperbilirubinemia and Hepatic Dysfunction in Patients Undergoing Cardiac Surgery: Predictors and Outcome - A single Centre Prospective Study

Background: We aim to assess the incidence and perioperative risk factors for hyperbilirubinemia and hepatic dysfunction after cardiac surgery and determine its influence on early operative outcome. Methods: This prospective observational study was conducted on 485 patients who underwent cardiac surgical procedures from June 2022 to October 2023. Postoperative hyperbilirubinemia was defined as serum total bilirubin >2.0 mg/dl. Results: The overall incidence of post operative hyperbilirubinemia was 24.5% (119 patients). Total and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase was measured preoperatively and at day 1, day 2 and day 5. Patients undergoing valve repair or replacement had the highest incidence of hyperbilirubinemia (37.1%), followed by coronary artery bypass grafting with concomitant valve surgery (35.3%), congenital heart surgery (24.5%), and coronary artery bypass alone (12.4%). Post operative hyperbilirubinemia was associated with increased duration of inotropic support (p=0.0001), mechanical ventilation (p=0.0001), intensive care unit stay (p=0.001), hospital stay (p=0.006), and mortality (p=0.014). The perioperative factors associated with postoperative hyperbilirubinemia were increased preoperative bilirubin level (p<0.0001), preoperative prothrombin time (p<0.0001), cardiopulmonary bypass time (p=0.026), aortic cross clamp time (p=0.004), and blood transfusion units (p=0.0001). A significant increase of total bilirubin, aspartate aminotransferase, and alkaline phosphatase were noted in the second postoperative day. Significant relation was seen between hypotension and alkaline phosphatase, and aspartate aminotransferase change but hypothermia had not affected alanine aminotransferase, total bilirubin and indirect bilirubin change. Conclusions: Post operative hyperbilirubinemia is seen in patients undergoing cardiopulmonary bypass and is associated with high hospital mortality. The factors associated with its occurrence are increased preoperative bilirubin level, preoperative prothrombin time, cardiopulmonary bypass time, aortic cross clamp time, and blood transfusion units. Persistent hyperbilirubinemia is associated with a worse outcome than early transient hyperbilirubinemia.

Cisplatin Monotherapy as a Treatment Option for Patients with HER-2 Negative Breast Cancer Experiencing Hepatic Visceral Crisis or Impending Visceral Crisis.

Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80mg/m2, every 3-4weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. 33 female patients (24/33 hormonal-positive) with the mean age 53.84years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87months and median overall survival 2.67months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.

The Study of Efficacy and Safe of Lamivudine in Patients with Severe Acute Hepatitis B

Objectives: Lamivudin has been approved for the treatment of chronic hepatitis B but experience with lamivudin treatment for acute severe hepatitis B is still limited. Fulminant hepatitis develops in 1% of patients with acute hepatitis B. Severe acute hepatitis B in immunocompetent patients may progress to fulminant hepatitis and death. Aim: To evaluate the efficasy of lamivudine for the treatment of acute severe hepatitis B virus infection in imunocompetent adults in Clinic for infectious diseases Banja Luka. Patients and methods: In the period of 2006-2024 years, 12 immunocompetent patients (4 women, 8 men, age 24-77 years) with severe acute hepatitis B were treated with lamivudin. All 12 patients fulfil at least two of the criteria for severe acute hepatitis B infection: 1. hepatic encephalopathy; 2. total bilirubin 210 micromole per litre; and severe coagulopathy (international normalized ratio-INR was 4.5 ± 6.4 or prothrombin time-PT < 40%). All patients had evidence of severe hepatocyte lysis. Nine patients had rapid increase of total bilirubin and contemporary decrease of alanine aminotransferase level, which escalate risk of development of fulminant hepatitis B. All patients received lamivudin at a dose 100 mg per day. Results: Ten patients responded well to the treatment and their biochemical parameters improved rapidly. Within 1-6 months, the HBsAg was undetectable in 10 out of 12 investigated patients. Protective anti-HBs antibodies developed in 10 of them in 1-6 months. The corticosteroid therapy was short-term in 2 of 12 patients. Two patient developed fulminant hepatitis B and died after the lamivudine therapy was initiated. Lamivudine treatment was well tolerated in all patients. Conclusion: Lamivudin induces a prompt clinical, biochemical and serological response in immunocompetent patients with severe acute hepatitis B. Early treatment with lamivudine probably decreases the risk of progression to fulminant hepatitis in patients with severe acute hepatitis B.

