scholarly journals Phenytoin-induced chronic liver enzyme elevation and hepatic fibrosis: A case report

2018 ◽  
Vol 8 (4) ◽  
pp. 184-187 ◽  
Author(s):  
Brent Curry ◽  
Lisa Mican ◽  
Tawny L. Smith

Abstract Background: Liver fibrosis results from chronic damage to the liver. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and may even require liver transplantation. A liver biopsy is considered the “gold standard” method for the assessment of liver fibrosis; however, ultrasonography can also detect changes in the hepatic parenchyma due to fibrosis. Although reports in the literature describe phenytoin-induced hepatic injury, often this rare occurrence is usually accompanied by a hypersensitivity reaction. Case report: Our patient is a 50-year-old female with history of schizoaffective disorder, bipolar type, who had been admitted to a state psychiatric facility. She has a history of seizure disorder, which had been well controlled with phenytoin since 2011. Mild-to-moderate elevations in her liver enzymes were noted during therapy but normalized once phenytoin was discontinued. An ultrasound of the patient's liver in January 2016 showed changes of fatty infiltration and fibrosis. Conclusion: This case differs from other cases reported in the literature that describe phenytoin-induced hepatic injury. The majority of these cases are accompanied by immune-allergic features. To our knowledge, there have been no reported cases in the literature of prolonged liver enzyme elevation resulting in phenytoin-induced hepatic fibrosis.

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253070
Author(s):  
Morven Cunningham ◽  
Marco Iafolla ◽  
Yada Kanjanapan ◽  
Orlando Cerocchi ◽  
Marcus Butler ◽  
...  

Background and aims Immune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management. Methods Patients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed. Results Of 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145–324 for immunotoxicity, N = 103; M = 74, 95% CI 59–92 for other causes; ratio of means 0.34, 95% CI 0.19–0.60, p = <0.001) and higher ALT:AST ratio (M = 1.27, 95% CI 0.78–2.06 for immunotoxicity, M = 0.69, 95% CI 0.59–0.80 for other causes, ratio of means 0.54, 95% CI 0.36–0.82, p = 0.004). Immunotoxicity was more often seen in patients with prior CPI exposure (41.2% of immunotoxicity vs 15.9% of patients without, p = 0.01), anti-CTLA-4 –containing ICI treatments (29.4% of immunotoxicity vs 6.8% of patients without, p = <0.001) and other organ immunotoxicity (76.5% of immunotoxicity vs 19.2% of patients without, p = <0.001). Cause for enzyme elevation was established in most patients after non-invasive investigation. Liver biopsy was reserved for four patients with atypical treatment response. Conclusions Liver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure.


2020 ◽  
Vol 32 (11) ◽  
pp. 1466-1469 ◽  
Author(s):  
Ben L. Da ◽  
Robert A. Mitchell ◽  
Brian T. Lee ◽  
Ponni Perumalswami ◽  
Gene Y. Im ◽  
...  

2012 ◽  
Vol 102 (3) ◽  
pp. e107-e113 ◽  
Author(s):  
Leyla Akın ◽  
Selim Kurtoglu ◽  
Ali Yikilmaz ◽  
Mustafa Kendirci ◽  
Ferhan Elmalı ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10013-10013 ◽  
Author(s):  
Ruth Lydia Ladenstein ◽  
Ulrike Poetschger ◽  
Dominique Valteau-Couanet ◽  
Juliet Gray ◽  
Roberto Luksch ◽  
...  

10013 Background: We tested dose-reduced scIL2 in combination with DB-LTI and oral isotretinoin and evaluated toxicity and efficacy in high-risk neuroblastoma patients (EudraCT:2006-001489-17). Methods: High-risk patients (stage 4 ≥1y; stage 4 < 1y with MYCN amplification (MNA); stage 2, 3, 0-21y with MNA) received high intensity induction (rapid COJEC or N5-MSKC and TVD for insufficient response), surgery, high dose therapy with busulfan/melphalan and local radiotherapy. Patients ≤9 months between diagnosis and HDT/SCT who achieved at least a partial response prior to HDT/SCT and without progression thereafter were randomized to receive up to 5 cycles of 100mg/m2 DB-LTI (d8-17) ± 3x106 IU/m2 scIL2 (d1-5; d8, d10, d12, d14, d16) and 160mg/m2 oral isotretinoin (d19-32). Results: Between 04/2014 and 06/2018, 408 patients from 18 countries were randomized. Median follow-up is 1.8 years. Stage, age, MNA, induction treatments and remission status were well balanced between randomization arms. The 2yrs-EFS and -OS for DB-LTI (205 pts) vs. DB-LTI&scIL2 (203 pts) was 64%±4%vs63%±5% (p = 0.844) and 83%±3%vs74%±4% (p = 0.337). For patients in CR the 2yrs-EFS was 69%±5% for DB and 66%±6% for DB&scIL2. Patients with evaluable disease prior DB or DB&scIL2, the end of treatment response rate was 57% (26% CR, 31% PR) vs 52% (27% CR, 25% PR) with 2yrs-EFS rates of 58%±7% and 64% ±8%, respectively. Grade 3&4 toxicity was lower in the group with DB vs DB&scIL2 for fever (14%vs31%, p < 0.001) and pain (7%vs18%, p = 0.005), and no significant difference was seen for general condition (17%vs22%,ns), allergy (3%vs3%,ns), capillary leak (4%vs8%,ns), liver enzyme elevation (20%vs27%, ns) and neurological toxicities (2%vs2%,ns). Conclusions: We previously reported grade 3&4 toxicity to DB short-term infusion (STI) ± 10x6x106IU/m2 scIL2 for general condition (16%vs41%, p = 0.000), fever (14%vs40%, p = 0.000), allergic reaction (10%vs20%, p = p = 0.006), capillary leak (4%vs15%, p = 0.004), liver enzyme elevation (17%vs23%, ns), central neurotoxicity (3%vs8%, p = 0.034) and pain (16%vs26%, p = 0.048). Our results indicate that DB-LTI and dose-reduced scIL2 clearly reduced the toxicity profile, but showed absence of benefits of scIL2. DB-LTI achieved 2yrs-EFS in line with DB-STI (Ladenstein, Lancet Oncology 2018; Yu, NEJM, 2010) and a response rate > 50% supporting its use as standard of care IT. Clinical trial information: EudraCT:2006-001489-17.


HIV Medicine ◽  
2004 ◽  
Vol 5 (5) ◽  
pp. 334-343 ◽  
Author(s):  
P Meraviglia ◽  
M Schiavini ◽  
A Castagna ◽  
P Vigano ◽  
T Bini ◽  
...  

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