Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New treatment options for chronic hepatitis C (HCV) infection are examined. Studies show the efficacy of interferon alfa-2b in normalization of serum alanine aminotransferase and histological improvement in necroinflammatory liver disease. However, 70 to 80 percent experiencing normalization usually relapse within 1 year after treatment. Ten to 20 percent will have a sustained response lasting at least 3 years. Ideas for improving treatment response include longer initial treatment regimens, increasing dosages of interferon alpha, or adding another agent to interferon alpha. Based on encouraging study results, the interferon/ribavirin combination has been approved by the Food and Drug Administration (FDA) in HCV patients relapsing following interferon alpha monotherapy. So far the FDA has approved interferon alfa-2b, interferon alfa-2a, alfacon-1, and interferon alfa-2b/ribavirin as treatments for HCV; ribavirin alone is not effective against HCV infection. Other drugs are being tested with interferon alpha but have not generated enough substantive data. Thymosin, an immune modulator that enhances the body's production of interferon and interleukin rather than attacking HCV directly, is also being investigated. Oral dosing of interferon is in clinical trials for hepatitis B, and the results may be applicable to HCV. Alternative therapies are gaining wider interest such as using milk thistle for liver regeneration or using licorice root for quelling liver inflammation. As for transmission risk, there is little evidence supporting sexual activity as a major risk factor, however, some risk is reported with anal intercourse, sex during the menstrual cycles, and years of cohabitation with an infected partner.
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PMID:Can science meet the challenges of the HCV pandemic: new treatment options for chronic hepatitis C. 1136 38

For several years, interferon alpha-1, also known as interferon alpha-D, has been studied for treatment of various viral diseases, such as hepatic fibrosis caused by hepatitis B, herpes simplex virus keratitis, and bovine respiratory diseases in calves. Currently, recombinant human interferon alpha-D (rHuIFNalphaD) is expressed intracellularly in Escherichia coli or secreted by Bacillus subtilis and Saccharomyces cerevisiae. In this report, we describe the process of obtaining a relatively high-yield secretion of biologically active recombinant rHuIFNalphaD using the Pichia pastoris system. The process produced as high as 0.7 mg of purified protein per 20 ml of shake culture of rHuIFNalphaD with better bioactivity than the commercially available rHuIFNalphaD molecule produced in E. coli.
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PMID:High-yield expression and purification of human interferon alpha-1 in Pichia pastoris. 1148 99

Chronic infection with the hepatitis B virus (HBV) affects 350 million people worldwide, or approximately 5% of the global population, and commonly results in cirrhosis and hepatocellular carcinoma. Until recently, the only available treatment was injectable interferon alpha and response rates were suboptimal. Moreover, this expensive and toxic therapy had little applicability in the endemic regions of the world, i.e., Asia and Africa. The realisation that orally available nucleoside and nucleotide agents may effectively control this infection opened a new era in the management of chronic hepatitis B. Oral lamivudine recently became approved for treatment of hepatitis B worldwide. It is free of significant toxicity, improves liver histology and rapidly diminishes HBV DNA levels; lamivudine is expected to become the first-line therapy of choice. Nevertheless, the consistent emergence of lamivudine-resistant variants mandates the need to develop additional therapeutic agents. Adefovir dipivoxil, a nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might eventually be used in combination with lamivudine and therefore reduce the incidence of drug resistance. There is a critical need to advance the research of hepatitis B antiviral agents so that effective combination therapies can become widely available.
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PMID:Current pharmacotherapy for hepatitis B infection. 1158 97