Efficacy and safety of biologics in primary sclerosing cholangitis with inflammatory bowel disease: A systematic review and meta-analysis.

Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics. Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

Efficacy and Safety of Conversion Surgery for Advanced Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy.

The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed. The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P<0.05) and 15.6 months (P<0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P<0.05) and 45.0 months (P<0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P<0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P<0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P<0.05) and 21.7 months (P<0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up. HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.

The influence of alcohol dependence on the course of chronic heart failure in patients with HIV infection

Introduction. Alcohol dependence is a condition, the consequences of which are severe in persons with cardiovascular diseases and immunodeficiency. The purpose of the study is to evaluate the influence of alcohol dependence on the course of chronic heart failure (CHF) in persons infected with human immunodeficiency virus (HIV). Materials and methods. A clinical study including 240 HIV-infected patients, 160 of them were diagnosed with CHF, 72 had alcohol dependence. AUDIIT scale was used for diagnostics of alcohol dependence. All patients underwent echocardiography, NT-proBNP concentration was determined in blood plasma, serum - content of SRB, transferrin, ferritin, iron, potassium, sodium, bilirubin, creatinine, urea, uric acid, AST, ALT, GGTP activity. Statistical calculations: Kolmogorov-Smirnov, Mann-Whitney methods, odds ratios and risks. Results. Congestion, lower heart rate prevailed in the group of patients with alcohol dependence. On the background of alcohol dependence in blood serum there was a decrease in the level of total cholesterol, transferrin, potassium, an increase in total bilirubin and GGTP activity, a decrease in the number of platelets. Increase in NT-proBNP concentration was found in blood plasma. Discussion. Alcohol is characterized by cardiotoxic effect, and regular ethanol consumption is associated with the development of non-ischemic dilated cardiomyopathy and CHF. Echocardiographic findings suggest a predominance of right atrial and left ventricular dilatation in the group of patients with alcohol dependence among all patients with CHF infected with HIV due to the formation of cardiomyopathy. Conclusion. Alcohol dependence is a condition aggravating the course of CHF in HIV-infected patients, which is manifested by higher values of blood plasma NT-proBNP, with CHF more often acquiring a congestive character. The course of CHF in HIV-infected patients against the background of alcohol dependence is accompanied by liver dysfunction - 3.5 times increase the chance of cholestasis development, 2.5 times increase the chances of death within 2 months after admission to hospital.

