Acetaminophen-Induced Hepatotoxicity:a Comprehensive Update

Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades,and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes.APAP hepatotoxicity remains a global issue;in the United States,in particular,it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases.The pathophysiology,disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated,and adverse patient outcomes with increased morbidity and mortality continue to occur.Although APAP hepatotoxicity follows a predictable timeline of hepatic failure,its clinical presentation might vary.N-acetylcysteine (NAC) therapy is considered as the mainstay therapy,but liver transplantation might represent a life-saving procedure for selected patients.Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level,with focus on the underlying molecular signaling pathways.

Drug-induced liver injury: Do we know everything?

Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.

Acute liver failure complicating jejunojejunal intussusception presentation in a gastric bypass patient

Over 200?000 weight loss procedures are performed annually in the United States. Physicians must therefore be cognizant of the unique array of complications associated with these procedures. We describe a case of jejunojejunal intussusception in a gastric bypass patient who presented with acute liver failure (ALF) due to acetaminophen (APAP) toxicity. Our patient is a 29 year-old female who had undergone Roux-en-Y gastric bypass surgery seven years prior. She was evaluated in the emergency department for confusion. Her family reported a 3-wk history of progressive abdominal pain and vomiting, for which she had ingested 40 acetaminophen/oxycodone tablets over the past 2 d. Physical examination showed icteric sclerae, a distended abdomen, and grade?I?encephalopathy. She fulfilled the criteria for ALF and was listed for liver transplantation. Abdominal computed tomography scan revealed a jejunojejunal intussusception. She underwent emergent exploratory laparotomy and resection of the infarcted intussusceptum and the previous jejunojejunostomy. She had rapid clinical improvement, with decreasing liver enzymes and improved hepatic synthetic function. She had complete resolution of coagulopathy and encephalopathy, and was removed from the liver transplant list. She was discharged home 20 d after hospitalization with normal liver tests. This case demonstrates that acute abdominal catastrophes can potentiate liver injury in the setting of acetaminophen toxicity. Encephalopathy may obscure history and physical exam findings. This case also exemplifies the pitfalls in the management of the bariatric surgery patient and the importance of multispecialty collaboration in patients presenting with organ failure.

An Update on Treatment of Drug-Induced Liver Injury

Drug-induced liver injury (DILI) has been linked to more than 1,000 medications and remains the most common cause of acute liver failure in the United States. Here, we review the most current literature regarding treatment and make recommendations for the management of this relatively common disease. Since treatment of DILI remains largely elusive, recent studies have attempted to define new management strategies for these difficult patients. Early diagnosis and withdrawal of the suspected medication is the mainstay of treatment of DILI. For acetaminophen and Amanita mushroom poisoning, there are specific therapies in use. Finally, there are other possible management mod-alities for DILI, including corticosteroids and ursodeoxycholic acid.