Prognostic factors and long-term effects of ursodeoxycholic acid on liver biochemical parameters in patients with primary biliary cirrhosis

Hoogstraten, H. J. F. van; Hansen, Bettina E.; Buuren, Henk R. van; Kate, Fiebo J.W. ten; Berge‐Henegouwen, G. P. Van; Schalm, Solko W.

doi:10.1016/s0168-8278(99)80222-0

Cited by 41 publications

(35 citation statements)

References 23 publications

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“…The dual predictive nature of AST levels should be examined in larger populations of patients with longer follow-up to confirm this finding. The strong predictive value of TB in PBC patients is in agreement with several studies and enforces the belief that TB is the best prognostic predictor in PBC [44,45]. Our findings indicate TB value is effective in predicting long-term adverse outcome-free survival of PBC patients irrespective of subtypes at entry (Fig.…”

Section: Discussionsupporting

confidence: 91%

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

Yang

Wang

et al. 2015

Clinic Rev Allerg Immunol

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Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

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Section: Discussionsupporting

confidence: 91%

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

Yang

Wang

et al. 2015

Clinic Rev Allerg Immunol

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“…A marked improvement in biochemical parameters is frequently reported (van Hoogstraten et al, 1999); however, this improvement is not reflected in the overall rate of progression of histological stage associated with chronic cholestatic liver disease or the clinical symptoms of the patients (Neuberger, 2000). In order to provide new insights into the understanding of the effects of therapeutic bile acids, in vitro studies have been done.…”

Section: Resultsmentioning

confidence: 99%

“…The expression and function of these transport proteins are known to be significantly altered during cholestasis (Muller and Jansen, 1997). Since UDCA enriches the bile in cholestatic patients receiving treatment (Lindor et al, 1998), a preferential uptake of UDCA by the transporters could explain the observed improvement in biochemical indices (van Hoogstraten et al, 1999).…”

Section: Resultsmentioning

confidence: 99%

“…Serum liver tests and histopathological suggest improvement of liver function in patients treated with UDCA. In most of the cases, UDCA shows a favorable effect on biochemical indices (van Hoogstraten et al, 1999) but not on symptoms or the progression of histological stage (Neuberger, 2000). Indeed, the recent report by Neuberger 'URSO -panacea or placebo?'…”

Section: Introductionmentioning

confidence: 99%

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Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

2002

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Cholestasis results from hepatocyte dysfunction due to the accumulation of bile acids in the cell, many of which are known to be cytotoxic. Recent evidence implicates competitive antagonism of key cytotoxic responses as the mechanism by which certain therapeutic bile acids might afford cytoprotection against cholestasis. In this work, we compare the relative cytotoxicity of bile acids in terms of dose-and time-dependence. To better elucidate the controversy related to the therapeutic use of ursodeoxycholate (UDCA) in cholestatic patients, we also evaluated the effects of bile acid combinations. Viability of Wistar rat hepatocytes in primary culture was measured by LDH leakage after 12 and 24 h exposure of cells to the various bile acids. All unconjugated bile acids caused a dose-dependent decrease in cell viability. The tauro-and glyco-conjugates of chenodeoxycholate (CDCA) and UDCA were all less toxic than the corresponding unconjugated form. Although relatively non-toxic, UDCA caused synergistic cell killing by lithocholate (LCA), CDCA, glyco-CDCA (GCDC) and tauro-CDCA (TCDC). Glycoursodeoxycholate decreased the toxicity of GCDC, but potentiated the toxicity of unconjugated CDCA and LCA. The tauro-conjugate of UDCA had no significant effect. These data suggest that at cholestatic concentrations, bile acid-induced cell death correlates with the degree of lipophilicity of individual bile acids. However, these results indicate that the reported improvement of biochemical parameters in cholestatic patients treated with UDCA is not due to a direct effect of UDCA on hepatocyte viability. Therefore, any therapeutic effect of UDCA must be secondary to some other process, such as altered membrane transport or nonparenchymal cell function.

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“…Many randomized trials, combined analyses of randomized trials, and longterm observational studies have shown that UDCA improves liver functional tests [3][4][5] and delays histological progression [6][7][8] in PBC patients. In addition, recent reports have indicated that UDCA may prolong survival in PBC patients, particularly in patients with non-advanced PBC [9][10][11][12]. However, response to UDCA is variable in patients with PBC, with some patients experiencing complete normalization of liver biochemistry and others showing only minor biochemical improvements.…”

Section: Introductionmentioning

confidence: 99%

Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis

et al. 2009

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Prognostic factors and long-term effects of ursodeoxycholic acid on liver biochemical parameters in patients with primary biliary cirrhosis

Cited by 41 publications

References 23 publications

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism

Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis

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