Advances in the management of idiosyncratic drug-induced liver injury.

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Impact of Prior Drug Allergies on the Risk, Clinical Features, and Outcomes of Idiosyncratic Drug-Induced Liver Injury in Adults.

BACKGROUND: Prior drug allergies are common and may increase susceptibility to adverse medication effects. The aim of this study was to compare the frequency, clinical features, and outcomes of DILI among patients with and without a history of prior drug allergy. METHODS: The EMR at a large liver referral center was searched for all DILI encounters using ICD-10 T-codes for drug poisoning/toxicity and K-71 codes for toxic liver injury between 10/1/2015 and 9/30/2019. Clinically significant liver injury was identified using predefined laboratory criteria, and cases were adjudicated using a 5-point expert opinion scale: 1/2/3 = probable DILI and 4/5 = non-DILI. Drug allergy was defined as a history of anaphylaxis, hives, rash, or pruritus after drug exposure. RESULTS: Among 766,930 patient encounters, 127 unique patients met inclusion criteria with 72 (56.7%) cases adjudicated as probable DILI and 55 (43.3%) as non-DILI. In the probable DILI group, the most frequent suspect drug classes were: antimicrobials (41.9%), herbal and dietary supplements (9.5%), and antineoplastics (8.1%). Twenty-three of the 72 DILI patients (31.9%) had a history of drug allergy before the DILI episode compared to 16 (29.1%) of the 55 non-DILI cases (p = 0.89). However, none of the allergy drugs and suspect DILI drugs were the same although many were in the same drug class. DILI patients with a prior drug allergy were more likely to be female (73.9% vs. 44.9%, p = 0.04) and have lower serum bilirubin (4.0 vs. 7.8, p = 0.08) and INR (1.1 vs. 1.6, p = 0.043) levels at presentation. The likelihood of death or liver transplantation among probable DILI cases with prior drug allergy was lower than those without prior drug allergy (0% vs. 8.2%, p = 0.35). The suspect drug was subsequently documented in the "Drug Allergy" section of the EMR in only 23 (31.9%) of the 72 probable DILI patients, and these patients were more likely to present with a rash (7% vs. 2%, p = 0.006) and higher serum bilirubin levels (10.5 vs. 4.7, p = 0.008) compared to those in whom the suspect drug was not listed as "drug allergy." CONCLUSION: A prior drug allergy history was not associated with a greater likelihood of developing DILI compared to other causes of acute liver injury. However, the probable DILI patients with a history of prior drug allergy tended to have less severe liver injury and clinical outcomes. The low rate of suspect drug documentation in the "Drug Allergy" section of EMR after a DILI episode is of concern and could lead to avoidable harm from inadvertent suspect drug re-challenge.

Combining K-72 Hepatic Failure with 15 Individual T-Codes to Identify Patients with Idiosyncratic Drug-Induced Liver Injury in the Electronic Medical Record.

BACKGROUND: The aim of this study was to determine the utility of combining three K72 codes (hepatic failure) with 15 individual T-Codes (drug toxicity/poisoning) to identify potential DILI cases. METHODS: The EMR was searched for encounters that had a K72 code combined with a T-code that also met minimal liver injury laboratory criteria between 10/1/15 and 9/30/18. After manual chart review, a DILIN expert opinion causality score (1-5) was assigned to each case. RESULTS: Among the 345 patient encounters identified, mean age was 57 years, 53% were male, and 89% Caucasian. Thirty-seven cases (10.7%) were adjudicated as probable DILI with antibiotics being the most frequently identified suspect drugs. Of the 308 non-DILI cases, liver injury was most commonly due to congestive hepatopathy (38%) and hepatic metastases (15%). The probable-DILI cases were significantly more likely to have hepatocellular liver injury (57% vs 32.5%, p = 0.01), higher total bilirubin levels (7.7 vs 4.6 mg/dl, p = 0.03), and more severe liver injury scores (p < 0.01). The K72.0 (acute/ subacute hepatic failure) yielded the most DILI cases (29) compared to K72.9 (13) and K72.1 (0). The positive predictive value of the searching algorithm was 10.7% and improved to 15% when using only the K72.0 codes. CONCLUSIONS: K72 codes combined with drug poisoning T-codes had a low positive predictive value in identifying patients with idiosyncratic DILI. These data support further refinement of ICD-10-based algorithms to detect DILI cases in the EMR.

De Novo Inflammatory Bowel Disease Rarely Occurs During Posttransplant Immunosuppression.

OBJECTIVES: De novo chronic idiopathic inflammatory bowel disease (CIIBD) is reported to occur at higher rates in posttransplant patients than that of the general population. The previous reports, however, included patients with primary sclerosing cholangitis (PSC), a known association with CIIBD. Hence, we investigated how often posttransplant de novo CIIBD occurs in the absence of PSC. METHODS: We identified 185 posttransplant adults without a history of PSC or CIIBD, who had undergone colonoscopy between July 2013 and June 2020. Biopsies were reviewed and clinical data were gathered. RESULTS: CIIBD-like colitis accounted for 1.1% (2/185) of our cohort. The 2 affected patients were already taking multiple immunosuppressive therapies. They were initially placed on standard CIIBD maintenance therapy, but then required escalation therapy. One patient had persistent active colitis despite escalation therapy, while the other subsequently had resolution of symptoms and developed quiescent disease. CONCLUSIONS: The incidence of CIIBD-like colitis in our study population was lower than what has been previously described. Both patients had a poor response to standard CIIBD therapy, raising the question whether their diagnosis is truly de novo CIIBD or another immunologic process.

