BACKGROUND & AIMS: Long-term ursodeoxycholic acid (UDCA) therapy slows the progression of primary biliary cirrhosis. This study examined the effect of UDCA therapy on survival free of liver ...transplantation in a large group of patients.
METHODS: Data from three clinical trials were combined in which patients with primary biliary cirrhosis were randomly assigned to receive UDCA (n = 273) or placebo (n = 275). After 2 years, patients from French and Canadian studies received UDCA for up to 2 years. Patients from the American study remained on their assigned treatment for up to 4 years.
RESULTS: Survival free of liver transplantation was significantly improved in the patients treated with UDCA compared with the patients originally assigned to placebo (P < 0.001; relative risk, 1.9; 95% confidence interval, 1.3-2.8). Subgroup analyses showed that survival free of liver transplantation was significantly improved in medium- and high-risk groups (serum bilirubin level, 1.4 to 3.5 or > 3.5 mg/dL; P < 0.0001 and P < 0.03, respectively) and histological stage IV subgroup (P < 0.01).
CONCLUSIONS: Long-term UDCA therapy improves survival free of liver transplantation in patients with moderate or severe disease. An effect in patients with mild disease is probably not found because they do not progress to end-stage disease in 4 years. (Gastroenterology 1997 Sep;113(3):884-90)
Background—Fatigue is a frequent and debilitating symptom in patients with primary biliary cirrhosis (PBC). Aims—To study fatigue in relation to sleep, depression, and liver disease severity. ...Methods—Patients with PBC completed validated self report questionnaires measuring fatigue, sleep quality, depression, and functional capacity. Verbally reported fatigue and observer rated measure of depression and ursodeoxycholic acid (UDCA) use were recorded. Liver biochemistry and tests to rule out metabolic causes of fatigue were performed. Results—Mean age of the 88 patients enrolled was 57 years; 86% were female and mean duration of disease was 6.6 years. Median bilirubin was 13 μmol/l (mean 18.6). Verbally reported fatigue (for more than six months) was present in 60 patients (68%). The self rated Fatigue Severity Score (FSS) correlated well with verbally reported fatigue (p=0.0001). The FSS did not correlate with age, duration of disease, serum bilirubin, Mayo Risk Score, or UDCA use, but correlation was seen with sleep quality. Fatigued patients had more sleep problems and higher depression scores than non-fatigued patients. Self rated depression was present in 28% (17/60) of fatigued compared with 4% (1/28) of non-fatigued patients. Conclusions—Long term fatigue affected 68% of the patients with PBC but it was not related to the severity of their liver disease. Poor sleep quality and depression were commonly associated with fatigue.
In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible ...association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines.
We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009.
No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03.
Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study.
To document the natural history of asymptomatic primary biliary cirrhosis and identify prognostic features that would predict the development of symptomatic disease.
A retrospective chart review of ...all patients with abnormal liver biochemical tests and antimitochondrial antibody-positive, liver biopsy-compatible primary biliary cirrhosis who were seen in a single tertiary care center between 1983 and 1994 was performed. Statistical analysis using Cox regression was employed to compare survival of the study population with an age- and gender-matched control population and to identify potential prognostic variables.
Ninety-one patients were included. Median age at presentation was 53.2 yr. Ninety percent were female. Median follow up was 61.2 months (range 7-206 months). Thirty-six percent (33 patients) became symptomatic with 11% (10 patients) progressing to death or liver transplant. Median predicted length of survival from onset of disease for the entire cohort was 14 yr. Patient survival was less than that predicted for an age- and gender-matched control population (p < 0.05). Univariate and multivariate analysis on a broad spectrum of clinical, biochemical, and histological features at the time of initial presentation failed to reveal any prognostic variables that would distinguish those who would become symptomatic from those who would remain symptom-free. Specifically, three primary variables of interest (associated autoimmune disorders, hepatomegaly, and histological stage) were not found to predict prognosis.
Patients who present with asymptomatic primary biliary cirrhosis have a shorter life span than the general population. Presently, there are no prognostic features that identify the patients who will develop progressive disease from those who will remain symptom-free. Therefore, treatment should be offered to all patients.
Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. ...Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5× the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2× ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC ± features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH. (HEPATOLOGY .)
Objectives To determine whether attending diabetes education is associated with blood glucose self‐monitoring among unselected older adults in routine clinical care.
