Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serological markers of hepatitis B virus (HBV) replication were assessed in a randomized, controlled trial of prednisone withdrawal followed by alpha-interferon in the treatment of chronic hepatitis B. HBV DNA levels in more than 700 serial serum samples from 41 patients were determined by a sensitive and quantitative solution hybridization assay. Results were compared with HBV DNA polymerase (DNAp) activity and hepatitis B e antigen (HBeAg) in 21 untreated controls and 20 treated patients. Among treated patients, the mean pretherapy HBV DNA values were higher in nonresponders than in responders. During prednisone treatment, DNA levels increased an average of 2.1-fold in responders and 1.4-fold in nonresponders. During the 2-week rest interval between prednisone and interferon, DNA values fell an average of 57% in responders. In contrast, the mean DNA values in nonresponders did not change during the same interval. This early distinction between responders and nonresponders was not apparent from DNAp or HBeAg results. During interferon treatment, HBV DNA became undetectable in responders and remained negative during a 1-year follow-up. DNA in nonresponders declined to 14% of baseline during interferon treatment but increased to pretherapy levels after treatment. DNAp values generally paralleled HBV DNA values, but DNAp activity showed more variability and lower sensitivity than did the hybridization assay results. HBeAg values varied independently of HBV DNA and DNAp with a much delayed decline in responders. These results indicate that HBV DNA, when measured quantitatively by a sensitive solution hybridization assay, is an early predictor of the effects of antiviral agents on replication.
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PMID:Quantitation of hepatitis B viral DNA by solution hybridization: comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy. 265 8

The future of patients with chronic hepatitis (HC) due to B virus depends above all on the tendency of the interaction between viral activity and immune response. Viral activity (replication) (RV) can be expressed in these patients by two variants: a) "complete" or "early", associated with the presence in serum of HBsAg, HBeAg, and significant DNA polymerase activity, and b) "incomplete" or "late", in which anti-HBe is found in serum and there are scant or no histopathologic changes ("healthy carriers" in some cases). In prolonged infections viral replication declines gradually, although viral capsid protein continues to be synthesized and DNA-HBV is integrated into the genome. Viral replication per se does not condition the histologic damage (DH) expressive of liver cirrhosis with HBV (HCB). Other publications take a different view of this problem. The increase in viral replication often is proportional to a rise in serum GPT (an expression of histologic damage), but viral replication is not always associated with a progressive disease course. The immune defense leads to cytolysis and subsequent elimination of the HB virus. Some patients with high HBsAg levels have little active forms of liver cirrhosis; the DNA-HBV integrated would be capable of producing HBsAg but not HBcAg. It is precisely this that induces the response of cytotoxic T lymphocytes at the level of the hepatocyte surface. The presence in serum of anti-HBe IgM would be related to the expression of HBcAg on the hepatocyte membrane and/or the liberation of HBcAg particles by lysed hepatocytes. The relationship between the degree of histologic damage and serum aminotransferase levels is better established.
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PMID:[Viral replication, histologic damage and enzymatic activity in chronic hepatopathies caused by B virus]. 266 54

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
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PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study. 268 91

In 21 patients from the out-patient clinic of the Internal Medicine Department of our hospital with chronic hepatitis (HC) due to B virus (HBV) and anti-HBC (IgG) serology but not HBsAg, a study was made of the possible correlation between viral replication levels (RV) --as expressed by DNA polymerase values (DNAp)-- and, respectively, histologic changes and serum enzyme movements (GPT, GOT). Our study parted from the diverse criteria cited in the literature concerning the role assigned to viral replication per se and/or immune response per se in the genesis of histologic damage (DH). All patients exhibited signs of moderate clinical and enzymatic activity. The levels of viral replication in the group studies were significant (compared to a control group), which supports the thesis that a certain degree of viral replication, although very attenuated, persists in these patients and is the basis of the continued histological damage that eventually leads to liver cirrhosis (CH) and its derivatives, often with little clinical translation. As regards histologic damage, the correlation with DNAp is reciprocal and of moderate significance, supporting the criterion that the multiform expression of histologic damage in liver cirrhosis due to HBV (HCB) (cellular necrosis, intracellular degenerative phenomena, inflammatory cellular infiltrate, fibrosis) is, at the very least, unproportional to the degree of viral replication and can even be reciprocal. Only the severity of the overall hepatic process remains a function of immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Viral replication, histologic damage and enzymatic activity in chronic hepatopathies caused by B virus. Analysis of 21 patients]. 276 33

Patients with chronic hepatitis B with active viral replication had a significantly greater fall in DNA polymerase and hepatitis-Be antigen when treated with interferon and acyclovir together than when treated with either interferon or acyclovir alone. Apart from fatigue and thrombophlebitis, tolerance of the combination therapy was excellent. The combination therapy appears the most promising for conversion of a state of active viral replication into virus latency.
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PMID:Acyclovir enhances the antiviral effect of interferon in chronic hepatitis B. 286 16

