Imatinib and liver toxicity

Imatinib is a specific tyrosine kinase inhibitor which has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia and c-KIT (CD117)-positive gastrointestinal stromal tumours. It has been associated with hepatotoxicity ranging from abnormal liver function tests to acute liver failure along with chronic hepatitis B reactivation. We report the case of a patient who was started on adjuvant treatment with imatinib following resection of a primary gastrointestinal stromal cell tumour of jejunum and developed severe hepatotoxicity. There was no history of risk factors for liver disease, and a search for the underlying causes of hepatotoxicity was unremarkable. Imatinib was stopped and she was treated with steroids which resulted in dramatic improvement of liver function tests. Liver biopsy in this case was not performed because liver function tests improved following discontinuation of imatinib and treatment with steroids. Repeat imaging did not reveal any evidence of tumour recurrence.

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Hepatic Safety of Itraconazole

Journal of Cutaneous Medicine and Surgery ◽

10.1177/120347540200600302 ◽

2002 ◽

Vol 6 (3) ◽

pp. 210-213 ◽

Cited By ~ 9

Author(s):

Aditya K. Gupta ◽

Elisabeth Chwetzoff ◽

James Del Rosso ◽

Robert Baran

Keyword(s):

Liver Function ◽

Fungal Infections ◽

Package Insert ◽

Liver Function Tests ◽

Pulse Therapy ◽

Continuous Therapy ◽

Function Tests ◽

Published Report ◽

History Of ◽

Observation Period

Background: As the use of the newer oral antifungal agents for the treatment of superficial fungal infections becomes more widespread, the issue of safety surrounding their use is becoming an increasingly important consideration. Itraconazole is effective and well tolerated, with most side effects being minor and reversible. The most common adverse events are gastrointestinal upset, headache, and transient skin reaction. There have also been rare reports of hepatitis. Objective: To assess the hepatic safety of pulse and continuous itraconazole in the treatment of onychomycosis. Methods: An analysis was performed on all itraconazole clinical trials sponsored by Janssen Research Foundation in the treatment of onychomycosis, where there was an assessment of laboratory safety. A review of the published literature was also undertaken to assess the hepatic safety of itraconazole in common practice. Results: The data indicate that itraconazole pulse treatment is safe, with no significant differences in the number of code 4 abnormalities (baseline value is in the normal range and at least two values, or the last testing in the observation period, exceed twice the upper limit of normal) in the liver function parameters studied: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. The incidence of all the code 4 abnormalities was below 2%. In the literature there are reports of symptomatic hepatitis with itraconazole continuous therapy but no published report of symptomatic hepatotoxicity using the pulse regimen. Conclusions: Itraconazole pulse therapy for onychomycosis appears to be safe, especially from the perspective of potential liver damage. In the itraconazole package insert liver function tests are recommended for patients receiving continuous itraconazole for periods of time exceeding 1 month. There is no such monitoring requirement for the pulse regimen unless the patient has a history of underlying hepatic disease, the liver function tests are abnormal at baseline, or at any time that there is the development of signs or symptoms suggestive of liver dysfunction.

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Sclerosing cholangitis in a patient treated with nivolumab

BMJ Case Reports ◽

10.1136/bcr-2021-241700 ◽

2021 ◽

Vol 14 (5) ◽

pp. e241700

Author(s):

Sam Talbot ◽

Vivienne MacLaren ◽

Heather Lafferty

Keyword(s):

Liver Function ◽

Sclerosing Cholangitis ◽

Biliary Tree ◽

Liver Function Tests ◽

High Dose ◽

Mr Cholangiopancreatography ◽

Small Cell Lung ◽

Function Tests ◽

Stage 4 ◽

History Of

A 69-year-old retired miner with stage 4 non-small-cell lung cancer presented with a 2-month history of obstructive liver function tests following nivolumab immunotherapy. His case had not responded to high dose prednisolone or mycophenolate and he was admitted for investigation. MR cholangiopancreatography demonstrated areas of intrahepatic biliary tree beading and stricturing, in keeping with sclerosing cholangitis. Prednisolone and mycophenolate were stopped and ursodeoxycholic acid commenced with subsequent partial improvement of the patient’s liver function tests.

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Clinical and Laboratory Findings of Lead Hepatotoxicity in the Workers of a Car Battery Manufacturing Factory

Iranian Jornal of Toxicology ◽

10.32598/ijt.10.2.327.1 ◽

2016 ◽

Vol 10 (2) ◽

pp. 1-6

Author(s):

Bita Dadpour ◽

◽

Reza Afshari ◽

Seyed Reza Mousavi ◽

Sina Kianoush ◽

...

Keyword(s):

