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)

Recent advances in basic science and clinical trials have demonstrated that IFNs and myeloid hematopoietins play crucial roles in host defense against pathogens and immune surveillance. Here we have reviewed the biologic functions of GM-CSF, G-CSF, IFN-alpha and IFN-gamma. For patients with neutropenia resulting from cytotoxic chemotherapy, bone marrow transplantation, congenital agranulocytosis and cyclic neutropenia, therapeutic uses of GM-CSF and G-CSF were reviewed. Application of these growth factors to patient management represents a major contribution of biotechnology to a difficult area of therapeutics in febrile, neutropenic patients. Because IFN-alpha plays crucial roles in antiviral responses, its clinical applications in hepatitis B and C, human papilloma virus, HIV infection and malignancy were discussed. The use of IFN-gamma in bacterial prophylaxis in patients with chronic granulomatous disease was also presented. Advances in clinical applications of IFNs and hematopoietic growth factors serve as a paradigm for further development to investigate the use of other important cytokines in modern therapeutics.
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PMID:Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons. 904 17

The hepatitis B virus (HBV) is the world's most important chronic virus infection. The immunomodulator interferon-alpha (IFN alpha) is the only clinically applied drug available, despite its low response rate (approximately 30%) even in highly selected chronic carriers. Antiviral nucleoside analogues have proven to be potent inhibitors of viral replication in vitro, but their significant adverse effects which are, at least partially, due to their nonspecific body distribution, have forced the cessation of their clinical development in the past. For example, vidarabine causes severe neuromuscular toxicity, and fialuridine has caused fatal cases of liver and kidney failure in a recent clinical trial. Furthermore, the potential clinical application of (modified) antisense oligodeoxynucleotides, which are very specific inhibitors of viral replication, is hampered by their nonspecific body distribution, instability in serum and poor cell penetration. As infection and replication of HBV mainly occur in liver parenchymal cells, selective targeting of antiviral nucleoside analogues as well as antisense oligodeoxynucleotides to the liver would theoretically improve therapeutic efficacy. At present, conjugates of vidarabine and neoglycoproteins have entered clinical trials, and initial data suggest that therapeutic concentrations are achieved at lower dosages with minor adverse effects. These data have stimulated preclinical research on other liver-specific drug carriers for the selective delivery of HBV-active drugs such as glycosylated polymers and neolipoproteins: these approaches are outlined in this paper.
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PMID:Targeting hepatitis B therapy to the liver. Clinical pharmacokinetic considerations. 885 35

It has recently been shown that thymosin-alpha1(T-alpha1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-alpha1 treatment in patients with hepatitis B e antibody (anti-HBe) and HBV-DNA-positive chronic hepatitis. Thirty-three patients were randomly assigned to receive either T-alpha1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN-alpha) three times weekly (16 patients) for 6 months. At baseline, both groups were comparable concerning age, sex, liver histology, and alanine transaminase (ALT) levels. At the end of treatment, complete response (defined as ALT normalization and HBV-DNA loss) occurred in 5 of 17 (29.4%) in the T-alpha1 group and in 7 of 16 (43.8%) in the IFN-alpha group (P = not significant). After a follow-up period of 6 months, a complete response was observed in 7 of 17 (41.2%) in the T-alpha1 group and in 4 of 16 (25%) in the IFN-alpha group (P = n.s.). Compared with the results observed in a group of 15 patients never treated with IFN-alpha and followed for 12 months, the rate of complete response was significantly higher in the IFN-alpha group at the end of therapy (1 of 15 vs. 7 of 16, respectively; P < .05) and in the T-alpha1 group at the end of follow-up (1 of 15 vs. 7 of 17, respectively; P < .05). Unlike IFN-alpha, T-alpha1 was well tolerated by all patients. The only side effect, reported by some, was local discomfort at injection sites. The results of this trial suggest that T-alpha1 is able to reduce HBV replication in patients affected by anti-HBe-positive chronic hepatitis. Furthermore, compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV-DNA loss. In conclusion, T-alpha1 appears to be a safe and effective alternative treatment for anti-HBe-positive chronic hepatitis. The benefit of this agent in producing long-term inhibition of HBV replication must be confirmed by future trials.
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PMID:A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B. 885 75

