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Biomedical subjects

M Bassendine

Publications and source records attributed to M Bassendine.

15 recordsLinked to original sources
PubMed2005

Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C.

BACKGROUND: For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown. AIMS: To assess whether antiviral therapy (either interferon alpha or peginterferon alpha combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease. PATIENTS: Cases with mild chronic hepatitis C. METHODS: A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies. RESULTS: Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon alpha-2b and ribavirin, compared with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with genotype 1. CONCLUSIONS: For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.

Adult↗
PubMed2005

Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial.

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

Adult↗
PubMed2004

Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels.

BACKGROUND AND AIM: Fatigue is the commonest symptom in primary biliary cirrhosis (PBC), affecting individuals at all stages of disease. The pathogenesis of fatigue in PBC is unknown although rat models suggest a central nervous system (CNS) cause. We examined the hypothesis that a CNS abnormality related to cholestasis, rather than cirrhosis per se, underlies this symptom. PATIENTS AND METHODS: Fourteen patients with precirrhotic PBC (stage I-II disease), four patients with stage III-IV PBC, and 11 healthy women were studied using cerebral magnetisation contrast imaging and proton magnetic resonance spectroscopy (MRS). RESULTS: The globus pallidus magnetisation transfer ratio (MTR), a quantifiable tissue characteristic that may be abnormal in the presence of normal magnetic resonance imaging, was significantly reduced in precirrhotic PBC patients compared with healthy controls. These measurements correlated with blood manganese levels and were more abnormal in the more fatigued subjects. There were no differences in MRS measurements between the three study groups, suggesting that the abnormal MTR was not related to hepatic encephalopathy. CONCLUSION: This study suggests that impairments in liver function in PBC may adversely affect the brain long before the development of cirrhosis and hepatic encephalopathy, possibly as a result of altered manganese homeostasis within the CNS.

Adult↗
PubMed2001

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function. CONCLUSIONS: Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.

Adult↗
PubMed2001

Osteoporosis in primary biliary cirrhosis revisited.

BACKGROUND: Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied. AIMS: To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex. DESIGN: Retrospective review of a large cohort of well characterised PBC patients. PATIENTS: A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD). RESULTS: In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were -0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than -2.0 and 85 had T scores less than -2.5. No factors predictive of osteoporosis were found in affected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were -1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation. CONCLUSIONS: Osteoporosis is not a specific complication of PBC.

Absorptiometry, Photon↗
PubMed1998

[Pretreatment with prednisolone enhances the effect of human lymphoblastoid interferon in chronic hepatitis B].

Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25 mg/kg/day) or placebo followed by two weeks rest, and were then given human lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice weekly for 11 weeks. There were statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38% (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22 cirrhotic patients (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome. Prednisolone pre-treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis B. Interferon treatment (with and without prednisolone) should be used with caution in patients with cirrhosis and avoided in patients with evidence of hepatic decompensation.

Adult↗
PubMed1996

Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.

BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.

Administration, Oral↗
PubMed1996

Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.

BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B. METHODS: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS: Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment. CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.

Adult↗
PubMed1995

Defective repair of O6-methylguanine-DNA in primary Sjögren's syndrome patients predisposed to lymphoma.

OBJECTIVE: To investigate a role for mutation in the aetiogenesis of autoimmune disease by examining levels of repairing enzyme for the promutagenic DNA base lesion, O6-methylguanine, in lymphocyte extracts from patients with autoimmune diseases. We included primary Sjögrens syndrome (PSS) patients because of the additional relevance of their being at increased risk (> 40-fold) of developing lymphoma. METHODS: Lymphocytes were prepared from patients with PSS (n = 22) (12 with parotid gland enlargement, an indicator of extensive lymphoproliferation), rheumatoid arthritis (n = 12), primary biliary cirrhosis (n = 11), osteoarthritis (n = 12), and healthy individuals (n = 11). MGMT amounts were determined in lymphocyte extracts by direct enzyme assay and expressed in relation to total extract DNA, protein, or cell number. RESULTS: We found no defect in the repairing methyltransferase enzyme between any of the groups, except in PSS patients at increased risk of developing lymphoma (those with enlarged parotid glands): p < 0.0001 and p = 0.0056, compared with healthy controls and PSS patients without parotid gland swelling, respectively. CONCLUSIONS: Our findings implicate persistence of O6-methylguanine-DNA in the aetiology of lymphoma associated with PSS, and raise the possibility that an alternative repair process for O6-methylguanine-DNA, nucleotide excision repair, might be defective in autoimmune disease.

