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A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis.

Wang L, Guo GY, Wang JB, Zhou XM, Yang Q, Han ZY, Li Q, Zhang JW, Cai Y, Ren XL, Zhou X, Chen RR, Shi YQ, Han Y, Fan DM - Sci Rep (2015)

Bottom Line: We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014).Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant.However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xian, 710032, Shaanxi Province, China.

ABSTRACT
Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.

No MeSH data available.


Related in: MedlinePlus

Baseline serum levels of LAMP-2 were increased in PBC, especially in patients with stage III-IV or TBIL > 1mg/dL.(a) Elevation of baseline serum LAMP-2 levels in patients with PBC. Sera of 102 PBC patients, 126 HBV patients, 114 HCV patients, 27 IC patients, and 84 healthy volunteers were evaluated for the serum LAMP-2 levels at baseline by ELISA. (b) Correlation between baseline LAMP-2 level and ALP activity. No significance correlation was found in patients with PBC between baseline LAMP-2 level and ALP activity (r = 0.198, p = 0.058). (c) Serum levels of LAMP-2 were increased in PBC patients with stage III-IV or TBIL > 1mg/dL. Data are expressed as median with interquartile range.
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f1: Baseline serum levels of LAMP-2 were increased in PBC, especially in patients with stage III-IV or TBIL > 1mg/dL.(a) Elevation of baseline serum LAMP-2 levels in patients with PBC. Sera of 102 PBC patients, 126 HBV patients, 114 HCV patients, 27 IC patients, and 84 healthy volunteers were evaluated for the serum LAMP-2 levels at baseline by ELISA. (b) Correlation between baseline LAMP-2 level and ALP activity. No significance correlation was found in patients with PBC between baseline LAMP-2 level and ALP activity (r = 0.198, p = 0.058). (c) Serum levels of LAMP-2 were increased in PBC patients with stage III-IV or TBIL > 1mg/dL. Data are expressed as median with interquartile range.

Mentions: To determine the baseline serum levels of LAMP-2 in PBC, we measured the LAMP-2 in serum samples before treatment collected from PBC patients and controls by Enzyme-linked immunosorbent assay (ELISA) (Fig. 1a). The baseline serum LAMP-2 was significantly higher in patients with PBC (884.26 ng/mL in average, ranged from 559.12-1126.87), than those in patients with HBV (386.45 ng/mL in average, ranged from 112.07-681.55, p<0.001), HCV (245.33 ng/mL in average, ranged from 96.89-385.46, p<0.001), IC (302.26 ng/mL in average, ranged from 25.56-561.35, p<0.001), and healthy controls (128.33 ng/mL in average, ranged from 37.92-207.00, p<0.001). However, no significant difference in baseline serum LAMP-2 was observed among the control groups. We also divided patients as control into three clinical groups with different cirrhosis stages, hepatitis without cirrhosis, compensated cirrhosis and decompensated cirrhosis, to evaluate the effect of cirrhosis stage on baseline serum LAMP-2. Although there was a slight elevation of serum LAMP-2 in the decompensated cirrhosis group, no statistically significant difference among the three groups was found (Supplementary Figure 1). The elevation of baseline LAMP-2 in PBC patients may be accompanied by elevated level of ALP. However, no correlation was found between baseline serum LAMP-2 and ALP activity (r = 0.198, p = 0.058, Fig. 1b).


A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis.

Wang L, Guo GY, Wang JB, Zhou XM, Yang Q, Han ZY, Li Q, Zhang JW, Cai Y, Ren XL, Zhou X, Chen RR, Shi YQ, Han Y, Fan DM - Sci Rep (2015)

Baseline serum levels of LAMP-2 were increased in PBC, especially in patients with stage III-IV or TBIL > 1mg/dL.(a) Elevation of baseline serum LAMP-2 levels in patients with PBC. Sera of 102 PBC patients, 126 HBV patients, 114 HCV patients, 27 IC patients, and 84 healthy volunteers were evaluated for the serum LAMP-2 levels at baseline by ELISA. (b) Correlation between baseline LAMP-2 level and ALP activity. No significance correlation was found in patients with PBC between baseline LAMP-2 level and ALP activity (r = 0.198, p = 0.058). (c) Serum levels of LAMP-2 were increased in PBC patients with stage III-IV or TBIL > 1mg/dL. Data are expressed as median with interquartile range.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403591&req=5

f1: Baseline serum levels of LAMP-2 were increased in PBC, especially in patients with stage III-IV or TBIL > 1mg/dL.(a) Elevation of baseline serum LAMP-2 levels in patients with PBC. Sera of 102 PBC patients, 126 HBV patients, 114 HCV patients, 27 IC patients, and 84 healthy volunteers were evaluated for the serum LAMP-2 levels at baseline by ELISA. (b) Correlation between baseline LAMP-2 level and ALP activity. No significance correlation was found in patients with PBC between baseline LAMP-2 level and ALP activity (r = 0.198, p = 0.058). (c) Serum levels of LAMP-2 were increased in PBC patients with stage III-IV or TBIL > 1mg/dL. Data are expressed as median with interquartile range.
Mentions: To determine the baseline serum levels of LAMP-2 in PBC, we measured the LAMP-2 in serum samples before treatment collected from PBC patients and controls by Enzyme-linked immunosorbent assay (ELISA) (Fig. 1a). The baseline serum LAMP-2 was significantly higher in patients with PBC (884.26 ng/mL in average, ranged from 559.12-1126.87), than those in patients with HBV (386.45 ng/mL in average, ranged from 112.07-681.55, p<0.001), HCV (245.33 ng/mL in average, ranged from 96.89-385.46, p<0.001), IC (302.26 ng/mL in average, ranged from 25.56-561.35, p<0.001), and healthy controls (128.33 ng/mL in average, ranged from 37.92-207.00, p<0.001). However, no significant difference in baseline serum LAMP-2 was observed among the control groups. We also divided patients as control into three clinical groups with different cirrhosis stages, hepatitis without cirrhosis, compensated cirrhosis and decompensated cirrhosis, to evaluate the effect of cirrhosis stage on baseline serum LAMP-2. Although there was a slight elevation of serum LAMP-2 in the decompensated cirrhosis group, no statistically significant difference among the three groups was found (Supplementary Figure 1). The elevation of baseline LAMP-2 in PBC patients may be accompanied by elevated level of ALP. However, no correlation was found between baseline serum LAMP-2 and ALP activity (r = 0.198, p = 0.058, Fig. 1b).

Bottom Line: We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014).Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant.However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders.

View Article: PubMed Central - PubMed

Affiliation: Division of Hepatology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xian, 710032, Shaanxi Province, China.

ABSTRACT
Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.

No MeSH data available.


Related in: MedlinePlus