Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Chronic hepatitis B is defined by the persistence of circulating HBs antigen for more than 6 months. Between 15 and 25% of chronic HBV carriers die prematurely of complications (mainly cirrhosis and hepatocellular carcinoma). (2) Patients with chronic hepatitis B rarely clear the virus spontaneously, but viral replication ceases in approximately 10% of patients annually, with disappearance of HBe and viral DNA, and emergence of anti-HBe antibodies. (3) Active viral replication and histologically proven liver necrosis are risk factors for progression to cirrhosis. (4) Antiviral treatments have been assessed only in patients with active viral replication. (5) Interferon alfa has been widely tested in the clinical setting. In one trial, in which patients were followed for 7 years, mortality was lower in the treatment group than in untreated controls. (6) Interferon alfa must be injected, and its administration may be followed by adverse effects such as a 'flu-like syndrome (frequently), psychiatric problems and potentially severe thyroid disorders. (7) Interferon alfa monotherapy for 4-6 months (possibly extended to 8-9 months) remains the first-line treatment for chronic hepatitis B. (8) Lamivudine has documented antiviral efficacy but its effect is only temporary in many patients. In the only trial comparing lamivudine with interferon alfa, lamivudine was no more effective than interferon in the short term (on the basis of serological and histological end points), despite a bias in its favour. Trials of lamivudine + interferon alfa in patients who fail to respond to interferon monotherapy have given unfavourable results. (9) Adverse effects are infrequent on lamivudine, but pharmacovigilance is required to assess potential hepatic and pancreatic effects at the dose used in this indication. (10) The long-term effects of lamivudine are unknown, especially on the risks of cirrhosis, hepatocarcinoma and the selection of resistant mutants. (11) Pending further data, lamivudine should be used only in clinical trials and cohort studies.
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PMID:Treatment of chronic hepatitis B: interferon alfa first. 1150 53

Hepatitis C virus (HCV) is a widespread infectious disease in humans with the negative implication of becoming chronic in most persons. Patients infected with HCV are at risk of liver cirrhosis or hepatocellular carcinoma at later stages. In contrast to hepatitis A and hepatitis B, there is no immunization yet available, neither prophylactic nor therapeutic. Thus, there is an urgent need to develop a safe, protective vaccine against this fatal disease. Developing countries are even more at risk for HCV. There are currently a number of scientific approaches aimed towards solving this problem. Taking both risks and costs of immunization into consideration, a peptide-based vaccine may be a reasonable prophylactic protection. Also, it might be of therapeutic use in already infected patients by increasing a specific CTL response against HCV. In our lab, we are focusing on immunopotentiating reconstituted influenza virosomes (IRIVs) as carriers for immunogenic HLA-A2-restricted core epitopes to induce peptide-specific cytotoxic T lymphocytes (CTLs). The IRIVs are similar to liposomes, but in addition contain influenza-derived hemagglutinin and neuraminidase on their outer surface which makes them fusogenic, thus, permitting antigen delivery to host cells. So far, virosomes have been successfully used for vaccine development and as a result a virosomal vaccine against both influenza virus (Inflexal) BERNA) and hepatitis A virus (HAV) (Epaxal) BERNA) already exist on the market. This paper focuses on the importance of development of a successful vaccine against HCV and, more specifically, we discuss the use, advantages and disadvantages of a peptide-based vaccine. A brief report of our latest findings will be included.
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PMID:Perspectives: towards a peptide-based vaccine against hepatitis C virus. 1174 97

