Prediction of Transarterial Chemoembolization (TACE) - Outcome by pre- and postinterventional 13C-Methacetin breath test

BACKGROUND: Liver function is one of the most important parameters for the outcome of transarterial chemoembolization (TACE). The Liver Maximum Capacity (LiMAx) -Test is a bedside test that provides a real-time option for liver function testing. The objective of this pilot study is to investigate the suitability of the LiMAX test for estimating the TACE outcome. OBJECTIVE AND METHODS: 20 patients with intermediate-stage hepatocellular carcinoma (HCC) received a LiMAx test 24 h pre and post TACE. In addition, laboratory values were collected to determine liver function and model for endstage liver disease (MELD) scores. The success of TACE was assessed 6 weeks post intervention by morphological imaging tests using modified response evaluation criteria in solid tumors (mRECIST). RESULTS: Patients with an objective response (OR = CR + PR) according to mRECIST post TACE have significantly higher values in the pre-interventional LiMAx test than patients with a non-OR (PD or SD) post TACE (rb(14) = 0.62, p = 0.01). Higher pre-interventional LiMAx values therefore indicate OR. Patients with a disease control (DC = CR + PR + SD) according to mRECIST post TACE have significantly higher values in the pre-interventional LiMAx test than patients with a non-DC (PD) post TACE (rb(14) = 0.65, p = 0.01). Higher pre-interventional LiMAx values therefore indicate DC. The bi-serial correlations of LiMAx values pre and post TACE with the outcome OR or DC are descriptively stronger than those of MELD with OR or DC. This suggests that the LiMAx test correlates better with the treatment response than the MELD score. CONCLUSIONS: For the first time, we were able to show in our study that patients who are scheduled for TACE could benefit from a LiMAx test to be able to estimate the benefit of TACE. The higher the pre-interventional LiMAx values, the higher the benefit of TACE. On the other hand, laboratory parameters summarized in the form of the MELD score, had significantly less descriptive correlation with the TACE outcome.

Pharmacokinetics of caffeine: A systematic analysis of reported data for application in metabolic phenotyping and liver function testing

Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages. Caffeine is almost completely metabolized in the liver by the cytochrome P-450 enzyme system mainly to paraxanthine and the additional products theobromine and theophylline. Besides its stimulating properties, two important applications of caffeine are metabolic phenotyping of cytochrome P450 1A2 (CYP1A2) and liver function testing. An open challenge in this context is to identify underlying causes of the large inter-individual variability in caffeine pharmacokinetics. Data is urgently needed to understand and quantify confounding factors such as lifestyle (e.g. smoking), the effects of drug-caffeine interactions (e.g. medication metabolized via CYP1A2), and the effect of disease. Here we report the first integrative and systematic analysis of data on caffeine pharmacokinetics from 147 publications and provide a comprehensive high-quality data set on the pharmacokinetics of caffeine, caffeine metabolites, and their metabolic ratios in human adults. The data set is enriched by meta-data on the characteristics of studied patient cohorts and subjects (e.g. age, body weight, smoking status, health status), the applied interventions (e.g. dosing, substance, route of application), measured pharmacokinetic time-courses, and pharmacokinetic parameters (e.g. clearance, half-life, area under the curve). We demonstrate via multiple applications how the data set can be used to solidify existing knowledge and gain new insights relevant for metabolic phenotyping and liver function testing based on caffeine. Specifically, we analyzed (i) the alteration of caffeine pharmacokinetics with smoking and oral contraceptive use; (ii) drug-drug interactions with caffeine as possible confounding factors of caffeine pharmacokinetics or source of adverse effects; (iii) alteration of caffeine pharmacokinetics in disease; and (iv) the applicability of caffeine as a salivary test substance by comparison of plasma and saliva data. In conclusion, our data set and analyses provide important resources which could enable more accurate caffeine-based metabolic phenotyping and liver function testing.

Pericarditis Caused by Enterococcus faecium with Acute Liver Failure Treated by a Multifaceted Approach including Antimicrobials and Hemoadsorption

Background. Sepsis and septic shock are still life-threatening diseases with a high mortality rate. We report a complex case of peritonitis with pericarditis and acute liver failure caused by septic shock. Potentially hepatotoxic antibiotic therapy levels were monitored using the liver maximum capacity (LiMAx®) test, and standard treatment was supplemented by adjunctive hemoadsorption with CytoSorb®. Case Presentation. The case features a 29-year-old woman with a history of Crohn’s disease and cachexia. Peritonitis caused by Enterococcus faecium was diagnosed later due to an ileum perforation. The hematogenic spread led to pericarditis. In addition, sepsis-related acute liver failure complicated antimicrobial therapy further. The combination of standard therapy, anti-infective medication, and blood purification was associated with inflammation control, hemodynamic stabilization, and a concomitant decrease in vasopressor support. An efficient, sustained reduction in plasma bilirubin levels was achieved while maintaining liver function. Conclusions. This case shows how complex infectious diseases with an atypical infectious focus resulting in septic shock can be successfully treated. A combination of antimicrobial (tigecycline and caspofungin) and long-term adjunctive hemoadsorption therapy was administered while hepatotoxic antibiotic medication was monitored by liver function testing.

