Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.
...
PMID:Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities. 914 69

Interferon therapy is used widely for chronic hepatitis C but only a minority of treated patients achieve a long-lasting sustained response. We have developed, by logistic regression, a mathematical model to estimate the probability of sustained response in an individual patient with chronic hepatitis C when treated with interferon-alpha (IFN-alpha). The model, which includes age, sex, disease duration, pretreatment serum gamma-glutamyl-transpeptidase, alanine aminotransferase and virus genotype, was developed from a database of 307 patients and validated in a new set of 200 patients. It performed well as goodness-of-fit (P = 0.71 and P = 0.15 in the development and test sample, respectively) and discrimination (area under receiver operating curve = 0.79 in the development and 0.78 in the test sample, respectively). This model may provide decision support in the treatment of chronic hepatitis C with IFN-alpha.
...
PMID:A model to predict long-term sustained response to interferon therapy in chronic hepatitis C. 918 28

Patients with biopsy-proven chronic hepatitis C, who failed to respond to a previous course of either recombinant (rIFN-alpha) or lymphoblastoid (Ly IFN-alpha) interferon-alpha, were randomized to receive either leucocyte (Le) IFN-alpha (patients) or a second course of the same IFN-alpha (controls), to compare the efficacy and safety of these treatment schedules. All patients received the same dose of IFN-alpha as was used during their previous treatment (3 million units (MU) or 6 MU three times weekly) for 6 months. Patients with a normal alanine aminotransferase (ALT) value at month 6 were treated for a further 6 months. All patients were followed-up for 12 months after treatment. A total of 69 patients were enrolled, 44 in the Le IFN-alpha group and 25 in the control group. At the end of the treatment period, 13 of the 44 patients (29.5%) in the Le IFN-alpha group had a biochemical response (normal ALT) and six of 44 (13.6%) patients had undetectable serum hepatitis C virus (HCV) RNA. At the end of the follow-up period, 10 patients (22.7%) had normal ALT values and serum HCV RNA was undetectable in three (6.8%). None of the patients in the control group showed normal ALT values at any time. Genotype 1b tended to be more frequent among non-responders (61 vs 45%): basal gamma-glutamyl transpeptidase (gamma-GT) values were lower in responders than in non-responders (33.3 +/- 11.70 Ul-1 vs 58.4 +/- 33.04; P = 0.01). Le IFN-alpha was well tolerated by all patients. These results support the use of Le IFN-alpha in patients with chronic hepatitis C who are non-responders to a previous treatment with recombinant or lymphoblastoid IFN-alpha.
...
PMID:Human leucocyte interferon-alpha in chronic hepatitis C resistant to recombinant or lymphoblastoid interferon-alpha: a randomized controlled trial. 918 30

To investigate correlations between the interval between blood transfusion and the start of IFN therapy, and IFN efficacy, we studied chronic hepatitis C patients with a history of blood transfusion. The subjects were 122 patients with chronic hepatitis C and a history of blood transfusion at 64 institutions. The patients were treated with high or low-dose IFN. High-dose therapy consisted of intramuscular injection of human lymphoblastoid interferon (HLBI), 6 x 10(6) IU daily for 2 weeks, then 3 times a week for 22 weeks, and low-dose interferon therapy of intramuscular injection of HLBI, 6 x 10(6) IU daily for 2 weeks, then 3 x 10(6) IU 3 times a week for 22 weeks. Normal serum ALT levels for 6 months or more after completing IFN (complete response) were found in 44/122 (36.2%) patients and HCV RNA was no longer detectable after completing IFN therapy in 19/68 (27.9%). Patients in whom the interval between blood transfusion and the start of IFN therapy was less than 20 years had significantly higher rates of HCV RNA-negative complete response than those in whom the interval was 20 years or more (p < 0.039). When chronic HCV infection is caused by blood transfusion, the efficacy of IFN depends on the duration of chronic HCV infection. Since the duration of HCV infection is a factor in predicting efficacy, early IFN therapy may be more effective.
...
PMID:Duration of chronic HCV infection and efficacy of interferon in chronic hepatitis C patients with a history of blood transfusion. The Study Group for Treatment of Hepatitis in the Kyushu Area. 920 20

