Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight patients with chronic (mean 52 months) type B hepatitis (chronic active hepatitis and active cirrhosis) and markers of active viral replication (presence of HBeAg and HBV-DNA in serum) were treated with Ara-AMP for 7-12 weeks. The mean follow-up time was 18.3 months. All but one patient responded to treatment. In seven patients, HBeAg and HBV-DNA became negative and developed anti-HBe. One patient lost HBsAg as well as HBeAg and HBV-DNA. HBcAg in liver tissue became undetectable or greatly reduced in the seven patients in whom it was strongly positive. Aminotransferase and immunoglobulin levels reverted to normal in the seven responders and remained normal through the entire follow-up period. A second liver biopsy, performed after completion of therapy, showed improvement in six of eight cases, with disappearance of lobular activity. Two patients treated for 12 weeks developed a severe polyneuropathy lasting for 6 months. A 7-week course of Ara-AMP seems to induce long-lasting inhibition of viral replication, along with an improvement in liver function tests and liver histology, without significant side effects. On the other hand, a 12-week course was associated with the development of a severe and prolonged polyneuropathy.
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PMID:Prolonged inhibition of hepatitis B virus replication with vidarabine monophosphate in chronic active type B hepatitis. 242 52

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.
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PMID:Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate. 257 92

Therapy for chronic hepatitis B virus (HBV) infection is primarily directed at those patients with evidence of replicative infection because they are most at risk for developing chronic hepatitis, cirrhosis, and possibly hepatocellular carcinoma (HCC). Although a number of agents or therapeutic approaches have been tested against HBV infection, only a few have been subjected to controlled clinical trial. Corticosteroid therapy, particularly if prolonged, may be harmful and should be avoided. Adenine arabinoside monophosphate (Ara-AMP) has potent inhibitory effects on HBV replication, but its use is limited by severe neurotoxicity. At present, prolonged treatment with alpha interferon offers the most promise as a beneficial therapy for chronic type B hepatitis. Alpha interferon consistently induces permanent clearance of hepatitis B e antigen (HBeAg) and HBV DNA from serum more often than in untreated patients. Present efforts are directed at determining the factors predictive of a favorable response to interferon, and attempting to increase the response rate by using alpha interferon in combination with other antiviral or immunomodulatory agents.
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PMID:Treatment of chronic type B hepatitis. 262 Mar 10

Adenine arabinoside monophosphate (ara-AMP) is a potent antiviral agent against hepadnaviruses but its use in the treatment of chronic hepatitis B is hampered by severe neurotoxic side effects, which are dose dependent. In order to reduce these adverse reactions and to adopt the lysosomotropic approach to antiviral chemotherapy, ara-AMP was coupled to lactosaminated human serum albumin (L-HSA), a neoglycoprotein which specifically penetrates hepatocytes. In mice with Ectromelia virus hepatitis, ara-AMP coupled with L-HSA was selectively delivered to liver cells in which it was released in a pharmacologically active form. Moreover in woodchucks with WHV hepatitis and in patients with chronic HBV infection, coupled ara-AMP inhibited hepadnavirus replication at a dose (1.5 mg/kg/day) 3-6 times lower than the free drug. A clinical study using a 28-day period of treatment with conjugated ara-AMP at 1.5 mg/kg/day has now been started. In the first 6 patients the treatment has been completed. The conjugate inhibited virus growth without producing any side effects. L-HSA-ara-AMP conjugate must be given by intravenous infusion. New hepatotropic conjugates of ara-AMP have been recently prepared which could be administered by bolus intravenous injection or by intramuscular route. These complexes might assure a better compliance in patients with hepatitis B virus infection for a long lasting liver targeted antiviral treatment.
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PMID:Liver targeting of adenine arabinoside monophosphate (ara-AMP) by coupling to lactosaminated human serum albumin. 852 36

We report the case of a hepatitis B virus chronic carrier in whom features of severe autoimmune hepatitis developed concurrently with the emergence of a hepatitis Be antigen-negative variant. Corticosteroid administration failed to normalize serum transaminase activity and resulted in increased viral multiplication. Adenine arabinoside monophosphate treatment allowed simultaneous inhibition of hepatitis B virus multiplication and remission of autoimmune features. This observation indicates that hepatitis Be antigen-negative variants can induce autoimmune hepatitis and adds support to the hypothesis that autoimmune hepatitis can be triggered by hepatotropic viruses. Patients with both features should first be treated with adenine arabinoside monophosphate. This observation indicates that hepatitis Be antigen-negative variants can induce autoimmune hepatitis and adds support to the hypothesis that autoimmune hepatitis can be triggered by hepatotropic viruses. Patients with both features should first be treated with adenine arabinoside monophosphate.
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PMID:Concurrent emergence of hepatitis B e antigen-negative hepatitis B virus variant and autoimmune hepatitis cured by adenine arabinoside monophosphate. 982 38

