Multaq : Hepatitis A, B, C, D, and E viruses are the major hepatotropic viruses that cause liver disease in humans (there is no hepatitis F). Some other viruses can also cause acute liver disease in otherwise healthy individuals. In most cases, these viruses cause systemic diseases that concurrently affect the liver. These viruses include dengue virus, yellow fever virus, and Epstein-Barr virus (EBV), which causes mononucleosis. Individuals with mononucleosis can suffer from a mild form of acute hepatitis that always resolves. Available data suggest that poxvirus and measles virus cause hepatitis in children.
Some viruses that are generally harmless in healthy individuals may cause liver disease in patients with compromised immune systems. These viruses may infect patients with AIDS or cancer. They may also infect patients who have received organ transplants and are taking medications that suppress their immune systems. The most important of these viruses is cytomegalovirus, or CMV. CMV can cause hepatitis in recipients of organ transplants, including transplanted livers. CMV can also cause hepatitis and serious bile duct abnormalities in patients with AIDS.
Some doctors will test patients with chronic hepatitis for antibodies against CMV and EBV. These viruses are endemic in the human population, and the detection of IgG antibodies means virtually nothing. Furthermore, these two viruses do not cause any significant chronic liver disease in people with normal immune systems. If someone tells you that you have chronic hepatitis caused by EBV or CMV, you should be suspicious and see another doctor.
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There are two main types of therapeutically available alphainterferons for patients with hepatitis B and hepatitis C: unmodified and pegylated. Unmodified interferons are the proteins themselves, and two extremely similar ones (essentially identical from a clinical perspective) are most often used in the United States for patients with hepatitis B: interferon alpha-2a (Roferon) and interferon alpha-2b (Intron A). Different sized and shaped polyethylene glycol (antifreeze) molecules have been covalently (a type of chemical bond) added to these interferons to prolong their half-lives in the body. This pegylation process has allowed for decreased frequency of injections with better steady-state blood levels.
The two pegylated alpha-interferons available in the United States are peginterferon alpba-2a (Pegasys) and peginterferon alpha-2b (Peg- Intron). Because the different manufacturers have sponsored different studies with different doses of these various interferon alpha preparations for hepatitis B, it is complicated to discuss precise dosing and protocols “formally” recommended for each one. I believe that interferon alpha-2a and interferon alpha-2b are clinically equivalent. I also believe that peginterferon alpha-2a and peginterferon alpha-2b are clinically equivalent in terms of safety and efficacy. Therefore, I will use the terms interferon alpha and peginterferon alpha and not specify between them as to the 2a and 2b forms.
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The U.S. Food and Drug Administration has currently approved three nucleoside analogues that inhibit the hepatitis B virus polymerase: lamivudine (Epivir-HBV), adefovir (Hepsera), and entecavir (Bara- clude). Over the next several years, there likely will be additional similar drugs of this type approved for chronic hepatitis B. While the basic mechanism of action of all of these drugs is the same, there are some differences, primarily in dosing and potential for the virus to become resistant.
Given that several drugs have been recently approved for certain patients with chronic hepatitis B, we still do not know the best option for each patient. Provided here is some general information about which patients with chronic hepatitis B should be considered for treatment and what can be expected from treatment with these drugs. It is likely that over the next few years, the results of clinical trials and various recommendations from professional societies will modify the way doctors use these available drugs and any similar new drugs. Different doctors are also likely to have their own preferences using these approved drugs.
Patients should have chronic hepatitis B (longer than six months with infection) documented by the presence of HBsAg in their blood. To be eligible for treatment, patients should have replicative hepatitis B infection, that is, they should have detectable HBeAg and/or viral DNA in their blood. Prior to commencing treatment, patients should have a liver biopsy to confirm the diagnosis and demonstrate inflammation. Patients who have clinical complications of cirrhosis, such as ascites, encephalopathy, and/or bleeding esophageal varices, should probably not be treated, except in research studies or as part of a pretransplant protocol. Patients with biochemical evidence of compromised liver function, including low blood albumin concentration, elevated bilirubin concentration, or significantly prolonged prothrombin time, should probably not be treated. Patients with significantly low platelet counts, low white blood counts, or significant anemia should probably not receive an alpha-interferon; however, the exact cutoff values for exclusion are not agreed upon by all doctors. Patients with hypothyroidism, hyperthyroidism, or diabetes mellitus and poorly controlled blood sugars should not be treated with an alpha-interferon until these conditions are medically controlled.
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