Digestive diseases
-
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.
-
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.
-
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.
-
Acute kidney injury (AKI) is a common complication of advanced cirrhosis. Type 1 hepatorenal syndrome is the best-known and most severe form of AKI, and it has a precise definition and a set of specific diagnostic criteria. More recently, it has become recognized that milder degrees of renal dysfunction also have a negative impact on patient outcome in various patient populations. Key Messages: Several definitions and criteria for staging the severity of AKI have been proposed, including the RIFLE (Risk, Injury, Failure, Loss of Function and End-Stage Renal Disease) group, the Acute Kidney Injury Network (AKIN), and the Kidney Disease: Improving Global Outcome (KDIGO) group. All of them incorporate some changes of serum creatinine and urine output in the definition and staging of AKI. The hepatology community has mostly embraced the AKIN diagnostic and staging criteria and has applied them in the prognostication of patients with advanced cirrhosis. However, the AKIN criteria have not been strictly applied in all studies on cirrhosis. This is partly related to the fact that changes in urine output are difficult to assess in advanced cirrhosis, and partly related to the difficulty in defining the baseline serum creatinine from which the change in serum creatinine is calculated. This has led to some confusion in the interpretation of results of the various studies on AKI in cirrhosis. More recently, some investigators have suggested incorporating the AKIN criteria with setting a lower limit of serum creatinine of 1.5 mg/dl in determining the diagnosis and prognosis of AKI in cirrhosis. ⋯ This is an ongoing debate as to how best to define AKI in cirrhosis. In the near future there should be prospective clinical trials that will clarify which diagnostic and staging criteria of AKI will best serve the cirrhotic population.