The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a model of hepatitis B virus (HBV)-induced disease. Several published studies have used this experimental animal model system to demonstrate potential antiviral therapies for chronic HBV infections. However, there has been little comparative information available on compounds used in clinical anti-HBV studies in WHV-infected woodchucks, thereby making interpretations of the potential relative effectiveness of new antiviral agents in humans more difficult. In this report, using a series of placebo-controlled studies, we compared the relative effectiveness of several nucleoside analogues that have been used in clinical trials for the treatment of chronic HBV infection against WHV replication in chronically infected woodchucks. Adenine-5'-arabinoside monophosphate (Ara-AMP [vidarabine]), ribavirin, (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC [lamivudine]), and famciclovir (oral prodrug of penciclovir) induced depressions in viremia and intrahepatic WHV-DNA replication that were consistent with their relative effectiveness in anti-HBV human clinical trials. As observed in HBV-infected patients, 3' azido-3'-deoxythymidine (AZT [zidovudine]) had no effect on WHV replication in these studies. These experimental results more firmly establish chronic WHV infection in woodchucks as an accurate and predictive model for antiviral therapies against chronic HBV infection in humans and provide a baseline for comparative antiviral effects of other experimental antiviral agents in the WHV/woodchuck model system.
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PMID:Treatment of chronic woodchuck hepatitis virus infection in the Eastern woodchuck (Marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis B virus infection in humans. 1079 94

To preliminarily observe the antiviral effect of receptor-targeted drug, the Lactosaminated Human Serum Albumin Arabinoside Adenine Monophosphate (L-HSA-Ara-AMP), 10 patients with chronic type B hepatitis (HBsAg, HbeAg/HBV DNA positive) were treated with this drug for 5 days. The daily dose of L-HSA-Ara-AMP was 35 mg/Kg (containing 1.5 mg Ara-AMP), whereas the usual daily dose of free Ara-AMP is 10 mg/Kg. In 10 patients treated, three patients' HBeAg became negative and six patients' HBeAg titer fell. Anti-HBc IgM all became negative in 4 anti-HBc IgM positive patients. In 8 HBV DNA positive patients, four patients' HBV DNA became negative and the other four patients' HBV DNA decreased. HBsAg remained positive in all of the ten patients. No adverse effects were observed. The results showed that L-HSA-Ara-AMP inhibits HBV as effective as free Ara-AMP, but at a daily dose 6.7 times lower than free Ara-AMP.
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PMID:[Preliminary clinic observation on the inhibition of HBV by receptor-targeted drug L-HSA-AraAMP]. 1251 62

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
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PMID:AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis. 1990 Apr 20

We studied the effect of acute ammonia poisoning and CCl4-induced subacute hepatitis on activities of AMP deaminase and adenosine deaminase in rat liver. Both models of liver failure were accompanied by an increase in activities of AMP deaminase and adenosine deaminase in the cytoplasmic fraction of the liver (by 2.4-4.2 times compared to the control). A direct correlation was found between activities of AMP deaminase and adenosine deaminase. We believe that two parallel pathways of AMP degradation are activated simultaneously, which leads to rapid depletion of adenylate reserves under pathological conditions.
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PMID:Activation of AMP deaminase and adenosine deaminase in the liver during ammonia poisoning and hepatitis. 2116 Oct 45

BACKGROUND Berberine, a herbal extract, has been reported to protect against inflammatory disorders. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway can be activated by berberine and inhibited by the synthetic, reversible AMP-competitive inhibitor, Compound C. The aim of this study was to investigate the effects of berberine on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) in mice via the AMPK pathway. MATERIAL AND METHODS BALB/c mice were treated with berberine, with or without Compound C, followed by treatment with Con A. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue histology was performed to evaluate hepatic injury and AIH. Cytokine levels in serum and hepatic tissue were measured by enzyme-linked immunoassay (ELISA) and used quantitative polymerase chain reaction (qPCR). Levels of phosphorylated acetyl coenzyme-A carboxylase (ACC), representing AMPK activation, were detected by Western blotting. RESULTS Serum ALT and AST levels were significantly reduced by berberine (100 and 200 mg/kg/day) in mice with Con A-induced hepatitis. Berberine also reduced Con A-induced hepatocyte swelling, cell death, and infiltration of leukocytes. Serum levels of tumor necrosis factor (TNF)-alpha, interferon (IF)-gamma, interleukin (IL)-2, and IL-1beta were reduced by berberine pre-treatment; levels of serum IL-10, an anti-inflammatory cytokine, was elevated. These protective effects of berberine on Con-A-induced AIH were reversed by treatment with Compound C. CONCLUSIONS In a murine model of Con A-induced AIH, berberine treatment reduced hepatic injury via activation of the AMPK pathway. Further studies are recommended to determine the potential therapeutic role for berberine in AIH.
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PMID:The Effects of Berberine on Concanavalin A-Induced Autoimmune Hepatitis (AIH) in Mice and the Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase (AMPK) Pathway. 2928 90


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