Uclaf Causality Assessment Method Scale Research Articles

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota.

Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism. First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut-liver axis. The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum, which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway. The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Safety of prescribed herbal medicines for hepatic and renal function of polypharmacy patients with stroke: A single-center retrospective study

In Korea, herbal medicines (HMs) are primarily used to treat diseases. Patients with stroke are generally older and take several conventional medicines (CMs) to address other underlying diseases, which is known as polypharmacy. Therefore, there is a growing concern about hepatotoxicity and nephrotoxicity due to drug interactions between HMs and CMs. Therefore, this study retrospectively investigated liver and renal tests in patients with stroke treated with polypharmacy to clarify the safety of simultaneous HM and CM administration. The medical records of 111 patients with stroke treated at a single center and who met the inclusion criteria between March 1, 2017, and March 1, 2022, were reviewed. The HMs and HM prescription frequency, CMs, and liver and kidney test results were recorded. Additionally, the Roussel Uclaf Causality Assessment Method and Kidney Disease Improving Global Outcome scores were documented, which are standard criteria for assessing liver and kidney injury, respectively. The study included 53 men and 58 women (average age: 67.8 years). On average, the patients took 6 types of CMs. No patient showed liver injury during the co-administration of CMs and HMs. Only 1 patient had initial hepatic damage but recovered after taking HMs. Furthermore, 2 patients had liver test abnormalities 2 times the upper limit of normal, possibly from Seogyeong-tang and atorvastatin, with Roussel Uclaf Causality Assessment Method scale scores of 3 and 5, respectively. No patient had a renal injury. HM is safe for patients with stroke taking multiple CMs. However, consulting an HM expert is essential to avoid hepatotoxicity, nephrotoxicity, and other adverse effects. These results highlight the benefits of Korea's dual medical system.

A Multiple Logistic Regression Model Based on Gamma-Glutamyl Transferase as a Biomarker for Early Prediction of Drug-Induced Liver Injury in Vietnamese Patients.

The discovery of new biomarkers and the causality of drug-induced liver injury (DILI) is a major focus in modern medicine. Alcoholism is considered a risk factor for DILI. However, the extraction and assessment of alcohol history are difficult due to noncooperation by patients and intermittent management. Therefore, we conducted a case-control study of 1277 patients diagnosed with DILI according to the Roussel Uclaf Causality Assessment Method scale to evaluate gamma-glutamyl transferase (GGT) as a biomarker for predicting DILI in Vietnamese patients, where the proportion of alcoholism is quite high. Further, we built and validated a logistic regression model to predict the risk of DILI in hospitalized patients. The risk of DILI increased by 10% for 1 UI/L higher levels of GGT before prescription (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.01). A history of alcoholism was not a risk factor for DILI occurrence (OR, 1.83; 95%CI, 0.99-3.04; P = .057). A logistic regression model was successfully built and validated based on age; sex; initial levels of alanine aminotransferase, alkaline phosphatate, GGT, likelihood score of the suspected drug, and history of liver disease; the area under the receiver operating characteristic curve of the model was 0.883 (95%CI, 0.868-0.897). Our results thus suggest the necessity of exercising caution when prescribing to patients without a history of alcoholism but having high GGT levels. This model can be applied clinically to assess the risk of DILI before prescribing to reduce the risk of DILI in the patient.

Research Progress of Pharmacogenomics in Drug-Induced Liver Injury.

Background: Drug-induced liver injury (DILI) is a common and serious adverse drug reaction with insufficient clinical diagnostic strategies and treatment methods. The only clinically well-received method is the Roussel UCLAF Causality Assessment Method scale, which can be applied to both individuals and prospective or retrospective studies. However, in severe cases, patients with DILI still would develop acute liver failure or even death. Pharmacogenomics, a powerful tool to achieve precision medicine, has been used to study the polymorphism of DILI related genes.Summary: We summarized the pathogenesis of DILI and findings on associated genes and variations with DILI, including but not limited to HLA genes, drug metabolizing enzymes, and transporters genes, and pointed out further fields for DILI related pharmacogenomics study to provide references for DILI clinical diagnosis and treatment.Key Messages: At present, most of the studies are mainly limited to CGS and GWAS, and there is still a long way to achieve clinical transformation. DNA methylation could be a new consideration, and ethnic differences and special populations also deserve attention.

