Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis:: A randomized placebo-controlled trial

被引:157
作者
Färkkilä, M
Karvonen, AL
Nurmi, H
Nuutinen, H
Taavitsainen, M
Pikkarainen, P
Kärkkäinen, P
机构
[1] Univ Helsinki, Cent Hosp, Dept Med, Div Gastroenterol, Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland
[3] Tampere Univ, Cent Hosp, Dept Med, Div Gastroenterol, SF-33520 Tampere, Finland
[4] Turku Univ, Cent Hosp, Dept Med, Div Gastroenterol, Turku, Finland
[5] Medivire, Helsinki, Finland
关键词
D O I
10.1002/hep.20457
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/ MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases gamma-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (-337 +/- 54 U/L, P <.05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (-0.50 +/- 0.13, P <.01). The number of patients with improvement of stage (P <.05) and grade (P <.05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated.
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页码:1379 / 1386
页数:8
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