Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our group has investigated 204 intravenous drug users for the presence of GBV-C-RNA by means of reverse transcriptase polymerase chain reaction (RT-PCR). The majority of the individuals tested were male, their age ranging from 16 to 63 years, and the duration of intravenous drug use from one to 40 years. We detected GBV-C-RNA in 46 of the 204 IVDUs (22.5%) with its prevalence peaking in the age group between 21 to 30 years while decreasing with advancing age. Similarly, its frequency was found in inverted relation to the duration of drug use. The present findings strongly hint at the host's immune system's capacity to clear hepatitis GBV-C as opposed to the other blood-borne hepatitis viruses. From the liver function tests performed we could not detect any statistically significant difference regarding ALT elevation observed in GBV-C-positive as compared to GBV-C-negative individuals. To date, GBV-C in most cases does not appear to cause any serious liver disease.
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PMID:Hepatitis GBV-C infection in intravenous drug users. 1043 44

The positive predictability of anti-HCV ELISA is low, especially, in blood donors and in healthy populations. False positive anti-HCV results pose some difficulties in medical practice and in blood screening. The aim of this study was to identify the factors associated with true hepatitis C virus (HCV) infection among anti-HCV ELISA-positives. A case-control analysis was conducted using 354 subjects who were positive for anti-HCV ELISA. All subjects were tested for true HCV infection using the reverse transcriptase polymerase chain reaction (RT-PCR). Tests for serum alanine aminotransferase (ALT), fasting glucose, HBsAg, anti-HBc antibody, alpha-fetoprotein, platelet count and ultrasound of liver were also performed. Epidemiological data were obtained by self-administered questionnaires. Out of 354 subjects, 202 (57.1%) were positive for HCV by RT-PCR and 152 were negative and used as the control group. In multivariate analysis, blood transfusion (odds ratio, OR 2.3, 95% confidence interval, CI 1.3-4.0), elevated ALT (OR 2.2, 95% CI 1.2-4.3) and higher anti-HCV ELISA ratios (more than 3; OR 1.7, 95% CI 1.3-2.1) were associated with true HCV infection. Thrombocytopenia was also associated with the presence of HCV in univariate analysis. These results suggest that a history of blood transfusion, elevated ALT and a high score on anti-HCV ELISA ratios are associated with true HCV infection among anti-HCV ELISA-positives.
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PMID:Factors associated with positive predictability of the anti-HCV ELISA method with confirmatory RT-PCR. 1064 40

Screening blood donations for anti-HCV antibodies and alanine aminotransferase (ALT) serum levels generally prevents the transmission of hepatitis C virus (HCV) by transfusion. The aim of the present study was to evaluate the efficiency of the enzyme immunoassay (EIA) screening policy in identifying potentially infectious blood donors capable to transmit hepatitis C through blood transfusion. We have used a reverse transcriptase (RT)-nested polymerase chain reaction (PCR) to investigate the presence of HCV-RNA in blood donors. The prevalence of HCV-RNA positive individuals was compared with the recombinant immunoblot assay (RIBA-2) results in order to assess the usefulness of both tests as confirmatory assays. Both tests results were also compared with the EIA-2 OD/C ratio (optical densities of the samples divided by the cut off value). ALT results were expressed as the ALT quotient (qALT), calculated dividing the ALT value of the samples by the maximum normal value (53UI/l) for the method. Donors (n=178) were divided into five groups according to their EIA anti-HCV status and qALT: group A (EIA> or = 3, ALT<1), group B (EIA> or = 3, ALT>1), grou (1< or = EIA< 3, ALT<1), group D (1< or = EIA<3, ALT>1) and group E (EIA< or = 0.7). HCV sequences were detected by RT-nested PCR, using primers for the most conserved region of viral genome. RIBA-2 was applied to the same samples. In group A (n=6), all samples were positive by RT-nested PCR and RIBA-2. Among 124 samples in group B, 120 (96.8%) were RIBA-2 positive and 4 (3.2%) were RIBA-2 indeterminate but were seropositive for antigen c22.3. In group B, 109 (87.9%) of the RIBA-2 positive samples were also RT-nested PCR positive, as well as were all RIBA-2 indeterminate samples. In group C, all samples (n=9) were RT-nested PCR negative: 4 (44.4%) were also RIBA-2 negative, 4 (44.4%) were RIBA-2 positive and 1 (11.1%) was RIBA-2 indeterminate. HCV-RNA was detected by RT-nested PCR in 3 (37.5%) out of 8 samples in group D. Only one of them was also RIBA-2 positive, all the others were RIBA-2 indeterminate. All of the group E samples (controls) were RT- nested PCR and RIBA-2 negative. Our study suggests a strong relation between anti-HCV EIA-2 ratio > or = 3 and detectable HCV-RNA by RT-nested PCR. We have also noted that blood donors with RIBA-2 indeterminate presented a high degree of detectable HCV-RNA using RT-nested PCR (75%), especially when the c22.3 band was detected.
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PMID:Diagnosis of hepatitis C virus in Brazilian blood donors using a reverse transcriptase nested polymerase chain reaction: comparison with enzyme immunoassay and recombinant protein immunoblot assay. 1105 36

