No abstract

SUMMARY BackgroundCoeliac disease affects up to 1% of the population and the British Society of Gastroenterology recommends long-term follow-up of these patients, although the absolute risk of complications is small.

Summary Background : Population data supporting an association between the autoimmune cholestatic liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis and coeliac disease, is limited and at times contradictory. Aim : To explore the relationship between coeliac disease and both primary biliary cirrhosis and primary sclerosing cholangitis within the General Practice Research Database, a UK‐based longitudinal primary care database. Methods : We identified 4732 people with diagnosed coeliac disease and 23 620 age‐ and sex‐matched controls within the General Practice Research Database. We calculated the prevalence of primary biliary cirrhosis and primary sclerosing cholangitis for both the coeliac disease and control group. Results : There was a higher prevalence of primary biliary cirrhosis in adults with coeliac disease, compared with controls [0.17% vs. 0.05%, odds ratio 3.63 (95% confidence interval: 1.46–9.04)]. Primary sclerosing cholangitis was also more common in the coeliac disease group [0.04% vs. 0%, fishers exact test (P = 0.03)]. Conclusions : There was a threefold or greater increase in risk of both primary biliary cirrhosis and primary sclerosing cholangitis in people with coeliac disease compared with the general population. The association with primary biliary cirrhosis was weaker than in some reports and it is difficult on the basis of this study to justify screening patients with coeliac disease for either primary biliary cirrhosis or primary sclerosing cholangitis.

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12.10% +/- 6.08 of standard; 2P < 0.05) and non-significantly lower factor VII coagulant activity (8.24% +/- 4.99 of standard) and fibrinogen concentrations (0.10 +/- 0.08 g. l-1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2.62 +/- 1.03 IU; 2P < 0.01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1.2, factor XII and C1 inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P = 0.02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1.74 +/- 0.15 mmol.1(-1): 2P < 0.0001) but also in VLDL cholesterol (0.28 +/- 0.08 mmol.1(-1); 2P < 0.001) and IDL cholesterol (0.17 +/- 0.03 mmol.1(-1); 2P < 0.0001). There were also lower triglyceride levels associated with LDL (0.07 +/- 0.01 mmol.1(-1); 2P < 0.0001), IDL (0.03 +/- 0.01 mmol.1(-1); 2P < 0.01) and VLDL (0.27 +/- 0.14; 2P = 0.05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.