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Biomedical subjects

I V Weller

Publications and source records attributed to I V Weller.

90 records · Page 5Linked to original sources
PubMed1984

Contribution of low level HBV replication to continuing inflammatory activity in patients with anti-HBe positive chronic hepatitis B virus infection.

The relationship between the histological diagnosis and serological and tissue markers of HBV replication in 41 Greek and 29 British patients with chronic HBV infection were studied. All the nine Greek and 13 British patients who were HBeAg positive had HBV-DNA in serum and HBcAg expression in the hepatocytes. The majority (73%) of these patients had active liver disease. Forty seven per cent of the Greek and 19% of the British patients who were anti-HBe positive continued to display HBcAg in the liver with or without HBV-DNA detected in serum. All but three of these patients had persistently active liver disease. Continuing inflammatory activity in the liver, however, was also found in 31% of anti-HBe positive patients who had no evidence of HBV replication. In these patients, other factors such as delta agent, NANB viruses, alcohol abuse or an autoimmune reaction initiated by HBV may be contributory.

Chronic Disease↗
PubMed1984

Clinical, biochemical, serological, histological and ultrastructural features of liver disease in drug abusers.

Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers.

Adult↗
PubMed1984

Analysis of the molecular state of HBV-DNA in the liver and serum of patients with chronic hepatitis or primary liver cell carcinoma and the effect of therapy with adenine arabinoside.

The pattern of replicative intermediates seen in the liver of HBe antigen and antibody positive patients was determined. During the phase of HBe antigenaemia the 3.2 Kb species of HBV-DNA (complete HBV genome) is present in the liver but not in the serum. When HBe antigen to antibody seroconversion occurs, either spontaneously or during antiviral therapy, the 3.2 Kb and lower molecular weight intermediates disappear from the liver and the 3.2 Kb band appears transiently in the serum. Integrated HBV-DNA was found in one of 15 patients during the period of HBe antigenaemia and in three of seven patients in the HBe antibody positive phase of the chronic infection before detection of primary liver cell carcinoma. Integrated sequences were found in tumour tissue of two patients with primary liver cell carcinoma who were anti-HBc positive but were absent from the tissues of two patients developing primary liver cell carcinoma at a late stage of autoimmune liver disease. These studies suggest that integration of the HBV genome occurs rarely or in only a small proportion of hepatocytes during the early (HBe antigen positive) phase of infection in Caucasians. They also show that not all primary liver cell carcinomas necessarily contain HBV-DNA.

Adult↗
PubMed1983

Failure to detect nucleic acid homology between some non-A, non-B viruses and hepatitis B virus DNA.

Some studies suggest that there is antigenic and nucleic acid homology of one type of non-A, non-B hepatitis virus with hepatitis B viral (HBV) proteins and DNA. Using molecular hybridization under high and low stringency conditions with high specific activity 32P-HBV DNA as a probe, serum and liver samples from patients and nonhuman primates infected with non-A, non-B hepatitis were examined. Our results provide no evidence of significant homology between the DNA extracted from serum and liver of patients and nonhuman primates infected with one type of non-A, non-B hepatitis and HBV DNA.

Animals↗
PubMed1983

Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration.

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.

Acyclovir↗
PubMed1983

Significance of delta agent infection in chronic hepatitis B virus infection: a study in British carriers.

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease.

Adolescent↗
PubMed1983

Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy.

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative.

DNA-Directed DNA Polymerase↗
PubMed1982

The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles.

Existing methods for detecting complete virus particles in the serum of patients with chronic HBV infection are either insensitive or indirect. A method is described in which Dane particle-associated DNA is extracted from a small volume of serum and detected by molecular hybridization using 32P-labeled cloned HBV-DNA or HBV-DNA extracted from the serum of an immunosuppressed patient, followed by autoradiography and densitometry. There was a positive correlation between the amount of HBV-DNA detected using HBV particle-derived and cloned HBV-DNA probes. The amount of HBV-DNA detected in serum samples showed a positive correlation with the HBV-DNA polymerase. The method was more sensitive than the DNA polymerase and HBeAg assays in detecting complete virus particles. It may be useful in determining the level of infectivity in patients and in monitoring response to antiviral therapy.

Cloning, Molecular↗
PubMed1982

The pathology of hepatitis A in man.

Liver biopsies from 17 patients with serologically established hepatitis A were examined by light microscopy. Biopsies were taken from 2 to 27 weeks after onset of symptoms. All showed acute hepatitis, usually with centrilobular lesions but also commonly with a striking portal and periportal inflammatory reaction, resembling that seen in chronic active hepatitis. The infiltrate was rich in plasma cells. Centrilobular cholestasis was common and occasionally severe. Neither cholestasis nor the periportal lesion appeared to be related to patient age or to the timing of liver biopsy. All patients made a full recovery and none developed chronic liver disease. The histological changes differed from those reported in children and in chimpanzees in the presence of centrilobular lesions, but resembled them in that the latter two groups also had periportal lesions. These lesions may lead to a false impression of impending chronicity if the aetiology of the hepatitis is not known at the time of liver biopsy.

Adult↗
PubMed1982

Effects of prednisolone/azathioprine in chronic hepatitis B viral infection.

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial.

Azathioprine↗
PubMed1982

Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP).

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.

Adult↗
PubMed1981

Clinical and histological features of a group of patients with sporadic non-A, non-B hepatitis.

Twelve serologically proven cases of non-A, non-B (NANB) hepatitis have been described. The clinical course was mild in 11 patients. One patient, however, presented in portal systemic encephalopathy and required steroid treatment. Nine of the 12 patients continued to exhibit raised transaminase (AST) activities six or more months after the onset of the acute hepatitis. In these immunoglobulin concentrations were normal and autoantibodies were not present in significant titre. Four patients had evidence of previous hepatitis B infection, suggesting that the route of transmission of NANB might be similar to that of hepatitis B virus. A further four patients gave a history which suggests a possible parenteral mode of transmission. Liver biopsies were carried out both in the acute (8 cases) and chronic (6 cases) phases of the disease. Histological findings in liver biopsies covered the whole spectrum of acute and chronic hepatitis and 1 patient had cirrhosis. One notable feature in these biopsies was the presence of fatty changes.

Acute Disease↗
PubMedDate not supplied

Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients.

Human T-lymphotropic virus type III (LAV, HTLV-III) is aetiologically linked to acquired immune deficiency syndrome (AIDS) and persistent general lymphadenopathy (PGL). Specific radioimmunoassays (RIA), enzyme-linked assays, immunofluorescence assays (IFA) and immunoblotting techniques are being used widely to detect serum antibodies to HTLV-III in infected patients and in those at risk of infection. However, these assays do not functionally identify those antibodies that neutralize the infectivity of the virus. We have used three methods of titrating serum neutralizing factors: inhibition of syncytium induction, neutralization of envelope pseudotypes of vesicular stomatitis virus (VSV) and reduction of infectivity of HTLV-III for a cell line permissive to virus replication. We report here that sera from subjects in various disease categories possess only low-level neutralizing activity, even when antibodies to viral membrane antigens are present in high titre. Envelope pseudotypes prepared from four HTLV-III isolates made in three different countries are equally sensitive to neutralization by positive sera, including sera from patients yielding two of the virus isolates.

Acquired Immunodeficiency Syndrome↗