Aged↗
PubMed1994

Major histocompatibility complex class-II alleles in primary biliary cirrhosis.

The major histocompatibility complex (MHC) class-II alleles at the DRB1, DQB1 and DPB1 loci were investigated in 40 patients with primary biliary cirrhosis (PBC) and 43 local healthy controls. Restriction fragment length polymorphism (RFLP) was used for DRB1 typing. DQB1 and DPB1 regions were amplified using the polymerase chain reaction (PCR) and then probed with 32P-labelled allele-specific oligonucleotide probes. There was an increased frequency of DR8 (10% compared to 4% in controls), and a decreased frequency of DR2 (18% compared with 28% in controls) in patients with PBC, but the differences were not significant. There were no significant differences for the other DR alleles, the seven DQ alleles, or the eight DP alleles. In conclusion, no significant MHC class-II associations with primary biliary cirrhosis have been demonstrated.

Alleles↗
PubMed1993

Sex hormone binding globulin and non-protein-bound oestradiol in postmenopausal patients with primary biliary cirrhosis and normal controls.

Several studies have suggested that patients with primary biliary cirrhosis (PBC) have an increased risk of a number of medical conditions related to their oestrogen levels. This study has measured sex hormone binding globulin (SHBG) binding capacity, total oestradiol levels and percentage non-protein-bound (NPB) oestradiol and calculated the concentration of NPB oestradiol, in postmenopausal subjects in the following groups; normal controls, early PBC, advanced PBC and advanced PBC who were receiving therapy. Mean SHBG levels were higher in all groups of patients with PBC than in controls. No significant difference was observed in total or biologically active oestradiol between the four groups.

Aged↗
PubMed1988

Lymphocytes from patients with primary biliary cirrhosis spontaneously secrete high levels of IgG3 in culture.

The origin of the raised serum IgG3 in primary biliary cirrhosis has been examined. Blood lymphocytes from patients with PBC and from age- and sex-matched controls were cultured, and the culture supernatants were assayed for IgG and IgG3. Lymphocytes from PBC patients spontaneously synthesized a higher percentage IgG3/total IgG than did control lymphocytes, as determined by ELISA. The increased synthesis of IgG3 in culture correlated with serum IgG3 in the patients. This strongly suggests that the raised serum IgG3 in these patients is due to increased synthesis of this isotype. Following PWM stimulation, the proportion of IgG3/IgG synthesized by normal (and most PBC) lymphocytes increased and the difference in IgG3 synthesized by PBC and control lymphocytes became less marked. The kappa/lambda light chain ratio of the IgG3 was assayed by ELISA but no evidence was found for clonally restricted synthesis of IgG3 by PBC blood lymphocytes.

Cells, Cultured↗
PubMed1986

Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody.

A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30 000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with 131I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. Sixteen patients with PHC were given 1 mg of purified antibody labelled with 1 mCi of 131I by slow intravenous injection. In 8 out of 9 patients with PHC arising in non-cirrhotic livers, good tumour images were obtained on gamma camera or rectilinear scans, but in 7 patients who had developed PHC on the background of established hepatic cirrhosis, no tumour images were seen. Subsequent studies revealed that the 30K antigen recognised by this antibody was present in increased quantity on PHC cells and the regenerating liver cells in cirrhosis. We conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease.

Adolescent↗
PubMed1978

Serum factor affecting neutrophil function during acute viral hepatitis.

Sera from eight of 17 patients with acute viral hepatitis was deficient in its ability to support neutrophil bactericidal function in vitro. This defect appeared to be related to the viral infection itself. Sera from patients with drug hepatitis or mechanical obstructive jaundice did not show this effect.

Acute Disease↗