A gene expression profile-based approach to screen the occurrence and predisposed host characteristics of drug-induced liver injury: a case study of Psoralea corylifolia Linn.

Liver Injury Associated With Drugs and Complementary and Alternative Medicines in India

Objective To explore the clinical and pathological features of drug-induced liver injury (DILI) due to non-steroidal anti-inflammatory drugs (NSAIDs). Methods The medical records of patients with discharged diagnosis of drug-induced liver injury, which were searched from the Hospital Information System of Shijiazhuang Fifth Hospital from January 1, 2013 to December 31, 2016, were collected and analyzed retrospectively. The patients with DILI due to NSAIDs were enrolled into the NSAIDs group and the patients with DILI due to other drugs were enrolled into the control group. The general conditions, results of laboratory tests, and detection results of liver histopathology in patients in the 2 groups were recorded. The score of Roussel Uclaf Causality Assessment Method (RUCAM), clinical type and classification, pathological type and classification, and clinical outcome evaluation of the DILI patients in the 2 groups were performed according to the relevant standards by the members of research team. Results A total of 385 patients were enrolled into the study, including 63 cases in the NSAIDs group and 322 cases in the control group. The differences of sexual distinction, age, and clinical manifestation were not statistically significant (P>0.05 for all). The results of types and severity classification of DILI based on R value showed that the differences of the proportion of patients with different DILI types and classifications between the 2 groups were not statistically significant (P>0.05 for all). Forty-one and 142 patients underwent liver biopsy in the NSNIDs group and the control group, respectively. The results of liver biopsy showed that the proportion of patients with type of vascular injury in the NSAIDs group was significantly higher than that in the control group [4.9% (2/41) vs. 0 (0/142), χ2=7.003, P=0.049]; the incidences of inflammation in the portal area and proliferation of bile duct in the NSAIDs group were statistically lower than those in the control group [(63.4%(26/41) vs. 93.7%(133/142), χ2=25.544, P 0.05]. There were no death in both groups. Conclusions The clinical manifestations and clinical outcomes of patients with DILI due to NSAIDs were similar to those due to other drugs. The pathological characteristics of liver were that the incidence of inflammation and proliferation of bile duct in the portal area was lower than that of other drugs, and the incidence of hepatocyte steatosis was higher than that of other drugs. Vascular injury was also observed. Key words: Chemical and drug induced liver injury; Anti-inflammatory agents, non-steroidal; Pathology, clinical

Drug induced liver injury and its relationship to autoimmune hepatitis

This Month in Gastroenterology

It can be difficult to distinguish between drug-induced liver injury (DILI) and liver injury associated with sepsis (sepsis induced liver injury, SILI). The aims of the study were to compare clinical and biochemical features between DILI and SILI and identify distinguishing characteristics that might assist in diagnosing these conditions. Retrospective cohorts of all DILI cases diagnosed in Iceland 2009-2024 and SILI 2006-2024 were divided into hepatocellular and cholestatic (CS/mixed) patterns. Patients had: > 5× upper limit of normal (ULN) of ALT and/or > 2× ULN in ALP. RUCAM and expert opinion were used in the causality assessment of DILI, and SILI patients had to fulfil international consensus criteria. Overall 275 DILI patients (median age 59 years, 63% females), 153 with SILI (67 years, 49% females) were included. Among patients with HC type, 57% with SILI and only one (0.9%) with DILI had normal liver tests 2 weeks after the event. The peak value of AST was 1794 (IQR 931-3526) IU/L in HC type of SILI but 584 (315-1013) IU/L in DILI, p < 0.001. CS/mixed type of SILI resolved also significantly faster while CS/mixed pattern of DILI had significantly higher ALP at onset and peak ALT than SILI. SILI had 30% mortality compared to DILI (2%) p < 0.001. Marked elevation of AST and rapid resolution with a HC pattern of liver injury favours the diagnosis of SILI. Cholestatic/mixed SILI also resolves rapidly in contrast to CS/mixed DILI that is associated with markers of more pronounced liver injury.