Children with chronic hepatitis B, face life long disease and complications of cirrhosis and hepatocarcinoma. Naturally, it is estimated that half to two third of the children will clear the hepatitis Be antigen during childhood. Treatments aim to increase the HBe Ag to Ab seroconversion rate, which may also favour the loss of HBs antigen, ultimate goal. Interferon alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to increase the HBe ag loss from 11% in control group to 26% in treated patients (5 MU/square meter body surface area for six months) at one year, and 33% at 18 months. Side effects include mainly fever, flu like symptoms, and growth impairment during the treatment phase. Nucleotide analogues have now emerged as a promising alternative to treat chronic hepatitis B. The optimal dose for children is established to 3 mg/kg once daily up to 12 years old. Efficacy trials show complete virologic response in 23% of all treated patients after one year, as compared to 13% in the placebo group, and in 34% of patients with basal transaminases above two times upper limit of normal; versus 16% in controls. Lamivudine inhibits viral DNA which favours cellular immune response. Lamivudine resistance due to variant viruses is observed in 19% of children after one year. Other nucleotide analogues, such as entecavir and adefovir will soon be tested in children, and combination with Lamivudine may improve results. Finally, vaccine technology is being tested in adults, to induce a cellular immune response towards hepatitis B antigens, but no clinical benefit has so far been established.
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PMID:[Hepatitis B in children: natural history and therapy]. 1199 83

Children with chronic hepatitis B are at risk of developing long-term complications such as cirrhosis and hepatocarcinoma. It is estimated that half to two-thirds of affected children will clear the hepatitis B e antigen (HBeAg) naturally before reaching adulthood. As in adults, treatments in children accelerate the virological response (DNA negativity and HBeAg loss, with anti-HBe seroconversion), which is associated with normalization of transaminase levels. Treatments also favor subsequent loss of hepatitis B surface antigen (HbsAg), the ultimate goal for minimizing long-term consequences. Interferon-alpha was the first approved treatment for pediatric chronic hepatitis B, and was shown to promote DNA negativity and HBeAg loss in 26% of treated patients (6 MU/m(2) body surface area for 6 months) at 1 year and 33% at 18 months (versus 11% in controls). 10% of treated patients also lost HBsAg. Adverse effects mainly included fever, flu-like symptoms and growth impairment during the treatment phase. Nucleotide analogs have now emerged as promising alternatives for the treatment of chronic hepatitis B. Lamivudine dose-ranging studies showed a higher clearance in children, and the optimal dosage was established to be 3 mg/kg once daily in children up to 12 years of age. Efficacy trials showed complete virological response (HBeAg loss and DNA negativity) in 23% of all treated patients after 1 year, and in 34% of patients with initial transaminase levels >2 x the upper limit of normal. Lamivudine resistance due to mutant/variant viruses is observed in 19% of children after 1 year, a figure that may increase by an average of 20% per year. Other nucleotide analogs, such as adefovir, will soon be tested in children, and have shown promising results in adults without so far demonstrating viral resistance. Finally, therapeutic vaccines aiming to induce a cellular immune response towards hepatitis B antigens are being tested in adults, but no clinical benefit has so far been established.
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PMID:Drug treatment of pediatric chronic hepatitis B. 1203 72

