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.
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.
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 firstdetected 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.
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.
In 2007, an assessment centre approach (a structured interview, a case-based discussion and a communication exercise) was implemented to replace the traditional interview for entry to core medical ...training. Feedback was obtained from 53 of 69 assessors, all consultants and most with extensive experience of the traditional system. Each station was rated by around 20 interviewers. This overwhelmingly rated the new process as useful in assessing the candidate (>90% for all stations). Comparison with the previous system was only provided by between 12 and 21 people per station. The structured interview was rated better (n=12), undecided (8), or worse (1); the case-based discussion better (16), or undecided (3); the communication station better (8), undecided (3), or worse (1). There is still work to do on the best components to include but the principle of multiple assessments to examine differing parts of the person specification seems, subjectively, to be supported.
Summary
Background
Treatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub‐optimal treatment response with most ...requiring long‐term therapy.
Aim
The United Kingdom Autoimmune Hepatitis (UK‐AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches.
Methods
The United Kingdom Autoimmune Hepatitis study is a cross‐sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected.
Results
In total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non‐transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non‐transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype.
Conclusions
There are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis.
Background Endoscopic retrograde cholangio-pancreatography (ERCP) is an important tool in the management of pancreato-biliary disease. Objective To compare the current practice of ERCP in a district ...general hospital with those reported in the 2007 British Society of Gastroenterology (BSG) ERCP audit and assess access to the service. Design This was a service evaluation study. Data were collected retrospectively for all people who underwent ERCP. Demographic, clinical and procedure related data were collected and analysed. Setting Sunderland Hospital. Results 236 patients (median age 70 years, 56% women) underwent ERCP. The median period from referral to patient review was 1.0 day. The median period from the decision to carry out an ERCP to the actual procedure date was 3 days. All patients had radiological imaging before their first procedure. 96% patients had their bloods checked within 1 week of the procedure. The most common indication was related to choledocholithiasis and its complications. The mean doses of midazolam and diazemul used were 4.4 mg and 11.1 mg, respectively. The selective biliary cannulation rate was 92%. Sphincterotomy, biliary stent insertion and complete stone extraction were achieved in 94%, 85% and 88% of patients before the procedure. Complications that occurred as a result of ERCPs were as follows: bleeding (1.7%), pancreatitis (3.8%), cholangitis (0.4%) and renal failure (0.4%). The 30-day death rate was 4.6%. However, none of these were procedure related. Conclusions The structure of the ERCP services at Sunderland Royal Hospital provides patients with a high-quality and accessible service. The technical success rate and sedation rate were better than those reported in the BSG ERCP audit. The complication rate and procedure-related mortality were comparable to the BSG audit and much below the published figures.
A randomized, double‐blind, 1‐year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a ...maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin.
Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died of liver failure after 3 months.
Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients.
No patient developed skeletal symptoms. Fifty‐seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p < 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (‐3.5% vs. placebo +0.5%, p < 0.05), as did trabecular bone volume (‐6% vs. ‐2.8%, p < 0.005) and resorption surface (‐11% vs. +2%, p < 0.02) on serial bone biopsy.
Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the “cost/benefit” ratio.
Twenty‐nine patients with a positive antimitochondrial antibody titer ≥1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline ...phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer ≥1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.
The prognosis of patients with asymptomatic primary biliary cirrhosis has been uncertain. Cases of primary biliary cirrhosis in 95 patients from two centers are presented: 70 patients from a regional ...referral center (Freeman Hospital, FH) and 25 from an international tertiary referral center (King's College Hospital, KCH) with similar mean age at diagnosis and duration of follow-up (median, 12 months). During follow-up, 19 of 70 FH patients and 15 of 25 KCH patients developed symptoms (P less than 0.001); the mean time to symptom appearance was 43 months at FH and 35 months at KCH (P = 0.0012). Twenty-five of 95 patients died, 15 of 34 subjects who had developed symptoms (all liver-related deaths) and 10 of 61 who remained asymptomatic (all non-liver-related deaths) (P less than 0.001). Hepatic mortality was worse than among the normal population (P less than 0.05). A comparison of those patients developing symptoms with 111 at FH and 165 at KCH who presented with symptoms suggests no difference in survival once hepatic symptoms appear. In both centers, hepatic mortality was strongly related to symptom appearance in asymptomatic primary biliary cirrhosis: patients developing symptoms resemble those with symptoms at presentation. Other differences between the centers may reflect different referral patterns.
Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 ...year period. The two groups were well-matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin (MCD 5 mumol/L 95% confidence interval (CI) 1 to 12 at 1 year and 5 mumol/L (95% CI 1 to 9) at 2 years), alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group median rise 2 mumol/L (95% CI 1 to 9). Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.
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