Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleoside analog 2',3'-dideoxyinosine, currently being used to treat patients infected with the human immunodeficiency virus, has been shown to inhibit viral replication in certain cell culture systems of hepatitis B virus and the duck model of chronic hepatitis B infection. We studied the effect of dideoxyinosine on viral replication in patients with chronic hepatitis B. In the initial dose-finding phase, patients received sequential 2-wk courses of dideoxyinosine in escalating doses of 3, 6 and 9 mg/kg/day. In the second, long-term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of dideoxyinosine on hepatitis B were assessed by serial measurements of ALT, hepatitis B virus DNA and DNA polymerase activity in serum. Six patients completed the dose-finding phase, and five patients continued into the long-term treatment phase. No significant differences were seen in serum aminotransferases, hepatitis B virus DNA levels or DNA polymerase activity at any time during treatment when compared with pretreatment levels. All patients remained positive for HBeAg during treatment and during 6 mo of follow-up. Thus at the doses tested, dideoxyinosine had no appreciable effect on viral replication in patients with chronic hepatitis B.
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PMID:A pilot study of 2',3'-dideoxyinosine for the treatment of chronic hepatitis B. 139 94

In Okinawa prefecture, prevalence of hepatitis B surface antigen (HBsAg) among blood donors is 3.5% and is twice as high as the average for the whole of Japan (1.5%), and is the highest in Japan (p less than 0.005). In contrast, mortality rates of both liver cirrhosis (LC) and primary liver cancer (PLC) in Okinawa are the lowest in Japan. Many epidemiological studies have shown that the positive rate of HBsAg correlates with mortality rate of PLC. To elucidate the cause of this epidemiological discrepancy, cross-sectional seroepidemiological studies and a prospective clinical study were conducted. In the cross-sectional studies, the following results were obtained; (1) Positive rate of HBsAg among patients with LC in Okinawa was 15.2% and lower than the average for the whole of Japan (23.4%). A similar comparison among patients with hepatocellular carcinoma showed 24.4% in Okinawa Vs. 31.4% in the whole of Japan. (2) The age-specific hepatitis B e antigen positive rate among 829 HBsAg positive health examinees tend to decrease with increase in age; 50% in less than 20 years old age group, 15.7% in third decade and 2-3% or less in 30 or more age group. Of the 829, 431 HBsAg positive subjects were referred our liver out-patient clinic. Then, of the 431, 27 (6.3%) were diagnosed or suspected as having chronic hepatitis and one (0.2%) was diagnosed as having cirrhosis. Of the 431, 381 (88.4%) were diagnosed as healthy HBsAg carrier, the great majority (94.0%) of whom had positive reaction of anti-HBe antibody and normal values of both GOT and GPT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Correlation between hepatitis B virus infection and chronic liver disease in Okinawa]. 140 58

Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors.
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PMID:Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience. 141 85

About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon-alpha in the treatment of HBeAg-positive chronic hepatitis.
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PMID:Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole. 142 52

We studied gamma-interferon production of phytohemagglutinin-stimulated peripheral blood mononuclear cells in response to alpha-interferon in hepatitis B virus carriers and healthy individuals. The magnitude of gamma-interferon production was significantly higher in patients with anti-HBe antibody than in patients with HBe antigen and healthy individuals. Furthermore, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells from patients with active liver injury [serum alanine aminotransferase (ALT), greater than 40 U/L], but not that from patients with inactive liver injury (serum ALT, less than 40 U/L) or healthy individuals. These results suggested that alpha-interferon could enhance the cellular immune response against hepatitis B virus by augmenting the endogenous production of gamma-interferon in patients with active liver injury, implying that the responsiveness to alpha-interferon might be responsible for liver cell injury.
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PMID:Effects of alpha-interferon on gamma-interferon production of peripheral blood mononuclear cells in hepatitis B virus carriers. 143 Jan 5

In a 47-year-old male patient a tonsillar swelling was pointed out in May, 1991. Lymph node biopsy revealed that he had malignant lymphoma (diffuse large cell type). He had no hepatic dysfunction on admission, but because of positive hepatitis B (HB) antigen and negative HB antibody, he was diagnosed as an asymptomatic HB carrier. The staging examination showed that he had stage IIA lymphoma. Treatment with the COP-BLAM regimen was initiated on June 8. But the level of serum GOT and GPT increased to 286 IU/l and 392 IU/l, respectively. Serum DNA polymerase also increased to 9492 cpm. Interferon-alpha (3 x 10(6) units daily) was administered intramuscularly from June 8. Serum DNA polymerase decreased to zero on September 2, and his HBe antibody became positive indicating seroconversion. COP-BLAM chemotherapy without prednisolone was initiated from September 9 and complete remission was achieved. He was discharged from our hospital on September 25. It has been frequently reported that asymptomatic HB antigen carriers developed fulminant hepatitis during the course of chemotherapy. Our case suggests that it is necessary to continue chemotherapy in order to attain seroconversion by early use of interferon-alpha, when lymphoma patients display aggravated hepatic dysfunction and increased DNA polymerase levels.
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PMID:[Successful interferon-alpha treatment of hepatitis B developing during chemotherapy of malignant lymphoma]. 143 50

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

Viral sequence and host immune response were investigated in an unusual, asymptomatic chronic hepatitis B virus carrier (human leukocyte antigen type A24, Bw61, Bw62, Bw6, DRw11, DRw52, DQw7) who was consistently nonreactive for antibody to HBc and had a normal ALT level over a 5-yr study period. The precore and core region DNA sequences of virus isolated from his serum had seven silent mutations that resulted in no changes in the amino acid sequence of the adr HBsAg subtype. He had no abnormalities in the number of peripheral blood T or B cells and no HBcAg-specific suppressor T cells. His lymphocytes proliferated in vitro in response to phytohemagglutinin, pokeweed mitogen, Staphylococcus aureus and tetanus toxoid but not to recombinant HBcAg. Unlike other HBsAg carriers and hepatitis B virus-immune individuals, his monocytes did not ingest beads coated with HBcAg. Failure to produce antibody to HBc was not due to an hepatitis B virus variant but to a selective immune system defect in this asymptomatic HBsAg carrier.
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PMID:Chronic hepatitis B virus infection in an anti-HBc-nonreactive blood donor: variant virus or defective immune response? 153 7

Spontaneous loss of HBsAg is infrequent in adult HBV carriers. Little is known about this serological change in children. In a prospective study of 420 hepatitis B virus-carrier children who were observed for 1 to 12 yr (mean = 4.3 yr), spontaneous loss of HBsAg occurred in 10 patients, with an average incidence of 0.6%/yr. The HBsAg clearance rate was significantly higher in children who had anti-HBe; children who were at an older age on entry; children whose mothers were HBsAg-; or children with severe liver histological changes detected while they were HBeAg+. Children who seroconverted from HBeAg to anti-HBe before the age of 6 or who had a peak serum ALT level above 100 IU/L were more likely to clear HBsAg. In all 10 patients who became HBsAg-, serum hepatitis B virus DNA became undetectable by both spot hybridization and the polymerase chain reaction, suggesting a complete clearance of the virus from serum. After the loss of HBsAg, the anti-HBs levels were higher in the children born to carrier mothers than in those born to noncarrier mothers. These findings suggest that chronic hepatitis B virus-carrier children rarely lose HBsAg, especially if they have been infected during the perinatal period and have mild histological changes. The poor humoral immune response to HBsAg may be a contributing factor in the establishment of carrier status during horizontal infection but may not be primarily involved in the establishment of carrier status during perinatal infection.
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PMID:Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection. 154 19

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.
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PMID:A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg. 155 34


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