UMLS:C0019158 - FACTA Search

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

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

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

The development of this guideline was initiated and coordinated by the Netherlands Association of Gastroenterologists and Hepatologists (Nederlandse Vereniging van Maag-Darm-Leverartsen). The aim is the establishment of national standards in the evaluation and antiviral treatment of patients with chronic hepatitis B virus (HBV) infection. This includes recommendations on the initial evaluation of patients, choice and duration of antiviral therapy, follow-up after antiviral therapy and monitoring of patients not currently requiring antiviral therapy. The initial evaluation of chronic HBV-infected patients should include testing of liver biochemistry, virus serology and abdominal imaging. In patients without cirrhosis, antiviral treatment is recommended for those with a serum HBV DNA of at least 1.0 x 105 c/ml (>or=2.0 x 10(4) IU/ml) in combination with: a) elevation of serum alanine aminotransferase (ALAT) level above twice the upper limit of normal during at least three months, and/or b) histological evidence of porto-portal septa or interface hepatitis on liver histology. In patients with cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1.0 x 10(4)c/ml (>or=2.0 x 10(3) IU/ml) or higher, independent of ALAT levels or histological findings. If the patient has decompensated cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1000 c/ml (>or=200 IU/ml) or higher. Patients who do not have an indication for antiviral treatment should be monitored because there is a risk of (re)activation of disease activity. Monitoring every three to six months is recommended for HBeAg-positive and HBeAg-negative patients with high viraemia (HBV DNA >or=1.0 x 10(5) c/ml or >or=2.0 x 10(4) IU/ml) and normal ALAT levels. For patients with serum HBV DNA below 1.0 x 10(5) c/ml (<2.0 x 10(4) IU/ml) the recommended frequency of monitoring is every three to six months for HBeAg-positive patients and every six to 12 months for HBeAg-negative patients. Peginterferon (PEG-IF N) therapy should be considered as initial therapy in both HBeAg-positive and HBeAg-negative patients without contraindications for treatment with this drug because of the higher chance of achieving sustained response compared with nucleos(t)ide analogue therapy. In patients starting nucleos(t)ide analogue therapy, the use of lamivudine is not preferred if long-term antiviral treatment is expected due to the high risk of antiviral resistance against this drug. Of the currently licensed nucleos(t)ide analogues, entecavir has the lowest risk of antiviral resistance (compared with lamivudine, adefovir and telbivudine), while suppression of viral replication seems most profound with either entecavir or telbivudine. The recommended duration of treatment with PEG-IF N is one year for both HBeAg-positive and HBeAg-negative patients. In HBeAg-positive patents, nucleos(t)ide analogue therapy should at least be continued until HBeAg seroconversion and a decline in HBV DNA to below 400 c/ml (80 IU/ml) has been achieved and maintained for six months during therapy. Whether nucleos(t)ide analogue therapy can be safely discontinued in HBeAg-negative patients is unknown; usually prolonged or indefinite antiviral treatment is necessary. Patients receiving PEG-IF N should be monitored once a month, while three monthly monitoring suffices for those receiving nucleos(t)ide analogues. Genotypic analysis of the HBV polymerase is indicated if an increase in serum HBV DNA of at least 1 log(10) c/ml (IU/ml) compared with the nadir value is observed during nucleos(t)ide analogue therapy. Antiviral therapy should be changed as soon as possible in case of confirmed genotypic resistance. Adding a second antiviral agent seems beneficial over switching to another agent. With the availability of multiple new antiviral drugs for the treatment of chronic hepatitis B, effective treatment is now possible for more patients and for longer periods. However, the complexity of HBV therapy has also increased. Nowadays, virtually all chronic HBV-infected patients can be effectively managed, either by inducing sustained off-treatment response or by maintaining an on-treatment response.
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PMID:Treatment of chronic hepatitis B virus infection - Dutch national guidelines. 1866 60

We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from approximately 50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +/- 1.7 A. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies.
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PMID:Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel. 1898 44

The wide use of lamivudine in chronic hepatitis B has produced a monotonic increase in patients with lamivudine resistance. Therefore, treating lamivudine resistance in chronic hepatitis B is a major concern in clinical practice for the treatment of hepatitis B virus (HBV). There is conflicting evidence on the outcome of pegylated interferon alpha (PEG-IFN alpha) therapy against lamivudine-resistant HBV, which is due to mutations in the YMDD motif. We experienced a patient with chronic hepatitis B who was successfully treated with PEG-IFN alpha-2a after the development of virologic and biochemical breakthrough during lamivudine therapy. Virologic breakthrough was associated with the emergence of YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN alpha-2a for 12 months resulted in an undetectable serum level of HBV DNA and the resolution of hepatitis, and the virologic response was maintained over 16 months after cessation of PEG-IFN alpha-2a.
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PMID:[A case report of treatment with pegylated interferon alpha for lamivudine-resistant chronic hepatitis B virus infection]. 1911 46

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