| Background and Aims Primary biliary cirrhosis(PBC) is a chronic autoimmune liver disease. Ursodeoxycholic acid(UDCA) is the only FDA-approved drug for PBC. About 60% of patients with PBC are responsive to UDCA treatment. A number of studies have shown that vitamin D plays important roles in immunoregulation. Vitamin D supplementation can significantly improve response rates of antiviral treatment of chronic hepatitis c or hepatitis b. However, the associations of vitamin D with autoimmune liver diseases, and particularly PBC, are yet to be defined. Therefore, we did this retrospective clinical study to evaluate whether vitamin D supplementation can improve the response rate of patients with PBC to UDCA treatment.Methods Patients diagnosed with PBC between January 2007 and July 2013 were enrolled from our hospital. Clinical data were retrieved from the case records. Patients were then divided into two groups: UDCA monotherapy group and combination therapy group(vitamin D plus UDCA). Barcelona criteria and Paris I criteria were used to evaluate response to treatment. Differences in response rates between two groups werecompared by chi-square. Univariate and Multivariate logistic regression analysis were performed to identify the factors that influence the treatment response.Results 1) A total of 167 patients with PBC were included in this study, 133 were female and 34 were male. Average age at diagnosis was 52.8±9.9 years old. Out of 167 patients, 150 had liver biopsies, among whom 95 were in Phase I-II,55 were in Phase III-IV. According to the Child-Pugh classification of liver function, 118 were Class A and 49 were Class B. In 167 patients with PBC, 67(40.1%) patients had skin itching, 73(43.7%) patients had fatigue, splenomegaly was identified in 108(64.7%) patients, esophageal gastric varices was detected in 80(47.9%) patients, ascites was identified in 45(26.9%) patients and 17(10.2%) patients had xanthomas. Average values of ALT, AST, ALP, GGT, TBIL and ALB in the patients with PBC were 59.4±23.9 IU/L, 69.1±32.5 IU/L, 336±261 IU/L, 355±247 IU/L, 31.0±18.9mmol/L and 39±4g/L, respectively. In PBC patients, ALT, AST and TBIL were slightly evaluated, ALP and GGT were significantly increased. Among autoantibodies, AMA was positive in 76.6% of the patients, AMA-M2 positive rate was 65.3%, the combined AMA and AMA-M2 was positive in 82.0% of patients. Positive rates for ANA, anti-Sp100 and anti-Gp210 were 92.8%, 8.4% and 30.5%, respectively. According to Barcelona criteria and Paris I criteria, the overall response rates were 59.9%(100/167) and 61.7%(103/167), respectively. Out of 167 patients, 83(49.7%) were responsive in both assessment systems. And consistency between Barcelona criteria and Paris I criteria was not good(Kappa=0.535). 2) Ninety-six patients with PBC were included in combination therapy group, and 71 patients were included in UDCA monotherapy group. There were no statistical differences in baseline characteristics. With Barcelona criteria, the rate of response of combination therapy group was higher than UDCA monotherapy group(66.7% v.s. 50.7%,p=0.037). With Paris I criteria, the response rate of combination therapy group was also higher than UDCA monotherapy group(68.8% v.s. 52.1%,p=0.029). On Univariate analysis, with Barcelona criteria, treatment without vitamin D(p=0.038), age>54 years old(p=0.006), Phase III-IV(p=0.002), ALT>2′ULN(p=0.008), AST>2′ULN(p=0.004), GGT>5′ULN(p=0.002), TBIL>20.5mmol/L(p=0.001) were found to be correlated with poor treatmentresponse. With Paris I criteria: treatment without vitamin D(p=0.030), Phase III-IV(p=0.014), ALT>2′ULN(p=0.000), AST>2′ULN(p=0.000), ALP>3′ULN(p=0.000), GGT>5′ULN(p=0.001), TBIL>20.5mmol/L(p=0.000), ALB<38g/L(p=0.009) and CHO>1′ULN(p=0.013) were found to be correlated with poor treatment response. On multivariate analysis, with Barcelona criteria, treatment without vitamin D(OR:2.353; 95%CI: 1.126-4.916, p=0.023), age>54 years old(OR: 2.654; 95%CI: 1.218-5.785, p=0.014), Phase III-IV(OR: 2.381; 95%CI: 1.096-5.019, p=0.048), GGT>5′ULN(OR: 2.550; 95%CI: 1.160-5.604, p=0.020) and TBIL>20.5mmol/L(OR: 2.405; 95%CI:(1.097-5.269, p=0.028) were independently associated with poor treatment response. With Paris I criteria, treatment without vitamin D(OR: 2.736; 95%CI: 1.212-6.178, p=0.015), Phase III-IV(OR: 2.684; 95%CI: 1.070-6.732, p=0.035) and TBIL>20.5mmol/L(OR: 2.779; 95%CI: 1.160-6.655, p=0.022) were independently associated with poor treatment response.Conclusion 1) PBC mainly affects mid-aged women. Common manifestatons are skin itching, fatigue, splenomegaly and esophageal gastric varices. Patients usually have high ALP and GGT level. Disease-specific autoantibodies(i.e. AMA, AMA-M2 and ANA) are more likely to be detected in patients with PBC. The treatment response rate to UDCA is about 60%. 2) Treatment response rate in combination therapy with vitamin D and UDCA is significantly higher than in UDCA monotherapy. 3) Treatment without vitamin D, Phase III-IV and TBIL>20.5mmol/L are independent factors associated with poor response to UDCA treatment. |
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