In endemic areas infection with hepatitis B virus is a common cause of chronic liver disease in childhood. High levels of viral replication and mild ALT abnormalities are the rule in children infected perinatally and many of them are likely to maintain viral replication through their youth. Conversely about 90% of children infected later in life clear HBeAg and achieve sustained remission of liver disease before reaching adulthood. The eventual outcome of infection and disease in these patients remains unpredictable as reactivation of liver damage and viral replication may occur after several years of sustained remission. Cirrhosis is a rare and early complication of chronic HBV infection in children, and a risk factor for hepatocellular carcinoma. IFN therapy can accelerate HBV DNA clearance, improving the spontaneous anti-HBe seroconversion rate in Caucasian children by two to three times. Hepatitis delta is the most severe form of chronic viral hepatitis in childhood. Cirrhosis can be diagnosed in up to 26% of patients at presentation, and few cases respond to IFN therapy. Hepatitis C is relatively rare in children. Before the discovery of HCV, blood transfusions were the most common source of infection. Hepatitis C is usually a mild, asymptomatic disease in otherwise healthy children, but has a poor propensity to spontaneous remission over the years. For this reason, and based on the experience in adults, IFN treatment is now being evaluated.
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PMID:Chronic viral hepatitis in childhood. 886 29

This open label study was initiated to assess the safety and efficacy of lymphoblastoid interferon-alpha (IFN-alpha) and thymosin alpha 1 (T alpha 1) in the treatment of 11 patients with chronic hepatitis B, who had failed to respond to standard IFN-alpha 2b therapy, and in four interferon naive patients. These fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus (HBV) DNA positive patients were given T alpha 1 (1 mg) subcutaneously (s.c.) on 4 consecutive days. Low-dose lymphoblastoid IFN-alpha (3 MU) was administered intramuscularly (i.m.) on the fourth day. Beginning with the second and for the subsequent 25 weeks, patients self-administered T alpha 1 twice weekly in the morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN-alpha. Patients were followed-up for 12 months. Nine (60%) of the 15 patients, including six (55%) of the 11 patients previously treated with IFN-alpha 2b, responded by losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six of the nine responders seroconverted to HBsAg negativity. Significant improvements in the Knodell histological activity index were observed in the responders and no significant adverse effects were observed. Combination low-dose lymphoblastoid IFN-alpha and T alpha 1 treatment may provide a safe and potentially effective therapeutic approach in chronic hepatitis B. These results require confirmation in future randomized controlled studies.
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PMID:Combination low-dose lymphoblastoid interferon and thymosin alpha 1 therapy in the treatment of chronic hepatitis B. 887 80

A literature review of patients chronically infected with hepatitis B virus (HBV) treated with natural human interferon alpha (nHuIFN-alpha) given parenterally every day for 28 days revelated that even the daily dose of (5 x 10(6)IU) of IFN-alpha inhibits cellular metabolism. As a result of metabolic block, the number of blood elements were diminished. Furthermore treated patients recorded several different adverse reactions. In contrast, among patients treated with the oral form of nHuIFN-alpha non metabolic block occurred and no adverse reactions were seen, even though the therapy lasted much longer. Two years after initiation of parenteral IFN-alpha therapy, the loss of HBV-BeAg was 53.8% and 28.8% of the patients had undergone seroconversion. In contrast, 77% of patients on oral interferon lost HBV-BeAg and 74% serconverted and normalized their biochemical liver function. The results suggest that the nHuIFN-alpha given orally and parenterally activate two different mechanisms responsible for virus elimination.
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PMID:Natural human interferon alpha may act differently when given parenterally or orally to patients chronically infected with hepatitis B virus. 887 64