Recurrent hepatitis C virus (HCV) in liver transplant patients is a major cause of graft loss, liver failure, and need for retransplantation. The results available to date with the use of interferon alfa (IFN-alpha) in the treatment of recurrent HCV in liver transplant patients have been disappointing. The aim of this study was to evaluate the efficacy and clinical utility of post-transplant combination therapy with IFNalpha2b (3 million units 3 times weekly) and oral ribavirin (1,200 mg/d) for a duration of 6 months, followed by maintenance with ribavirin alone for an additional 6 months. Twenty-one liver transplant recipients with recurrent hepatitis C infection (HCV-RNA-positive; active hepatitis without rejection on biopsy) were enrolled in this study. Pretreatment serum alanine transaminase (ALT) levels were at least two times the upper limit of normal. Before treatment, all patients were HCV-RNA-positive and mean HCV-RNA titers were 125 million genome-equivalents/mL. Mean pretreatment histological score was 6.3 +/- 2. After 6 months of combination therapy, all 21 patients had normal ALTs. Ten patients (48%) cleared HCV-RNA from their serum, as assessed by polymerase chain reaction (PCR), and HCV-RNA levels decreased significantly in the others (P = .0001). Improvement in histological score was seen in all patients after combination therapy (P = .0013). During maintenance ribavirin monotherapy, ALT remained normal in all but 1 of the 18 patients who tolerated therapy. HCV-RNA reappeared in 5 patients, but HCV-RNA levels did not return to pretreatment levels (P = .0004). Comparison of pretreatment and postribavirin monotherapy liver biopsies revealed improvement in all but 1 of the 18 patients who tolerated ribavirin (P = .0002). Side effects were restricted to anemia, which necessitated cessation of ribavirin therapy in 3 patients. No patient experienced graft rejection during the study period. These results are significantly better than those reported with IFN-alpha monotherapy. Most importantly, there was a complete absence of graft rejection. These results suggest that the combination of IFN-alpha and ribavirin is effective in reducing HCV-RNA levels and ameliorating hepatocellular injury in recurrent HCV after liver transplantation, and that maintenance therapy with ribavirin monotherapy can maintain the biochemical and histological response.
...
PMID:Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation. 925 67

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.
...
PMID:Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B. 927 24

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.
...
PMID:Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group. 930 8

Response to interferon-alpha (IFN-alpha) treatment in hepatitis C is poorer when cirrhosis is present. In the third Australian multicentre hepatitis C trial, Aushep-3, we examined the efficacy and tolerability of an intensive 24-week course of interferon-alpha 2a in Child-Pugh grade A patients with chronic hepatitis C and cirrhosis. This was an open uncontrolled trial of 4.5 million units (MU) of IFN-alpha 2a daily for 24 weeks; follow-up was 48 weeks. Chronic hepatitis C and cirrhosis were confirmed histologically. HCV RNA was determined in serum by reverse transcriptase polymerase chain reaction (PCR), and viral genotyping was by line-probe assay. Treatment response was defined as a reduction of alanine aminotransferase (ALT) to less than 1.5 times the upper limit of normal (and by at least 50% of pretreatment values) at weeks 20 and 24. Sustained response was defined as normal serum ALT after treatment from trial week 28 until week 48. Among the 56 patients, a treatment response occurred in 18 (32% by intention-to-treat; 42% of those who completed treatment) and eight (14%) had a sustained response. At 24 weeks, HCV RNA was not detectable in 12 of 17 treatment responders, and remained negative at 48 weeks in six of eight sustained responders. Treatment response by genotype occurred in 75% of patients with HCV type 2, in 38% with HCV type 3a and in 12% with HCV genotype 1. Sustained response occurred in only one (4%) patient with HCV genotype 1 but in five (20%) with genotypes 2 or 3a. Among 13 patients withdrawn, nine were for adverse effects, most often haematological; 10 others underwent dose reduction for adverse effects. It is concluded that a sustained biochemical and viral response to treatment with IFN-alpha 2a can be obtained in some patients with hepatitis C and cirrhosis, particularly those with genotypes 2 or 3a. Therefore, patients with cirrhosis should be considered for interferon treatment on an individual basis. Genotyping may improve case selection, but vigilance is required for haematological complications.
...
PMID:Efficacy and tolerance of a 6-month treatment course of daily interferon-alpha 2a for chronic hepatitis C with cirrhosis. The Australian Hepatitis C Study Group. 931 Sep 30

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.
...
PMID:Long term recombinant interferon alpha treatment in MS with special emphasis to side effects. 934 19

The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT) normalization. Of the 50 untreated patients, 30 (60%) cleared HBeAg, but only 21 (42%) normalized ALT after HBeAg loss. Compared with the untreated patients, IFN-treated patients had similar cumulative rates of HBeAg clearance (P = .48), but higher rates of ALT normalization (P = .016) and of HBsAg loss (P = .028). During follow-up, liver-related death occurred in 8 treated patients, caused by liver failure in 5 and hepatocellular carcinoma (HCC) in 3; all 8 had continued to be HBeAg-positive with elevated ALT. None of the treated patients undergoing remission developed liver-related complications. At univariate analysis, life expectancy was longer in treated patients showing sustained remission than in those who did not (5-year survival: 100% vs. 81%; P = .048). Fourteen untreated patients died (from liver failure in 10 and HCC in 4); all but 3 had continued to be HBeAg-positive with elevated ALT. Cox's model identified age and ALT normalization as the only significant predictors of survival. In conclusion, in patients with HBeAg-positive compensated cirrhosis, virological and biochemical remission following IFN therapy is associated with improved survival.
...
PMID:Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP). 936 81


<< Previous 1 2 3 4 5 6 7 8 9 10

---