Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia … (original) (raw)
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Hepatology (Baltimore, Md.), 1996
A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (∼ 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.
A conjugate of adenine arabinoside monophosphate phate (ara-AMP) has been studied both in Europe and (ara-AMP) with the liver-targeting molecule lactosami-the United States 1-5 with controversial results on long-nated human serum albumin (L-HSA) was administered term efficacy. A metaanalysis 6 of six randomized, con-by intravenous infusion for 28 days to eight patients trolled studies showed a significantly larger percentage with chronic type B hepatitis. The daily dose varied of hepatitis B e antigen (HBeAg) loss and HBV-DNA among the patients, ranging from 34 mg/kg to 53 mg/ negativation in the treated group. However, the painful kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). sensory peripheral neuropathies and severe myalgias Pharmacokinetic analysis indicated that, at every dose caused by this drug limited its use and led to its with-tested, the conjugate was disposed of without accumula-drawal in Britain and the United States. 7 In order to tion. Viral DNA serum levels fell markedly during treat-reduce these adverse reactions, the lysosomotropic ap-ment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neu-proach to antiviral chemotherapy 8,9 was adopted, and rotoxic side effects of free ara-AMP or other adverse clin-ara-AMP was conjugated with lactosaminated human ical reactions. It produced a significant increase both in serum albumin (L-HSA). 10-13 L-HSA is a neoglycopro-serum alkaline phosphatase activity and platelet num-tein which selectively enters into hepatocytes 14 after ber, and a small but significant decrease in erythrocyte binding to the asialoglycoprotein receptor. 15 In labora-number. These laboratory parameters returned to nor-tory animals, L-HSA-ara-AMP was selectively taken mal levels within 2 months after treatment. The conju-up by the liver, where the drug was released in a phar-gate induced the production of small amounts of anti-macologically active form. 10-13,16 In preliminary clinical bodies (Ç20 pmol of conjugate bound by 1 mL of serum)
A conjugate of adenine arabinoside monophosphate phate (ara-AMP) has been studied both in Europe and (ara-AMP) with the liver-targeting molecule lactosamithe United States 1-5 with controversial results on longnated human serum albumin (L-HSA) was administered term efficacy. A metaanalysis 6 of six randomized, conby intravenous infusion for 28 days to eight patients trolled studies showed a significantly larger percentage with chronic type B hepatitis. The daily dose varied of hepatitis B e antigen (HBeAg) loss and HBV-DNA among the patients, ranging from 34 mg/kg to 53 mg/ negativation in the treated group. However, the painful kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). sensory peripheral neuropathies and severe myalgias Pharmacokinetic analysis indicated that, at every dose caused by this drug limited its use and led to its withtested, the conjugate was disposed of without accumuladrawal in Britain and the United States. 7 In order to tion. Viral DNA serum levels fell markedly during treatreduce these adverse reactions, the lysosomotropic apment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neu-proach to antiviral chemotherapy 8,9 was adopted, and rotoxic side effects of free ara-AMP or other adverse clinara-AMP was conjugated with lactosaminated human ical reactions. It produced a significant increase both in serum albumin (L-HSA). 10-13 L-HSA is a neoglycoproserum alkaline phosphatase activity and platelet numtein which selectively enters into hepatocytes 14 after ber, and a small but significant decrease in erythrocyte binding to the asialoglycoprotein receptor. 15 In laboranumber. These laboratory parameters returned to nortory animals, L-HSA-ara-AMP was selectively taken mal levels within 2 months after treatment. The conjuup by the liver, where the drug was released in a phargate induced the production of small amounts of antimacologically active form. In preliminary clinical bodies (Ç20 pmol of conjugate bound by 1 mL of serum)
Gut, 1995
This study compared the response to adenine arabinoside 5'-monophosphate (ARA AMP) in 60 patients with chronic hepatitis B according to the pretreatment serum hepatitis B virus DNA concentration. The level of hepatitis B virus replication was defined as low (30 patients) or high (30 patients) when serum hepatitis B virus DNA concentration was below or above 100 pg/ml, respectively. Patients received a 28 day course of ARA AMP and a second course of ARA AMP was given six months later to patients with persistent hepatitis B virus replication. At the end of the first course of ARA AMP, 11 of the patients (37%) with low replication and one of the patients (3%) with high replication became negative for hepatitis B virus DNA (p=0.0012); five of the patients (17%) with low replication and none of the patients with high replication had HBe seroconversion (p=0.06). Two of these five patients lost HBsAg. Kinetics of serum hepatitis B virus DNA during treatment showed a considerable but transient antiviral effect of ARA AMP. Three of 32 retreated patients became negative for hepatitis B virus DNA and one patient had HBe seroconversion. In conclusion, ARA AMP exerts a considerable but transient antiviral effect on hepatitis B virus. Complete and sustained inhibition of hepatitis B virus replication was only obtained in the patients with low hepatitis B virus replication. (Gut 1995; 36: 422-426) Keywords: hepatitis B virus, purine nucleoside.
Gut, 1985
A randomised controlled trial was conducted in 29 HBV carriers who had been HBs and HBe antigen positive for more than six months. Fifteen patients were treated with ARA-AMP 10 mg/kg/day given as intramuscular injections 12 hours apart for five days followed by 5 mg/kg/day for 23 days. The 14 controls received no treatment. Serum HBV-DNA polymerase, and HBV-DNA decreased in all patients during therapy. Six treated patients lost serum HBV-DNA polymerase, HBV-DNA and HBeAg, HBsAg concentrations decreased, and five developed anti-HBe. One of these six patients lost HBsAg and developed anti-HBs. No such changes were observed in the control group over a similar 18 month period of observation. A four week course of ARA-AMP inhibits HBV replication and in a significant minority of patients this is long lasting and is associated with a reduced level of inflammatory activity in the liver.
