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)

Chronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse chronic sequalae such as cirrhosis and hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among immunomodulatory agents, levamisole, BCG, picibanil and interleukin-2 have been shown to be ineffective. Corticosteroid therapy is also ineffective and can cause deleterious effects in chronic HBV infection. Thymosin-alpha 1 therapy is currently in phase III clinical trial. Among antiviral agents, acyclovir, dideoxynucleosides, suramin, zidovudine and ganciclovir have been shown to be ineffective and have intolerable side effects. While adenine arabinoside (Ara-A) and its monophosphate derivative (Ara-AMP) are effective agents if the treatment course is long enough, they have been withdrawn from investigative use because of their substantial neuromuscular toxicity. Interferon-alpha may directly inhibit HBV replication and enhance hepatocyte HLA class I antigen expression with subsequent increase of T-cell mediated cytotoxicity. Randomized, controlled clinical trials have shown that 25% to 50% of adult patients with elevated alanine transaminase (ALT) levels lost HBeAg and HBV-DNA when treated with IFN-alpha at a dose of 5MU daily or 10 MU three times a week for 3 to 6 months. In view of the fact that the response rate is far from satisfactory, particularly in Asian patients, combination therapies including interferon alpha with Ara-AMP, acyclovir, didoxynucleoside or interferon-gamma have been studied. Most forms of combination therapy have been shown to be of limited effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Drug therapy in patients with chronic type B hepatitis]. 754 84

We studied the role of an "early" 4-month course of interferon therapy on posttransfusion viral hepatitis C (PTH-C). Paired serum samples of 51 consecutive recipients, taken before and 7-20 days after blood transfusion, were prospectively tested for hepatitis C virus ribonucleic acid (HCV RNA) using the polymerase chain reaction assay. Seven recipients experienced seroconversion of HCV RNA after transfusion. Two of the seven patients underwent an early 4-month course of interferon alpha therapy at a dose of 3 mU per day for 5 days during the first week, then three times a week for the subsequent 15 weeks. The first patient was treated at a very early stage of acute PTH-C and responded well to interferon therapy. Acute PTH-C in the second patient was prevented by interferon therapy. Both patients had normal serum alanine aminotransferase levels and tested negative for anti-HCV and HCV RNA 12 months after the end of treatment. Four of the five patients not on interferon therapy developed abnormal serum alanine aminotransferase activities more than five times the normal upper limit (383 +/- 143 IU/L) at 2-18 weeks after transfusion. All four patients experienced seroconversion of anti-HCV, and three patients developed chronic hepatitis. This study suggests that early long-term interferon therapy has the potential to prevent PTH-C.
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PMID:Early interferon therapy and abortion of posttransfusion hepatitis C viral infection. 756 Aug 32

Ten patients with chronic hepatitis C, six of whom had not responded and four of whom had responded in a non-sustained fashion to interferon-alpha treatment alone, were given interferon alpha-2b and ribavirin in combination during 24 weeks. Interferon alpha-2b was given subcutaneously, at a dose of 3 MU thrice weekly, together with ribavirin orally, at a dose of 1,000-1,200 mg/day. All four patients with a prior non-sustained response to interferon alone had normal alanine aminotransferase (ALT) levels at the end of treatment as well as during follow-up (> or = 24 weeks post treatment). Furthermore, all four lost serum HCV-RNA at the end of treatment and three continued to be negative during follow-up. Among patients with a prior non-response to interferon alone three of six had normal ALT levels at the end of treatment and one at follow-up. Two of six became HCV-RNA negative at cessation of treatment, one of whom was negative also at follow-up. All former non-sustained responders and one of six non-responder patients thus showed a sustained biochemical response with eradication of HCV-RNA from serum in all cases but one. It is concluded that combination therapy with interferon alpha-2b and ribavirin offers a chance of sustained biochemical response with eradication of the viremia in patients who have not shown a persistent response to interferon-alpha alone.
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PMID:Combined treatment with interferon alpha-2b and ribavirin for chronic hepatitis C in patients with a previous non-response or non-sustained response to interferon alone. 762 6

