Acute liver failure following atorvastatin dose escalation: Is there a threshold dose for idiosyncratic hepatotoxicity?

Abstract

The bulk of hepatotoxicity (drug induced liver injury, DILI) cases in clinical practice is idiosyncratic in nature. This assumption is based on the apparent absence of dose dependency and the unpredictability of the reaction, which presents after a relatively long latency period of drug exposure in susceptible individuals. Recent evidence suggests that the administration of high oral daily dose of drugs that undergo extensive hepatic metabolism does influence the risk of developing idiosyncratic DILI (IDILI) [1,2]. We report a patient safely treated with atorvastatin at a standard therapeutic dose for more than a year who developed acute liver failure and rhabdomyolysis after doubling the daily dose of the drug ( Supplementary Fig. 1).An 85-year-old woman was admitted in February 2014 because of a 4-day history of worsening drowsiness, anorexia, jaundice, dark-yellow-coloured urine, and vomiting. Since early January, she had complained of fatigue, decreasing ability to walk, and sleepiness. Eighteen months prior to the episode six intracoronary stents were placed. Past medical history included diabetes mellitus, hypercholesterolemia, arterial hypertension, and essential tremor. She had been receiving atorvastatin (40 mg daily) since June 2012, along with furosemide, ramipril, omeprazole, aspirin, metformin, and phenobarbital for more than 3 years. She had no toxic habits and denied taking over-the-counter drugs, herbal remedies, dietary supplements, or grapefruit. Five months before admission, the atorvastatin dose was increased to 80 mg daily due to deficient lipaemic control. Liver and renal biochemistry at the time of starting atorvastatin and repeatedly checked thereafter up to September 2013 (prior to atorvastatin dose escalation), had remained within the normal range. On admission, blood pressure was 131/68 mmHg and heart rate 78/min. Physical examination revealed jaundice, confusion, and pronounced asterixis. Her body mass index was 29.5 kg/m 2 . Diagnostic work-up showed elevated alanine aminotransferase (

Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan criteria: A RCT

“…The discordance between the publication and the registration information might decrease the validity of their findings [2]. Whether or not the high recurrence rate (68.9%) after PH affected RFS was not reported by Yin et al…”

“…Furthermore, the mean age in the far eastern population was 52 and 54 years for the partial hepatectomy patients and TACE patients, respectively. This compares with a median age of 69.9 years in the study from the Newcastle group [2]. Excluding patients 70 years or older is likely to have introduced a selection bias to the study, since older patients are more likely to have significant co-morbidities that would preclude major liver resection.…”

Target patients for partial hepatectomy and relationship between PLT and prognosis in BCLC B HCC

“…Clinical practice guidelines for HCC state that drug-eluting beads (DEB) had similar response rates when compared with conventional TACE [1]. However, DEB is recommended for its less systemic adverse events.…”

“…Qing Pang and his associates stated in their letter that patients with a high preoperative PLT had significantly worse OS and recurrence free survival (RFS). This statement was based on a small sample size, retrospective clinical study, which was recently reported [1]. A careful look at this retrospective study [3] showed aspartate amino-transferase to platelet ratio (APRI) but not PLT, to be associated with poor prognosis in patients with HCC.…”

The rescue of DCD rodent livers grafts: Is there HOPE?

“…To the Editor: We read with great interest the letter by Kopp et al regarding our study on machine perfusion of rat livers, donated after cardiac death (DCD). Our goal was to compare the two main liver perfusion techniques, normothermic (NMP) and hypothermic oxygenated perfusion (HOPE) in terms of liver function and injury in a transplant model, closely adapted to the clinical situation [1].…”