Hepatotoxicity by Drugs: The Most Common Implicated Agents.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Idiosyncratic drug-induced liver injury (DILI) is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov). According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab

Clostridium difficile infections. An increasing problem in westernized medicine [editorial]

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)Clostridium difficile sýkingar (e. Clostridium difficile infections (CDI)) hafa verið þekkt heilsufarsvandamál í fleiri áratugi. Mikilvæg rannsóknarvinna hefur aukið þekkingu okkar á klínískum greiningaraðferðum, faraldsfræði og meðferð þessara iðrasýkinga. Tíðni CDI hefur farið vaxandi víðast hvar á Vesturlöndum og meinvirkari stofnar hafa komið fram. Faraldrar hafa einnig brotist út á mörgum stöðum í heiminum og fleiri alvarlegar sýkingar og aukin dánartíðni hafa fylgt í kjölfarið. Kostnaður heilbrigðiskerfisins hefur aukist að sama skapi sökum þessa. Afleiðingar CDI eru langvarandi spítalalegur vegna hvimleiðs niðurgangs, blóðsýkingar og lost í kjölfar hennar, ristilrof og brottnám ristils. Í byrjun þessa áratugar var lýst faröldrum í Quebec í Kanada af CDI þar sem tilfellum fjölgaði gífurlega ásamt fjölgun alvarlegra afleiðinga þessara sýkinga.1 Faraldrar þessir einkenndust af fjórum til fimm sinnum hærra nýgengi af CDI og aukinni dánartíðni frá 4,5% árið 1991 upp í 22% árið 2004.1 Faröldrum af þessu tagi hefur einnig verið lýst í Evrópu. Fjöldi CDI tilfella í Bandaríkjunum virðist sífellt fara vaxandi og á síðustu árum hefur verið áætlað að um 450.000-750.000 tilfelli eigi sér stað þar í landi á ári.2 Sterk tengsl á milli sýklalyfjanotkunar og CDI hefur verið þekkt áratugum saman en aukning af CDI tengd notkun prótónupumpuhemla hefur nýlega verið lýst.3-

Secondary sclerosing cholangitis in critically ill patients: current perspectives.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSecondary sclerosing cholangitis (SSC) is a term used for a group of chronic cholestatic disease affecting the intra- and/or extrahepatic biliary tree with inflammation and progressive stricture formation, which can lead to biliary cirrhosis. A newly recognized form of SSC is secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Pathogenesis is believed to involve ischemic injury of intrahepatic bile ducts associated with prolonged hypotension, vasopressors administration, and/or mechanical ventilation in patients treated in the intensive care unit (ICU). Patients diagnosed with SSC-CIP have no prior history of liver disease and no known pathologic process or injury responsible for bile duct obstruction prior to ICU treatment. Reasons leading to ICU treatment are many including multitrauma, burn injury, cardiac surgery, severe pneumonia, other infections, or bleeding after abdominal surgery. Patients have in common prolonged ICU admission. SSC-CIP is associated with rapid progression to liver cirrhosis and poor survival with limited treatment options except a liver transplantation. Transplant-free survival is around 17-40 months, which is lower than in other SSC patients. During the initial stages of the disease, the clinical symptoms and biochemical profile are not specific and easily missed. Biliary casts formation may be considered pathognomonic for SSC-CIP since most patients have them in early stages of the disease. Increased awareness and early detection of the disease and its complications is considered to be crucial to improve the poor prognosis

Clinical management of patients with drug‐induced liver injury (DILI)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadDrug-induced liver injury (DILI) should be considered in all patients with recent elevation of liver tests without obvious etiology and normal hepatobiliary imaging. There is currently no biomarker that is helpful in diagnosis which relies on clinical and laboratory findings. Diagnosis is dependent on temporal relationship with a recently started drug or herbal and dietary supplement and elevated liver tests with exclusion of competing etiologies. The implicated agent should be discontinued and the patient should be observed closely. This is particularly important in patients with jaundice who have approximately 10% risk of liver related mortality and/or need for liver transplantation. There is no specific therapy for DILI which is only symptomatic such as for itching. Patients with jaundice and coagulopathy usually require hospitalization

Mortality associated with drug-induced liver injury (DILI)

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Pancreatic mass leading to left-sided portal hypertension, causing bleeding from isolated gastric varices.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Mucinous cystic neoplasms (MCN) are an uncommon form of exocrine neoplasms of the pancreas. Symptoms are most often vague and this makes the diagnosis more difficult. The current case is one of three cases yet reported where the MCN caused left-sided portal hypertension leading to the formation of isolated gastric varices and subsequent bleeding from the varices. In the previously reported cases the main symptom was hematemesis. However in the current case the patient experienced no hematemesis, only isolated incidents of dark coloured diarrhea, but the main symptoms were those of iron-deficiency anemia. We present the case report of a 34-year-old woman who presented with dizziness and lethargy and was found to have 12 cm MCN in the pancreas

Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review

Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: “corticosteroids” and “drug-induced liver injury”. Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33–50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33–100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI