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《2010AASLD自身免疫性肝炎的診斷和治療指南》內(nèi)容預(yù)覽

Autoimmune hepatitis (AIH) is a generally unresolv-ing inflammation of the liver of unknown cause. A working model for its pathogenesis postulates that environmental triggers, a failure of immune tolerance mechanisms, and a genetic predisposition collaborate to induce a T cell–mediated immune attack upon liver antigens, leading to a progressive necroinflammatory and fibrotic process in the liver.
Onset is frequently insidious with nonspecific symptoms such as fatigue,jaundice, nausea, abdominal pain, and arthralgias atpresentation,but the clinical spectrum is wide, rang-ing from an asymptomatic presentationto an acutesevere disease.
The diagnosis is based on histologic abnormalities, characteristic clinical and laboratory findings, abnormal levels of serum globulins, and the presence of one or more characteristic autoantibod-ies.
Women are affected more frequently than men (sex ratio, 3.6:1).and the disease is seen in all ethnic groups and at all ages.There are no robust epidemiological data on AIH in the United States. In Norway and Sweden, the mean incidence is 1 to 2 per 100,000 persons per year, and its point prevalence is 11 to 17 per 100,000 persons per year.A similar incidence and prevalence can beassumed for the Caucasian population of North America.
Data on the natural progression of untreated disease are derived principally from experiences published prior to the widespread use of immunosuppressive agents for AIH and before the detection of the hepati-tis C virus (HCV).
These studies showed that as many as 40% of patients with untreated severe disease died within 6 months of diagnosis,and that survi-vors frequently developed cirrhosis, esophageal varicesand subsequent hemorrhage.
An acute onsetof illness is common ( 40%),and an acute severe presentation, characterized by hepatic encephalopathywithin 8 weeks of clinical symptoms, is sometimesseen.
Three randomized, controlled treatment trials estab-lished that prednisone alone or in combination withazathioprine improved symptoms, laboratory tests, his-tological findings, and immediate survival.
Thesestudies led to the acceptance of immunosuppressiveregimens as the standard in treatment, and supportedan autoimmune pathogenesis of the disease. However,these studies were completed decades ago before thediscovery of HCV. Therefore, HCV infection couldnot be excluded in these studies and one can assumethat several of these patients were indeed infected withHCV. Liver transplantation has also evolved as aneffective treatment for the decompensated patient, andthe 5-year patient and graft survivals now exceed80%

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