Method A cross‐sectional ...population‐based study was carried out on 15 190 people with diabetes aged 65–79 years. Subjects were identified using a registry of doctor‐diagnosed diabetes derived from administrative data, and attendance at diabetes education centres (DECs) was determined from a separate registry of DEC utilization for 2006. Outcomes were derived using administrative data. The primary outcome was prescriptions filled for glucose self‐monitoring supplies. The secondary outcomes were prescriptions for antihypertensive drugs, prescriptions for lipid‐lowering drugs and eye examinations.
Results DEC attendance was associated with glucose self‐monitoring, after adjusting for baseline differences between attendees and non‐attendees (adjusted odds ratio 6.45, 95% confidence interval 5.61 to 7.42). All of the secondary outcomes were also independently associated with DEC attendance.
Conclusions This study suggests that diabetes education is associated with self‐management behaviour in real‐world clinical care. These findings support the effectiveness of self‐management education programmes to increase self‐care behaviours.
Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are ...retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.
Treatment of patients with primary biliary cirrhosis (PBC) using ursodeoxycholic acid (UDCA) leads to a reduction in serum bilirubin. The first objective of this study was to assess the performance ...of certain prognostic indicators for PBC after the introduction of treatment with UDCA. Serum bilirubin is an important prognostic indicator for PBC and an important component of the Mayo model for grading patients into risk categories. In an analysis of patients enrolled in the Canadian multicenter trial, the Mayo score was calculated before and after treatment with UDCA. After treatment, the Mayo score continued to divide patients with PBC into groups with varying risk. In addition, the serum bilirubin alone was shown to do the same even after the introduction of treatment with UDCA. A second objective was to establish whether UDCA had an effect on long‐term (2‐ to 6‐year) survival in patients with PBC.
Antibodies to carbonic anhydrase II (CAII) have been reported to be specific to anti-mitochondrial antibody (AMA)-negative primary biliary cirrhosis (PBC). We examined whether antibodies to CAII are ...specific for AMA-negative PBC or a nonspecific response in autoimmune liver disease. Antibody assays to CAII, by western immunoblot (dilution 1:200), were performed on sera from 16 AMA-negative PBC patients, 21 AMA-positive PBC patients, 21 autoimmune hepatitis type 1 (AIH) patients, and 18 alcoholic liver disease (ALD) patients. CAII antibody activity was found in 8 of 16 (50%) of the AMA-negative PBC patients, 9 of 21 (43%) of the AMA-positive PBC group, 10 of 21 (48%) of the AIH group, and in 3 of 18 (17%) of the ALD control group. There was no difference in the prevalence of CAII antibody reactivity between the AMA-negative PBC, AMA-positive PBC, and AIH groups. In conclusion, we determined that CAII antibodies are detected with equal frequency in AMA-positive PBC and AIH. Given that CAII antibodies have been reported in other nonhepatic autoimmune diseases, we conclude that CAII antibodies are likely a nonspecific marker of autoimmunity rather than specific for AMA-negative PBC.
Background & Aims: Hepatic osteodystrophy is a complication of primary biliary cirrhosis (PBC). Allelic polymorphisms of the vitamin D receptor (VDR) gene are related to bone mineral density (BMD) in ...normal cohorts and those with primary osteoporosis. We sought to establish the prevalence of reduced bone mass in PBC, correlate BMD with VDR gene polymorphisms, and identify risk factors for the development of hepatic osteodystrophy.
Methods: Seventy-two female patients with PBC were evaluated prospectively. Clinical information, BMD assessment, disease severity, and osteoporosis risk factors were documented, and multivariate regression modeling was performed.
Results: Twenty-four percent of the patients were osteoporotic at the lumbar spine and 32% at the femur. Severe bone loss (z score <−2.0) occurs 4 times more frequently in patients with PBC compared with controls. Body weight (
P = 0.003) and postmenopausal status (
P = 0.012) correlated independently with BMD. VDR genotype (
P = 0.01) correlated with lower BMD at the spine only.
Conclusions: Osteoporosis is a common complication of PBC. VDR genotype predicts lower BMD in patients with PBC. Studies are warranted to investigate the mechanism(s) by which VDR as well as other candidate genes may contribute to the development of hepatic osteodystrophy in PBC.
GASTROENTEROLOGY 2000;118:145-151
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