Nonalcoholic steatohepatitis (NASH) is a condition characterized by hepatomegaly, elevated serum aminotransferase levels, and a histologic picture similar to alcoholic hepatitis in the absence of alcohol abuse. Most patients with NASH are obese women, and many have diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. NASH has also been associated with a number of metabolic conditions, surgical procedures, and drug treatments. Most patients are asymptomatic. The most common sign of NASH is hepatomegaly. Stigmata of chronic liver disease are rare. Laboratory abnormalities include a 2-4-fold elevation of serum aminotransferase levels; other liver function test results are usually normal. Histologically, there is moderate to severe macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and/or fibrosis. The pathogenesis of NASH is poorly understood, but lipid peroxidation and oxidative stress are the leading culprits. The natural history of NASH is unknown, but NASH seems to be a stable disease in most patients. Treatment of NASH is unproven, but weight reduction is recommended in obese patients. Small pilot studies of several drugs have shown promise, but large randomized clinical trials are awaited. Orthotopic liver transplantation is the treatment of choice for end-stage liver disease secondary to NASH.
Orthotopic liver transplantation (OLT) is the best treatment for end-stage liver disease. Limited data exist on the access of minorities to OLT. The aim of this study was to determine whether disparities exist among black and white OLT patients. Data were collected from the United Network for Organ Sharing on black and white 18 -70 year-old OLT waiting list registrants (n ؍ 29,013) and OLT recipients (n ؍ 15,805) between 1994 and 1998. Standardized transplant ratios were generated by comparing the racial distribution of OLT patients with the US population. Demographic and clinical characteristics of OLT registrants were compared by race. Multivariate analyses were performed to identify predictors of time to OLT and the likelihood of dying or receiving OLT within 4 years, controlling for severity of illness and other factors. The standardized transplant ratio for black OLT recipients (0.65) was significantly lower than the standardized transplant ratio for white OLT recipients (1.05). Blacks were younger and sicker than whites. After adjustment for severity and other factors, time to OLT among recipients did not differ by race (P > .05). Blacks were more likely to die or become too ill for OLT while waiting (P < .001). Blacks were less likely to receive OLT within 4 years (P < .001). In conclusion, adult blacks were underrepresented among OLT patients. Although waiting times were similar once listed, black race affected outcomes while awaiting OLT. The process of referral and evaluation for OLT should be investigated further. (Liver Transpl 2004; 10:834-841.)
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.
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