Digestive diseases
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Meta Analysis
Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis.
Refractory ascites represents a significant complication of decompensated cirrhosis, associated with increased mortality rates. The aim of this meta-analysis was to evaluate whether response to treatment with tolvaptan is associated with improved overall survival in cirrhotic patients with refractory ascites. ⋯ The outcomes of the meta-analysis support the prognostic role of tolvaptan response in patients with cirrhosis and refractory ascites, as it was shown to lead to significantly improved overall survival. These findings should be confirmed by future large-scale studies, while efficient biomarkers should be identified in order to accurately predict response to tolvaptan and discriminate patients that would benefit from its administration.
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Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. ⋯ Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.
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The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. ⋯ This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.
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Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. ⋯ The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome.
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Hepatocellular carcinoma (HCC) is a major health concern, and early HCC diagnosis is a primary radiological concern. The goal of imaging liver cirrhosis is the early identification of high-grade dysplastic nodules/early HCC since their treatment is associated with a higher chance of radical cure and lower recurrence rates. The newly introduced MRI contrast agent gadoxetic acid (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, Gd-EOB-DTPA) has enabled the concurrent assessment of tumor vascularity and hepatocyte-specific contrast enhancement during the hepatobiliary phase (HBP), which can help to detect and characterize smaller HCCs and their precursors. ⋯ Due to this capability of identifying the precursors and biological behavior of HCC, EOB-MRI has rapidly become a key imaging tool for the diagnosis of HCC and its precursors, despite the scarce MRI availability throughout Europe. With increasing experience, EOB-MRI may eventually be established as the diagnostic imaging modality of choice in this setting. Full recognition by the Western EASL-AASLD guidelines is expected.