Autoimmune Hepatitis Disease

Autoimmune hepatitis is a disease in which the body's immune system attacks liver cells. This leads to an inflammatory reaction in the liver (hepatitis). Autoimmune hepatitis is more common among women than men, but it occurs globally in children and adults of both sexes in diverse ethnic groups. The precise cause of autoimmune hepatitis is not clear. There has been evidence implicating measles virus, hepatitis viruses, cytomegalovirus, and EpsteinBarr virus as initiators of the disease; the most convincing evidence is related to hepatitis viruses. This is a chronic disease and it can last for years without obvious manifestation of the disease symptoms. It can lead to cirrhosis (scarring and hardening) of the liver and eventually liver failure.

Symptoms

Symptoms of autoimmune hepatitis range from mild to severe. Because severe viral hepatitis (caused by hepatitis C or B or both ) or hepatitis caused by certain drugs (oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, interferon, pemoline, minocycline, and atorvastatin) have the same symptoms, tests will be needed for an exact diagnosis of autoimmune hepatitis. Fatigue is probably the most common symptom of autoimmune hepatitis. Other symptoms include enlarged liver, jaundice, itching, skin rashes, joint pain, abdominal discomfort, nausea, vomiting, loss of appetite, dark urine, pale or gray colored stools.

Autoimmune hepatitis is an inflammatory liver disease characterized by the presence of high transaminases, circulating autoantibodies, hypergammaglobulinemia, histological evidence of hepatitis and responsiveness to immunosuppressive treatment. In autoimmune hepatitis, activated T cells and macrophages either directly attack liver parenchymal cells or induce tissue damage by the release of several proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interferon IFN-gamma (INF-gamma).

Murine models for autoimmune hepatitis: There are three experimental mouse models of T cell dependent liver injury. D-galactosamine (GalN)-sensitized mice challenged with either T cell activating anti-CD3 monoclonal antibody (mAb) or with the superantigen staphylococcal enterotoxin B (SEB) develop severe liver injury characterized by internucleosomal DNA fragmentation as well as by histological hallmarks of hepatocyte apoptosis, both preceding the increase of plasma transaminases. In the third experimental model, the administration of the T cell mitogen concanavalin A (Con A) to unsensitized mice also results in hepatic apoptosis and the ensuing necrosis. Anti-CD3 mAb as well SEB or Con A induce the release of systemic TNF, INF gamma and various other cytokines.

Treatment of autoimmune hepatitis: Autoimmune hepatitis in humans is classified as either type I or II, based on the presence of anti-nuclear (ANA) and/or smooth muscle (SMA) antibodies in type I, and liver/kidney microsomal antibody for type II. The ten-year survival rate in untreated patients is approximately 10%. Both types of autoimmune hepatitis are treated with corticosteroids such as prednisone as well as other immunosuppressive drugs such as azathioprine, mycophenylate mofetil, cyclosporine or tacrolimus. Patients who progress to end stage liver disease and/or cirrhosis may also need a liver transplant. Therefore, alternative treatment options are needed. Therapeutic approaches that either inhibit immune-mediated mechanisms or directly inhibit liver cell damage show promise.

CAM therapy against hepatitis: The CAM therapies tried out clinically include, antioxidants, thymic extract, zinc, Chinese herbs, Glycyrrhiza glabra (licorice), and Oxymatrine (derived from Sophora japonica). Several herbal medicinal products and supplements have been identified with potential virological and/or biochemical effects in the treatment of chronic hepatitis C infection. Studies of thymic extract, zinc and Bing Gan decoction in combination with interferon-alpha, and oxymatrine alone have demonstrated greater clearance of the hepatitis C virus than control treatment. Normalisation of liver enzymes has been greater during treatment with vitamin E, Glycyrrhiza glabra, CH100, Yi Zhu decoction and Yi Er Gan Tang decoction than with the control treatment. Anecdotal evidence suggests that many more complementary therapies are currently available to and popular with patients and further research into these interventions is warranted to establish their role in the treatment of hepatitis.

Study at NIH CAM Center: Our studies are aimed at addressing the mechanism underlying use of CAM therapy in ameliorating hepatitis and liver damage. The global aim of the current study is to identify the apoptotic mechanisms induced by plant derived cannabinoids in immune cells. We have selected cannabidiol (synthetic and that obtained from hemp seed oil) because it is non-psychoactive and our preliminary data suggest that it can trigger apoptosis in immune cells and act as an anti-inflammatory agent. We will test its efficacy in the treatment of autoimmune hepatitis in mouse models. This research will open new avenues with wide-ranging clinical applications in the therapy of a number of other inflammatory diseases.

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