Antibody against the recombinant protein Y19 deriving from non-structural region 3 (NS3) of the hepatitis C virus (HCV) genome was measured in the serum from 300 patients with nonA-nonB chronic liver disease including serial serum samples from these patients by using an enzyme linked immuno-sorbent assay. Simultaneously, antibodies to a synthetic core peptide (AR142) and the recombinant peptide of NS 3-4 region (C-100) were tested. Anti-Y19 antibody was detected in 83.3%, 65.2% and 76.6% of patients with nonA-nonB chronic hepatitis (n = 144), liver cirrhosis (n = 46) and hepatocellular carcinoma (n = 43), respectively. In sera of other chronic liver disease, the detection rate of anti-Y19 antibody was significantly low comparing to nonA-nonB chronic liver disease. Positive rates of the patients for AR142 antibody and C-100 antibody were similar to the one for Y19 antibody. Patients positive for Y19 antibody have a tendency to be positive for C-100 antibody. Serum Y19 antibody level during and after treatment with natural interferon alpha (IFN-alpha; 5MU, 24 weeks) was studied in 33 patients with chronic hepatitis C. The effectiveness of IFN therapy did not correlate with the Y19 antibody level before the treatment. In most cases Y19 antibody level decreased relating to the improvement of the serum ALT level during the treatment. Y19 antibody level declined not only during IFN treatment but after the treatment in Responder group (as assessed by normal ALT for 6 months after the treatment; n = 14). Whereas, in Non-responder group (the rest of Responder group; n = 16) Y19 antibody level was maintained to the level at the end of the treatment or elevated again to the level before the treatment. In Responder group, 6 of 7 cases in whose serum HCV-RNA disappeared at 6 months after the treatment, had decrease of Y19 antibody to less than 20% of the pretreatment level and Y19 antibody became undetectable in 4 cases at 6 months after the treatment. One case in whom Y19 antibody did not decrease by the treatment had an increase of serum ALT level and a relapse of the disease at 12 months after the treatment. 5 of 6 cases in "Responder" group that HCV-RNA remained positive had more than 20% of Y19 antibody level of the pretreatment level at 6 months after the treatment. Therefore the decrease of Y19 antibody level was closely related to the efficacy in terms of serum ALT level and HCV-RNA level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical significance of antibody to Y19 protein in nonA and nonB chronic liver disease]. 768 28

Through a pilot study which includes a clinical, molecular and immunopathological approach to the chronic Hepatitis induced by HBV or by HCV, we determined that 66% of HBsAg carriers are in the "non viremic" phase. The positive HBeAg "viremic" carriers showed HBV-DNA quantitation which varies between > 50 pg to > 100 pg. Both types of carries are infected with the "wild" type HBV. Each subgroup of positive surface antigemia carriers demonstrated a differential immunopathological response. So far, 96% of the HCV carriers investigated, showed HCV-RNA associated to repeatedly positive anti-HCV antibodies. Those patients with increased ALT values uniformly expressed liver histopathological signs of inflammation caused by HCV; demonstrating also the presence of peripheral blood mononuclear cells infected with HCV. At the present, the genotypes investigation indicates a predominance of HCV genotype II (1b). Autoimmune phenomenons associated to HCV have been detected only in 3 patients. The therapeutic approach with interferon alpha applied to the HCV infection preliminary showed similar results to those reported worldwide. Currently, a comprehensive approach to the chronic HBV and chronic HCV infections requires the application of Immunochemistry, Molecular Biology and Cellular Immunology combined technologies.
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PMID:[Immunoclinical, molecular and immunopathologic approach to chronic viral hepatitis. Therapeutic considerations]. 776 16

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant (KT) recipients. To assess the efficacy and safety of therapy with interferon alpha we conducted a prospective study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b (IFNa) 3 million units three times weekly (scheduled) for 6 months (group A). 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period (group B). All the patients in both groups had had stable renal function for at least one year. All patients in both groups had a positive HCV viremia at the beginning of the study. Patients of group A were treated for 142 +/- 34.8 days (range 65-168); elevated serum aminotransferase (ALT) levels decreased rapidly and significantly from 100.3 +/- 48.9 to 37.7 +/- 13.9 IU/L (P = 0.001); 10 patients (77%) were "responders," whereas the others experienced a decrease in ALT values but without reaching the normal ranges. With a mean follow-up of twelve months after discontinuation of IFNa therapy, 8 responders--i.e., 80%--relapsed within 1-20 weeks. Only 4 patients had no detectable HCV viremia at the end of the IFNa; two of them already have abnormal values of ALT. Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment. Side effects of IFNa (fatigue, anorexia, weight loss) were frequent, and 3 patients decided to drop out of the treatment. The hematological tolerance was good although there was a significant decrease in hemoglobin (11.9 +/- 1.7 vs. 13.4 +/- 1.7 g/dl; P = 0.0044). In group B, serum ALT levels did not significantly decrease (84.2 +/- 47.6 vs. 105.2 +/- 68.8 IU/L). At the end of the study period serum ALT levels were significantly lower in group A than in group B (37.7 +/- 13.9 vs. 84.2 +/- 47.6 IU/L, P = 0.013). The major concern in group A was the occurrence of 5 renal failures. Kidney transplant biopsies showed edema, no significant tubulitis, scarcely scattered interstitial inflammatory cellular infiltration, and mesangial thickening. Four patients received methylprednisolone pulses but renal function improved in only two cases. We were not able to discover predictive factors of renal failure. We conclude that IFNa therapy is effective in controlling disease activity--i.e., reducing amino-transferase levels in KT patients with chronic hepatitis C, although relapse and detection of HCV RNA after the cessation of treatment were observed, respectively, in 80% and 100% of patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients. 777 Sep 30

