Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis: Results of a 14-year cohort study

Abstract

The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long‐term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver‐related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow‐up of 5.8 years (range, 1.3‐14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long‐term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. (HEPATOLOGY 2013)

Biochemical and Histological Effectiveness of Long-term Use of Fenofibrate for Asymptomatic Primary Biliary Cholangitis

“…Since aPBC patients exhibiting an incomplete biochemical response to UDCA in the first three months generally have a poor outcome, a new therapeutic approach is needed for these patients [28] . According to several studies in Japan, bezafibrate successfully lowers the levels of biliary liver enzymes in patients with PBC [29][30][31][32] .…”

Old and Novel Therapies for Primary Biliary Cirrhosis

“…[18][19][20][21][22][23] The first study, which included patients treated for a median of 7.5 years, clearly indicates that UDCA improves survival free of transplantation in PBC as compared with the expected survival calculated according to the Mayo Risk Score. 18 However, the effect was not as good because the survival of PBC patients treated with UDCA was significantly lower than that predicted for an ageand sex-matched population.…”

“…Several definitions of optimal biochemical response to UDCA have been proposed, and $40% of patients fulfill at least one criterion of incomplete biochemical response (►Table 1). [19][20][21][22][23] These patients have an increased risk of progression events, and decreased survival. Therefore, patients with suboptimal biochemical response to UDCA delineate the group of patients in whom further single or combined treatments with UDCA are needed.…”

Novel Aspects in the Management of Cholestatic Liver Diseases

“…Beside serum bilirubin, serum alkaline phosphatase (ALP) has emerged as an excellent surrogate, although there is still some debate about the optimal cutoff for ALP, probably 1.5-2.0 upper limit of normal [9] . Assessing biochemical response at 6 versus 12 months has been proposed but further validation is needed [10] . All these response criteria have been independently and externally validated with Paris criteria discriminating best in a very large UK study [11] .…”