Thymosin alpha1 (Talpha1), a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement, was originally developed by Alpha 1 Biomedicals for the treatment of hepatitis B virus (HBV) infection. SciClone developed and launched Talpha1, under the trade name Zadaxin, for the treatment of HBV and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of non-small cell lung cancer (NSCLC), hepatocellular carcinoma, AIDS and malignant melanoma. Talpha1 is able to potentiate the action of cytokines and also reduce the hematological toxicity of cytotoxic drug therapy (cyclophosphamide-, 5-fluorouracil-, dacarbazine- or ifosfamide-based regimens). These studies also demonstrated the mechanism of action of Talpha1 and its role as an immune system enhancer. By July 2001, it was in phase III trials in the US in combination with PEGylated interferon-alpha, and later the same month it was approved in the Philippines. SciClone received expanded approval for HBV and HCV infection in Mexico in July 2001. Talpha1 has been launched in Argentina, China, Peru, the Philippines and Singapore for the treatment of chronic HBV infection. The product subsequently received expanded approval for the treatment of both HBV and HCV infection in Argentina. Marketing approval was granted in India for HBV infection in February 2001. The company was working to expand this approval to include HCV infection. In March 2000, approval for treatment of HBV infection was granted in Thailand, Laos and Malta. Approval was also granted in Sri Lanka and Brunei in August 1999. In September 2000, SciClone announced that approval had been expanded to include the treatment of HCV infection as well as the previously approved HBV indication in both Peru and Sri Lanka. In January 1999, SciClone received approval for Talpha1 in Venezuela for the treatment of HBV and HCV infection. The company also filed a marketing application in New Zealand for Talpha1 to treat HBV infection. The drug was approved in South Korea in April 2000, as an influenza vaccine adjuvant and this was expected to be expanded to indude use for treatment of both HBV and HCV infections. In July 2001, it was approved in In September and October 2000, SciClone was granted patents in Mexico and Canada, respectively, for the use of Talpha1 for the treatment of HCV infection. In June 2000, SciClone was issued a Notice of Allowance by the US Patent and Trademark Office for use of Talpha1 in the treatment of HBV infection. The EPO granted a patent, exclusively licensed to SciClone, for the use of Talpha1 as a monotherapy or in combination with interferon, to treat for HCV infection. In April 2001, SciClone received a Notice of Allowance for a US patent covering newly described analogs of Talpha1. The patent gave the Philippines as an adjuvant to chemotherapy for the treatment of various cancers. In December 2001, Talpha1 entered a phase 1 trial program in Europe, with patient enrolment planned for 2002. SciClone exclusive composition-of-matter rights to several families of Talpha1 analogs that could have proprietary therapeutic or biologic distinctions from Talpha1. The company was issued US patents covering the use of Talpha1 for the treatment of HCV infection in August 1998 and the treatment of HBV infection in September 1999. A Notice of Allowance for a second US patent covering the use of Talpha1 was issued in October 1999. In April 1999, SciClone received allowance of a patent from the EPO covering the use of Talpha1 in small cell and non-small cell lung cancer. In August 2001, SciClone received a notice of allowance for patent protection in Japan covering the use of Talpha1. The patent, which extends until 2012, also covers the use of Talpha1 in combination with interferon-alpha for the treatment of HCV infection. SciClone was previously granted a Japanese patent for the use of Talpha1 in the treatment of HBV infection.
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PMID:Thymosin alpha1. SciClone Pharmaceuticals. 1209 May 42

Infection, including viral infection, still cause serious complication in the course of chemotherapy. Recognition of viral infections, monitoring, prophylaxis and treatment is aimed at reducing the number of infected patients, mitigating the cause of the disease and limiting deaths directly linked with infections in paediatric cancer patients. Viruses from the herpes group (HSV, VZV, EBV, CMV) are particularly dangerous. They can cause not only asymptomatic and local infectious but also general diseases and can reactivate, especially after BMT. Hepatoropic viruses (HBV, HCV) often lead to breaks in chemotherapy, while chronic viral hepatitis can lead to fibrosis, cirrhosis and even primary hepatocellular carcinoma. CMV, RSV, adenovirus influenza and parainfluenza virus cause diffuse interstitial pneumonitis and are also associated with a high rate of mortality. In this paper, we present the most frequency viral infection in children with malignant diseases, their methods of diagnosis and treatment.
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PMID:[Viral infection in children with malignant diseases]. 1457 9

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

Human HepG2 hepatoma cells are highly permissive for influenza virus type A and type B, even without the addition of trypsin, and they exhibit a marked cytopathic effect. This property greatly facilitates the primary isolation of influenza viruses. Virus replication was significantly reduced by the plasmin(ogen)-specific inhibitor tranexamic acid, and this suggests a potential role played by the plasminogen/tissue plasminogen activator complex at the surface of HepG2 cells. This might represent a new approach for study of the interrelations of this complex with influenza viruses.
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PMID:High permissivity of human HepG2 hepatoma cells for influenza viruses. 1558 26

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.
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PMID:Treatment of chronic hepatitis C in children. 1559 40

Neuraminidase inhibitors have been widely used in Japan since 2001, and several side-effects of their use have been reported. However, erythema toxicum has rarely been described as a side-effect of these drugs in patients with liver function disorder. Here, we report a case of generalized rash after treatment with the neuraminidase inhibitors zanamivir and oseltamivir administered prophylactically to prevent influenza infection in two patients with hepatoma associated with liver cirrhosis.
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PMID:A side effect of neuraminidase inhibitor in a patient with liver cirrhosis. 1572 87


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