Liver Function ◽

Liver Toxicity ◽

Lead Concentration ◽

Serum Alkaline Phosphatase ◽

Clinical Signs ◽

Clinical Manifestations ◽

Liver Function Tests ◽

Gamma Glutamyl Transferase ◽

Function Tests ◽

Glutamyl Transferase

Background: Occupational lead poisoning is common in workers of some industries, but lead hepatotoxicity has rarely been reported. Several animal studies have revealed lead induced liver damage but clinical studies concerning the manifestations of lead induced liver toxicity in humans are scares. This study was designed to investigate the clinical manifestations and pathological parameters of hepatic dysfunction and its relationship with blood and urine lead concentrations in a car battery-manufacturing workers. Methods: This cross sectional study was carried out in Mashhad, Iran, during April-June 2011. One hundred and twelve workers underwent blood and urine sampling for determination of lead concentrations and liver function tests. Clinical signs and symptoms of possible lead hepatotoxicity were investigated. Results: Mean (±SD) age of the workers was 28.78 (±5.17) yr with a daytime work of 8.67 (±1.41) h and mean work duration of 3.89 (±2.40) yr. Mean blood lead concentration (BLC) and urine lead concentration (ULC) were 398.95 (±177.41) µg/l and 83.67(±50) μg/l, respectively. We found no correlation between the clinical findings and BLC or ULC. A weak correlation (R: 0.27, P=0.087) between serum alkaline phosphatase concentration and BLC was obtained. No significant relationship was found between other liver function tests and BLC or ULC. Conclusion: We found no specific clinical and laboratory abnormalities of liver in the workers of car battery manufacturer who had chronic lead toxicity. Further investigations with more specific laboratory tests such as LDH5 and gamma glutamyl transferase (GGT) as well as novel biomarkers of metal induced hepatotoxicity might be helpful in evaluating lead hepatotoxicity.

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Elevated Liver Function Tests not from a Statin – A Case History of Garcina Cambogia Associated with Hepato-toxicity

Journal of Clinical Lipidology ◽

10.1016/j.jacl.2017.04.085 ◽

2017 ◽

Vol 11 (3) ◽

pp. 823

Author(s):

James Trippi

Keyword(s):

Liver Function ◽

Case History ◽

Liver Function Tests ◽

Function Tests ◽

History Of ◽

Elevated Liver Function Tests

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Clinical outcomes of non-variceal upper gastrointestinal bleeding and its relation to aspirin and anticoagulants.

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.3222 ◽

2020 ◽

Vol 8 (B) ◽

pp. 11-19

Author(s):

Hend Radwan ◽

Ehab Elsayed ◽

Hesham Alshabrawi

Keyword(s):

Blood Transfusion ◽

Liver Function ◽

Gastrointestinal Bleeding ◽

Clinical Outcomes ◽

Upper Gastrointestinal Bleeding ◽

Liver Function Tests ◽

Gi Bleeding ◽

Function Tests ◽

History Of ◽

Upper Gastrointestinal

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a life-threatening emergency that requires an urgent management. Antiplatelet (e.g., aspirin) and anticoagulant drugs are widely chronically used in various cardiac and coronary artery diseases. These drugs increase the risk of NVUGIB as they may cause ulceration of the upper gastrointestinal (GI) mucosa directly or may cause bleeding or rebleeding. The management of NVUGIB is complicated as the risk between GI bleeding episodes and cardiovascular attacks needs to be well managed. AIM: The aim of this study is to determine the impact of antiplatelets (aspirin) and anticoagulants use on the morbidity, mortality, and clinical outcomes in patients presented with non-variceal GI bleeding. PATIENTS AND METHODS: A total of 105 patients presented with melena and/or hematemesis and diagnosed by upper GI endoscopy were enrolled in a prospective cohort study. Patients were sub-grouped according to their use of antiplatelets, anticoagulants, or none (controls). Patients were excluded if they had portal hypertension or nonsteroidal anti-inflammatory drugs (NSAIDs) use and divided into five groups: Group I – patients who had not taken anticoagulants and antiplatelet; Group II – patients on heparin, warfarin, and LMWH only; Group III – patients on aspirin only; Group IV – patients on clopidogrel and ticlopidine with or without aspirin; and Group V – patients on combined anticoagulants and antiplatelet. All patients were subjected to clinical, laboratory (complete blood count, liver function tests, renal function tests, prothrombin time, and partial thromboplastin time), and endoscopic investigations. Clinical details were reported including admission, blood transfusion, rebleeding, and mortality. RESULTS: Full medical history revealed that 43 patients were diabetic, 45 patients were cardiac, and 67 patients were hypertensive. Regarding the history of analgesic drug intake, 38 patients used NSAIDs and 29 of them used non-selective NSAIDs and 8 patients used selective NSAIDs. There were non-significant differences among the studied groups with NVUGIB regarding sex, hematemesis only presentation, melena only presentation, liver function tests, and endoscopic findings. On the other hand, there were statistically significant differences between the studied groups with NVGIB regarding increasing age, NSAIDs use whatever selective or non-selective, decrease level of HB, WBCs, serum albumin, bleeding profile, kidney function tests, clinical presentation in the form of hematemesis and melena, need for blood transfusion, history of associated diseases, especially being cardiac patients, rebleeding after 6 and 12 months, and mortality. CONCLUSION: Aspirin intake may be associated with less favorable clinical outcomes in patients with NVUGIB, while combined anticoagulants and antiplatelets seem to be associated with the worse outcomes.

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Histologic patterns of liver injury induced by anti-PD-1 therapy

Gastroenterology Report ◽

10.1093/gastro/goz044 ◽

2019 ◽

Vol 8 (1) ◽

pp. 50-55 ◽

Cited By ~ 2

Author(s):

Dongwei Zhang ◽

John Hart ◽

Xianzhong Ding ◽

Xuchen Zhang ◽

Michael Feely ◽

...

Keyword(s):

Liver Injury ◽

Liver Function ◽

Autoimmune Hepatitis ◽

Gastrointestinal Symptoms ◽

Liver Function Tests ◽

Function Tests ◽

Immune Mediated ◽

Advanced Malignancies ◽

Periodic Monitoring ◽

History Of

Abstract Background Nivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1 (PD-1)—have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them. Methods Eight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients. Results Seven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy. Conclusions Our study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients.

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