Browsing by Author "Phillips, Elizabeth"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    A 68-Year-Old Woman With Unexplained Liver Enzyme Elevation and Active Chronic Hepatitis: Beware of Drug-Induced Autoimmune-Like Hepatitis
    (Elsevier, 2023-10-04) Dara, Lily; Ghabril, Marwan; Phillips, Elizabeth; Kleiner, David; Chalasani, Naga; Medicine, School of Medicine
    This patient’s case history (void of protected health information) was discussed in a multidisciplinary meeting including hepatologists (LD, MG), a pathologist (DK), an immunologist (EP) with NC as moderator. We summarize the case history and discussion in the following article.
  • Thumbnail Image
    Item
    Clinical features, outcomes, and HLA risk factors associated with nitrofurantoin-induced liver injury
    (Elsevier, 2023) Chalasani, Naga; Li, Yi-Ju; Dellinger, Andrew; Navarro, Victor; Bonkovsky, Herbert; Fontana, Robert J.; Gu, Jiezhun; Barnhart, Huiman; Phillips, Elizabeth; Lammert, Craig; Schwantes-An, Tae-Hwi; Nicoletti, Paola; Kleiner, David E.; Hoofnagle, Jay H.; Drug Induced Liver Injury Network; Medicine, School of Medicine
    Background & aims: Nitrofurantoin (NTF) is widely used for the treatment (short-term) and prevention (long-term) of urinary tract infections. We aimed to describe the clinical characteristics, outcomes, and HLA risk factors for NTF-induced liver injury (NTF-DILI) among individuals enrolled in the Drug Induced Liver Injury Network (DILIN). Methods: Seventy-eight individuals with definite, highly likely, or probable NTF-DILI were enrolled into DILIN studies between 2004-2020. HLA alleles were compared between NTF-DILI and three control groups: population (n = 14,001), idiopathic autoimmune hepatitis (n = 231), and non-NTF DILI (n = 661). Results: Liver injury was hepatocellular in 69% and icteric in 55%. AST > ALT was more common in the 44 long-exposure (≥1 year) NTF-DILI cases than in the 18 short (≤7 days) and 16 intermediate (>7 to <365 days) exposure cases (73% vs. 33% vs. 50%, respectively, p = 0.018), as was ANA or SMA positivity (91% vs. 44% vs. 50%, respectively, p <0.001), and corticosteroid use (61% vs. 27% vs. 44%, respectively, p = 0.06). In long-term NTF-DILI, bridging fibrosis, nodularity or cirrhosis, or clinical and imaging evidence for cirrhosis were present in 38%, with massive or sub-massive necrosis in 20%. No one in the short-term exposure group died or underwent transplantation, whereas 7 (12%) patients from the other groups died or underwent transplantation. After covariate adjustments, HLA-DRB1∗11:04 was significantly more frequent in NTF-DILI compared to population controls (odds ratio [OR] 4.29, p = 1.15 × 10-4), idiopathic autoimmune hepatitis (OR 11.77, p = 7.76 × 10-5), and non-NTF DILI (OR 3.34, p = 0.003). Conclusion: NTF-DILI can result in parenchymal necrosis, bridging fibrosis, cirrhosis, and death or liver transplantation, especially with long-term exposure, and is associated with HLA-DRB1∗11:04. To mitigate against serious liver injury associated with NTF, regulators should revise the prescribing information and consider other mitigation strategies. Impact and implications: Nitrofurantoin is a recognized cause of drug-induced liver injury (DILI). In this study consisting of a large cohort of well-phenotyped individuals with nitrofurantoin-induced liver injury, two distinct patterns of liver injury were identified: liver injury associated with short-term exposure, which is generally self-limiting, and liver injury associated with long-term exposure, which can lead to advanced fibrosis, cirrhosis and liver failure. HLA DRB1∗11:04 is a risk factor for liver injury due to long-term nitrofurantoin exposure. Our findings are important for regulators as well as physicians prescribing and pharmacists dispensing nitrofurantoin.
  • Thumbnail Image
    Item
    HLA-B*53:01 is a significant risk factor for liver injury due to phenytoin and other anti-epileptic drugs in African Americans
    (Wolters Kluwer, 2024) Nicoletti, Paola; Dellinger, Andrew; Li, Yi-Ju; Barnhart, Huiman; Phillips, Elizabeth; Chalasani, Naga; Drug Induced Liver Injury Network (DILIN) investigators; Medicine, School of Medicine
    Introduction: To investigate human leukocyte antigen alleles associated with liver injury due to antiepileptic drugs (AEDs) in African Americans (AA). Methods: In this study, 21 AA with AED drug-induced liver injury (DILI), 176 AA with DILI due to non-AEDs, and 5816 AA population controls were included. Results: HLA-B*53:01 was significantly associated with aromatic AED-DILI (odds ratio: 4.52, 95% confidence interval: 2.42-8.44, P = 1.46 × 10 -5 ). Phenytoin DILI showed the strongest association with HLA-B*53:01 (odds ratio: 9.17; 95% confidence interval: 3.61-23.28, P = 1.1 × 10 -5 ). The HLA-B*53:01 allele was carried by 8 of 9 AA phenytoin DILI cases. Discussion: HLA-B*53:01 is a significant risk factor of liver injury due to antiepileptics, particularly phenytoin, in AA.
  • Thumbnail Image
    Item
    Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN]
    (Elsevier, 2023) Halegoua-DeMarzio, Dina; Navarro, Victor; Ahmad, Jawad; Avula, Bharathi; Barnhart, Huiman; Barritt, A. Sidney; Bonkovsky, Herbet L.; Fontana, Robert J.; Ghabril, Marwan S.; Hoofnagle, Jay H.; Khan, Ikhlas A.; Kleiner, David E.; Phillips, Elizabeth; Stolz, Andrew; Vuppalanchi, Raj; Medicine, School of Medicine
    Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN). Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069. Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01.