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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 199 records · Page 11Linked to original sources
PubMed1989

Histological improvement after anti-viral treatment for chronic hepatitis B virus infection.

Sequential liver biopsies were taken from 66 patients with chronic hepatitis B virus (HBV) infection being followed in randomised controlled trials of therapy with alpha interferons or adenine arabinoside 5'-monophosphate. In the group of 23 patients responding to treatment with the permanent loss of HBe antigen and HBV-DNA from their serum, there was a significant reduction in hepatic inflammatory activity and none developed cirrhosis. In contrast, inflammatory activity continued in the group of 24 patients that did not respond to therapy, and in the group of 19 patients who received no therapy. Two untreated controls progressed to cirrhosis. Further studies confirmed that in those clearing HBeAg and HBV-DNA from the serum, HBcAg and HBeAg were also lost from the liver. This study demonstrates that, as in natural seroconversion, successful treatment of chronic HBV infection is associated with loss of hepatic as well as serum markers of HBV replication, and is followed by a reduction in hepatic inflammation. Antiviral therapy may prevent progression to cirrhosis in some cases.

Adolescent↗
PubMed1989

Interferon therapy for chronic non-A non-B and chronic delta liver disease in haemophilia.

The case histories of a carrier of haemophilia A with chronic post transfusion non-A non-B hepatitis and a severe haemophiliac with chronic delta hepatitis are described. Therapy with lymphoblastoid alpha interferon resulted in improvement of NANB and HDV related chronic hepatitis and resolution of HIV related thrombocytopenia. Interferon may modulate replication of more than one transfusion transmitted virus in the haemophiliac.

Adolescent↗
PubMed1989

Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.

Adult↗
PubMed1989

Subclasses of antibodies to hepatitis B core antigen in chronic HBV infection: changes during treatment with alpha interferons and predictors of response.

Response to interferon therapy in chronic hepatitis B virus (HBV) carriers is preceded by the appearance of IgM class anti-HBc (antibody to hepatitis B core antigen). The temporal relationship and magnitude of the IgM anti-HBc response is variable suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins, induced by interferon. IgG 1, 2, 3, and 4 class anti-HBc did not change during therapy, but IgG 3 anti-HBc was significantly lower in responders than non-responders. IgG anti-HBc of all subclasses was absent in two Chinese HBV carriers. Lower than normal titres of anti-HBc (p less than 0.001) were detected in human immunodeficiency virus antibody positive (anti-HIV) HBV carriers. These data indicate the presence of altered immunity to the nucleocapsid antigens in these two types of chronic HBV carrier that are known to respond poorly to antiviral therapy.

Adolescent↗
PubMed1989

Antenatal screening for hepatitis B is medically and economically effective in the prevention of vertical transmission: three years experience in a London hospital.

We describe our experience over a three-year period in the detection of antenatal patients with hepatitis B virus (HBV) carriage, and the successful prevention of vertical transmission in the infants of HBsAg-positive women. Nine of the 26 infants born to HBsAg-positive mothers were considered to be at high risk of infection. Eight of these nine remained HBsAg-negative after passive or passive/active immunization. The majority of infants tested had anti-HBs antibody titres above 10 i.u./l from the first month. In comparison with the cost of caring for patients with chronic hepatitis B infection and decompensated cirrhosis, non-selective testing of pregnant women for HBsAg is found to be cost effective.

Carrier State↗
PubMed1989

Treatment of chronic hepatitis delta virus (HDV) infection with human lymphoblastoid alpha interferon.

Ten patients with evidence of continuing HDV replication were treated with lymphoblastoid alpha-interferon and eight more were followed as a non-randomized control group. Four out of eight patients who completed one year of follow-up had cleared HDV-RNA from the serum whilst none of the control group did so. In these four responding cases there was a transient increase in transaminase levels during treatment and in two, this was followed by improvement. One patient also cleared HBV and seroconverted to anti-HBs (antibody to hepatitis B surface antigen--HBsAg). In one patient with sustained loss of HDV, recurrence of HDV infection was detected 18 months after completion of treatment. These data suggest that alpha-interferon can inhibit HDV replication in the short term but relapse after one to two years may occur. Inhibition of HDV-RNA is associated with improvement in the inflammatory liver disease and now larger studies are required to determine whether it influences survival.