Utility of a Computerized ICD-10 Algorithm to Identify Idiosyncratic Drug-Induced Liver Injury Cases in the Electronic Medical Record.

INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is an important cause of liver injury that is difficult to diagnose and identify in the electronic medical record (EMR). OBJECTIVE: Our objective was to develop a computerized algorithm that can reliably identify DILI cases from the EMR. METHODS: The EMR was searched for all encounters with an International Classification of Diseases, Tenth Revision (ICD-10) T code for drug toxicity and a K-71 code for toxic liver injury between 1 October 2015 and 30 September 2018. Clinically significant liver injury was defined using predetermined laboratory values. An expert opinion causality score (1-3 = probable DILI, 4/5 = non-DILI), Roussel Uclaf Causality Assessment Method (RUCAM) score, and severity score was assigned to each case. RESULTS: Among the 1,211,787 encounters searched, 517 had both an ICD-10 T code and a K-71 code, with 257 patients meeting the laboratory criteria. After excluding 75 cases of acetaminophen hepatotoxicity, the final study sample included 182 cases of potential DILI, with antineoplastics and antibiotics being the most frequently implicated agents. Causality assessment identified probable DILI in 121 patients (66.5%), whereas 61 (33.5%) had an alternative cause of liver injury. Although age, sex, race, and suspect drugs were similar, the probable DILI cases were more likely to present with a hepatocellular injury profile and have more severe liver injury than the non-DILI cases (p < 0.05). CONCLUSION: A computerized algorithm based on a combination of ICD-10 codes identified 182 potential DILI cases with 121 true positives, 61 false positives, and a positive predictive value of 66.5%. Future studies incorporating natural language processing may further improve the utility of this algorithm in identifying high-causality idiosyncratic DILI cases.

Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy.

BACKGROUND: Pembrolizumab immunotherapy has been associated with hepatotoxicity in 1%-10% of oncology patients treated in clinical trials. AIM: To describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumab METHODS: Liver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug-induced liver injury was adjudicated by expert opinion. RESULTS: Seventy (14.3%) of the 491 pembrolizumab-treated patients developed liver injury at a median of 62 days (6-478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver-directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow-up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug-induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow-up. CONCLUSIONS: Oncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow-up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.

Hepatitis C Screening in Commercially Insured U.S. Birth-cohort Patients: Factors Associated with Testing and Effect of an EMR-based Screening Alert.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates. METHODS: All birth-cohort outpatients between 2010 and 2015 were identified. HCV-Ab test results, clinical, and demographic variables were extracted from the EMR, and factors associated with testing were analyzed by logistic regression. True birth-cohort HCV screening rates were determined by detailed chart review for all outpatient visits during one calendar month. An automated Best Practice Alert was used to identify unscreened patients at the point of care, and to prompt HCV testing. Screening rates before and after system-wide implementation of the BPA were compared. RESULTS: The historic HCV-Ab testing rate was 11.2% (11,976/106,753). Younger age, female gender, and African American, Asian, or Hispanic ethnicity, and medical comorbidities such as chronic hemodialysis, HIV infection, and rheumatologic and psychiatric comorbidities were associated with higher testing rates. However, during the one-month sampling period, true age cohort-based testing was performed in only 69/10,089 patients (0.68%). Following the system-wide implementation of the HCV BPA, testing rates increased from 0.68% to 10.76% (P<0.0001). CONCLUSIONS: We documented low HCV-Ab testing rates in our baby boomers population. HCV testing was typically performed in the presence of known risk factors or established liver disease. The implementation of an EMR-based HCV BPA resulted in a marked increase in testing rates. Our study highlights current HCV screening gaps, and the utility of the EMR to improve screening rates and population health.

Racial and ethnic group variations in service use in a national sample of Medicare home health care patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus is known to affect adults in racial and ethnic minority groups disproportionately. When diabetes mellitus-related symptoms lead to the need for skilled care in the community-dwelling Medicare population, physicians can order the Medicare home health care (HHC) benefit, and Medicare-certified home health agencies can deliver it. Little is known about the extent to which racial and ethnic disparities exist in types and patterns of HHC services delivered to Medicare beneficiaries with diabetes mellitus when they are approved for the Medicare HHC benefit. This was examined by comparing racial and ethnic groups in terms of measures of HHC service use in a nationally representative sample of Medicare HHC beneficiaries with a primary diagnosis of type 2 diabetes mellitus. Uniform clinical data from the Outcome and Assessment Information Set were linked with Medicare HHC claims for beneficiaries who received a complete episode of HHC in 2002. In the study sample (n=9,838), 62% of participants self-identified as white, 22% African American, 12% Hispanic, and 3% Asian. Nearly all (99%) participants in all racial and ethnic groups received skilled nursing services. Controlling for numerous sociodemographic and health-related covariates and geographic region of the country, African-American participants received fewer nurse visits per week and fewer visits per week from all clinical disciplines combined than whites (both P<.001), and Hispanic participants were less likely than whites to receive physical therapy (adjusted odds ratio (AOR)=0.640, 95% confidence interval (CI)=0.543-0.754, P<.001) or home health aide (AOR=0.716, 95% CI=0.582-0.880, P=.002) services. Lower use of skilled nursing and rehabilitation services by African Americans and of rehabilitation services by Hispanics warrant further clinical and research attention.