Although the occasional occurrence of glomerulonephritis associated with hepatitis C virus (HCV) infection has been reported recently in the literature, the type described has been mainly membranoproliferative glomerulonephritis (MPGN); membranous glomerulonephritis (MGN) is very rare. In this paper, two cases of MGN associated with HCV infection are reported. Case 1 was a 56-year-old male who had positive HCV Ab and HCV RNA. The diagnosis of chronic active hepatitis was verified by liver biopsy. Laboratory data showed proteinuria (5g per day), hematuria and hypocomplementemia by hemolytic assay. Renal biopsy led to the diagnosis of MGN in stage II. The patient was treated with interferon alpha for 6 months, resulting in improvement of hypocomplementemia, transient reduction of GOT and GPT during the course of treatment. The GOT and GPT were aggravated again after the completion of therapy. No improvement was seen in proteinuria and hematuria, and HCV Ab remained positive. Case 2 was a 69-year-old male who had positive HCV Ab and HCV RNA, and had normal liver function. Subsequently, his GOT value was slightly elevated. Proteinuria (2g per day) was demonstrated. The diagnosis of MGN in stage II was made on the basis of renal biopsy. The clinical characteristics of these two cases suggest that MGN is a type of glomerulonephritis associated with HCV infection.
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PMID:[Two cases of membranous glomerulonephritis associated with hepatitis C virus infection]. 781 54

To evaluate the efficacy of recombinant interferon alpha-2b in the treatment of patients with acute post-transfusion hepatitis C, a randomized controlled trial was conducted in 33 acute post-transfusion hepatitis C patients; 16 patients received 3 million units of subcutaneously injected recombinant interferon alpha-2b 3 times a week for 3 months and 17 patients without specific treatment were used as controls. At the end of the interferon treatment, 13 (81%) patients in the interferon-treated group normalized serum alanine aminotransferase compared with only six (35%) patients in the control group (p < 0.01). One year after completion of the interferon treatment, nine (56%) patients in the interferon-treated group and six (38%) patients in the control group normalized serum alanine aminotransferase (p = 0.35). Serum HCV-RNA measured by reverse transcription-polymerase chain reaction was positive in all patients at the time of enrollment and then became undetectable in 13 (81%) patients in the interferon-treated group and two (12%) patients in the control group at the end of interferon treatment (p < 0.001). One year after completion of the interferon treatment, seven (44%) patients in the interferon-treated group and two (13%) patients in the control group had persistent undetectable serum HCV-RNA (p = 0.08). Using a logistic regression model, the lower pretreatment level of serum HCV-RNA measured by quantitative branched DNA signal amplification assay was the only predictor for a favorable response to the interferon treatment in acute hepatitis C patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized controlled trial of recombinant interferon alpha-2b in the treatment of Chinese patients with acute post-transfusion hepatitis C. 789 Sep

The aim of the study was to evaluate the safety and effectiveness of interferon alpha-2b with or without concomitant corticosteroid treatment in patients with chronic hepatitis B. Fifty-six patients were randomly allocated to two treatment groups. Group I (n = 25) received interferon alpha-2b (INTRON A, Schering-Plough Corporation) 5 million unit subcutaneously, three times a week for 24 weeks. Group II (n = 31) received interferon according to the same protocol and prednisolone in decreasing doses of 60, 40, 20 mg for 6 weeks. The two groups were well matched for demographic, biochemical, virological and histologic features. Both groups were followed up for 24 weeks after treatment. No statistical difference was observed between the two groups at the end of the follow-up in alanine aminotransferase values, HBV DNA negativation, HBeAg loss, anti-HBe seroconversion and the Knodell score. The greater proportion of HBsAg clearance in the combination group, particularly in patients with low alanine aminotransferase values, was, however, not significant. In patients with low alanine aminotransferase values, only the Knodell score was significantly decreased in patients treated with interferon and prednisolone. The only factor which was found to be a predictor of response was the assumed duration of hepatitis. These findings showed that a concomitant short administration of corticosteroids during the first weeks of interferon therapy did not improve results with interferon alone.
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PMID:A randomized, controlled trial of interferon alfa-2b alone and with simultaneous prednisone for the treatment of chronic hepatitis B. French Multicenter Group. 793 Apr 73

Nine patients with chronic hepatitis C who responded with normal or near-normal serum alanine aminotransferase (s-ALT) levels during an initial interferon alpha-2b treatment course, but who had subsequent relapses with elevated s-ALT levels after treatment cessation, were retreated once (3 patients) or twice (6 patients). The liver histological findings before the first and after the last treatment course were compared. The mean follow-up time between the initial and the follow-up assessment was 44 months (range 34-53). The histological findings were classified as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) or cirrhosis (Ci) by using a numerical scoring system assessing each portal zone separately. In the initial biopsy, 2 patients were classified as having CPH and 7 as having CAH, 2 of whom with signs of cirrhosis. According to the conventional classification, 4/9 (44%) patients improved after treatment, 3/9 (33%) remained unchanged, and 2/9 (22%) deteriorated. The mean histological scores for the necro-inflammatory parameters: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis improved, but the changes did not reach statistical significance. We conclude that repeated interferon alpha-2b treatment courses are probably beneficial in patients with chronic hepatitis C who show a non-sustained response to interferon, since studies on the natural course of chronic hepatitis C have indicated a progressive deterioration of the histological picture in many untreated patients, most marked among those with CAH.
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PMID:Long-term histological outcome in patients with chronic hepatitis C treated repeatedly with interferon alpha-2b without sustained response. 798 68


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