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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (2) : 255-263    https://doi.org/10.1007/s11684-012-0227-1
RESEARCH ARTICLE
Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study
Jiangyi Zhu1, Yongquan Shi1, Xinmin Zhou1, Zengshan Li2, Xiaofeng Huang2, Zheyi Han1, Jianhong Wang1, Ruian Wang2, Jie Ding1, Kaichun Wu1, Ying Han1(), Daiming Fan1()
1. State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ?China; 2. Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Abstract

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13–15 mg?kg-1?day-1) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1–2 but still progressed in patients at stages 3–4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3–4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

Keywords primary biliary cirrhosis      ursodeoxycholic acid      Chinese      biochemical response      therapeutic efficacy     
Corresponding Author(s): Han Ying,Email:hanying@fmmu.edu.cn; Fan Daiming,Email:daimingfan@fmmu.edu.cn   
Issue Date: 05 June 2013
 Cite this article:   
Jiangyi Zhu,Yongquan Shi,Xinmin Zhou, et al. Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study[J]. Front Med, 2013, 7(2): 255-263.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0227-1
https://academic.hep.com.cn/fmd/EN/Y2013/V7/I2/255
Clinical stageHistological stage
12341234
Sex ratio(female: male)6∶019∶618∶215∶13∶09∶234∶412∶3
Age at diagnosis (year)38.33±16.2948.64±9.8150.76±7.1957.67±7.2143.00±13.2549.80±8.5351.29±7.6256.93±8.09
Tab.1  The baseline characteristic of PBC patients
Fig.1  The effects of UDCA on fatigue and pruritus of PBC patients. Sixty-seven PBC patients were administrated with UDCA for 2 years at the dose of 13-15 mg?kg?day. Before treatment, 43 and 35 patients presented fatigue (26 mild and moderate, 17 severe) and pruritus (23 mild and moderate, 12 severe) respectively. Fatigue and pruritus were scored as following: grade 1, none; grade 2, mild; grade 3, moderate; grade 4, severe and grade 5, permanent or tough. (A) The scores of fatigue and pruritus before (pre-treatment) and 2 years after treatment (post-treatment) were compared by Wilcoxon signed rank test. * <0.05 vs. pre-treatment. (B and C) Symptomatic patients were divided into 3 groups according to the extent of symptoms: mild (grade 2), moderate (grade 3) and severe (grades 4 and 5). Shown was the percentage of cases whose fatigure (B) or pruritus (C) was aggravated, unchanged or alleviated.
ClinicalstageVariables(normal range)Stage 1Stage 2Stage 3Stage 4
Pre-treatmentPost-treatmentPre-treatmentPost-treatmentPre-treatmentPost-treatmentPre-treatmentPost-treatment
ALT(0-40 IU/L)21.83±7.4621.33±7.1689.63±39.7543.00±9.16*96.66±61.4757.37±33.52*55.33±32.4339.00±23.38
AST(0-40 IU/L)18.75±5.8320.67±5.5991.27±66.5839.66±5.77*92.79±44.6149.50±29.15*76.07±36.1145.01±17.07*
ALP(15-121 IU/L)54.00±10.1544.82±13.99272.09±138.79124.67±28.77*455.73±269.24205.50±72.89*392.07±296.08137.50±43.13*
γ-GT(8-52 IU/L)31.67±12.5529.98±17.20253.45±92.9456.33±34.01*420.91±245.36195.30±108.09*234.67±124.8878.50±60.40*
Albumin(37-55 g/L)43.56±3.7741.91±2.9041.08±2.6638.40±2.3841.50±2.7939.78±4.2836.15±5.6733.13±4.33
Bilirubin(3.4-20.5 μmol/L)10.17±4.4012.63±5.7513.87±5.1412.1±8.0244.74±50.7228.47±14.3541.27±26.0834.73±6.49
Cholesterol(3.5-6.5 mmol/L)4.69±1.574.92±1.565.80±1.526.03±1.676.87±3.806.47±2.164.49±1.193.79±1.02
Prothrombin index(80%-120%)118.67±26.09121.16±24.26125.41±26.87116.86±33.65116.87±27.56107.25±31.2576.78±18.5484.67±21.54
Immunoglobulin M(0.5-3.0 g/L)1.34±0.871.52±0.735.21±3.483.94±2.756.76±6.364.73±2.316.17±5.254.21±2.13
Tab.2  Changes in laboratory variables in patients throughout the study
Fig.2  The dynamic changes of ALP and γ-GT of PBC patients treated with UDCA. Sixty-seven PBC patients were administrated with UDCA for 2 years at the dose of 13-15 mg?kg?day. The ALP (A) and γ-GT (B) levels were measured at the indicated time points during 2-year follow-up and plotted according to the clinical stages. The dotted lines represented upper limit of normal ranges.
Histological stageClinical stagePre-treatmentPost-treatment
Stage 1Stage 2Stage 3Stage 4Stage 1Stage 2Stage 3Stage 4
Stage 12---2---
Stage 2121--31-
Stage 3-221-113
Stage 4--12--03
Tab.3  The stage distribution of PBC patients before and after UDCA treatment
Pre-treatmentPost-treatmentStatistic valueP value
Portal inflammation2.64±0.492.07±0.62-2.4190.016*
Piecemeal necrosis2.00±1.041.64±1.01-1.0360.300
Lobular necrosis2.07±1.211.43±1.02-1.6990.089
Ductular proliferation2.00±1.171.14±0.81-1.9160.068
Bridging fibrosis0.86±0.771.79±1.31-2.2840.031*
Cholestasis1.00±1.041.21±1.12-0.5070.612
Tab.4  The histological feature of PBC patients before and after UDCA treatment
Fig.3  Effect of UDCA treatment on histological characteristics. Fourteen PBC patients received liver biopsy before and 2 years after UDCA treatment. Shown are typical cases. (A and C) Before treatment. (B and D) 2 years after treatment. One patient at stage 2 got paired-biopsy pre-(A) and post-treatment (B). Portal inflammatory infiltration lessened significantly after 2-year treatment. Another patient at stage 4 got paired-biopsy pre-(C) and post-treatment (D). Before treatment, bile duct proliferation (arrowhead in C) and inflammatory infiltration was seen in the portal and bridging necrosis formed. After treatment, bile duct proliferation (arrowhead in D) and portal inflammation were significantly alleviative but bridging fibrosis had still progressed 2 years after treatment.
Clinical stageStage 2n/N (%)Stage 3n/N (%)Stage 4n/N (%)Total rate
Paris criteria21/25 (84%) * D12/20 (60%) #7/16 (44%)65.6%
Barcelona criteria22/25 (88%) * D14/20 (70%) #9/16 (56.3%)73.8%
Tab.5  Status of biochemical response in different clinical stages by two criteria
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