Adult↗
PubMed1988

Hepatitis B viral infection.

Although the strategy of replication of hepatitis B virus has now been described, the majority of the compounds that have activity against the virus have been identified by empirical means. Vidarabine, acyclovir, and interferons alpha and beta are capable of inhibiting hepatitis B virus replication; however, at the present time, optimal treatment regimens have not been defined. The effects of interferons alpha and beta given in short courses are only transient. Longer courses of intermittent therapy have resulted in seroconversion rates of up to 50 percent in Western European carriers. It is becoming apparent that patients infected with hepatitis B virus in adult life have a relative deficiency of interferon alpha, and it is these patients who have the best responses to protracted courses of intermittent therapy.

Acyclovir↗
PubMed1988

Hepatocellular carcinoma: clinical, aetiological and pathological features in British patients.

We have examined the clinical, prognostic, aetiological and pathological features of 41 consecutive British patients with hepatocellular carcinoma (HCC). Presenting symptoms were often vague, and patients were generally in poor condition at diagnosis, 56% being of WHO grade 2 performance score or higher. Ascites (46%) and jaundice (35%) were often present at diagnosis, and the median duration of survival from diagnosis was only 6 weeks. Only initial performance grade (p less than 0.0001) and serum bilirubin concentration (p = 0.02) significantly affected prognosis. Serum alphafoetoprotein (AFP) was positive by counter-immune electrophoresis in only 34%, but increased to 68% when radioimmunoassay was used. Cirrhosis was present in 33 patients (80%) and was most often cryptogenic (12) or alcoholic (7) in origin. Serum HBsAg was detected in 5 patients (12%) and, of the remainder tested, 21% had serological evidence of past HBV exposure. None of 8 serum HBsAg-negative tumour specimens had detectable HBV-DNA integration into the tumour cell genome. Liver-cell dysplasia was noted in 56% of patients with liver biopsies predating the diagnosis of HCC, and in 78% of biopsies taken at the time of HCC diagnosis. The commonest histological pattern was trabecular (71%). Other forms were rare; the fibrolamellar pattern was only seen in 2 patients.

Adolescent↗
PubMed1988

Acute and chronic hepatitis delta virus infection: direct or indirect effect on hepatitis B virus replication?

In a large population of patients, chronic hepatitis delta virus (HDV) infection was usually associated with absence of hepatitis B virus (HBV) replication. However, acute HDV superinfection progressing to chronic HDV infection in two hepatitis B e antigen (HBeAg)-positive HBV carriers and coinfection in two other patients who progressed to chronic HBV (HBeAg-positive) and HDV infection was associated with continuing high-level HBV replication for several years. Thus HDV infection does not always inhibit HBV replication. The hypothesis that the different effects of HDV coinfection and superinfection on HBV replication may stem from variability in the capacity of the host to produce and respond to interferon is discussed.

Acute Disease↗
PubMed1988

Human hepatocellular carcinoma tumor xenografts. Their androgen-receptor status and growth responses to castration.

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivo studies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.

Animals↗
PubMed1988

Virus-host interaction in chronic hepatitis B virus infection.

The clearance of HBV-infected cells from the liver is probably dependent on an interplay between the interferon system and the cellular limb of the host immune response. Although the importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells is established in chronic HBV infection, further studies are needed during the early phase of acute HBV infection. The relative importance of pre S sequences as inducers and targets of the virus neutralizing humoral immune response is becoming established, but their precise place will await the development of in vitro models of hepadnavirus infection and precise definition of the mechanism of viral uptake. Our understanding of the mechanisms underlying the development of chronic HBV infection is still incomplete. When this occurs in adult life, deficient production of alpha interferon and suppression of the ability of the host to respond to interferon are probably important factors, and the role of suppression of the humoral response remains to be determined. In the neonate, specific suppression of the cell-mediated immune response, perhaps because of exposure to soluble HBe antigen or to modulating quantities of maternally derived antinucleocapsid antibodies at a time when the immune system is "immature," may be involved. In each of these postulated mechanisms the virus has neutralized one important host defense. Increasing the response rate to therapy with interferon or synthetic antiviral compounds will depend on identifying the cause in each patient and devising specific therapies to reverse the host-virus balance in favor of the host defenses.

