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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of HCV correlated hepatitis is an important argument, because of the great incidence and prevalence of this disease. At the end of the Eighties, the IFN was the first substance used for HCV correlated hepatitis therapy. The IFN monotherapy with a dose of 3-6 MU for 6-12 months eradicates the infection in the 15% of cases, and cause an histological temporary improvement in a variable number of patients that keep the infection. In the following years, the research on evaluation of the efficacy of the recombinant interferons or interferons made with genetics engineering (IFN alpha 2a, IFN alpha 2b and IFN Consensus) has given results comparable with the results obtained with IFN alpha. Later, it started the experimentations with IFN associated to other substances, for example IFN-ribavirin combination therapy. The treatment IFN-Ribavirin eradicates the infection in 30% of the patients with the genotype 1b and in 60% with the genotype 2 or 3, while this treatment is less efficacious in the patients with the genotype 4. Recently, it started to use the PEG IFN. The pegylation is the combination of a polietylen-glicole molecule with the IFN molecule, so as to prolong its half-life and reduce the dose only one a week, with reduction of the collateral effects. Some studies has shown that the use of PEG-IFN in monotherapy could help the patients with advanced liver complaint. Successive studies are directed to show the efficacy of the PEG-IFN and ribavirin combination therapy. Recent researches put in evidence new substances, that could represent the future for HCV correlated hepatitis therapy. Between these substances we have to highlight the interleukin, the inhibitors of the viral multiplication and the inhibitors of IMPDH (Inosine monophosphate dehydrogenase). At the beginning of 2002 has made the improvement of HCV vaccine known. Actually, in the USA there are in progress human experimentations, and the production of gamma-globuline, that could be effective to prevent the infection.
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PMID:[Recent trends in the therapy of hepatitis C]. 1291 Aug 8

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.
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PMID:Safety of interferon beta treatment for chronic HCV hepatitis. 1469 60

Major progress has been made in the treatment of chronic hepatitis C virus (HCV) infection over the 18 years since Hoofnagle et al. initially documented response of non-A non-B hepatitis to interferon alfa. Current optimal therapy with pegylated interferon alfa (PEG-IFN) and ribavirin results in sustained virologic response rates of just over 50%. With an estimated 2.7 million Americans with active HCV infection, we can anticipate a large number of potential treatment failures with the current standard of care. At this time, no therapy is approved by the US Food and Drug Administration for treatment failures of PEG-IFN and ribavirin. Maintenance interferon therapy with the goal of prevention of disease progression rather than viral eradication appears to offer an option for HCV treatment failures with advanced disease. Alternative medical strategies to reduce hepatic fibrosis are also under investigation. With the relatively static number of available organs for transplantation, prevention of disease progression and decompensation is essential for an impact to be made upon the predicted rates of HCV morbidity and mortality in the next 10 to 20 years.
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PMID:Maintenance therapy for chronic hepatitis C. 1570 Dec 99

The increasing number of elder patients with advanced liver diseases requires a special medical competence in this field. The process of aging influences pharmacokinetic and pharmacodynamic properties. Medical measures in elder patients have to submit in particular a careful utility/risk-analysis. The most severe liver disease is the decompensated cirrhosis with its complications. Medical treatment of common cirrhotic complications is not age-dependent. Also the antiviral-therapy with nucleosid analoga in chronic hepatitis B, with or without cirrhosis, can be applied in elder patients without restrictions. However in elder patients with chronic hepatitis C the indication for antiviral treatment is restricted only to a limited number of patients. Important aspects justifying the therapy with PEG-Interferon plus Ribavirin also in elder patients are disease progression, a good clinical condition as well as the motivation of the patient. The established concepts for treatment of autoimmune hepatitis and primary biliary cirrhosis are applicable to elder patients in the same way. The hepatocellular carcinoma is a complication of liver cirrhosis and a frequent malignant tumor in this group of patients. For therapy of hepatocellular carcinoma surgical and interventional procedures are available, partially with a curative account. The systemic medical treatment is disappointing until now. The liver transplantation is generally not a realistic option for aged patients.
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PMID:[The elder patient with advanced liver disease]. 1593 86

