Ursodeoxycholic acid in the treatment of primary biliary cirrhosis
Sübutlu məlumatların xülasələri
15.02.2016 • Sonuncu dəyişiklik 15.02.2016
Editors
Ursodeoxycholic acid may not have any significant benefits on all-cause mortality, all-cause mortality or liver transplantation, pruritus, or fatigue in patients with primary biliary cirrhosis, although it seems to have a beneficial effect on liver biochemistry measures.
Meta-analyses
A Cochrane review included 16 studies with a total of 1 447 subjects. Fourteen trials compared ursodeoxycholic acid with placebo and two trials compared ursodeoxycholic acid with 'no intervention'. The percentage of patients with advanced primary biliary cirrhosis at baseline varied from 15% to 83%, with a median of 51%. The duration of the trials varied from 3 to 92 months, with a median of 24 months.
The results showed no significant difference in effect between ursodeoxycholic acid and placebo or 'no intervention' on all-cause mortality (45/699 (6.4%) versus 46/692 (6.6%); RR 0.97, 95% CI 0.67 to 1.42; 14 trials); on all-cause mortality or liver transplantation (86/713 (12.1%) versus 89/706 (12.6%); RR 0.96, 95% CI 0.74 to 1.25; 15 trials); on serious adverse events (94/695 (13.5%) versus 107/687 (15.6%); RR 0.87, 95% CI 0.68 to 1.12; 14 trials); or on non-serious adverse events (27/643 (4.2%) versus 18/634 (2.8%); RR 1.46, 95% CI 0.83 to 2.56; 12 trials). Ursodeoxycholic acid did not influence the number of patients with pruritus (168/321 (52.3%) versus 166/309 (53.7%); RR 0.96, 95% CI 0.84 to 1.09; 6 trials) or with fatigue (170/252 (64.9%) versus 174/244 (71.3%); RR 0.90, 95% CI 0.81 to 1.00; 4 trials). Portal pressure, varices, bleeding varices, ascites, and hepatic encephalopathy were not significantly affected by ursodeoxycholic acid.
The median Jadad score was 3 (range 1 - 5). A number of trials. Neither mortality (OR 0.94, 95% CI 0.60 to 1.48) liver transplantation (OR 0.83, 95% CI 0.52 to 1.32), mortality or liver transplantation (OR 0.90, 95% CI 0.65 to 1.25), pruritus, fatigue, autoimmune conditions, quality of life, liver histology, or portal pressure were significantly affected by ursodeoxycholic acid. However, ursodeoxycholic acid significantly reduced ascites, jaundice, and biochemical
variables such as serum bilirubin and liver enzymes. Ursodeoxycholic acid was not significantly associated with adverse events.
Ursodeoxycholic acid significantly decreased serum bilirubin concentration (MD -8.69 µmol/l, 95% CI -13.90 to -3.48, I² = 0%; 881 patients; 9 trials) and activity of serum alkaline phosphatases (MD -257.09 U/L, 95% CI -306.25 to -207.92, I² = 0%; 754 patients, 9 trials) compared with placebo or no intervention. Ursodeoxycholic acid also seemed to improve serum levels of gamma-glutamyltransferase, aminotransferases, total cholesterol, and plasma immunoglobulin M concentration. Ursodeoxycholic acid seemed to have a beneficial effect on worsening of histological stage (random; 66/281 (23.5%) versus 103/270 (38.2%); RR 0.62, 95% CI 0.44 to 0.88; 7 trials).
A systematic review
including 11 RCTs with a total of 1 272 subjects was abstracted in DARE. There was no difference between UDCA and placebo in the incidence of death (OR 1.21, 95% CI 0.71 to 2.04), liver related death (OR 0.72, 95% CI 0.22 to 2.32), liver transplantation (OR 1.27, 95% CI 0.78 to 2.07), death or liver transplantation (OR 1.26, 95% CI 0.87 to 1.82) and in the development of complications of liver disease (OR 1.10, 95% CI 0.64 to 1.90).
Individual trials
In a Swedish multi-centre trial 116 patients were randomised to receive ursodeoxycholic acid (UDCA) 500 mg/day (n=60) or placebo (n=56)
. During a follow-up of 2 years, UDCA improved serum enzyme values but not survival, symptoms, serum bilirubin levels, or liver histology. It was concluded that UDCA in a dosage of 7.7 mg/kg body weight is of little benefit in PBC.
In a double-blind, placebo-controlled 2-year trial of UDCA conducted in 180 patients, treatment failure was delayed in UDCA-treated patients (p=0.0003, log rank test)
. Seven patients receiving UDCA died or required liver transplantation, compared with 12 patients in the placebo group (p=0.18). No patient discontinued UDCA because of side effects or toxicity. At the study closure, the patients originally receiving placebo were switched to active drug, and prospective follow-up was continued for 3 years. Patients were censored at the time of transplantation, voluntary withdrawal or crossover of the placebo group. The survival of the two groups was adjusted for risk scores
at the time of entry to the study. At the time of analysis, the patients receiving placebo had a significantly increased risk of death and/or requiring transplantation (relative risk 2.6, p=0.04) compared with the UDCA-treated patients.
In a nationwide Canadian trial 222 patients were randomised to receive UDCA 14 mg/kg body weight daily (n=111) or placebo (n=111) for 24 months
. Although treatment was not associated with any improvement of symptoms, survival or need for liver transplantation, the serum bilirubin, alkaline phosphatase and aminotransferase levels were significantly improved.
151 patients were randomised within 4 strata (according to bilirubin levels and liver histology) to receive UDCA 10 - 12 mg/kg at bedtime (n=77) for 2 years or placebo (n=74)
. UDCA induced major improvements in liver function tests and histology in patients with low bilirubin levels (> 35 µmol/l). Patients treated with UDCA tended to develop a treatment failure less frequently than those who received placebo.
90 patients were randomised to receive UDCA, colchisine or placebo in a 2-year study
. There were significantly fewer drop-outs for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. UDCA significantly reduced serum activities of aminotransferase, alkaline phosphatase, and GGT compared with placebo. Colchisine improved liver function tests only modestly.
A combination of UDCA (500 mg/day) and methotrexate (10 mg/week) did not improve the clinical response compared with UDCA (500 mg/day) alone in a RCT of 25 patients followed for a period of 48 weeks
.
Ədəbiyyat
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