The incidence of GBV-C/hepatitis G virus (GBV-C/HGV) infection after blood transfusion is unknown in Brazil. Many studies have so far addressed its relationship with blood transfusion, but its association with liver disease was not confirmed. A prospective study was carried out between 1996 and 1999 in Rio de Janeiro. Ninety three patients who received blood transfusion during cardiac surgery were followed for six months and blood samples were drawn before and after surgery to determine antibodies to GBV-C/hepatitis G virus (anti-HGenv) using a step sandwich immunoassay and GBV-C/HGV-RNA using reverse transcriptase polymerase chain reaction. The alanine aminotransferase (ALT) levels were serially determined as well as clinical data compiled related to hepatitis. Prior to surgery, anti-HGenv was present in 35.5% (33/93) of patients and 4.3%(4/93) were found to be viremic. Seroconversion following transfusion was observed in 9 patients and 4 additional individuals became viremic for a total incidence of 23% (13/56). Six months after blood transfusion, only 4 of those nine patients previously antibody positive still had anti-HGenv detectable in serum. No patients had clinical or laboratory evidence of acute hepatitis and no correlation was found with GBV-C/HGV infection and number of blood units transfused (p = 0.37). This study highlights the importance of using both HGV-RNA PCR and anti-HGenv to accurately estimate the magnitude of GBV-C/HGV infection. The observed high prevalence and incidence rates show that this infection is common in Brazil; however, no clinical or biochemical evidence of liver disease was demonstrated in the period of study and longer longitudinal observation is needed to define any pathogenic effect.
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PMID:The incidence of GB virus C / hepatitis G virus infection in Brazilian patients who received blood transfusion during cardiac surgery. 1117 63

Bacterial endotoxin (lipopolysaccharide; LPS) augments the hepatotoxicity of a number of xenobiotics including allyl alcohol. The mechanism for this effect is known to involve the inflammatory response elicited by LPS. Upregulation of cyclooxygenase-2 (COX-2) and production of eicosanoids are important aspects of inflammation, therefore studies were undertaken to investigate the role of COX-2 in LPS-induced enhancement of liver injury from allyl alcohol. Rats were pretreated (iv) with a noninjurious dose of LPS or sterile saline vehicle and 2 h later were treated (ip) with a noninjurious dose of allyl alcohol or saline vehicle. COX-2 mRNA was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and liver injury was assessed from activities in serum of alanine and aspartate aminotransferases (ALT and AST, respectively) and from histology. Liver injury was observed only in rats cotreated with LPS and allyl alcohol. Serum ALT activity was increased by 4 h after administration of LPS and continued to increase through 8 h. COX-2 mRNA was detectable at low levels in livers from rats receiving only the vehicles at any time up to 8 h. Expression of COX-2 mRNA was increased by 30 min after administration of LPS and remained elevated through 6 h. Allyl alcohol treatment alone caused an increase in COX-2 mRNA at 4 h (2 h after allyl alcohol) that lasted less than 2 h. In livers from rats cotreated with LPS and allyl alcohol, levels of COX-2 mRNA were greater than levels seen with either LPS or allyl alcohol alone. The increased expression of COX-2 mRNA was accompanied by an increase in the concentration of prostaglandin (PG) D(2) in plasma. Plasma PGD(2) concentration was increased to a greater extent in rats treated with LPS plus allyl alcohol compared to allyl alcohol or LPS alone. Pretreatment with the COX-2 selective inhibitor, NS-398, abolished the increase in plasma PGD(2) and reduced the increase in ALT and AST activities observed in rats cotreated with LPS and allyl alcohol. NS-398 did not affect liver injury from allyl alcohol alone administered at a larger, hepatotoxic dose. In addition, ibuprofen, a nonselective inhibitor of cyclooxygenases, did not protect against liver injury from LPS plus allyl alcohol. In isolated hepatocytes PGD(2), but not PGE(2), reduced the concentration of allyl alcohol required to cause half-maximal cytotoxicity. These results suggest that products of COX-2 play a role in the augmentation of allyl alcohol-induced liver injury by LPS.
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PMID:Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide. 1144 26

