AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose [3.2 (2.0-4.4) mmol/L in NICCD vs 4.1 (3.4-5.1) mmol/L in BA and 4.0 (3.4-4.6) mmol/L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol/L in N ICCD vs 4.57 (3.81-5.26) mmol/L in BA and 4.00 (3.24-4.74) mmol/L in INC, P = 0.0155] levels. The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range):0.54 (0.40-0.74)] than that in BA patients [0.77 (0.72-0.81), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045]. A much higher AST/ALT ratio was found in NICCD patients [2.46 (1.95-3.63)] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA/D-Bil ratio [3.36 (1.98-4.43) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA/TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) in BA patients and 24.2 (21.4-26.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION:NICCD has significantly different bio- chemical indices from BA or INC. TBA excretion in NICCD appeared to be more severely disturbed than that of bilirubin and cholesterol. AIM: To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS: Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients who whom homo-zygous or compound heterozygous SLC25A13 mutation and / or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with ch RESULTS: Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all Measures were expressed as median (interquartile range): 178.0 (111.2-236.4) μmol / L in NICCD vs 112.0 (84.9-153.9) μmol / L in BA and 103.0 (70.9-135.3) μmol / L in INC, P = 0.0001] The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol / L in NICCD vs 134.0 (115.9-151.2) μmol / L in BA and 87.3 (63.0-123.6) μmol / L in INC , P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U / L in NICCD vs 108.0 (62.0-199.0) U / L in BA and 84.5 (46.0-166.0) U / L in INC, P = 0.0001] ; aspartate aminotransferase [AST 74.0 (53.5-150.0) U / L in NICCD vs 153.0 (115.0-239.0) U / L in BA and 130.5 (81.0-223.0) U / L in INC, P = 0.0006]; albumin [34.9 30.7-38.2) g / L in NICCD vs 38.4 (36.3-42.2) g / L in BA and 39 .9 (37(0.4-4.1) mmol / L in BA and 4.0 (3.4-4.6) mmol / L in NICCD vs. 4.1 (3.4-5.1) mmol / L in BA and 4.0 L in INC, P = 0.0014] and total cholesterol [TCH 3.33 (2.97-4.00) mmol / L in N ICCD vs 4.57 (3.81-5.26) mmol / L in BA and 4.00 (3.24-4.74) mmol / L in INC, The D-Bil to total bilirubin (T-Bil) ratio was significantly lower in NICCD patients [all measures are expressed as median (inter-quartile range): 0.54 (0.40-0.74)] than that in BA A much higher AST / ALT ratio was found in NICCD patients [2.46 (1.95-3.63), P = 0.001] and that in INC patients [0.74 (0.59-0.80), P = 0.0045] ] compared to BA patients [1.38 (0.94-1.97), P = 0.0001] and INC patients [1.48 (1.10-2.26), P = 0.0001]. NICCD patients had significantly higher TBA / D-Bil ratio [3.36 ) vs 0.85 (0.72-1.09) in BA patients and 1.04 (0.92-1.14) in INC patients, P = 0.0001], and TBA / TCH ratio [60.7 (32.4-70.9) vs 24.7 (19.8-30.2) 24.2 (21.4-2 6.9) in INC patients, P = 0.0001] compared to the BA and INC groups. CONCLUSION: NICCD has significantly different bio- chemical indices from BA or INC. TBA excretion in NICCD was to be more severely disturbed than that of bilirubin and cholesterol.