How the Underlying Etiology of Cirrhosis Impacts Response to SBRT

In the US, incidence rates of hepatocellular carcinoma (HCC) have more than tripled and death rates have doubled since 1980. In 2022, it is expected for 41,260 new cases to be diagnosed with 30,520 deaths. Many etiologies contribute to the development of HCC including alcoholic cirrhosis, cryptogenic cirrhosis, HCV, HBV, NASH, and genetic disorders like hereditary hemochromatosis. An increasing number of patients are not candidates for curative options such as resection or transplant and the role of alternative liver directed as therapies has increased. SBRT has emerged as a safe and effective option, but there is little known about the outcomes related to the etiology of the HCC. The purpose of this study is to characterize the rates of toxicity and efficacy between different HCC etiologies in patients who were treated with SBRT. A single institutional database was compiled of all patients with HCC who were treated with SBRT. Patients with HCC etiologies of HCV, alcoholic cirrhosis, or NASH cirrhosis who received SBRT and monitored with liver function tests and imaging (MRI or CT) and were not transplanted were included Demographic information, disease etiology, all treatment courses, lab values, radiologic response, and follow-up were collected on all patients. SPSS was used to analyze the data. Consecutive patients (n = 37, 43 courses of radiation) who received SBRT between 2013- January 2022 were included. Most patients were male (n = 32, 86.5%) and average age was 64.73 ± 7.42 years (range: 50-82 years). A majority of patients had either HCV or HCV and alcoholic cirrhosis (n = 28, 75.7%) and there were no baseline difference in child Pugh score, tumor size, or number of prior treatments. Most patients were treated with 50Gy/5 fx (n = 26, 70.3%) with 5 others being treated with 45Gy/5fx to meet mean liver constraints. Most patients had a decrease in ALT (n = 22, 59.5%) while almost half of patients had a decrease in AFP (n = 14, 48.3%) at average follow-up of 11.84 ± 5.35 months. There was a significant correlation between HCC etiology and change in bilirubin with patients with HCV being more likely to have increases in total bilirubin (χ2 (6) = 17.5, p < 0.01). Patients with HCV induced cirrhosis may be more fragile and have a significant increased risk of toxicity after SBRT based on total bilirubin changes. Most patients did have a decrease in ALT showing potential for some improvement in liver function with SBRT. However, almost half of patients have some biologic efficacy with SBRT independent of HCC etiology. Further studies should include looking at the biologic differences in the etiologies and what treatment liver-directed therapies may be best for each population.

Evaluation of ceftriaxone pharmacokinetics in hospitalized Egyptian pediatric patients

This study aimed to evaluate ceftriaxone pharmacokinetics that affects the achievement of targets in the treatment of critically ill children (meningitis, pneumonia, urinary tract infection, peritonitis, and infective endocarditis( who were admitted to Zagazig University Pediatric hospital in Egypt to monitor for the drug adverse effects.Blood samples were obtained from 24 hospitalized pediatric patients (ages ranging from 2.5 months to 12 years) after administering the calculated dose of ceftriaxone via intravenous bolus route. Then, ceftriaxone plasma concentrations were measured using a validated HPLC method with ultraviolet detection. The pharmacokinetic analysis was conducted using Phoenix Winnonlin Program® software.Data for total and free ceftriaxone best fitted on a one-compartment model with the first-order elimination process. Clearance of ceftriaxone is reduced for patients with reduced kidney function and increased with those with augmented renal clearance. The volume of distribution and the free fraction are increased in these patients, especially those with hypoalbuminemia with a shorter half-life time were detected. A slight increase in total bilirubin and liver enzymes has been observed after treatment with ceftriaxone in these patients. Conclusion: In most critically ill pediatric patients, the current ceftriaxone treatment regimen (50 to 100 mg/kg) offers adequate pathogenic coverage. The clearance of free ceftriaxone in all patients correlates well with their renal function (eGFR), with r2 = 0.7252. During therapy with ceftriaxone at all doses ranging from 50 to 100 mg/kg, a rise in total bilirubin was observed in these patients. Moreover, liver enzymes (ALT and AST) increased moderately (p 0.0001). So, it is recommended to monitor total bilirubin and liver enzymes during the treatment with ceftriaxone, especially for a long duration (more than 5 days) or use another agent in patients with high baseline values.What is Known:• The dosing regimen of ceftriaxone (50 to 100 mg/kg) provided optimum therapeutic outcomes.• Some studies show data for total and free Ceftriaxone best fitted on a one-compartment model while other studies show data for total and free Ceftriaxone best fitted on a two-compartment model.What is New:• Up to my knowledge this is the first study ,considering individual pharmacokinetic analysis, conducted on hospitalized Egyptian pediatric population most of them with reduced kidney function with ages ranging from 2.5 months to 12 years. Data for total and free Ceftriaxone best fitted on a one-compartment model with linear clearance of the free ceftriaxone.• In all patients, total bilirubin and liver function tests were mildly increased, making them at risk for cholestasis or ceftriaxone-induced cholestatic hepatitis.

Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury

In recent years, cases of liver damage caused by ashwagandha herbal supplements have been reported from different parts of the world (Japan, Iceland, India, and the USA). Here, we describe the clinical phenotype of suspected ashwagandha-induced liver injury and the potential causative mechanism. The patient was admitted to the hospital because of jaundice. In the interview, it was reported that he had been taking ashwagandha for a year. Laboratory results showed an increase in total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), (gamma-glutamyl transpherase (GGT), alkaline phosphatase (ALP), total cholesterol, triglycerides, and ferritin. Based on clinical symptoms and additional tests, the patient was diagnosed with acute hepatitis and referred to a facility with a higher reference rate to exclude drug-induced liver injury. An R-value was assessed, indicative of hepatocellular injury. The result of the 24 h urine collection exceeded the upper limit of normal for copper excretion in urine twice. The clinical condition improved after intensive pharmacological treatment and four plasmapheresis treatments. This case is another showing the hepatotoxic potential of ashwagandha to cause cholestatic liver damage mixed with severe jaundice. In view of several documented cases of liver damage caused by ashwagandha and the unknown metabolic molecular mechanisms of substances contained in it, attention should be paid to patients reporting the use of these products in the past and presenting symptoms of liver damage.

Assessment of Biochemical Parameters in Sudanese Male Cigarette Smoker in Khartoum State in Omdurman

Background: Hundreds of thousands around the world die from a disease caused by smoking cigarettes. Cigarette smoking (CS) is considered a worldwide major cause of preventable morbidity and mortality. The main clinical consequences of prolonged exposure to CS are chronic respiratory diseases, increased incidence of a variety of cancers, cigarette smoking had a dangerous effect on the essential biochemical mechanisms on the human body. Objective: This study aimed to assess the liver function in Sudanese male cigarettes smoker to identify the influence of cigarettes smoking on the level of their parameters. Material and methods: The study was designed as case control and include 81 samples, which is divided into case (51 samples) and control group (30 samples). The data collected by the use of questionnaire and blood specimens, and the levels of the parameters is measured by A15 automation spectrophotometer. Then the collected data is analyzed by the use of SPSS. Results: The results of the study showed statistically significant increase in total bilirubin and liver enzymes in case group when compared with control group. The mean of plasma total bilirubin, GOT (AST), GPT (ALT), and ALP levels in case group is (0.663, 26.49, 18.82 and 159.27) and in control group is (0.543, 23.00, 14.30 and 146.63) with p. value (0.001, 0.041, 0.004 and 0.000) respectively. And showed statistically insignificant decrease in total protein and albumin in case group when compared with control group, the means of total protein and albumin in case group is (66.47 and 33.73) and in control group is (68.30 and 34.43) with p. value (0.322 and 0.403) respectively. Conclusion: The study concluded that there was significant increase in liver enzymes (GOT, GPT, and ALP) and total bilirubin in cigarette smoking. And significant decrease in total protein and albumin, in cigarette smoking when compared to nonsmoking.

The Frequency and Characteristics of Severe Liver-Related Adverse Events in Patients with Chronic Liver Diseases after Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Study

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.

Prognostic potential of liver injury in patients with dilated cardiomyopathy: a retrospective study

BackgroundLiver injury (LI) has been frequently observed in patients with dilated cardiomyopathy (DCM), whereas its prognostic value remains blurry. We attempted to appraise the prognostic effect of LI in patients with DCM.MethodsThis retrospective study included 523 patients with DCM. LI was defined as a threefold increase in aspartate transaminase (≥ 135 U/L) or alanine transaminase (≥ 180 U/L) or a twofold increase in total bilirubin (≥ 41 umol/L) during hospitalization. The population was segmented into non-liver injury (NLI) group and LI group based on liver function test data. To balance differences in covariates at baseline, 1:1 propensity score matching (PSM) was performed.ResultsPatients with LI had lower survival rate, compared with those with NLI (44.6% vs. 73.8%, P < 0.001). Similar results were also found in age (age > 50, 39.6% vs. 70.9%, P < 0.001; age ≤ 50, 51.3% vs. 79.5%, P < 0.001) and gender stratified analysis (male, 46.2% vs. 74.4%, P < 0.001; female 35.7% vs. 72.0%, P = 0.001). After PSM, the survival rate of patients with LI remained lower than those with NLI (44.6% vs. 64.1%, P = 0.019). Multivariable Cox regression analysis manifested that LI (hazard ratio [HR]: 1.692, 95% confidence interval [CI] 1.194–2.398, P = 0.003; HR: 1.675, 95% CI 1.078–2.604, P = 0.022, respectively) showed potent predictive effect on all-cause mortality in patients with DCM, both before and after PSM.ConclusionsThe occurrence of LI herald adverse outcomes in patients with DCM and attention to LI may be conducive to risk stratification and management.

