Prescribing habits in primary biliary cirrhosis

Verma, Abhishek; Rp, Jazrawi; Ahmed, HA; Northfield, T. C.

doi:10.1097/00042737-199908000-00001

Cited by 26 publications

(9 citation statements)

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“…Approximately 91% of gastroenterologists in UK prescribe UDCA to primary biliary cirrhosis patients despite conflicting evidence of UDCA effectiveness or safety [229]. …”

Section: Lessons To Be Learned What Masked Udca Toxicity?mentioning

confidence: 99%

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Kotb

2012

IJMS

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Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

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“…Approximately 91% of gastroenterologists in UK prescribe UDCA to primary biliary cirrhosis patients despite conflicting evidence of UDCA effectiveness or safety [229]. …”

Section: Lessons To Be Learned What Masked Udca Toxicity?mentioning

confidence: 99%

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Kotb

2012

IJMS

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“…Therefore, we think that colchicine should not be used outside randomized clinical trials. Considering that about 2.5 million patients in the world may have primary biliary cirrhosis (1), about 140,000 primary biliary cirrhosis patients may be receiving colchicine (10).…”

Section: Discussionmentioning

confidence: 99%

“…Colchicine is used for primary biliary cirrhosis patients (10) because it may slow progression (11) and improve liver biochemical tests and immunoglobulin levels (12)(13)(14). However, colchicine did not appear to affect clinical symptoms or liver histology (15).…”

Section: Introductionmentioning

confidence: 99%

Colchicine for Primary Biliary Cirrhosis: A Cochrane Hepato-Biliary Group Systematic Review of Randomized Clinical Trials

Yang

Gluud

2005

Am J Gastroenterology

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OBJECTIVES:Colchicine is used for patients with primary biliary cirrhosis due to its immunomodulatory and antifibrotic potential. The results from randomized clinical trials have, however, been inconsistent. We conducted a systematical review to evaluate the effect of colchicine for primary biliary cirrhosis. METHODS:We identified randomized clinical trials comparing colchicine with placebo/no intervention. We analyzed effects by fixed and random effects model. We investigated heterogeneity by subgroup and sensitivity analyses. RESULTS:We included 10 trials involving 631 patients, four of which were high-quality trials. No significant differences were detected between colchicine and placebo/no intervention regarding mortality (relative risk (RR), 1.21; 95% confidence interval (CI), 0.71-2.06), mortality or liver transplantation (RR = 1.00; 95% CI, 0.67-1.49), liver complications, liver biochemical variables, liver histology, or adverse events. Regarding mortality, an extreme case analysis favoring colchicine did not demonstrate beneficial effects of colchicine, whereas an extreme case analysis favoring placebo/no intervention demonstrated a detrimental effect of colchicine (RR = 2.28; 95% CI, 1.17-4.44). The number of patients without improvement of pruritus significantly decreased in the colchicine group (RR = 0.75; 95% CI, 0.65-0.87). However, this estimate was based on only 156 patients from three trials.CONCLUSIONS: There is insufficient evidence to support the use of colchicine for patients with primary biliary cirrhosis. As we are unable to exclude a risk of increased mortality, we recommend to use colchicine only in randomized clinical trials.(Am J Gastroenterol 2005;100:1876-1885)

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“…5 Drug-related adverse event rates as high as 35% leading to UDCA discontinuation are also reported among U.S. residents with PBC. 4 This far exceeds rates observed in published randomized controlled trials to date.…”

mentioning

confidence: 99%

“…Finally, medical therapies with questionable or no benefit for PBC are prescribed by 10%-15% of providers based on published reports. 5 Estimated rates of similar practices in the United States remain unknown.…”

mentioning

confidence: 99%

Practice variation in treatment of primary biliary cirrhosis and effect on clinical outcomes

Talwalkar¹,

Gossard²

2008

Hepatology

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Prescribing habits in primary biliary cirrhosis

Cited by 26 publications

References 0 publications

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Colchicine for Primary Biliary Cirrhosis: A Cochrane Hepato-Biliary Group Systematic Review of Randomized Clinical Trials

Practice variation in treatment of primary biliary cirrhosis and effect on clinical outcomes

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