An association between hepatotropic viruses, chiefly hepatitis C virus (HCV), occasionally hepatitis B virus (HBV), and mixed cryoglobulinemia has been widely reported. Alpha-interferon (IFN-alpha) has usefully been employed in the treatment of mixed cryoglobulinemia, particularly for liver and renal involvement. IFN-alpha treatment may be associated with neurological complications, including peripheral neuropathy. We describe an HBV positive patient with mixed cryoglobulinemia with recurrent purpura, mild sensory peripheral neuropathy, and active hepatitis treated with IFN-alpha. Rapid improvement of the purpura, liver enzymes, and cryocrit, and disappearance of serum HBV DNA were observed after a 4 week treatment period. However, concomitant worsening of the neuropathy prompted us to discontinue IFN-alpha. Although in this case, a positive effect of IFN-alpha on the clinico-serological and virological variables was confirmed, due to the possible exacerbation of neurological manifestations, a careful patient evaluation is necessary before starting IFN-alpha in patients with mixed cryoglobulinemia.
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PMID:Exacerbation of peripheral neuropathy during alpha-interferon therapy in a patient with mixed cryoglobulinemia and hepatitis B virus infection. 941 68

The efficacy of two different high-dose treatment of IFN-alpha 2b was evaluated in this study. Serum hepatitis C virus (HCV) RNA levels were semi-quantified by simplified reverse transcription-polymerase chain reaction. Seventy-one patients with chronic hepatitis C received 10 million units of IFN-alpha 2b daily for 2 weeks or twice a week for 24 weeks. Alanine aminotransferase (ALT) levels overall normalized in 78.1% and 51.6% of the cases at the end of the therapy and 6 months after that, respectively. HCV RNA disappeared in 71.9% and 35.7% of the patients at the end of the therapy and 6 months after that, respectively. There was no significant difference between the 2 different regimes. The efficacy of the treatment was fair in cases in which the pretreatment level of the viral amount was low. The results of this study indicate that daily administration of IFN in the first 2 weeks during 6-month course does not increase the efficacy of the therapy in such a high-dose treatment regime.
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PMID:Keio multicenter trial in high-dose interferon-alpha 2b treatment for chronic hepatitis C. Keio Interferon-alpha 2b Study Group. 889 59

Interferon alfa (IFN-alpha) treatment is effective in only a proportion of patients with chronic hepatitis B virus (HBV) infection. The mechanisms for therapeutic failure remain unknown but high levels of HBV replication are known to inhibit the immunopotentiating effects of IFN-alpha. In nine patients with chronic hepatitis B not responding to IFN-alpha monotherapy, we determined the virus-specific T-helper-cell responses during two consecutive therapeutic regimens: IFN-alpha alone and IFN-alpha in combination with a new potent inhibitor of HBV replication, lamivudine. By comparing the results obtained during the initial IFN-alpha monotherapy to those during the combination treatment, it was investigated whether complete inhibition of virus replication will enhance the interferon-induced immunoreactivity to HBV. Despite the rapid reduction to undetectable serum HBV DNA in all nine patients during the combination treatment, none sustained permanent hepatitis B e antigen (HBeAg) clearance during subsequent 12-month follow-up. HLA class II-restricted T-helper-cell responses to hepatitis B core antigen (HBcAg) showed no difference during IFN-alpha monotherapy and during the combination of lamivudine plus IFN-alpha. In contrast, a delayed T-cell activation occurred after a rebound in serum HBV DNA postcombination treatment, which lead to increased hepatocytolysis. These findings suggest that the profound inhibition of HBV replication by a nucleoside analogue does not restore the impaired virus-specific T-cell response in chronic HBV infection.
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PMID:Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection. 890 65

During therapy of chronic viral hepatitis B (CVHB), some patients treated with natural human interferon alpha (nHuIFN-alpha) lozenges failed to respond. These observations triggered studies aimed to determine whether there are markers predicting patients' response to therapy with nHuIFN-alpha lozenges. In these studies, 32 patients with CVHB were involved: 20 males and 12 females, 16-61 years of age with proven persistent hepatitis B viremia (HBV). Patients were evaluated for clinical, biochemical liver function, and virological markers of disease. During 300 days of treatment of the patients received 75-150 IU nHuIFN-alpha daily in form of lozenges. The responders to oral interferon therapy were those who had initially alanine amino transferase (ALAT) level higher than 100 IU (85.7% cure rate) and weak responses were observed among patients who had an initial ALAT level below 100 IU (9.0% response rate). Therefore, ALAT test in patients with CVHB may serve as a predicting indicator of the outcome of IFN lozenges therapy.
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PMID:Natural human interferon alpha given orally has different effects on patients with distinct forms of chronic viral hepatitis B. 891 25


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