Acute liver failure requiring transplantation caused by ulipristal acetate.

Ulipristal has recently been suspected to be hepatotoxic by the European Medicines Agency but the evidence base for hepatotoxicity is sparse. This is a brief formal report of a patient administered ulipristal for 6-8 weeks and who developed acute liver failure leading to liver transplantation. The explanted liver showed extensive hepatocyte necrosis and inflammation compatible with drug-induced liver injury and cirrhosis. The usual causes of acute hepatitis and cirrhosis were eliminated. There were no other potential causative drugs. This case suggests that ulipristal may cause acute hepatitis, with pre-existing cirrhosis probably contributing to the severity of liver injury observed in this case. Ulipristal prescribers must remain vigilant and monitor liver function in their patients.

Urgent Liver Transplantation for Dietary Supplements: An Under-Recognized Problem.

BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized. RESULTS: Of 2408 adult cases, 625 were characterized as a drug-induced liver injury. The majority of cases (n = 300) were due to acetaminophen toxicity, but the fourth highest category was due to HDS (n = 21). Of these 21 cases caused by HDS, 13 did not list the specific agent responsible, mean age was 36 years, and all cases occurred after 2007. There probably are more cases because 25% of all LT cases in the study did not list a specific reason for liver failure and 20% of all drug-induced liver failure did not list a specific drug. CONCLUSIONS: Herbal/supplement use is the fourth most common cause of drug-induced AHN requiring LT, albeit an underestimation of the problem. Detailed questioning of patients and their support systems regarding herbal/supplement use and better reporting are imperative to further define this problem and identify products that have the potential to lead to liver failure.

Role of Stem Cells Transplantation in Tissue Regeneration After Acute or Chronic Acetaminophen Induced Liver Injury.

PURPOSE: Acetaminophen-induced liver injury (APAP) is recognized as a frequent etiologic factor responsible for hepatic damage in the developed world. Management remains still elusive as treatment options are limited and their results are inconclusive. Consequently new strategies are explored at the experimental level. Mesenchymal stem cells (MSCs) present a promising modality as they can promote liver regeneration (LG) and compensate acute liver injury (ALI). MATERIALS AND METHODS: Our research was focused on articles related to drug-induced liver injury, mechanisms of liver regeneration (LG) after Acute Liver Injury (ALI) and recent experimental protocols of Mesenchymal Stem Cells (MSCs) transplantation after chemical insult. All these studies are cited on Pubmed and MedLine. RESULTS: This review has three distinct sections. First recent developments in ALI pathogenesis are presented. The second section covers cellular pathways and histological findings relevant to liver regeneration. The final chapter analyzes MSCs transplantation protocols after ALI and interrelation between liver regeneration and hepatic differentiation of MSCs. CONCLUSION: Adipose tissue stem cells (ADSCs) and (MSCs) transplantation represents a promising modality in severe ALI management although many aspects remain to be clarified.

Pemoline therapy resulting in liver transplantation.

OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and treated with pemoline, developed signs and symptoms of liver failure. Pemoline therapy was discontinued, but the patient's liver function continued to decline. Ultimately, a liver transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD treatment, has been associated with hepatotoxicity with the majority of cases occurring in pediatric patients. To our knowledge, this is the second reported case of pemoline-induced liver failure resulting in liver transplantation. The mechanism of action remains unclear, with several hypotheses being postulated including hypersensitivity reactions, dose-related phenomena, and autoimmune-mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to liver failure, this agent should not be considered first-line therapy for ADHD. Prior to initiating therapy, baseline liver function tests should be obtained and closely monitored, and parents and patients should be educated on the signs and symptoms of liver toxicity.