Nidah Shabbir Khakoo1, Shahnaz Sultan2, John M Reynolds3, Cynthia Levy4,5. 1. Department of Internal Medicine, University of Miami School of Medicine, Miami, FL, USA. 2. Department of Gastroenterology and Hepatology, University of Minnesota and Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USA. 3. Department of Health Informatics, Calder Memorial Library, University of Miami Miller School of Medicine, Miami, FL, USA. 4. Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, 1500 NW 12th Avenue, Suite 1101, Miami, FL, 33136, USA. clevy@med.miami.edu. 5. Schiff Center for Liver Diseases, University of Miami, Miami, FL, USA. clevy@med.miami.edu.
Abstract
BACKGROUND: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. METHODS: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94 IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. CONCLUSIONS: Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.
BACKGROUND: Bezafibrate (BZF) alone or in combination with ursodeoxycholic acid (UDCA) has been used to slow disease progression in patients with primary biliary cholangitis (PBC). We performed a systematic review and meta-analysis to assess the efficacy and harms of BZF monotherapy or combination therapy. METHODS: We performed a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception until January 2020, for randomized controlled clinical trials assessing BZF + UDCA versus UDCA monotherapy or BZF monotherapy versus UDCA monotherapy in PBC patients. Additionally, we systematically evaluated data on harms using seven observational studies. Pooled effect estimates were calculated for the outcomes of interest. The certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 7 randomized controlled trials with a total of 279 participants. Comparing BZF + UDCA to UDCA alone, a clinically significant improvement was observed in serum ALP with a mean difference (MD) of - 159.04 U/L (95% CI - 186.45 to - 131.62) and a reduction in gamma-glutamyltransferase (GGT) (MD - 106.94 IU/L; 95% CI - 151.99 to - 61.89), but not in total bilirubin (TB) or IgM levels. A statistically significant reduction in ALP levels was also noticed with BZF monotherapy compared to UDCA monotherapy. The effect of BZF + UDCA versus UDCA on mortality remains unclear. Across 5 observational studies including 106 patients, one death was reported due to advanced liver disease in an incomplete responder getting treatment with BZF + UDCA. Analysis of observational studies demonstrated improvement in pruritus intensity with BZF. CONCLUSIONS: Use of BZF alone or in combination with UDCA improved liver biochemistries in patients with PBC, but its effect on mortality, liver-related complications or quality of life remains unknown.
Authors: Carla F Murillo Perez; Jorn C Goet; Willem J Lammers; Aliya Gulamhusein; Henk R van Buuren; Cyriel Y Ponsioen; Marco Carbone; Andrew Mason; Christophe Corpechot; Pietro Invernizzi; Marlyn J Mayo; Pier Maria Battezzati; Annarosa Floreani; Albert Pares; Frederik Nevens; Kris V Kowdley; Tony Bruns; George N Dalekos; Douglas Thorburn; Gideon Hirschfield; Nicholas F LaRusso; Keith D Lindor; Kalliopi Zachou; Raoul Poupon; Palak J Trivedi; Xavier Verhelst; Harry L A Janssen; Bettina E Hansen Journal: Hepatology Date: 2018-04-06 Impact factor: 17.425
Authors: Willem J Lammers; Henk R van Buuren; Gideon M Hirschfield; Harry L A Janssen; Pietro Invernizzi; Andrew L Mason; Cyriel Y Ponsioen; Annarosa Floreani; Christophe Corpechot; Marlyn J Mayo; Pier M Battezzati; Albert Parés; Frederik Nevens; Andrew K Burroughs; Kris V Kowdley; Palak J Trivedi; Teru Kumagi; Angela Cheung; Ana Lleo; Mohamad H Imam; Kirsten Boonstra; Nora Cazzagon; Irene Franceschet; Raoul Poupon; Llorenç Caballeria; Giulia Pieri; Pushpjeet S Kanwar; Keith D Lindor; Bettina E Hansen Journal: Gastroenterology Date: 2014-08-23 Impact factor: 22.682