Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial

Henna Rautiainen, Päivi Kärkkäinen, A.-L Karvonen, Heimo Nurmi, Pekka Pikkarainen, Hannu Nuutinen, Martti Färkkilä

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to 111, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.
    Alkuperäiskielienglanti
    LehtiHepatology
    Vuosikerta41
    Sivut747-752
    Sivumäärä6
    ISSN0270-9139
    DOI - pysyväislinkit
    TilaJulkaistu - 2005
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Lainaa tätä

    Rautiainen, H., Kärkkäinen, P., Karvonen, A. -L., Nurmi, H., Pikkarainen, P., Nuutinen, H., & Färkkilä, M. (2005). Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology, 41, 747-752. https://doi.org/10.1002/hep.20646
    Rautiainen, Henna ; Kärkkäinen, Päivi ; Karvonen, A.-L ; Nurmi, Heimo ; Pikkarainen, Pekka ; Nuutinen, Hannu ; Färkkilä, Martti. / Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis : a three-year randomized trial. Julkaisussa: Hepatology. 2005 ; Vuosikerta 41. Sivut 747-752.
    @article{7b121c0dc78a43fb9075e68e7d50ad12,
    title = "Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial",
    abstract = "Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to 111, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22{\%} in group A but deteriorated 20{\%} in group B (P = .009). Fibrosis decreased 25{\%} in group A but increased 70{\%} in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34{\%} in group A (P = .02), but only 10{\%} in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.",
    author = "Henna Rautiainen and P{\"a}ivi K{\"a}rkk{\"a}inen and A.-L Karvonen and Heimo Nurmi and Pekka Pikkarainen and Hannu Nuutinen and Martti F{\"a}rkkil{\"a}",
    year = "2005",
    doi = "10.1002/hep.20646",
    language = "English",
    volume = "41",
    pages = "747--752",
    journal = "Hepatology",
    issn = "0270-9139",
    publisher = "John Wiley & Sons Ltd.",

    }

    Rautiainen, H, Kärkkäinen, P, Karvonen, A-L, Nurmi, H, Pikkarainen, P, Nuutinen, H & Färkkilä, M 2005, 'Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial', Hepatology, Vuosikerta 41, Sivut 747-752. https://doi.org/10.1002/hep.20646

    Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis : a three-year randomized trial. / Rautiainen, Henna; Kärkkäinen, Päivi; Karvonen, A.-L; Nurmi, Heimo; Pikkarainen, Pekka; Nuutinen, Hannu; Färkkilä, Martti.

    julkaisussa: Hepatology, Vuosikerta 41, 2005, s. 747-752.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis

    T2 - a three-year randomized trial

    AU - Rautiainen, Henna

    AU - Kärkkäinen, Päivi

    AU - Karvonen, A.-L

    AU - Nurmi, Heimo

    AU - Pikkarainen, Pekka

    AU - Nuutinen, Hannu

    AU - Färkkilä, Martti

    PY - 2005

    Y1 - 2005

    N2 - Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to 111, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

    AB - Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to 111, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

    U2 - 10.1002/hep.20646

    DO - 10.1002/hep.20646

    M3 - Article

    VL - 41

    SP - 747

    EP - 752

    JO - Hepatology

    JF - Hepatology

    SN - 0270-9139

    ER -

    Rautiainen H, Kärkkäinen P, Karvonen A-L, Nurmi H, Pikkarainen P, Nuutinen H et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology. 2005;41:747-752. https://doi.org/10.1002/hep.20646