Pericarditis caused by Enterococcus faecium with acute liver failure treated by a multifaceted approach including antimicrobials and hemoadsorption

BackgroundSepsis and septic shock are still life-threatening diseases with a high mortality rate. We report a complex case of peritonitis with pericarditis and acute liver failure caused by septic shock. Potentially hepato-toxic antibiotic therapy levels were monitored using the liver maximum capacity (LiMAx®) test and standard treatment was supplemented by adjunctive hemoadsorption with CytoSorb®. Case presentationThe case features a 29-year-old woman with a history of Crohn's disease and cachexia. Peritonitis caused by Enterococcus faecium was diagnosed later due to an ileum perforation. The hematogenic spread led to the pericarditis. In addition, sepsis-related acute-liver-failure complicated antimicrobial therapy further. The combination of standard therapy, anti-infective medication and blood purification was associated with inflammation control, hemodynamic stabilization and a concomitant decrease in vasopressor support. An efficient, sustained reduction in plasma bilirubin levels was achieved while maintaining liver function.ConclusionsThis case shows how complex infectious diseases with an atypical infectious focus resulting in septic shock can be successfully treated. A combination of antimicrobial (tigecycline and caspofungin) and long-term adjunctive hemoadsorption therapy was administered while hepato-toxic antibiotic medication was monitored by liver function testing.

February 2021 Imaging Case of the Month: An Indeterminate Solitary Nodule

No abstract available. Article truncated after first page. Clinical History: A 43 -year-old woman with no past medical history presented to the Emergency Room with complaints of right chest wall pain extending into the right upper quadrant. The patient was a non-smoker, denied any allergies, and was not taking any prescription medications. Physical examination showed the patient to be afebrile with normal heart and respiratory rates and blood pressure = 110/75 mmHg. Her room air oxygen saturation was 99%. The patient’s complete blood count and serum chemistries showed normal values. Her liver function testing and renal function testing parameters were also within normal limits. Which of the following represents an appropriate next step for the patient’s management? 1. Perform abdominal ultrasound 2. Perform chest radiography 3. Perform unenhanced chest CT 4. More than one of the above 5. None of the above …

Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients

Background: Single nucleotide polymorphisms (SNPs) of IL-28B and/or ICAM-1 could have a role in expecting a response from HCV infected patients to direct antiviral agents (DAAs). Objective: The aim of the current study was to investigate the impact of IL-28B rs12979860 and rs8099917, and, ICAM-1 rs281437 SNPs on response to treatment with sofosbuvir + Daclatsvir ± Ribavirin, among HCV-infected Egyptian patients. Methods: Whole blood genomic DNA was extracted from 120 participants (80 HCV-infected patients and 40 healthy volunteers). HCV-infected patients were subdivided into responders and nonresponders to DAAs. Liver function testing, anti-HCV antibodies, HCV-RNA viral load and HCV genotyping were performed. IL-28B and ICAM-1 SNPs were evaluated by real-time PCR. Results: ALT and AST levels were significantly higher among non-responder HCV infected patients (P = 0.001*). 90% of the patients had HCV genotype 4a and the remaining 10% had 4l genotype. Allelic discrimination revealed that IL-28B rs12979860 T, IL-28B rs809917 T and ICAM-1 rs281437 C alleles were more frequent among HCV-infected patients (responders or non-responders) than controls. However, IL-28B rs8099917 G allele was more frequent among healthy controls. Regarding the response to DAAs treatment, HCV-infected patients with IL-28B rs8099917 GG genotype showed a significantly earlier viral response compared to those carrying TT alleles. ICAM-1 rs281437 CT alleles were non significantly more frequent among responders. However, IL-28B rs12979860 alleles did not show any difference. Conclusion: Genotyping of IL-28B rs8099917 is a useful independent tool for expecting a response of Egyptian HCV-infected patients to DAAs.

Intelligent Liver Function Testing: Working Smarter to Improve Patient Outcomes in Liver Disease

Chronic liver disease (CLD) is a significant health problem affecting millions of people worldwide. In Scotland, CLD is a major cause of premature mortality. Liver function tests (LFTs) are a panel of frequently requested blood tests which may indicate liver disease. However, LFTs commonly contain at least one abnormal result, and abnormalities are rarely investigated to the extent recommended by national guidelines. The intelligent Liver Function Testing (iLFT) pathway is a novel, automated system designed to improve early diagnosis of liver disease. Initial abnormal LFT results trigger a cascade of reflexive testing to help identify the cause of any liver dysfunction. Algorithms combine these results with demographic and clinical data (such as patient age, body mass index, and alcohol intake) and fibrosis estimates to produce an electronic diagnosis and management plan. The pilot trial demonstrated that iLFT increased diagnosis of liver disease whilst remaining cost-effective. As such, iLFT has been fully operational across our region (NHS Tayside, Scotland) since August 2018. In the first year, iLFT generated over 2000 diagnoses from 1824 patient samples with an abnormality in the initial LFTs. The majority of these patients could be safely managed in primary care. iLFT allows maximal value to be obtained from liver blood tests across biochemistry, virology, immunology, and hematology with only minor changes to working practices. ‘Intelligent’, algorithm-led testing pathways break down the barrier between clinical and laboratory medicine and offer solutions to many of the challenges experienced in modern healthcare systems.