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)

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon-beta from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3 x 10(6) to 6 x 10(6) units of interferon-beta was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P less than 0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P less than 0.01) and at the third day (P less than 0.01) to the second week (P less than 0.05) of treatment, respectively. These results suggest that interferon-beta injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.
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PMID:Changes in ultrastructure of hepatocytes and liver test results before, during, and after treatment with interferon-beta in patients with HB(e)Ag-positive chronic active hepatitis. 149 52

Hepatitis B virus carriers, a 30-year-old man (case 1) and a 31-year-old man (case 2), associated with nephrotic syndrome were treated with interferon-beta. The nephrotic syndrome did not respond to corticosteroid therapy. Their HBs-Ag, HBe-Ag and HBc-Ab were positive. Renal biopsies revealed membranous glomerulonephritis in case 1 and mixed membranous and proliferative glomerulonephritis in case 2. Direct immunofluorescence studies showed strong granular staining of the GBM with IgG and using sandwich technique with anti-HBe antiserum, granular deposits were seen throughout the GBM. Patients were administrated mainly 3-6 x 10(6) IU/day interferon-beta intravenously for four weeks. After transitory elevation of serum transaminase, HBe-Ag and DNA-polymerase have disappeared with development of HBe-Ab (seroconversion) about six months after the end of interferon-beta administration. Then nephrotic syndrome has recovered in incomplete remission after a year and a half follow-up. The secondary renal biopsy in case 1 showed less intense deposits of HBe-Ag along GBM. These facts suggest that the improvement of proteinuria is associated with the decrease in HBV replication due to interferon therapy.
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PMID:[Clinical and histological observation of HBV glomerulonephritis treated with interferon-beta]. 208 50

The activities of 2',5'-oligoadenylate synthetase (2-5AS) in spleen and liver extracts obtained from mice treated with recombinant mouse interferon-beta (rMuIFN-beta) were investigated. The levels of the enzyme activity increased significantly in both spleen and liver extracts for 72 hours after the treatment with rMuIFN-beta (5 X 10(4)IU). The levels of the enzyme activity in spleen extracts correlated well with those in liver extracts. Therefore it is suggested that the assay of 2-5AS activity in peripheral blood mononuclear cells (PBMC) of patients infected with hepatitis B virus (HBV) is useful for monitoring the antiviral state of liver during IFN therapy. The activities of 2-5AS in PBMC obtained from patients with chronic hepatitis B (CHB) were significantly higher than those of healthy controls, resulting from the endogenous IFNs detected in the patients with CHB. Furthermore, the enzyme activities of PBMC in the patients with CHB increased significantly during IFN therapy as compared with IFN-untreated patients. This increase in the enzyme levels during IFN therapy correlated well with the decrease of DNA-polymerase (DNA-P) activities associated with HBV. These results indicate that the assay of 2-5AS detected in PBMC from the patients is valuable to determine the optimal IFN therapy for CHB.
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PMID:[2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells obtained from patients with chronic hepatitis B during interferon therapy]. 222 95

Two years or more after 35 patients (29 men and six women) with chronic hepatitis B were treated by interferon, we studied relationships of age, ALT activity, activity of serum DNA polymerase associated with the hepatitis B virus, serum levels of hepatitis B e antigen and activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells when treatment started in comparison with treatment results. Seventeen patients were given human lymphoblastoid interferon-alpha; the other 18 patients were given interferon-beta. We measured the activity of 2',5'-oligoadenylate synthetase in these mononuclear cells and found the rate of increase in vivo and in vitro; the correlation between the two was r = 0.68. This enzyme activity in the patients who became negative for DNA polymerase after interferon treatment increased more both in vivo and in vitro than in patients who did not became negative. Also, both the in vivo and in vitro activity increased more in patients who became negative for the e antigen after interferon therapy than in those who remained positive. In the first group, interferon was considered to be effective; in the second, ineffective. Of the patients who became negative, some developed e antibodies and some did not; the increase in this enzyme activity in the two groups was not significantly different. The increase in the activity of 2',5'-oligoadenylate synthetase activity could be used to predict the results of interferon treatment and is an index that can be used before treatment to predict the response.
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PMID:Relationship of the effects of interferon on chronic hepatitis B and the induction of 2',5'-oligoadenylate synthetase. 247 40

Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.
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PMID:Pharmacokinetics and biologic activities of human native and asialointerferon-beta s. 764 42

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 x 10(4) U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the King's College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.
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PMID:Interferon and cyclosporin A in the treatment of fulminant viral hepatitis. 771 17

To evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-beta, Chinese hamster ovary cell-derived glycosylated recombinant human interferon-beta and Escherichia coli-derived unglycosylated recombinant human interferon-beta were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon-beta expressed more cell-growth inhibitory action, 2'5'-oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon-betas. These results showed that the sugar chain structure of human interferon-beta affects its biological activity on human hepatoblastoma cells.
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PMID:Carbohydrate-dependent biological activities of glycosylated human interferon-beta on human hepatoblastoma cells in vitro. 778 83

We quantified serum hepatitis C virus RNA titers and determined hepatitis C virus subtypes in chronic hepatitis C patients treated with interferon-beta to investigate relationships among serum ALT response, serum hepatitis C virus titer and hepatitis C virus subtype. Of 146 chronic hepatitis C patients who received interferon-beta therapy, 24 patients with sustained serum ALT normalization (complete responders) and 26 patients without serum ALT normalization (nonresponders) were randomly selected. Detection, typing and quantitation of hepatitis C virus were performed by means of the "single-tube" polymerase chain reaction method. Of the 24 complete responders, 21 (87.5%) became negative for hepatitis C virus RNA, whereas 21 (80.8%) of the 26 nonresponders remained positive. Hepatitis C virus infections with types I, II, III, IV, II + III and III + IV occurred in 0 (0%), 22 (51.2%), 10 (23.3%), 1 (2.3%), 7 (16.5%) and 3 (7.9%) patients, respectively. The mean pretreatment hepatitis C virus RNA titer of complete responders (0.4 +/- 2.0 x 10(4) CID50/ml) was significantly lower than that of nonresponders (3.8 +/- 4.5 x 10(4) CID50/ml) (p < 0.01). Regardless of HCV subtype, patients with more than 10(4) CID50/ml of HCV did not show serum ALT normalization, whereas complete serum ALT response was seen in most cases with less than 10(2) CID50/ml HCV. These results show that mixed infections with different hepatitis C virus subtypes appear to be more common than previously reported and that the pretreatment serum level of hepatitis C virus RNA is a more important predictor of outcome of interferon therapy than is virus genotype.
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PMID:Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta. 824 55

Ribavirin is a nucleoside analog that inhibits the replication of many DNA and RNA viruses. To evaluate the efficacy of oral ribavirin, we randomly assigned 24 HBeAg-positive patients with chronic active hepatitis to a 12-wk course of treatment with 0.8 to 1.0 gm/ribavirin day, 3 mU interferon-beta three times a week intravenously or a combination of those drugs. Ribavirin, alone and in combination with interferon-beta, decreased hepatitis B virus levels in most patients, and mean serum hepatitis B virus DNA and DNA polymerase levels at the end of treatment were approximately half of baseline levels (p < 0.05). Interferon alone exerted the most inhibitory effect on hepatitis B virus activity (p < 0.01). During ribavirin treatment, changes in serum aminotransferase values varied considerably and the mean values did not change significantly, although interferon alone and the combination of interferon and ribavirin were associated with significant reductions in serum aminotransferase activities. Ribavirin was well tolerated, but we transiently reduced the dosage in two cases because of mild hemolytic anemia, although all patients completed the treatment schedule. The combination of interferon and ribavirin did not appear to result in greater toxicity. During the follow-up period (6 to 9 mo), HBeAg and hepatitis B virus DNA disappeared in one patient treated with ribavirin, in two treated with interferon and in two given the combination. These results indicate that ribavirin suppresses hepatitis B virus replication, although its effect is less than that of interferon, and that it may be useful as adjunctive therapy for chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pilot study of ribavirin and interferon-beta for chronic hepatitis B. 834 55

Interferon-beta was given weekly for 24 wk, at a dose of 3 million units, intravenously, to 10 patients with chronic hepatitis B who were serologically positive for HBsAg and HBeAg. Their condition was followed for 6 months after the end of therapy. Both serum hepatitis B virus-associated DNA-polymerase activity and alanine aminotransferase level became significantly lower during therapy and during the 6 months after the end of therapy than at the beginning of therapy. In five of 10 patients, the seroconversion from HBeAg positive to anti-HBe positive had occurred by 6 months after the end of therapy, and in four of these five patients, serum alanine aminotransferase level became normal. Weekly interferon-beta administration over 6 months seems effective in inducing seroconversion and in normalizing serum alanine aminotransferase level.
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PMID:A pilot study of long-term weekly interferon-beta administration for chronic hepatitis B. 842 16


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