Chronic viral hepatitis may now be controlled and, in many cases, permanently eradicated. Rapid advances in the antiviral therapy of chronic hepatitis C infection have resulted in a greater than 50% sustained response rate, with genotypes 2 and 3 now considered 'curable diseases.' Current hepatitis B therapy leads to significant improvement in liver histology and overall survival. These advances, coupled with the fact that 8% of the world population is chronically infected with viral hepatitis, has sparked considerable interest in this condition on the part of the pharmaceutical industry. In 2001, the most effective therapy for chronic hepatitis C is the combination of pegylated interferon alpha and oral ribavirin. The treatment of hepatitis B consists of either interferon alpha or oral lamivudine, while newer nucleoside/nucleotide analogues, alone or in combination with existing therapy, are being explored.
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PMID:Treatment of viral hepatitis--2001. 1158 99

Hepatitis C virus (HCV) has become a major contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV). It is estimated that 30% to 50% of patients with HIV are coinfected with HCV. Advances in antiretroviral therapy and improved life expectancy of HIV patients have resulted in an emergence of HCV-induced liver disease as a leading cause of significant morbidity and death in this population. Clinically, hepatitis C is a more severe disease in HIV-infected individuals, characterized by rapid progression toward end-stage liver disease. Highly active antiretroviral therapy is the mainstay of current acquired immunodeficiency syndrome management. One of the limiting side effects of combination therapy for HIV is hepatotoxicity, which is more common and often more serious in patients with underlying liver disease. Management of coinfected patients has no strict guidelines, but it is generally accepted that HIV infection needs to be treated before HCV. Hepatitis C in coinfected individuals is probably best treated using combination therapy (interferon alpha and ribavirin). It appears that combination therapy can safely be administered to this population and that previous concerns about ribavirin/zidovudine antagonism are unsubstantiated in clinical practice. Although initial results using only interferon alpha showed poor results in HIV coinfected patients, combination therapy seems to be as effective as in the general population. All HIV-HCV coinfected patients should be vaccinated against hepatitis B and hepatitis A; vaccines are safe and effective.
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PMID:Hepatitis C and human immunodeficiency virus coinfections. 1160 51

Hoffmann-La Roche has developed a PEGylated interferon alpha-2a, Pegasys, for the potential treatment of chronic hepatitis C and hepatitis B virus infection. It was first approved in Switzerland in August 2001 [418260] and was expected to be launched in September/October 2001 [419333]. In May 2000, Roche submitted a BLA to the US FDA, for approval to market Pegasys for the treatment of chronic HCV infection in non-cirrhotic and cirrhotic patients with compensated liver disease [329872], [348368], [367781]. Approval was still pending in December 2000 [387363], [392481]. Roche expects the US launch to take place in the second half of 2001 [400857]. In April 2001, Roche received a complete response letter from the FDA for Pegasys and was working with the FDA to address the questions raised in the letter [407595], [418310]. In August 2001, Roche expected approval for HCV in the US in 2002 and for HBV in 2004 [419333]. At this time, Roche planned to file an sNDA for combination with ribavirin [421285]. By March 2001, EU and Canadian filings had been made [401793]. Roche also planned to launch the product for chronic HBV infection and various malignancies in 2004 and 2005, respectively [400857]. Pegasys was filed for registration in Brazil in the first part of 2000 [418310]. As of December 1999, the drug was in phase II for HCV infection in Japan. It is being developed by Nippon Roche, which intended to extrapolate foreign phase III data for use in an NDA application in Japan [351804]. As a result of a meeting of Japan's PMSB in March 2001, Pegasys may be given priority in the review of its NDA, if submitted [403782]. In August 2001, Schering-Plough entered into a licensing agreement with F Hoffman-La Roche Ltd and Hoffmann-La Roche Inc that settles all patent disputes regarding the two companies' PEGinterferon products. Under the terms of the agreement, Schering-Plough and Roche will cross license to each other all patents applicable to Peg-Intron and Pegasys. The settlement agreement also includes a Schering-Plough sublicense of Enzon's branched PEG patents to Roche [418935], [418956]. Roche is collaborating with Maxim Pharmceuticals to develop PEG-IFN alpha-2a in conjunction with Maxim's Maxamine [378609]. In July 1998, Hoffmann-La Roche and Weston Medical signed a global agreement to license INTRAJECT (Weston's single-use, disposable, prefilled, needle-free injector for subcutaneous delivery of injectable liquid pharmaceuticals) for delivery of Pegasys [292119]. In April 1999, ABN Amro predicted annual sales of SFr 25 million in 2000, rising to SFr 75 million in 2002 [328676]. In September 2000, Merrill Lynch predicted sales of SFr 70 million in 2001, rising to SFr 700 million in 2004 [383742]. In March 2001, Deutsche Bank estimated that the product has sales potential of SFr 1600 million [421009].
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PMID:Pegasys (Hoffmann-La Roche). 1176 53