Carefully reviewing the history of diagnostic scales and paying more attention to the diagnostic value of Roussel - Uclaf causality assessment method scale for drug - induced liver injury

Currently, the diagnostic criteria for drug-induced liver injury (DILI) used in the clinical studies and related literature in China are very confusing, making it difficult to compare and extend the use of the results, conclusions, and experience of these studies. Therefore, it is necessary to carefully review the developmental history of diagnostic scales and unify the diagnostic criteria and related knowledge of DILI. Since its publication in 1993, Roussel Uclaf Causality Assessment Method (RUCAM) scale has been widely used to assess the causality between drugs and liver injury, both in DILI studies and decisions on the regulation of drugs which may cause liver injury, in order to provide a useful analytical framework for clinical physicians in the diagnosis of DILI. At present, RUCAM scale should still be used to assess causality and assist diagnosis, unless markers with diagnostic significance are found in future.

A detection algorithm for drug‐induced liver injury in medical information databases using the Japanese diagnostic scale and its comparison with the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method scale

Drug-induced liver injury (DILI) is one of the primary targets for pharmacovigilance using medical information databases (MIDs). Because of diagnostic complexity, a standardized method for identifying DILI using MIDs has not yet been established. We applied the Digestive Disease Week Japan 2004 (DDW-J) scale, a Japanese clinical diagnostic criteria for DILI, to a DILI detection algorithm, and compared it with the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale to confirm its consistency. Characteristics of DILI cases identified by the DDW-J algorithm were examined in two Japanese MIDs. Using an MID from the Hamamatsu University Hospital, we constructed a DILI detection algorithm on the basis of the DDW-J scale. We then compared the findings between the DDW-J and CIOMS/RUCAM scales. We examined the characteristics of DILI after antibiotic treatment in the Hamamatsu population and a second population that included data from 124 hospitals, which was derived from an MID from the Medical Data Vision Co., Ltd. We performed a multivariate logistic regression analysis to assess the possible DILI risk factors. The concordance rate was 79.4% between DILI patients identified by the DDW-J and CIOMS/RUCAM; the Spearman rank correlation coefficient was 0.952 (P < 0.0001). Men showed a significantly higher risk for DILI after antibiotic treatments in both MID populations. The DDW-J and CIOMS/RUCAM algorithms were equivalent for identifying the DILI cases, confirming the utility of our DILI detection method using MIDs. This study provides evidence supporting the use of MID analyses to improve pharmacovigilance.

A Case of Acute Pancreatitis and Acute Hepatitis Caused by Ingestion ofCeramium kondoi

In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoifor 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement.

Acute hepatitis associated with the use of levofloxacin

Background: Levofloxacin is a fluoroquinolone used globally to treat respiratory, skin, and genitourinary tract infections. It is generally well tolerated and there is a very low risk for liver injury in patients taking this antibiotic. Objective: We report an acute case of hepatitis following treatment with levofloxacin for pneumonia. Case summary: A 77-year-old white male (height, 162 cm; weight, 58 kg) with chronic bronchitis presented to the emergency department of the Hospital Curry Cabral, Lisbon, Portugal, with respiratory difficulty and productive cough. The patient had a history of chronic bronchitis, arterial hypertension, hypercholesterolemia, and benign prostatic hyperplasia, and was being treated with salmeterol 50 μg plus fluticasone 250 μg BID, and amlodipine 5 mg, simvastatin 20 mg, alfuzosin 10 mg, and finasteride 5 mg once daily. Initially, the patient refused admission and was sent home, medicated with levofloxacin 500 mg once daily (single dose) for pneumonia and acetaminophen 1 g (as needed, maximum TID) if axillary temperature exceeded 38.0°C (100.4°F). Three days later, the patient returned for a follow-up visit, and despite clinical and radiologic improvement, blood tests revealed a slight aggravation of anemia. On the seventh day of treatment with levofloxacin, the patient showed an elevation of transaminases. The temporal relation between the use of levofloxacin and the liver injury, the exclusion of other causes of hepatitis, and a compatible liver biopsy (conducted 14 days after identification of hepatitis) was consistent with the diagnosis of levofloxacin-associated hepatotoxicity. Levofloxacin treatment was stopped and the patient made a full recovery. The Naranjo Adverse Drug Reaction Probability Scale score for this association was “probable” (score 7) and the Roussel Uclaf Causality Assessment Method Scale score was “highly probable” (score 9). Unlike the 5 reported cases in the literature, this is the only case in which both a liver biopsy was performed in the course of the disease and the patient survived. Conclusion: The acute hepatitis observed in this elderly patient was probably associated with the administration of levofloxacin.