Lamivudine is a nucleoside analogue with potent inhibitory effects on hepatitis B virus (HBV) replication. Prolonged therapy is required for sustained suppression. However, HBV species with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) locus of the HBV RNA-dependent DNA polymerase conferring resistance to lamivudine may emerge after 9-10 months therapy with an incidence of 38 and 67% after 2 and 4 years of lamivudine therapy, respectively. During continued lamivudine therapy, patients with YMDD mutant HBV usually show serum alanine aminotransferase (ALT) and HBV DNA elevations at lower median levels than their baseline. Marked flare of serum ALT or acute exacerbation may occur as the result of CLT-mediated hepatocytolysis directed against YMDD mutants. Although viral clearance with or without emergence of distinct lamivudine-resistant mutants may occur after such exacerbations, 20% of the exacerbations are complicated with decompensation or even fatality. The exacerbations appear to be more severe than those that occur during the natural course of wild-type HBV chronic infection. In addition, some mutations may generate S gene truncation near 'transactivity-on-region'. Thus, the benefit of prolonged lamivudine therapy must be balanced against concern about YMDD mutants. Currently, the most cost-effective strategy is to select patients with stronger endogenous anti-HBV immunity, thereby increasing efficacy and shortening the duration of lamivudine therapy. New drugs and new strategies are needed to better achieve the goals of therapy and minimize the problem of YMDD mutants.
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PMID:Impact of YMDD mutations during lamivudine therapy in patients with chronic hepatitis B. 1159 91

Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.
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PMID:Lack of hepatotoxicity associated with nonnucleoside reverse transcriptase inhibitors. 1191 37

Hepatitis B virus (HBV) infection is a major global health concern and is the most common cause of chronic liver disease worldwide. The natural history and clinical outcomes of chronic HBV infection are determined by the viral replication cycle and the host immune responses. Treatment of chronic hepatitis B is directed at interrupting the natural history by suppressing HBV replication before development of any significant irreversible liver cell damage. Effective antiviral therapies should be followed by sustained suppression of HBV-DNA, normalization of transaminases levels and a stable stage of HBeAg seroconversion with persistence of circulating anti-HBeAg antibodies. Two major classes of antiviral therapeutic agents that have been approved for treatment of chronic hepatitis B are immunomodulating agents (i.e. interferon) and the nucleoside analogs (i.e. lamivudine). A 4-6 month course of interferon-alpha has resulted in improvement of survival in 20%-30% of patients with chronic hepatitis B who had elevated serum ALT levels without hepatic decompensation. Interferon-alpha therapy is associated with HBeAg seroconversion; normalization of ALT levels, reduced hepatic inflammation, and possibly reduced disease progression to cirrhosis and hepatocellular carcinoma. Interferon can also be used with caution in patients with early compensated cirrhosis. A 12-month course of lamivudine has been shown to be well tolerated and effective. Lamivudine can be used in decompensated cirrhosis and immunosuppressed patients and for prevention of recurrent HBV infection after liver transplantation. The response rates after 3 years of lamivudine therapy account for 40-65%. A major problem of antiviral treatment is the emergence of drug resistance conferred by mutations in the YMDD motif of HBV reverse transcriptase. The prevalence of YMDD mutations increases with longer durations of antiviral therapies and this has been detected in 20% of immunocompetent patients receiving lamivudine per year. Contentious issues remain when to stop the treatment if HBeAg seroconversion does not occur. Many new immunomodulatory therapies and antiviral agents are in various stages of clinical development and have shown some promise. Among newer HBV antivirals, adefovir dipivoxil, entecavir, emtricitabine, DAPD and clevudine appear to be at least as potent as lamivudine in suppressing HBV replication. In vitro studies have shown that YMDD mutations confer cross-resistance between lamivudine and emtricitabine. However, adefovir, dipivoxil, lobucavir, DAPD and possibly clevudine suppress replications of both YMDD mutants and wild types of HBV. Immunomodulatory approaches for treatment of chronic hepatitis B are conceptually attractive, but newer agents used to date (thymosin-alpha, interleukin-12, therapeutic vaccines) have not demonstrated sufficient efficacy for widespread use. Combinations of an immunomodulatory agent and nucleoside analog may improve the therapeutic efficacy and reduce the emergence of drug resistance. Nevertheless, combinations of interferon and lamivudine therapies do not confer such additional benefits. The next challenge for HBV treatment is to use antivirals in combination and/or in cyclical therapy to minimize the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post-treatment suppression of HBV. Randomized prospective control trials of combined antiviral therapies given simultaneously or sequentially are needed to establish safe and effective combined regimens that can be recommended for future treatment strategies.
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PMID:Management of viral hepatitis B. 1200 May 99