Medical Molecular Morphology, 2013
The clinical course of patients with chronic hepatitis B (CH-B) was greatly changed by the introduction of nucleoside analogues. We often encounter patients where the serum level of albumin recovers quickly following the treatment. In this study, we focused carefully on the changes in serum albumin level noted during nucleoside analogue therapy, in an effort to clarify the mechanism behind the restoration of albumin production. We observed changes in serum albumin levels during nucleoside analogue therapy in 12 patients with CH-B and studied the mechanism behind the restoration of albumin production following the therapy. The serum level of albumin was significantly increased very soon after the treatment was started. Prior to treatment with nucleoside analogues, the albumin signal for mRNA was only slightly seen in the peri-portal area, whereas 12 months after the treatment, the liver tissue presented an obvious signal of albumin mRNA. Serum levels of hepatocyte growth factor (HGF) were significantly decreased 12 months after the treatment. In this study, we demonstrated that nucleoside analogues decrease HGF through the suppression of hepatocyte damage, leading to the restoration of albumin production in patients with CH-B.
Vitamins in the treatment of chronic viral hepatitis
British Journal of Nutrition, 2011
Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic infections represent a major health problem worldwide. Although the efficacy of HBV and HCV treatment has improved, several important problems remain. Current recommended antiviral treatments are associated with considerable expense, adverse effects and poor efficacy in some patients. Thus, several alternative approaches have been attempted. To review the clinical experiences investigating the use of lipid- and water-soluble vitamins in the treatment of HBV- and HCV-related chronic infections, PubMed, the Cochrane Library, MEDLINE and EMBASE were searched for clinical studies on the use of vitamins in the treatment of HBV- and HCV-related hepatitis, alone or in combination with other antiviral options. Different randomised clinical trials and small case series have evaluated the potential virological and/or biochemical effects of several vitamins. The heterogeneous study designs and populations, the small number of...
1982
In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hourly, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity. Adenine arabinoside (ARA-A) is a synthetic purine nucleoside with a broad spectrum of antiviral activity against DNA viruses. Uncontrolled studies in HBsAg-positive chronic liver disease2-5 indicated that ARA-A can inhibit hepatitis B virus (HBV) replication transiently with no change in HBsAg concentration, HBeAg status, liver function tests, or histology. In a few patients, inhibition of DNA polymerase activity has been permanent with a later decrease in HBsAg concentration and loss of HBeAg. Recent uncontrolled studies with ARA-A and/or human leucocyte interferon have shown similar changes in 37% of treated patients.6 In a * This work was supported by the Ingram Fund and the Cancer Research Campaign. t MRC Training Fellow.
N-acetyl Cysteine Therapy as Adjunctive Therapy for Treatment of Acute Hepatitis A
Afro-Egyptian Journal of Infectious and Endemic Diseases, 2017
Background and study aim: Hepatitis A is an acute, usually mild and self-limiting disease affecting the liver. We aim to assess the effect of oral N-acetyl cysteine compared with placebo on length of hospital stay in adult patients who were admitted to the hospital with acute hepatitis A which might cause earlier resolution of hepatitis. Subjects and Methods: 40 patients were diagnosed as acute hepatitis A and classified into two groups, the first one involved 20 patients who received oral Nacetyl cysteine and supportive treatment, and the second one involved also 20 patients but they received placebo and supportive treatment. We measured complete blood count (CBC), kidney profile (KP), liver function test (LFT), blood glucose, C-reactive protein (CRP) and coagulation profiles on the day of presentation, and every other day till the day of discharge from the hospital. Serological tests were done for HAV Immunoglobulin M (IgM), HEV IgM, HBsAg, HBcIgM, antibody to Hepatitis C virus. Results: The mean length of hospital stay in the NAC group was 13.2 days compared with 14.3 days in the placebo group. Length of hospital stay differed significantly between groups. The mean time of reliving symptoms at presentation was 3.6 days in the NAC group and 4.4 days in the placebo group. The mean time of reliving symptoms at presentation was significantly lower in NAC group than in placebo group. Conclusion: use of oral NAC as adjunctive therapy for treatment of acute hepatitis A was safe in these patients and was associated with a shorter length of patient stay in the hospital.
Relationship Between Ischemic Modified Albumin (IMA) and Chronic Hepatitis B
Kafkas Journal of Medical Sciences, 2020
Aim: Ischemic Modified Albumin (IMA) is a molecule that is found to be elevated in liver diseases with liver damage. In our study, the relationship between IMA and chronic hepatitis B (CHB) was investigated. Material and Method: Patients with CHB who were admitted to the Infectious Diseases polyclinic in between April 2016 and September 2016 and the healthy control group were included in the study. Fifty-three of the patients (24 female, 29 male) with CHB and 51 (21 female, 30 male) were the healthy control group. Blood samples were taken and centrifuged and serums were stored at-80°C. IMA levels were measured by spectrophotometric method. IMA/albumin ratio (IMAR) was calculated. Results: IMA level was measured as 1.08±0.13 in CHB patients and 0.96±0.11 in control group (r=0.42, p<0.000). And, also, IMAR level was measured as 0.23±0.03 in CHB and 0.20±0.03 in control group (r=0.43, p<0.000). According to the control group, the IMA and IMAR level elevation was statistically very significant in CHB. However, there was no statistically significant difference between IMA and IMAR levels in CHB. Conclusion: In our study, IMA and IMAR levels were found to be high in patients with CHB. This significant elevation should be investigated in terms of reflecting liver damage in large studies with other noninvasive parameters followed in patients with CHB.