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)

Hepatitis C virus (HCV) transmission following a needlestick is an important threat to health care workers. We present the case of a 29-year-old medical intern who sustained a needlestick injury from a source patient known to be infected with both human immunodeficiency virus and HCV. The case patient subsequently developed acute HCV infection. The optimal strategy for diagnosing HCV infection after occupational exposures has not been defined. At a minimum, HCV antibody and alanine aminotransferase testing should be done within several days of exposure (to assess if the health care worker is already infected with HCV) and 6 months after percutaneous, mucosal, or nonintact skin exposure to blood or infectious body fluids from an HCV-infected patient. Currently, it is not possible to prevent HCV infection after exposure. However, recent data suggest that early treatment of acute HCV infection with interferon alpha may be highly effective in preventing chronic HCV infection. These data underscore the importance of identifying persons with acute HCV infection and promptly referring them to experienced clinicians who can provide updated counseling and treatment.
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PMID:Needlestick transmission of hepatitis C. 1224 29

Because there is a lack of data on the treatment outcome of patients who carry hepatitis C virus (HCV) genotype 6, we conducted a prospective study, to compare the effect of interferon and ribavirin therapy in HCV genotypes 1 and 6, of patients with seropositive anti-HCV, persistently elevated alanine transaminase levels, and detectable HCV RNA. Patients were treated with subcutaneous recombinant interferon alpha-2b and ribavirin for 12 months. Of 40 patients, 16 had genotype 6, and 24 had genotype 1. An end-of-treatment response was detected in 12 (75%) patients with genotype 6 and in 10 (41.6%) patients with genotype 1 (P=.05). A sustained virological response (SVR) was present in 10 (62.5%) patients with genotype 6 and in 7 (29.2%) patients with genotype 1 (P=.04). Genotype 6 has a better response than genotype 1 and is associated with a higher SVR.
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PMID:Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: a comparison with genotype 1. 1266 Sep 21

Retreatment of interferon-resistant chronic hepatitis C represents a significant clinical challenge. In an open-label, pilot study, the safety and efficacy of interferon alpha-2b, ribavirin, and amantadine were assessed. Twenty patients with chronic hepatitis C who had previously failed to respond to a course of interferon monotherapy followed by a course of combination therapy (10 patients received interferon alpha-2b [3 million units three times a week] plus ribavirin [800 mg/d] and 10 patients received interferon alpha-2b [3 million units three times a week] plus amantadine [200 mg/d]) were enrolled in this retreatment protocol. One month after discontinuation of their last regimen, patients started treatment with interferon alpha-2b (3 million units three times a week), ribavirin (1,000-1,200 mg/d), and amantadine (200 mg/d). Biochemical and virologic end points were monitored. Patients with hepatitis C virus (HCV) RNA levels of <100 copies/mL at the end of 24 weeks of therapy completed a 48-week course of interferon alpha-2b, ribavirin, and amantadine treatment. Of the enrolled subjects, 60% were male, 85% were white, 85% had HCV genotype 1, and 20% had histologic cirrhosis. The mean age +/- SD of the patients was 44.1 +/- 4.9 years, the mean baseline HCV RNA level +/- SD was 1,845,150 +/- 1,279,069 copies/mL, and the mean baseline alanine aminotransferase level +/- SD was 130 +/- 100 U/L. Five patients (25%) became HCV RNA negative (<100 copies/mL) after 24 weeks of treatment, with only three patients (15%) remaining HCV RNA negative at the end of 48 weeks of treatment. This end of treatment response was sustained 6 months after the discontinuation of treatment in only two patients (10%). In this interferon-resistant group, a treatment regimen of interferon alpha-2b, ribavirin, and amantadine was associated with only a 10% sustained viral eradication rate.
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PMID:Triple combination of interferon alpha-2b, ribavirin, and amantadine for treatment of chronic hepatitis C. 1270 87

Prevalence of infection with hepatitis C virus (HCV) is lower in children than in adults. The detection rate of anti-HCV antibodies in Western countries is 0.1-0.4% among children and adolescents. Prevalence of serologic response is higher in risk groups. HCV infection in children is usually asymptomatic, most of them have variations in serum levels of alanine aminotransferase (ALA). The laboratory exams for children are the same as those for adults. Histological progression may be faster in children than in adults. In this age group, HCV infection is considered as a special category, in which case it's possible to maintain the patient in observation without antiviral therapy. However, some studies with monotherapy showed that a regime with 1.75-3 MU/m2 of interferon alpha during 6-12 months induces a sustained viral response in 33-56% of the children. Although ribavirin hasn't yet been accepted for pediatric use, there have been several clinical tests in small groups with oral doses of 15 mg/kg a day, combined with interferon, during 12 months. The results are good. Pegylated interferon alpha is not authorized for pediatric use.
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PMID:[Children and adolescents with hepatitis C virus infection]. 1271 54

