Decreased Hepatic Functional Reserve Increases the Risk of Piperacillin/Tazobactam-Induced Abnormal Liver Enzyme Levels: A Retrospective Case-Control Study.

BACKGROUND: Piperacillin/tazobactam (PIPC/TAZ), which is a combination of a beta-lactam/beta-lactamase inhibitor, often causes liver enzyme abnormalities. The albumin-bilirubin (ALBI) score is a simple index that uses the serum albumin and total bilirubin levels for estimating hepatic functional reserve. Although patients with low hepatic reserve may be at high risk for drug-induced liver enzyme abnormalities, the relationship between PIPC/TAZ-induced abnormal liver enzymes levels and the ALBI score remains unknown. OBJECTIVE: This study aimed to elucidate the relationship between PIPC/TAZ-induced abnormal liver enzyme levels and the ALBI score. METHODS: This single-center retrospective case-control study included 335 patients. The primary outcome was PIPC/TAZ-induced abnormal liver enzyme levels. We performed COX regression analysis with male gender, age (≥75 years), alanine aminotransferase level (≥20 IU/L), and ALBI score (≥-2.00) as explanatory factors. To investigate the influence of the ALBI score on the development of abnormal liver enzyme levels, 1:1 propensity score matching between the ≤-2.00 and ≥-2.00 ALBI score groups was performed using the risk factors for drug-induced abnormal liver enzyme levels. RESULTS: The incidence of abnormal liver enzyme levels was 14.0% (47/335). COX regression analysis revealed that an ALBI score ≥-2.00 was an independent risk factor for PIPC/TAZ-induced abnormal liver enzyme levels (adjusted hazard ratio: 3.08, 95% coefficient interval: 1.207-7.835, P = 0.019). After 1:1 propensity score matching, the Kaplan-Meier curve revealed that the cumulative risk for PIPC/TAZ-induced abnormal liver enzyme levels was significantly higher in the ALBI score ≥-2.00 group (n = 76) than in the <-2.00 group (n = 76) (P = 0.033). CONCLUSION AND RELEVANCE: An ALBI score ≥-2.00 may predict the development of PIPC/TAZ-induced abnormal liver enzyme levels. Therefore, frequent monitoring of liver enzymes should be conducted to minimize the risk of severe PIPC/TAZ-induced abnormal liver enzyme levels in patients with low hepatic functional reserve.

Effect of Ceftriaxone Dosage and Albumin-Bilirubin Score on the Risk of Ceftriaxone-Induced Liver Injury.

The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve and is calculated from serum albumin and total bilirubin levels. However, the relationship between ceftriaxone (CTRX)-induced liver injury and ALBI score remains unknown. Therefore, we aimed to elucidate the risk of CTRX-induced liver injury based on the ALBI scores and CTRX dosage. This was a single-center, retrospective, case-control study of 490 patients and the primary outcome was CTRX-induced liver injury. We performed a COX regression analysis using age ≥75 years, male sex, alanine aminotransferase levels, ALBI score, and CTRX dosage regimen (4 ≥2 or 1 g/d) as explanatory factors. We also performed 1 : 1 propensity score matching between non-liver injury and liver injury groups. The incidence of liver injury was 10.0% (49/490). In COX regression analysis, CTRX 4 g/d was an independent risk factor for liver injury (95% coefficient interval: 1.05-6.96, p = 0.04). Meanwhile, ALBI score ≥-1.61 was an independent factor for liver injury (95% coefficient interval: 1.03-3.22, p = 0.04) with the explanatory factor of ≥2 and 1 g/d. The Kaplan-Meier curve indicated that the cumulative risk for CTRX-induced liver injury was significantly higher in the ALBI score ≥-1.61 group than in the ALBI score <-1.61 group before propensity score matching (p = 0.032); however, no significant differences were observed after propensity score matching (p = 0.791). These findings suggest that in patients treated with CTRX with ALBI score ≥-1.61, frequent liver function monitoring should be considered.

Risk evaluation of ampicillin/sulbactam-induced liver injury based on albumin-bilirubin score.