Polymyositis is a rare complication of interferon alpha treatment as a result of immune-modulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.
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PMID:A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. 1185 Jun 6

Periarteritis nodosa is a systemic vasculitis involving arteries with a diameter greater than 70-150 microns. Large vaccination against hepatitis B virus explains the decreased frequency of its association with hepatitis B virus observed in less than 10% of cases. Weight loss, fever, livedo, myalgias or arthralgias, mononeuropathy, gastrointestinal tract involvement, renal insufficiency, and cardiac failure are the most frequent clinical manifestations. Inflammatory syndrome and increased white blood cell count are common. Renal or digestive microaneurysms are present in more than 60% of cases. Prognosis is dependent of a five factors score corticosteroids with or without immunosuppressive drugs, result in 5-year survival rate over 60%. In hepatitis B virus-related periarteritis nodosa, corticosteroids are rapidly stopped; plasma exchanges in combination with antiviral agents (interferon alpha or lamivudine) give excellent results.
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PMID:[Periarteritis nodosa]. 1192 49

An interferon-stimulated response element (ISRE)/interferon regulatory element (IRE) spanning nucleotide coordinates 1091-1100 is present in the enhancer 1/X gene promoter region of the hepatitis B virus (HBV) genome. In the context of a minimal promoter element, the enhancer 1/X gene promoter ISRE/IRE was shown to be a functional regulatory site capable of mediating interferon alpha- (IFNalpha) and interferon-stimulated gene factor 3 (ISGF3)-specific transcriptional activation in transient transfection analysis. The enhancer 1/X gene promoter ISRE/IRE was also shown to mediate interferon regulatory factor (IRF) 1 and IRF7 activation of transcription from a minimal promoter construct. In contrast, IFNalpha and the IRFs had minimal effect on HBV transcription and replication in the context of the viral genome in cell culture.
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PMID:Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome. 1197 47

The hepatitis D virus (HDV), also called delta virus, is a small circular RNA virus. The HDV is dependent on the hepatitis B virus (HBV) and can cause infection in normal individuals with hepatitis B or yet, superinfect chronic HBV carriers. Three genotypes have already been cloned and sequenced. Infection with HDV has a worldwide distribution and a high HDV endemicity has been documented in the western Amazon region, in Brazil. It has been estimated that 18 million people are infected with this virus amongst the 350 million carriers of the HBV around the world. The HDV transmission and risk factors for infection are similar to those for HBV infection. The diagnosis is based on the immunohistological identification of HDAg in the liver and detection of IgM and IgG anti-HD in serum using RIA or EIA. The clinical course of hepatitis D is variable. Fulminant disease occurs more commonly in hepatitis B and D than in other forms of acute viral hepatitis. Chronic HDV infection is usually associated with severe histological changes in the liver and with a rapidly progressive course, that can lead to cirrhosis, liver failure and death. Treatment of chronic hepatitis D is currently unsatisfactory and interferon alpha is the only agent found to have some effect on the course of chronic hepatitis. Orthotopic liver transplantation is indicated for terminal cases of cirrhosis. Prophylaxis for HDV infection is possible by vaccination against the hepatitis B virus.
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PMID:[Hepatitis D]. 1201 28


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