Acute Disease↗
PubMed1988

Review: the treatment of hepatocellular carcinoma.

Surgical resection offers the only realistic hope of cure in hepatocellular carcinoma (HCC) but is usually not possible, either because the tumour is widespread throughout the liver at diagnosis, or because liver function is adversely affected by concomitant cirrhosis. The results of operation in early asymptomatic disease are, however, encouraging and efforts should be made to screen regularly the cirrhotic population at risk of HCC development. The prognosis for inoperable patients remains gloomy, though exciting new treatment methods exist which require extensive evaluation. An anthracycline given as single agent intravenous therapy is probably the current treatment of choice for inoperable patients, though only 20-30% will show a response. Intra-arterial therapy has not yet been convincingly shown to have any advantages over intravenous therapy. The evaluation of clinical trials in HCC would be made easier if response criteria were standardized and universally adopted, and if trials were properly controlled and of sufficient sample size to test adequately the hypothesis in question. This review deals only with the specific treatment of HCC. HCC prevention, the early diagnosis of HCC, and the relief of symptoms in HCC, though areas of obvious importance, are outside the scope of this review.

Carcinoma, Hepatocellular↗
PubMed1988

Non-invasive investigation of liver disease in haemophilic patients.

Liver biopsy specimens previously taken from 16 haemophilic patients with chronic non-A, non-B hepatitis were reviewed. The degree of fibrosis correlated with serum procollagen III peptide (sPIIIP) concentrations, measured both at the time of biopsy and 4.25 years later. Two patients with extremely high sPIIIP concentrations had collateral veins on computed tomography, suggesting portal hypertension. Twenty eight of 47 patients (60%) had splenomegaly on computed tomography, and of 28 patients in whom intravenous contrast medium was used, seven (25%) had collateral oesophageal veins. Serum procollagen III peptide estimations and computed tomography, both non-invasive investigations, indicated that hepatic fibrosis and portal hypertension had developed in a proportion of haemophilic patients with non-A, non-B hepatitis. Infection with the human immunodeficiency virus (HIV) may modify the course of this presumably cytopathic virus infection of the liver.

Adolescent↗
PubMed1988

Suppression of HIV p24 antigen and induction of HIV anti-p24 antibody by alpha interferon in patients with chronic hepatitis B.

Five HIV p24 antigen (p24Ag)-positive patients received alpha interferon during trials of therapy for hepatitis B. Four of these showed marked falls in p24Ag during treatment. One of the two patients who became p24Ag-negative [corrected] developed anti-p24 antibodies (anti-p24). Five out of nine p24Ag-negative HIV-antibody-positive patients showed a rise in anti-p24 titres during interferon therapy, whereas only two out of six untreated controls showed a similar rise. This study provides evidence that alpha interferon has anti-HIV activity in vivo.

Adult↗
PubMed1988

Management of non A, non B hepatitis: the problem and its treatment.

Non A, non B (NANB) hepatitis is caused by at least three, as yet unidentified, viruses and can occur as a result of blood transfusions, the use of blood products, covert or overt percutaneous exposure and epidemic waterborne outbreaks of infection. The three types of viruses are characterised by their incubation times; a short time of 2-4 weeks, a longer time of 6-12 weeks and a intermediate period for the waterborne NANB hepatitis virus. Acute NANB hepatitis is milder than HBV hepatitis with lower peak transaminase levels. However, some develop into fulminant hepatitis with a lower survival rate of 0.13%. Ten to 100% of acute patients progress to chronic NANB hepatitis. It was found that alpha-lymphoblastoid interferon at levels of 3-5 megaunits (MU) thrice weekly returned transaminase levels to normal within 6-8 weeks. Approximately 80% had normal levels by the eighth week of treatment and this was maintained on 2.5-3 MU thrice weekly; a well tolerated dose. Long term, low-dose therapy is needed to maintain remission.

Acute Disease↗