EUS-guided choledochoduodenostomy using a lumen-apposing metal stent in a patient with preexisting duodenal stent and ascites.

Video 1EUS-guided choledochoduodenostomy using a lumen-apposing metal stent in a patient with preexisting duodenal stent and ascites.

Toxicological safety evaluation of Qin-Zhi-Zhu-Dan formula in rats during the treatment and recovery periods.

Background: Qinzhi Zhudan Formula (QZZD), optimized from Angong Niuhuang Wan, consists of Radix Scutellariae, Fructus Gardeniae and Pulvis Fellis Suis. We had investigated the neuroprotective effects of QZZD and its active components, and demonstrated that it could treat cerebral ischemia and dementia through multiple pathways and mechanisms. Nevertheless, toxicological data on this formula still remains limited. In the study, we sought to examine the toxicological effects of QZZD during the treatment and recovery periods. Methods: We investigated potential toxicities of QZZD in Sprague-Dawley (SD) rats via 28-day gavage administration. SD rats were randomly divided into control group and treatment groups of A (0.5 g/kg/d QZZD), B (1.5 g/kg/d QZZD), and C (5.0 g/kg/d QZZD). The 56-day course includes treatment period (administration with water or QZZD once a day for 28 consecutive days) and recovery period (28 days). The rats received daily monitoring of general signs of toxicity and mortality, as well as weekly determination of body weight and food consumption. Moreover, the complete blood cell count, biochemistry, coagulation, and urine indicators, organ weights, and histopathological report were analyzed respectively at the end of the treatment and recovery periods. Results: There was no death related to the active pharmaceutical ingredients of QZZD during the treatment period. The maximum no observed adverse effect level (NOAEL) was 0.5 g/kg/d, which is approximately 16.7 times of the equivalent dose of clinical dose in rats. In group TB (1.5 g/kg/d QZZD) and TC (5.0 g/kg/d QZZD), there were adverse effects of blue coloring of tail skin, weight loss, a significant increase of total bilirubin (TBIL), blackening of liver and kidney in gross examination, hyperplasia of bile duct and karyomegaly of hepatocytes in histopathological examination. Besides, in females rats, the food consumption was reduced, while in male rats, there was decrease in triglycerides (TG) and slight increase in white blood cell (WBC) count and neutrophils. In group TC (5.0 g/kg/d QZZD), the indicators of red blood cell (RBC) count, hemoglobin (HGB) and hematocrit (HCT) were decreased slightly, while the platelet count (PLT) was increased. However, these changes were not considered to be toxicologically significant because they resolved during the recovery period. Conclusion: Overall, QZZD exhibited a good safety profile. The maximum no observed adverse effect level was 0.5 g/kg/d, and no target organs toxicity were identified. The present findings might confirm the safety of QZZD in clinical practices.

Toxicological evaluation of Hb cleanser® bitters on biochemical parameters in Wistar rats

This study was carried out to evaluate the effect of HB Cleanser bitters on biochemical parameters in male Wistar rats. Twenty-eight animals were assigned into four groups of seven animals each. Groups A, B, C received 1, 1.03 and 1.29 ml/kg of the HB bitters respectively while group D (control), received 1 ml normal saline. All administrations were done orally and daily for 28 days. The feed and fluid intake were measured daily and the body weight weekly. Phytochemical screening revealed the presence of saponins, flavonoids and cardiac glycosides. Acute toxicity results showed that the LD50 of HB Cleanser Bitters was greater than 5000 mg/kg with no mortality. There was a significant (P&lt;0.05) increase in body weight. In addition, HB bitters caused at 1 ml/kg significant (P&lt;0.05) increase in total bilirubin, conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and urea more than the other doses compared to negative control. A significant (P&lt;0.05) decrease was observed in the levels of total protein and albumin compared to negative control. The findings from this study showed that HB cleanser Bitters may adversely affect hepatic and renal indices and therefore should be used with caution.