Children with chronic hepatitis C may be ideal candidates for treatment with interferon alpha (IFNalpha) as they have liver disease at an early stage. However, adverse drug reactions need to be considered. The aim of this study was to conduct a systematic review of literature on interferon therapy of chronic hepatitis C in children, and to perform a meta-analysis of pooled data. A computerized search gave 18 articles on IFNalpha therapy in children with chronic hepatitis C; after exclusion of uncontrolled trials and of trials including patients with comorbidities, data from two studies could be pooled (48 patients). The outcomes assessed were biochemical, defined as normalization of alanine transaminase, and virologic, defined as HCV-RNA loss, both sustained at 24 months after enrollment. Results of the studies were homogenous. Risk difference was 37% (95%CI: 12.9-61) in favour of IFNalpha treated children for sustained biochemical response, and 36.8% (95%CI: 14.3-59.3) in favour of treated children for sustained HCV clearance, respectively. The differences were highly significant (P = 0.007 and P = 0.004, respectively). The histological end-point, as well as side-effects, could not be analysed, due to lack of data. This review identifies the poor methodology of the majority of the published trials. The study provides support for the efficacy of IFNalpha in improving both biochemical and virologic outcomes in chronic hepatitis C in children, but evidence is confined to these surrogate end-points.
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PMID:Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis]. 1275 40

Current therapies for chronic hepatitis B (CHB) have a number of limitations, and better treatment options are needed. Peginterferon alpha-2a (40 kDa) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a (40 kDa) in the treatment of CHB. In this phase II study, 194 patients with CHB not previously treated with conventional interferon-alpha were randomized to receive weekly subcutaneous doses of peginterferon alpha-2a (40 kDa) 90, 180 or 270 microg, or conventional interferon alpha-2a 4.5 MIU three times weekly. Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up. All subjects were assessed for loss of hepatitis B e antigen (HBeAg), presence of hepatitis B antibody (anti-HBe), suppression of hepatitis B virus (HBV) DNA, and normalization of serum alanine transaminase (ALT) after follow-up. At the end of follow-up, HBeAg was cleared in 37, 35 and 29% of patients receiving peginterferon alpha-2a (40 kDa) 90, 180 and 270 microg, respectively, compared with 25% of patients on conventional interferon alpha-2a. The combined response (HBeAg loss, HBV DNA suppression, and ALT normalization) of all peginterferon alpha-2a (40 kDa) doses combined was twice that achieved with conventional interferon alpha-2a (24%vs 12%; P = 0.036). All treatment groups were similar with respect to frequency and severity of adverse events. These results indicate that peginterferon alpha-2a (40 kDa) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg, suppression of HBV DNA, and normalization of ALT.
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PMID:Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. 1282 97

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
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PMID:Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C. 1474 43

Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT) are also evolving.
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PMID:Antiviral therapy for chronic hepatitis B: a review. 1503 42

To identify predictive factors of response to interferon alpha (IFN-alpha) plus ribavirin therapy in patients with chronic hepatitis C (CHC), the presence of lymphadenopathy (LyA) of the hepatoduodenal ligament and other variables were investigated. A total of 110 patients with histologically proven CHC were enrolled in this study. Ultrasound (US) was performed at the start and end of therapy and 6 months after stopping therapy. At baseline, LyA was present in 35 (43.7%) of 80 patients with alanine aminotransferase (ALT) values and grading was significantly higher than in the LyA-negative group. LyA was more frequent in nonresponders (nonR) than in relapsers (relR) or sustained responders (susR). Lymph node volume (LyV) was significantly lower in susR than in nonR or relR (p < 0.05). Under antiviral treatment, the reduction in LyV was significantly higher in nonR (p < 0.01); in susR and relR, it was not significantly reduced. LyA totally disappeared in two patients of the susR group. Logistic regression analysis confirmed only a positive association of susR with grading and a negative association with staging (p < 0.02 and p < 0.006). In conclusion, this study suggests that US evidence of LyA is useful in evaluating the severity of a given chronic hepatitis C, but it cannot be proposed as a predictive index of response to antiviral treatment.
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PMID:Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis. 1521 50

The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 mug pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy of blocking virus production (epsilon) and infected cell loss during treatment (mdelta) compared with patients with elevated ALT levels. Differences were significant for epsilon (P = .02) and delta (P = .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters epsilon, delta, and mdelta was observed in patients with elevated gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.
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PMID:Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels. 1572 1


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