Objective To analyze the characteristics of drug-induced liver injury (DILI) in children with acute lymphoblastic leukemia (ALL), so as to improve the physician′s understanding of chemotherapy DILI, and to guide clinical rational drug use. Methods One hundred and forty-three cases with ALL diagnosed in the Department of Hematology and Oncology in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2016 were analyzed retrospectively.Based on DILI diagnostic criteria and the RUCAM scale, the cases with a score of ≥3 points were considered to have chemotherapy DILI.Grouped by gender, age, immunotyping, risk and stage of chemo-therapy, the incidence of DILI was compared.The situation after DILI prevention was compared between two groups which was grouped according to whether the application of hepatoprotective drugs. Results One hundred and eight cases (75.52%) had DILI, 66 cases (61.11%) showed clinical manifestations of liver injury, and 42 cases (38.89%) had no clinical symptoms.Among all the cases 57.41%(62 cases) were mild liver damage, 25%(27 cases) were moderate liver injury and 17.59%(19 cases) were severe liver damage.The clinical types which were hepatocellular accounting for 79.63%(86 cases), cholestatic 7.41%(8 cases) and mixed 12.96%(14 cases). Male were 80 cases (79.21%) and female 28 cases(66.67%), but the incidence of DILI between different gender group had no statistical difference (χ2=2.524, P=0.112). Seventy-five cases(77.32%) were 8 points accounted for 21 cases(19.45%), 6-8 points accounted for 59 cases(54.63%)and 3-5 points accounted for 28 cases(25.92%). Eighty-nine patients (92.71%) were effective in the hepatoprotective group and 8 patients (66.67%) in the no hepatoprotective therapy group.The difference between the 2 groups was statistically significant (χ2=5.317, P=0.021). Conclusions The clinical symptoms of drug-induced liver injury in children with ALL chemotherapy are lack of specificity.They are mainly characterized by mild liver injury.The clinical type of hepatic injury is common in hepatocellular.The RUCAM score was mostly 6 to 8.There is no relationship between the incidence in ALL and gender, age, type of leukemia.The incidence with moderate risk type is higher than that of the standard and high-risk type.The incidence in induction remission stage is highest.Application of hepatoprotective drugs is beneficial to DILI prognosis. Key words: Child; Acute lymphoblastic leukemia; RUCAM scale; Chemotherapy; Drug-induced liver injury

Idiosyncratic drug-induced liver injury (DILI) can be caused by intravenous (IV) medications, but the characteristics of DILI caused by these agents are not known. The aim of this study is to characterize the clinical features of subjects with suspected DILI associated with IV agents enrolled into the Drug Induced Liver Injury Network Prospective Study. Subjects with suspected DILI due to IV medications with probable, highly likely, or definite casuality scores were eligible. Between 2004 and October 2010, 542 cases of DILI were adjudicated for causality, of which 32 were eligible for inclusion in this study. DILI was ascribed to a single IV agent in 27 subjects, and to multiple IV agents in 5 subjects. Antimicrobial agents (62%), antineoplastic agents (16%), and phenytoin (9%) were most commonly implicated. The pattern of liver injury was hepatocellular in 30%, mixed in 33%, and cholestatic in 37%. The peak alanine aminotransferase (ALT), alkaline phosphatase (AlkP), and total bilirubin were 686 ± 915 U/L, 623 ± 563 U/L, and 8.7 ± 10.3 mg/dL, respectively. The duration for ≥ 50% improvement from peak ALT, AlkP, and total bilirubin were 25 ± 37, 59 ± 69, and 20 ± 28 days, respectively. DILI severity was mild in 37%, moderate in 47%, severe in 13%, and fatal in 3%, with no liver transplantation. Their causality was adjudicated as definite in 5, very likely in 17, and probable in 10 subjects. The frequency of chronic DILI was 13%. Antimicrobial and antineoplastic agents are the most common IV agents to cause DILI. DILI ascribed to IV agents is relatively infrequent, but its outcomes are similar to those of the overall Drug Induced Liver Injury Network cohort.