Acute Hepatic and Renal Toxicity Assessment of Euphorbia huanchahana (Klotzsch &amp; Garcke) Boissier (Huachangana) in Holtzman Rats

Background: Euphorbia huachahana (Klotzch &amp; Garcke) Boissier (Huachangana) (EhKGBh) has been used for over a century for medicinal purposes in the Peruvian population; however, its safety and possible toxic effects of use have not been reported. The purpose of this study was to determine the acute hepatic and renal toxicity of EhKGBh in Holtzman rats. Methods: Analytical and experimental study. The population consisted of 52 rats of both sexes weighing between 300 and 350 g divided into four groups: G1 and G2 EhKGBh groups (26 rats each) and two control groups (10 rats each). The experimental group was administered EhKGBh at a single dose of 2000 mg/kg P.O. to demonstrate toxicity during the 14-day follow-up. A daily assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and conjugated bilirubin (CBIL) was performed. Results: Evaluation of the liver tissue showed mild changes in inflammation, predominantly vascular, with small clots. Kidney tissue did not show inflammatory or necrotic changes. However, we showed differences in the weight of the rats between both groups (p &lt; 0.004) and significant increases in TBIL (0.98–1.07 mg/dL), CBIL (0.43–0.45 mg/dL), AST (126.4–141.8 U/L), and ALP (254–298 U/L) but not ALT (39.7–41.1 U/L) (p &lt; 0.05). Conclusion: The single dose of EhKGBh extract at 2000 mg/kg has no toxicity, and there is no change in tissue toxicity during the 14-day follow-up.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

A phase I/II study of first-in-human trial of JAB-21822 (KRAS G12C inhibitor) in advanced solid tumors.

3089 Background: KRAS G12C mutation occurs in approximately 4% of non-small cell lung cancer (NSCLC), 1-2% of colorectal cancer (CRC) and other solid tumors in China. JAB-21822 (Jacobio, Beijing, PRC) is a highly selective, covalent oral inhibitor of KRAS G12C. Methods: NCT05009329 is an ongoing first-in-human, open label phase I/II study of JAB-21822 in patients with advanced solid tumors. The primary objective is to evaluate the safety and tolerability of JAB-21822. Other objectives include preliminary efficacy, pharmacokinetics, and biomarkers. Here we report the results from the dose escalation phase of the trial. Results: As of January 28th, 2022, 53 patients with a median age of 62 years (39-79) were enrolled in 5 different dose levels: 200mg QD, 400mg QD, 800mg QD, 400mg BID and 400mg TID. Most patients (55%) had ≥ 2 prior lines of therapy. No dosing-limiting toxicities were observed. Two treatment-related adverse events (TRAEs) were G4 neutropenia (1 in 400mg BID and 1 in 400mg TID). The most common TRAEs (≥ 10%) included anemia (24.5%), total bilirubin increase (20.8%), direct bilirubin increase (15.1%), proteinuria (13.2%) and indirect bilirubin increase (11.3%). Only Grade 1 and 2 TRAEs were observed in the QD cohorts. A total of 33 patients (22 NSCLC, 9 CRC and 2 pancreatic cancer) had at least 1 post-baseline tumor assessment; in the 800mg QD cohort, overall response rate (ORR) and disease control rate (DCR) were 50% (5/10) and 100% (10/10), respectively, including 4 non-confirmed partial response (PR); in the 400mg QD cohort had an ORR and DCR of 80% (4/5) and 100% (5/5) respectively, including 2 non-confirmed PR. Patients with NSCLC (400mg QD and 800mg QD), the ORR and DCR were 70% (7/10) and 100% (10/10), respectively, including 5 non-confirmed PR. With respect to the pharmacokinetics analysis, JAB-21822 was rapidly absorbed with an average Tmax of 2 hr and reached higher plasma exposures (Cmax and AUC0-24h) after a single dose and multiple doses at C1D8. Conclusions: JAB-21822 was well tolerated with impressive preliminary efficacy in patients with heavily treated solid tumors harboring KRAS G12C mutation. The study is enrolling patients in the expansion phase. Multiple JAB-21822-based combination trials are also ongoing. Clinical trial information: NCT05009329.