BACKGROUND: Drug-induced liver injury (DILI) is an adverse reaction caused by ampicillin/sulbactam (ABPC/SBT). The albumin-bilirubin (ALBI) score is an index of hepatic functional reserve. However, the relationship between ABPC/SBT-induced DILI and ALBI score remains unknown; therefore, we aimed to elucidate the risk of ABPC/SBT-induced DILI based on the ALBI score. METHODS: This was a single-center, retrospective, case-control study using electronic medical records. A total of 380 patients were enrolled in the present study, and the primary outcome was ABPC/SBT-induced DILI. The ALBI score was calculated using serum albumin and total bilirubin levels. In addition, we performed COX regression analysis using age ≥75 years, dose ≥9 g/day, alanine aminotransferase (ALT) ≥21 IU/L, and ALBI score ≥-2.00 as covariates. We also performed 1:1 propensity score matching between non-DILI and DILI groups. RESULTS: The incidence of DILI was 9.5% (36/380). According to COX regression analysis, the adjusted hazard ratio for ABPC/SBT-induced DILI with an ALBI score ≥-2.00 was 2.55 (95% confidence interval: 1.256-5.191, P = 0.010), suggesting that patients with baseline ALBI score ≥-2.00 may be at high risk for ABPC/SBT-induced DILI. However, significant differences were not observed in cumulative risk for DILI between non-DILI and DILI patients regarding an ALBI score ≥-2.00 after propensity score matching (P = 0.146). CONCLUSION: These findings suggest that ALBI score may be a simple and potentially useful index for predicting ABPC/SBT-induced DILI. In patients with an ALBI score ≥-2.00, frequent liver function monitoring should be considered to prevent ABPC/SBT-induced DILI.

Risk evaluation of carbapenem-induced liver injury based on machine learning analysis.

INTRODUCTION: Information regarding carbapenem-induced liver injury is limited, and the rate of liver injury caused by meropenem (MEPM) and doripenem (DRPM) remains unknown. Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of liver injury. Thus, we aimed to compare the rate of liver injury between MEPM and DRPM and construct a flowchart that can be used to predict carbapenem-induced liver injury. METHODS: We investigated patients treated with MEPM (n = 310) or DRPM (n = 320) and confirmed liver injury as the primary outcome. We used a chi-square automatic interaction detection algorithm to construct DT models. The dependent variable was set as liver injury from a carbapenem (MEPM or DRPM), and factors including alanine aminotransferase (ALT), albumin-bilirubin (ALBI) score, and concomitant use of acetaminophen were used as explanatory variables. RESULTS: The rates of liver injury were 22.9% (71/310) and 17.5% (56/320) in the MEPM and DRPM groups, respectively; no significant differences in the rate were observed (95% confidence interval: 0.710-1.017). Although the DT model of MEPM could not be constructed, DT analysis showed that the incidence of introducing DRPM in patients with ALT >22 IU/L and ALBI scores > -1.87 might be high-risk. CONCLUSIONS: The risk of developing liver injury did not differ significantly between the MEPM and DRPM groups. Since ALT and ALBI score are evaluated in clinical settings, this DT model is convenient and potentially useful for medical staff in assessing liver injury before DRPM administration.

Toxic Advanced Glycation End-Products-Dependent Alzheimer's Disease- Like Alternation in the Microtubule System.

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's Disease (AD). However, the detailed mechanism underlying T2DM-related AD remains unknown. In DM, many types of advanced glycation end-products (AGEs) are formed and accumulated. In our previous study, we demonstrated that Glyceraldehyde (GA)-derived Toxic Advanced Glycation End-products (Toxic AGEs, TAGE) strongly showed cytotoxicity against neurons and induced similar alterations to those observed in AD. Further, GA induced dysfunctional neurite outgrowth via TAGE-ß-- tubulin aggregation, which resulted in the TAGE-dependent abnormal aggregation of ß-tubulin and tau phosphorylation. Herein, we provide a perspective on the possibility that T2DM increases the probability of AD onset and accelerates its progression.

Pyridoxamine and Aminoguanidine Attenuate the Abnormal Aggregation of ß-Tubulin and Suppression of Neurite Outgrowth by Glyceraldehyde-Derived Toxic Advanced Glycation End-Products.

Diabetes mellitus (DM) has been identified as a risk factor for the onset and progression of Alzheimer's disease (AD). In our previous study, we demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (toxic AGEs, TAGE) induced similar alterations to those observed in AD. GA induced dysfunctional neurite outgrowth via TAGE-ß-tubulin aggregation, which resulted in the TAGE-dependent abnormal aggregation of ß-tubulin and tau phosphorylation in human neuroblastoma SH-SY5Y cells. However, the effects of inhibitors of AGE formation on dysfunctional neurite outgrowth caused by GA-induced abnormalities in the aggregation of ß-tubulin and tau phosphorylation remain unknown. Aminoguanidine (AG), an AGE inhibitor, and pyridoxamine (PM), a natural form of vitamin B6 (VB6), are effective AGE inhibitors. Therefore, the present study investigated whether AG or PM ameliorate TAGE-ß-tubulin aggregation and the suppression of neurite outgrowth by GA. The results obtained showed that AG and PM inhibited the formation of TAGE-ß-tubulin, mitigated the GA-induced suppression of neurite outgrowth, and reduced GA-mediated increases in tau phosphorylation levels. Collectively, these results suggest the potential of AG and PM to prevent the DM-associated onset and progression of AD.