Autoimmune Hepatitis Induced by Interferon Beta Therapy in a Patient with Multiple Sclerosis: A Case Report

Objective: To report a case of a woman who had multiple sclerosis and developed autoimmune hepatitis (AIH) induced by interferon beta therapy. Case Summary: A 35–year-old woman with multiple sclerosis was being treated with interferon beta when she presented with fatigue and jaundice. Liver biochemistry testing revealed acute hepatitis (alanine and aspartate aminotransferase values &gt;10 times the upper limit of normal) that was histologically consistent with AIH. Our patient had a score of 9 on the Roussel Uclaf Causality Assessment Method scale, indicating a high probability that hepatotoxicity in this case was related to interferon beta therapy. The patient had spontaneous clinical and biochemical improvement after stoppage of treatment. However, when she resumed interferon beta therapy, derangement of liver function reappeared, which again responded well to discontinuation of interferon. Discussion: Interferons can induce many autoimmune diseases due to their immunomodulatory effects. Autoimmune thyroid diseases and, to a lesser extent, skin and pulmonary involvement, are frequently reported during interferon alfa treatment for chronic hepatitis C. Several different forms of hepatotoxicity have also been described with interferon alfa and beta therapy, but few cases of AIH induced by interferon are reported in the literature. AIH has been described in association with interferon alfa therapy; however, this association with interferon beta therapy is extremely rare, and only a handful of cases have been described. Moreover, reports of previous cases were not rechallenged with the same medication, thereby failing to demonstrate firm evidence of causality. This is the first report of the disease reappearing upon drug rechallenge. In addition, we have shown that interferon-induced AIH can be suitably treated by drug withdrawal rather than by institution of steroid therapy. Conclusions: Practitioners need to be aware of the potential complication of AIH induced by interferon beta; this condition occurs independently of the typically benign enzyme elevations frequently reported with this drug.

Fatal acute hepatitis after sequential treatment with levofloxacin, doxycycline, and naproxen in a patient presenting with acute Mycoplasma pneumoniae infection

Background: The diagnosis of drug-induced liver injury relies on comprehensive clinical assessments due to the absence of an established biomarker or pathognomonic features of liver histology. However, prompt recognition of a culprit drug as the cause of liver injury is the most important aspect in the management of hepatotoxicity. Case summary: A 63-year-old white male (85 kg) was admitted because of community-acquired pneumonia with associated pericarditis and subclinical hepatitis, subsequently related to acute Mycoplasma pneumoniae infection (diagnostic positive immuno-globulin M enzyme immunoassay, on hospital days 5 and 20). The patient had received cisplatin and radiotherapy from March to May 2006, as treatment for pharyngolaryngeal squamous cell carcinoma T3N0M0 without subsequent evidence of localized or meta-static recurrent disease (last oncologic consultation, May 17, 2007). He reported alcohol ingestion until March 2006 but no known liver disease, blood transfusion, or exposure to mushrooms or industrial cleaning solvents. Results of serologic tests for viral and nonviral infectious hepatitis, iron and copper studies, and tests for autoantibodies were normal or negative. The patient became initially asymptomatic and fever disappeared following sequential treatment with levo-floxacin (500 mg BID), doxycycline (100 mg BID), and naproxen (500 mg TID). However, on hospital day 10 jaundice and a significant elevation (alanine aminotransferase, 1577 U/L; aspartate amino-transferase, 1754 U/L; alkaline phosphatase, 189 U/L) of serum transaminases appeared. Despite the discontinuation of all medication, the patient gradually deteriorated and died 27 days after admission due to acute fulminant hepatic failure. Autopsy revealed massive hepatic necrosis, inflammatory changes with presence of eosinophils, and cholestasis. An objective causality assessment scale (Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale) suggested that each of the 3 drugs could “probably” (score = 6) be related to the patient's fulminant hepatitis. The Naranjo Adverse Drug Reactions Probability Scale assessment for the same drugs indicated a “possible” causal relation (score = 2). Conclusion: We report a case of lethal hepatitis possibly/probably associated with levofloxacin, doxy-cycline, and naproxen in a patient with acute M pneumoniae infection.

Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug‐induced liver injury

Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (kappa(w)) test. A total of 249 ratings were generated. Between-observer agreement was 45% with a kappa(w) value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, kappa(w): 0.71). Concordance between the two scales was 24% (kappa(w): 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.