Chronic hepatitis B is one of the world's most common serious diseases with > 300 million patients worldwide. Currently recommended treatments include conventional interferon (IFN), lamivudine and adefovir. Recently, peginterferon-alpha2a (PEG-IFN-alpha2a, Pegasys; Hoffmann-La Roche & Co.) has been approved for use in patients with chronic hepatitis B in the US, the EU, Switzerland, Turkey and in several countries in the Asia-Pacific region. Several trials have been carried out using PEG-IFN-alpha2a (40 kDa) compared with conventional IFN, lamivudine monotherapy and a combination of PEG-IFN-alpha2a and lamivudine in patients with hepatitis Be antigen- (HBeAg) positive chronic hepatitis B, and patients with HBeAg-negative chronic hepatitis B. PEG-IFN-alpha2a was shown to be superior to conventional IFN in HBeAg-positive disease and to lamivudine in both HBeAg-positive and HBeAg-negative chronic hepatitis B. Although there was greater suppression of virus while on therapy, the combination of lamivudine and PEG-IFN-alpha2a did not enhance sustained response at the end of the 24-week follow-up period, compared with PEG-IFN monotherapy. In addition, approximately 3% of patients underwent hepatitis B surface antigen (HBsAg) seroconversion - the ultimate marker of therapeutic response, which is rarely seen following treatment with antiviral agents. The side effect profile was reasonable. PEG-IFN-alpha2a could become the treatment of choice in many patients with both HBeAg-positive and HBeAg-negative disease and, in those who fail to respond, consideration could then be given to the use of antiviral agents.
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PMID:Peginterferon-alpha 2a for the treatment of hepatitis B infection. 1601 86

Cirrhosis is the result of chronic inflammation and of the progressive increase of fibrosis. In France, hepatitis C infection is the second cause of cirrhosis after alcohol abuse. The other causes of cirrhosis are: hepatitis B infection, genetic haemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, drug-induced cirrhosis, secondary biliary cirrhosis, Wilson's disease and al-antitrypsin deficiency. Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis, the combination of pegylated interferon alpha (PEG IFN) with ribavirin in case of C viral cirrhosis, the PEG IFN and the nucleoside analogs in case of B viral cause; corticosteroids and immunosuppressive drugs in case of autoimmune cirrhosis; venesections in case of genetic haemochromatosis and stopping the drug in case of drug-induced cirrhosis. The complications of cirrhosis such as ascites, oesophageal varices, bleeding, hepatic encephalopathy and hepatocellular carcinoma mainly explain the high rate of morbidity and mortality. Liver transplantation is the established therapy for decompensated liver disease of any etiology significantly changed the outcome of patients with advanced cirrhosis.
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PMID:[Liver cirrhosis in adults: etiology and specific treatments]. 1625 95

Efficient assembly of hepatitis delta virus (HDV) was achieved by cotransfection of Huh7 cells with two plasmids: one to provide expression of the large, middle, and small envelope proteins of hepatitis B virus (HBV), the natural helper of HDV, and another to initiate replication of the HDV RNA genome. HDV released into the media was assayed for HDV RNA and HBV envelope proteins and characterized by rate-zonal sedimentation, immunoaffinity purification, electron microscopy, and the ability to infect primary human hepatocytes. Among the novel findings were that (i) immunostaining for delta antigen 6 days after infection with 300 genome equivalents (GE) per cell showed only 1% of cells as infected, but this was increased to 16% when 5% polyethylene glycol was present during infection; (ii) uninfected cells did not differ from infected cells in terms of albumin accumulation or the presence of E-cadherin at cell junctions; and (iii) sensitive quantitative real-time PCR assays detected HDV replication even when the multiplicity of infection was 0.2 GE/cell. In the future, this HDV assembly and infection system can be further developed to better understand the mechanisms shared by HBV and HDV for attachment and entry into host cells.
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PMID:Assembly of hepatitis delta virus: particle characterization, including the ability to infect primary human hepatocytes. 1722 85