Pediatric oncology patients are at risk of adverse drug events. The incidence and etiologies of liver injury in this population are not well characterized. We utilized a large, single-center pediatric oncology registry to investigate the incidence, causes, and outcomes of liver injury during treatment for solid tumor malignancies. We reviewed all young individuals (age <25 years) who received treatment for any solid tumor at the University of Michigan between January 2004 and July 2016. Subjects with liver injury meeting predetermined laboratory criteria were identified. Cases were independently reviewed by 2 expert hepatologists to assign a cause of liver injury. Clinical characteristics of drug-induced liver injury (DILI) and non-DILI cases were compared. Cases of liver injury occurring after bone marrow or liver transplant were excluded. Of 1136 solid tumor patients, 160 (14%) experienced liver injury, and the overall frequency of DILI was 4%. DILI was the leading identified cause of liver injury (31%), followed by infection (17%), metastatic/malignant biliary disease (13%), and perioperative liver injury (13%). Most DILI cases (>90%) were mild acute hepatocellular injury episodes that did not result in modification to the chemotherapy plan, and all DILI eventually resolved. Severe presentations involving jaundice and/or prolonged hospital course were significantly more common among non-DILI versus DILI cases (23% vs 2%, P < 0.001). DILI is the leading cause of liver injury events among pediatric solid tumor patients. In our registry, DILI was of mild severity and did not result in an alteration of the treatment plan in most patients. In contrast, non-DILI-related liver injury events, including infection, were more likely to have a more severe presentation and a complicated course with a greater mortality during follow-up.

ObjectiveTo use Gene Expression Omnibus (GEO) database coupled with Connectivity Map (CMap) databases to screen potential therapeutic drugs for osteonecrosis of femoral head (ONFH) rapidly.MethodsRaw genetic data with accession number GSE74089 that contained eight hip articular cartilage specimens from four ONFH patients and four healthy controls were obtained from the Gene Expression Omnibus (GEO) database and were then integrated using R to identify differentially expressed genes (DEGs). Subsequently, to identify several potential small molecular compounds that were most strongly negatively correlated with ONFH, a search query of DEGs was explored by using CMap.ResultsFiltering revealed 1937 DEGs with log (fold‐change) ≥1 and adjust P value < 0.001. Finally, a network of candidate targets for ONFH with 135 nodes and 660 edges was constructed through network topology analysis, including 96 up‐regulated genes and 39 down‐regulated genes. Several significant gene functions and signaling pathways associated with pathological processes of ONFH were identified via gene enrichment analysis. Based on the CMap database, some potential small molecular components that may be possible to counteract the effects of molecular signal imbalance for ONFH were identified. Neostigmine bromide with low CMap score and P value and specificity score was predicted to be the most candidate compound, involved in the “positive regulation of stem cell proliferation,” “regulation of protein autophosphorylation,” “VEGF signaling pathway,” and “ECM‐receptor interaction.”ConclusionsThe GEO and CMap databases can be effectively used in understanding the molecular changes in ONFH and provide a systematic manner to identify potential drugs for ONFH prevention and treatment. However, additional clinical and experimental research of the candidate compound is warranted.

FMO3 exacerbates hepatic endoplasmic reticulum stress in drug-induced liver injury by inhibiting CREB3/P4HB axis and activating TMAO-mediated PERK pathway.

EVALUATION OF DRUG-INDUCED LIVER INJURY BASED ON EHR AT THREE UNIVERSITY HOSPITAL IN KOREA

The Benevolent Bile: Bile Acids as Stimulants of Liver Regeneration

Causality assessment methods in drug induced liver injury: Strengths and weaknesses

Liver Injury Following Tinospora Cordifolia Consumption: Drug-Induced AIH, or de novo AIH?

Drug-Induced Liver Injury, Dosage, and Drug Disposition: Is Idiosyncrasy Really Unpredictable?