A 26-year-old patient developed HBsAg-, HBeAg-positive chronic active hepatitis arising from an acute infection 6 months earlier. Treatment with adenine arabinoside (Ara-A), 15 mg/kg/day administered as overnight infusions for three weeks, resulted in clinical and complete biochemical remission with normalisation of aminotransferases, loss of HBsAg, HBeAg and DNA polymerase, and appearance of Anti-HBs during follow-up for 9 months. Treatment of chronic hepatitis B infection using Ara-A for several weeks may be especially effective when initiated early in the course of the disease.
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PMID:Treatment of HBsAg-,HBeAg-positive chronic active hepatitis with adenine arabinoside. A case report with clinical remission and seroconversion to anti-HBs. 286

Foscarnet (trisodium phosphonoformate) is a new antiviral compound with in vitro inhibitory effects against the DNA polymerases of hepadna viruses. To study the effects of the drug in chronic hepadna virus infection, we treated ducks chronically infected with duck hepatitis B virus for 10 days with either low-dose foscarnet (50 mg/kg i.p. b.i.d.), high-dose foscarnet (250 mg/kg i.p. b.i.d.), or sterile water injections. Serum duck hepatitis B virus DNA and intrahepatic replicative forms of the virus were measured using molecular biological techniques with both a double-stranded radiolabeled DNA probe and a plus-strand (noncoding) specific RNA probe. We found a dose-related decrease in serum and intrahepatic duck hepatitis B virus DNA during treatment, with a rapid return toward baseline values after the cessation of treatment. There was a disproportionate decrease in the plus strand of viral DNA with treatment. We conclude that foscarnet exerts its effect in hepadna virus infection through inhibition of viral DNA polymerase. Further study is necessary to determine whether foscarnet, by itself or in combination with other treatment modalities, has a role to play in the treatment of chronic hepatitis B infections in humans.
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PMID:Foscarnet decreases serum and liver duck hepatitis B virus DNA in chronically infected ducks. 294 28

Forty-five patients with chronic hepatitis B were entered into a randomized controlled trial of recombinant human alpha-interferon therapy. All patients had hepatitis B surface antigen in serum for at least 1 yr and had stable serum levels of both hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen. During the 4-mo period of therapy, 10 of 31 (32%) treated patients and only 1 of 14 (7%) control patients became negative for serum hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase. All 10 patients who became negative for serum hepatitis B virus deoxyribonucleic acid subsequently had a marked improvement in serum aminotransferase activities and lost hepatitis B e antigen from serum, and 9 of them had improvement in liver histology. Comparison of responders to nonresponders indicated that female sex and a high initial level of serum aspartate aminotransferase correlated best with response to interferon therapy. These findings indicate that a 4-mo course of recombinant alpha-interferon can induce a remission in disease in approximately one-third of patients with chronic hepatitis B.
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PMID:Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B. 304 16

In a previous study a partial inhibition of viral replication was observed in HBeAg-positive patients after acyclovir (ACV) treatment. To assess those results and to evaluate different treatment regimens, a randomized controlled trial with ACV given at 45 mg/kg/day by continuous infusion (in 5 patients) or by intermittent 8-hourly infusion (in 6 patients) for 28 days versus placebo has been performed in 20 patients affected by chronic hepatitis positive for both HBsAg and HBeAg for at least 6 months. Patients were stratified for sex, presence of cirrhosis and homosexual activity. Modest inhibition of serum DNA polymerase activity was observed after intermittent ACV treatment but not with the continuous infusion. After a 8-12 months follow-up, 2 of 10 of the ACV-treated patients and 3 of the controls had become HBeAg-negative, with 1 and 2 seroconversions to anti-HBe in the treated and placebo group respectively. No adverse effects were observed in ACV-treated patients after continuous infusion, but 2 of 6 patients who received intermittent therapy had to stop treatment, because of abdominal colics and elevation of the serum creatinine. Our data confirm that ACV partially inhibits viral replication in HBeAg-positive patients but without significantly affecting the rate of seroconversion to anti-HBe.
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PMID:Treatment of chronic HBeAg-positive hepatitis with acyclovir. A controlled trial. 329 5

We have investigated the efficacy of recombinant alpha-interferon treatment of chronic hepatitis B virus (HBV) infection in two therapeutic trials. Forty-four patients positive for HBsAg, HBeAg, DNA polymerase and HBV-DNA were studied. Fourteen carriers were treated in the first trial with doses ranging from 18 to 50 million units (mu)/m2 3 times per week. Six of 14 treated carriers (43%) have a sustained loss of HBeAg, HBV-DNA and DNA polymerase. Four lost HBsAg (29%). Two of 11 (18%) untreated carriers lost HBeAg, but none lost HBsAg (P = 0.05). Nineteen patients were entered in a second trial to assess dose response. Fourteen were treated with doses ranging from 2.5 to 10 mu/m2. Five patients were untreated. Two treated patients seroconverted to anti-HBe, and a third cleared HBsAg and seroconverted to anti-HBs. None of the controls was anti-HBe-positive. Thus 9/28 (32%) carriers have lost replicating HBV versus 2/16 (13%) of untreated patients. Elevated pretreatment serum ALT concentrations and severe chronic active hepatitis were associated with inhibition of viral replication in treated patients suggesting that seroconversion may require an appropriate host response. The efficacy of recombinant interferon is restricted, but it may be of benefit in a proportion of carriers.
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PMID:Recombinant leucocyte interferon treatment of chronic hepatitis B. An analysis of two therapeutic trials. 329 8


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