Acute infection due to hepatitis C virus results in a chronic progression in 50-84% of cases. In the light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is very important to consider early treatment of acute hepatitis C before it progresses to the chronic form. The aim of this review is to evaluate the real efficacy and tolerance of Peg-interferon alpha-2b in monotherapy and in association with ribavirin in the treatment of patients affected by acute C hepatitis, to delineate the viral factors correlated with the sustained virological response and to consider when treatment should be started in relation to onset and what is the optimal duration of therapy. Also the pharmacodynamic and pharmacokinetic characteristics of PEG-IFN alpha-2b and ribavirin are reassessed. The analysis of literature demonstrates that Peg-interferon alpha-2b treatment is efficacious in terms of attaining sustained virological response (71-94% of cases). Treatment must be started within three months of onset and must be prolonged for three months. Only two studies have provided evidence the needed of a prolonged treatment for six months for genotype 1 infections. In all studies therapy has been generally well tolerated. Sustained virological response is independent of baseline viral load and of HCV genotypes in patients treated for six months, while in subjects treated for three months it seems to be dependent on HCV-genotype, with genotype 1 characterized by a less favourable outcome. Combination therapy with ribavirin does not seem to increase the response rate but could be proposed as a second choice to patients not responding to IFN monotherapy.
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PMID:PEG-interferon alpha-2b for acute hepatitis C: a review. 1769 45

Over the last years there has been considerable progress in the treatment of chronic hepatitis B. Five drugs are now approved for the treatment of this virosis: interferon alpha, lamivudine, adefovir, entecavir and telbivudine. Interferons (conventional or PEG) were the first medicine used in the treatment of hepatitis being able to lead the persistent response (loss of DNA-HBV and of AgHbe) to up to one third of treated cases. A large number of nucleoside/nucleotide analogues are, at present, available to treat hepatitis B. The efficacy of lamivudine, the first nucleoside analogue used, is limited by the high rate of resistance. Adefovir has efficacy comparable to that of lamivudine, but with low resistance rate. Entecavir and tenofovir have also been particularly active in the control of hepatitis B virus replication and are associated with minimal resistance development, even during long treatment regimens. Other drugs, such as telbivudine, emtricitabine and clevudine, will become new treatment options in the near future. Individuals co-infected with HIV/HBV are particularly difficult to manage and are nowadays able to benefit from combinations of drugs of the HAART therapy, which should be effective towards both viruses. The development of more potent antiviral drugs as well as new drug combinations, together with a better understanding of hepatitis B virus resistance mechanisms are important milestones to improve treatment efficacy and to diminish, in the future, the global burden of hepatitis B virus.
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PMID:[Advances in the treatment of hepatitis B]. 1787 70

Murine hepatic cytochrome P450 2A5 (CYP2A5), unlike most CYP enzymes, is upregulated during hepatitis and hepatotoxic conditions, but the common stimulus for its induction remains unknown. We investigated the involvement of oxidative stress in the regulation of CYP2A5 expression using an oxidative stress-sensitive glucose-6-phosphate dehydrogenase (G6PD)-deficient mouse model. Treatment of deficient and wild-type mice with the prototypical CYP2A5-inducer pyrazole for 72h led to a significantly greater degree of induction of CYP2A5 mRNA, protein and activity in deficient mice, with the greatest increase observed in animals homozygous for the deficiency. However, markers of oxidative stress including protein carbonyl, 8-hydroxydeoxyguanosine, malondiadehyde and 4-hydroxyalkenal levels were unaltered with pyrazole treatment. Furthermore, CYP2A5 expression was not altered in G6PD-deficient mice treated with the pro-oxidant menadione whereas DNA, lipid, and protein markers of oxidative stress were significantly increased. The antioxidant polyethylene glycol-conjugated catalase, while decreasing oxidative stress in menadione-treated mice, did not prevent the induction of CYP2A5 by pyrazole. Finally, the ER stress marker protein, GRP78, was increased following pyrazole treatment in G6PD-deficient compared to wild-type mice. These findings do not support a central role for generalized cellular oxidative stress in the regulation of CYP2A5 and suggest that additional factors related to G6PD-deficiency, such as ER stress, may be involved.
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PMID:Expression of cytochrome P450 2A5 in a glucose-6-phosphate dehydrogenase-deficient mouse model of oxidative stress. 1806 88


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