Glucocorticosteroids for primary biliary cirrhosis

Prince, Martin; Christensen, Erik; Gluud, Christian

doi:10.1002/14651858.cd003778.pub2

Cited by 24 publications

(8 citation statements)

References 53 publications

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“…The reported UDCA 25% drop of bilirubin level is of statistical significance, but is not of clinical significance, and does not go beyond improvement of surrogate markers [8,9,175,183–185,189]. It is to be noted however that steroids exert same effect on liver biochemical markers in PBC [190]. Moreover, the risk of development of hepatocellular carcinoma in patients with PBC who do not respond to UDCA biochemical control increases by time, with a 10 and 15 years incidence of 9% and 20% respectively [16].…”

Section: Udca As a Medicinementioning

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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Section: Udca As a Medicinementioning

confidence: 99%

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

Kotb

2012

IJMS

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“…As for corticosteroid therapy, though a consensus has not been achieved yet because of the lack of benefit for the overall prognosis of the participants as well as decrease of bone mineral density, an improvement of histological staging and inflammatory markers has been demonstrated by meta-analysis. 54 Therefore, the therapeutic option of including corticosteroid in this small subcategory group should be investigated by a large clinical study. The histological featuring of the livers would be the challenging theme with regard to the sub-classification of PBCs.…”

Section: Classification Of Pbc and Corticosteroid Therapymentioning

confidence: 99%

“…Though Poupon's overlap contained 17 cases whose liver histology was unrevealed, the IAHG score was from 10 to 17 (13 on average), which would meet Lindor's criteria. As for corticosteroid therapy, though a consensus has not been achieved yet because of the lack of benefit for the overall prognosis of the participants as well as decrease of bone mineral density, an improvement of histological staging and inflammatory markers has been demonstrated by meta‐analysis 54 . Therefore, the therapeutic option of including corticosteroid in this small subcategory group should be investigated by a large clinical study.…”

Section: Current Therapeutic Concepts For Pbcmentioning

confidence: 99%

Treatment of Primary Biliary Cirrhosis: A new challenge?

Fukushima

Ueno

Shimosegawa

2010

Hepatology Research

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Primary biliary cirrhosis (PBC) is characterized by unknown etiologies, anti-mitochondrial antibodies, injury of the biliary duct and the lack of a definite remedy. The etiologies of PBC have been well-discussed, including microorganisms and xenobiotics as the triggers for initiating the disease, and an abnormality of immune-tolerance. Recently, several animal models of PBC have been developed that may lead to the development of new therapies. Here, we reviewed the articles that address the etiology of PBC and the therapy for this disease for the confirmation of our current positions and future directions.

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“…Considering the established autoimmunity of the disease, corticosteroids and other immunosuppressive agents have been evaluated for therapeutic use in PBC. Prednisolone in combination with UDCA was proved to improve biochemical/histologic findings (144,145), however, not only the lack of survival benefit but also serious side-effects have precluded its use except for overlapping autoimmune hepatitis disease (146,147). Other immunosuppressive agents including budesonide (148), azathioprine (149), cyclosporine (150), mycophenolate mofetil (151), or methotrexate (152), and drugs with antifibrotic properties including penicillamine (153), colchicines (154), and silymarin (155) have been investigated, however, none of these drugs was shown to provide any additional benefit, in terms of clinically relevant events, when compared to UDCA monothreapy.…”

Section: Treatment Of Pbcmentioning

confidence: 99%

Primary biliary cirrhosis and liver transplantation

Akamatsu¹,

Sugawara

2012

Intractable Rare Dis Res

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Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5-and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival.

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Glucocorticosteroids for primary biliary cirrhosis

Abstract: There is insufficient data to support or reject the use of glucocorticosteroids for patients with primary biliary cirrhosis. It may be appropriate to consider a large prospective randomised clinical trial on this topic.

Cited by 24 publications

References 53 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

Treatment of Primary Biliary Cirrhosis: A new challenge?

Primary biliary cirrhosis and liver transplantation

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