We have analysed the dynamics of HBV variants related to Lamivudine resistance in 22 chronically infected patients during and after the end of Lamivudine therapy. Thirteen patients had a confirmed methionine mutation in the YMDD region of the reverse transcriptase domain determined by sequence analysis. They responded to therapy having a mean reduction of HBV DNA of 4.55 log (range 2.93-8.91). Nine patients partly responded to therapy, with a small decline of HBV DNA (mean reduction of 3.39 log, range 1.72-5.12) and no indication for an YMDD variant. Samples were re-analysed with a HBV Drug Resistance Line Probe assay (InnoLipa HBV-DR), which detected as low as 10% of a variant HBV population. With this assay, changes in the YMDD region were detected with a mean of 2 weeks (range -8 to 10) earlier than by an increase of HBV DNA levels. Increase of ALT was observed with a mean of 31 weeks (range 29-51) later than the methionine changes in the YMDD motif. Indications for a methionine into valine change could be determined in only one of the partial responders. An unexpected observation was the predominant presence of variant virus populations after end of therapy. In ten patients, we detected the wild type virus with a mean of 14 weeks after end of therapy (range 1-42 weeks). In three patients, no variant virus population could be detected at 25, 36 and 37 weeks, respectively, after cessation of treatment. This observation is important for the inclusion of the so-called naive patients in clinical trials.
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PMID:The dynamics of mutations in the YMDD motif of the hepatitis B virus polymerase gene during and after lamivudine treatment as determined by reverse hybridisation. 1212 23

Lamivudine, the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analog that prevents hepatitis B virus (HBV) DNA synthesis by competitively inhibiting the viral reverse transcriptase and DNA polymerase stages of HBV replication and by terminating proviral DNA chain extension. A dose-ranging study established that once daily oral lamivudine 3 mg/kg up to a maximum of 100 mg/day has the optimum efficacy and tolerability profile for achieving a maximal reduction in serum HBV DNA levels in children aged 2 to 12 years and adolescents aged 13 to 17 years with chronic HBV infection and active viral replication (chronic hepatitis B). Significantly more children and adolescents with chronic hepatitis B receiving lamivudine demonstrated a virologic response (undetectable serum hepatitis Be antigen and undetectable HBV DNA level) [23 vs 13%; p = 0.04] and/or biochemical response (55 vs 12%; p < 0.001) compared with placebo in a large, randomized, double-blind, 52-week phase III study. Despite the emergence of YMDD-variant HBV in 19% of lamivudine-treated children and adolescents, serum alanine aminotransferase and HBV DNA levels remained below baseline in these patients. Oral lamivudine is generally well tolerated by children and adolescents with chronic hepatitis B, with a similar tolerability profile to placebo at the recommended once daily dosage of 3 mg/kg up to a maximum of 100 mg/day.
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PMID:Lamivudine: in children and adolescents with chronic hepatitis B virus infection. 1226 43


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