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Background: In 1986, we reported a group of 29 patients who were positive in serum for antimitochondrial antibody (AMA), the disease-specific marker for primary biliary cirrhosis (PBC), but who had normal liver function test results and no symptoms of liver disease. However, liver histology was diagnostic or compatible with PBC in 24 patients and normal in only two. The aims of this 10-year follow-up study were to establish whether patients with AMA have very early PBC, to assess the outlook for such patients, and to follow the progression of the disease., Methods: All patients were assessed every year at our PBC clinic: records were reviewed, cause of death verified when applicable, and current clinical and biochemical data collected, including repeat liver histology as indicated. Serum samples from the original study were located. Original and follow-up serum samples were tested by ELISA for E2 components of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex., Findings: Five patients died during follow-up; no deaths were attributable to liver disease. Median follow-up of patients who survived was 17.8 years (range 11.0-23.9) from first-detected AMA to the last follow-up review. Overall, 22 (76%) developed symptoms of PBC and 24 (83%) had liver function tests persistently showing cholestasis. Repeat liver biopsy samples were obtained from ten patients; among these patients PBC progressed from Scheuer grade 1 to grade 2 in two and from grade 1 to grade 3 in two. No patient developed clinically apparent cirrhosis. ELISA of baseline serum samples from 27 patients was positive in 21, all of whom had original liver histology compatible with or diagnostic of PBC. Of the six patients who tested negative, only one had an original liver biopsy sample that was compatible with PBC., Interpretation: This study confirms that before the advent of any clinical or biomedical indications, individuals positive for AMA do have PBC. This finding extends the natural history of PBC back in some cases for many years. What determines the eventual progression to biochemically and clinically apparent disease is not yet understood. During our study no patient developed clinically apparent portal hypertension or cirrhosis. Thus, although the finding of a solitary persistently raised AMA is confirmation of a diagnosis of PBC, patients with AMA but no other signs or symptoms of PBC seem to have slow progression of the disease.

Background: Batten's disease is the most common progressive encephalopathy of childhood in Western countries. The major mutation is a 1kb deletion, which is carried by 81% of Batten's disease patients. We report on the use of direct gene analysis in the prenatal diagnosis of this disease., Methods and Findings: A Finnish woman with a son with Batten's disease came for genetic counselling for her current pregnancy. Electron microscopy of a chorionic villus sample gave suggestive findings. We used PCR to look for the intragenic microsatellite marker D16S298; 96% of Finnish Batten's disease patients carry allele 6 at this marker. The fetus and the affected son both carried the same high-risk genotype, 6/6. Both were homozygous for the 1 kb deletion. The pregnancy was terminated. Electron microscopy of the fetus showed typical Batten's disease changes., Interpretation: We have successfully used direct gene analysis in the prenatal diagnosis of Batten's disease.

The cytosolic phenol sulphotransferase gene (STP) was mapped to a region of chromosome 16, within the interval defined by human-rodent somatic cell hybrid breakpoints CY160(D) and CY12, which contains FRA16E. YAC and cosmid clones from this 16p interval were screened for the presence of STP. Two non-overlapping cosmid contigs were identified which contain STP-like sequences. Sequencing of these STP-like sequences confirmed that STP is contained within contig 343.1 and maps proximal to FRA16E, and that a related sulphotransferase STM, encoding the catecholamine-sulphating enzyme, is contained within contig 55.4 and maps to the adjacent hybrid interval CY12-CY180A. Thus two phenol sulphotransferase genes (STP and STM) have been finely localised to chromosome 16p12.1-p11.2, to the same region as CLN3, the gene for Batten disease. Both genes are therefore candidate genes for Batten disease.

The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.

160 consecutive patients with primary biliary cirrhosis (PBC) (M:F, 13:147; total samples 286), 140 patients with other chronic liver disease (CLD) (M:F, 75:65; total samples 200), and 28 patients with primary Sjögren's syndrome (all F; total samples 37), were examined for bacteriuria over 6 months by midstream urine (MSU) examination. The overall prevalence of bacteriuria in PBC was 11.2% (7.5% on first MSU), in CLD 12.1% (10.7% on first MSU), 18.4% in the 65 female CLD patients, 10.7% in Sjögren's syndrome patients (3.5% on first MSU). The prevalence of bacteriuria was related to the age of the patient (P less than 0.02) in PBC and to the presence or absence of cirrhosis in both PBC and CLD (P less than 0.02). There was no difference in the prevalence of bacteriuria between PBC and CLD patients taken as a whole or among females alone, cirrhotic or non-cirrhotic groups. In a second prospective study of the cumulative incidence of bacteriuria in PBC versus CLD and Sjögren's no significant differences between groups was observed but among 29 PBC patients the cumulative proportion of positive tests for bacteriuria after 5 months (monthly testing) was 34%. We conclude that there is no specific association between PBC and bacteriuria compared with the prevalence of bacteriuria in other CLD.