Total Kadar Bilirubin Pada Pasien Tuberculosis (TB) Paru Setelah 5 Bulan Mengkonsumsi Obat Anti Tuberkulosis (OAT) di Rumah Sakit Tentara Kota Binjai

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis which attacks the lungs and bronchi. Anti-tuberculosis drugs consist of isoniazid, ethambutol, pyrazinamide, rifampicin and streptomycin which must be consumed for 6 months. OAT has side effects, especially disturbing liver function, one of which is bilirubin. Bilirubin is a yellow pigment derived from the heme reshuffle of hemoglobin in the process of erythrocyte breakdown by reticuloendothelial cells. This research is desktiptif. This study aims to describe the total bilirubin levels in pulmonary tuberculosis patients after 5 months of consuming anti-tuberculosis drugs in TK.IV.01.07.02 Binjai Army Hospital in May-June. This study was taken from 53 samples of total bilirubin levels in tuberculosis patients who had consumed OAT for 5 months. The results of the 53 samples found normal total bilirubin levels of (77.40%) and increased by (22.60%). Frequency distribution in male sex (56.6%) women (43.4%). Total bilirubin levels increased more in male patients (13.21%). The increase in total bilirubin occurred at&gt; 56 years of age. Total bilirubin levels increased more in female patients (9.43%).

Dependence of blood biochemical parameters on various genotypes of the UGT1A1 gene associated with gilbert's syndrome.

Diagnosis of Gilbert's syndrome is based on the detection of homozygous carriage of an additional TA-repeat in the promoter of the UGT1A1 gene, leading to a decrease in the activity of the UGT enzyme. No large studies have been done in the Russian Federation on the prevalence of carriage of Gilbert's syndrome, as well as the biochemical and molecular profile of such patients. The aim of the study is to evaluate biochemical and molecular genetic parameters in patients with Gilbert's syndrome in Russia. The study included 124 healthy volunteers (group 1) and 5650 patients with suspected Gilbert's syndrome (group 2). The number of TA-repeats of the promoter region of the UGT1A1 gene was determined by the method of fragment analysis for all participants. The following biochemical parameters were analyzed for 299 patients from group 2: the level of bilirubin and its fractions, AST, ALT, cholesterol and LDL. In group 1 the prevalence of genotype (TA)6/(TA)6 was 39,52%, (TA)6/(TA)7 - 53,23%, (TA)7/(TA)7 - 7,26%, no rare forms were found. In group 2 the prevalence of genotype (TA)6/(TA)6 was 6,04%, (TA)6/(TA)7 - 20,05%, (TA)7/(TA)7 - 73,7%, rare alleles - 0,2%. Rare alleles included (TA)5/(TA)6, (TA)5/(TA)7, (TA)6/(TA)8 and (TA)7/(TA)8, as well as a new genotype not described in the literature previously - (TA)7/(TA)9. When assessing the level of total bilirubin and its fractions, a difference was revealed between the genotype of Gilbert's syndrome (TA)7/(TA)7 and the reference genotype (TA)6/(TA)6, and between genotypes (TA)7/(TA)7 and (TA)6/(TA)7. A significant increase in total bilirubin was demonstrated in carriers of a larger number of TA-repeats. There was no significant difference in the concentration of ALT, AST, cholesterol or LDL between different genotypes.The number of TA-repeats of the UGT1A1 gene affects the increase of total bilirubin and its indirect fraction, including the cases of rare allelic variants (TA≤5, TA≥8), but not the activity of ALT and AST and the lipid profile.