Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 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

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

Natural killer (NK) activity in the peripheral blood of patients with chronic liver disease was measured using 51Cr labeled K562 cells as target cells. NK activity was elevated but not significantly in patients with chronic hepatitis compared with healthy controls and significantly lower in the patients with hepatocellular carcinoma. The activity decreased in the order of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the level of NK activity in patients with chronic hepatitis did not correlate with the level of alanine aminotransferase (ALT), it tended to be elevated in association with elevation of ALT in patients treated with OK432, interferon-beta, glycyrrhizin or adenine arabinoside. In chronic liver disease, phytohemagglutinin (PHA) skin test showed a positive correlation with NK activity. In all patients who were treated with the immunopotentiator, OK432, and whose HBeAg became negative, NK activity was elevated during the treatment. These results suggest that the NK activity in peripheral blood may be related to hepatocytic injury even if this is not the effector mechanism of the injury.
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PMID:Natural killer activity in patients with chronic hepatitis treated with OK432, interferon, adenine arabinoside and glycyrrhizin. 304 May 9

We performed two courses of interferon-beta (IFN-beta) to a child with chronic hepatitis C. A complete response was not obtained by the first interferon treatment, however, the results of the second treatment differed from those of the first. Hepatitis C virus (HCV)-RNA remained negative and both aspartate aminotransferase and alanine aminotransferase levels remained normal after completion of the second course. From these results we estimated that HCV-RNA levels before IFN therapy could be significantly associated with the efficacy of this treatment. The serum level of HCV-RNA was 10(6) copies/50 microL before the first treatment, but was 10(3) copies/50 microL before the second course. We conclude that IFN therapy to children with hepatitis C should always be directed at providing a cure. Even if the clinical effects of the first course are minimal decreasing quantities of HCV-RNA still offer hope for cure by subsequent readministration.
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PMID:Relation between serum hepatitis C virus-RNA levels and efficacy of interferon-beta therapy. 757 60

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

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

We studied tolerance to subcutaneous (s.c.) administration of 6 million units of interferon-beta (IFN-beta), given three times per week for 6 months, and its efficacy in the treatment of 15 patients with chronic hepatitis C. At the end of the treatment, alanine aminotransferase (ALT) levels were significantly reduced (p = 0.024) in all patients, and 4 (27%) had a normal ALT value. However, at the end of the study (12 months), only 1 of these 4 had a sustained response. No patient cleared hepatitis C virus (HCV) RNA completely, but the RNA could be detected only by polymerase chain reaction (PCR) in the sustained responder. Adverse side effects to the s.c. IFN-beta were infrequent. Leukocyte (p = 0.012) and platelet (p = 0.013) counts decreased significantly during treatment but did not necessitate dose modifications. Thus, although s.c. IFN-beta at the dosage used had little efficacy in the treatment of chronic hepatitis C, the excellent tolerance to the treatment suggests that the effects of higher doses should be explored.
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PMID:Tolerance and efficacy of subcutaneous interferon-beta administered for treatment of chronic hepatitis C. 905 11

Following an acute episode of undifferentiated collagenosis/autoimmune disease with joint pain, a 50-year-old female patient with known long-standing chronic hepatitis B was treated orally with corticosteroids (30 mg prednisolone in decreasing doses over a period of six months). During this treatment, exacerbation of hepatitis B and massive flare-up under simultaneous treatment with lamivudine occurred (GOT 530 U/L, GPT 791 U/L). Serology was positive for HBs-Ag and anti-HBc-lgM. HBV-DNA titer was > 400,000 copies/ml in polymerase chain reaction. Considering the increased risk of reactivation of autoimmune phenomena during a six months therapy with interferon-alpha, an intensive combination therapy with interferon-beta and -gamma (2 weeks: 1 x 3 MIU nIFN-beta Fiblaferon i.v.; 3 weeks: 1 x 3 MIU nIFN-beta i.v. plus 1 x 50 microg rIFN-gamma Imukine) was carried out over five weeks. After two months this resulted in a complete viral and biochemical response. During an observation period of twelve months no reactivation of the autoimmune disease occurred.
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PMID:[Severe exacerbation of chronic hepatitis B during therapy with corticosteroids and lamivudine therapy and successful short-term combination therapy with interferon-beta and interferon-gamma]. 1277 56

To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-gamma system and a downregulated IFN-alpha and -beta system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.
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PMID:Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients. 1279 20

Re-treatment with interferon-alpha alone for chronic hepatitis C nonresponders to interferon-alpha monotherapy is almost ineffective. This multicentre, randomized, parallel-group, dose-finding study evaluated the efficacy of interferon-beta-1a in the treatment of chronic hepatitis C patients unresponsive to interferon-alpha. A total of 267 patients were randomized to one of four groups: subcutaneous interferon-beta-1a 12 MIU (44 microg) or 24 MIU (88 microg) administered three times weekly or daily. Patients were treated for 48 weeks and then followed up for an additional 24 weeks. There was a trend towards a dose-response relationship regarding virological [loss of detectable serum hepatitis C virus (HCV) RNA] and biochemical response (normalization of serum alanine aminotransferase). Overall, 22 patients (8.3%) had a virological response at the end of treatment; nine patients (3.4%) had a sustained virological response (SVR). Strikingly, 21.7% (5/23) of Chinese patients achieved SVR. Univariate analysis revealed that race was the only variable related to SVR [odds ratio (OR) 16.6; 95% CI 4.1-67.3; P < 0.0001]. Multiple logistic regression analysis also confirmed that more Chinese patients achieved SVR than non-Chinese patients (OR 12.3; 95% CI 2.6-59.3; P = 0.0017). In addition, complete clearance of HCV-RNA occurred earlier in Chinese than in non-Chinese responders (median 2 vs 30 weeks; P = 0.020). Thirty-six patients were withdrawn from treatment because of adverse events. Most adverse events were mild or moderate in severity. In conclusion, interferon-beta-1a provided considerable clinical benefit in Chinese patients with chronic hepatitis C unresponsive to interferon-alpha. The evaluation of interferon-beta-1a in this setting is progressing.
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PMID:Racial differences in responses to interferon-beta-1a in chronic hepatitis C unresponsive to interferon-alpha: a better response in Chinese patients. 1535 46


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