PMC5649119_01
Graphs of hepatic function parameters from Case 1 as patient transitioned from ursodeoxycholic acid (UDCA) to cholic acid (CA) therapy.. Note post-CA increases in bilirubin, transaminases, and total plasma cholesterol, which paralleled deterioration of the patients' clinical status.
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f1
Her stable pre-CA elevation in transaminase and bilirubin levels began to increase 7 days after initiation of CA, and continued to increase (See Figure 1 and Figure 2). She remained on CA therapy for a total of 37 days; due to worsening of clinical and laboratory parameters and no mutations identified in HSD3B7, CA was discontinued and UDCA restarted at 30 mg/kg/day ( Figure 1 and Figure 2).
Boxplots of hepatic function parameters from Case 1.. These indicate statistically significant (Student's T-test, performed with Rv3.2.0: *, p < 0.05; **, p < 0.005) elevations in all denoted parameters except alkaline phosphatase, while on cholic acid (CA) compared to ursodeoxycholic acid (UDCA) therapy.
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f2
Her stable pre-CA elevation in transaminase and bilirubin levels began to increase 7 days after initiation of CA, and continued to increase (See Figure 1 and Figure 2). She remained on CA therapy for a total of 37 days; due to worsening of clinical and laboratory parameters and no mutations identified in HSD3B7, CA was discontinued and UDCA restarted at 30 mg/kg/day ( Figure 1 and Figure 2).
PMC5649119_02
Graph of hepatic function parameters from Case 2 in the months before and after starting ursodeoxycholic acid (UDCA).. This demonstrated a marked improvement in liver function parameters.
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f3
At review 1 month later there was a significant improvement in liver function tests (total bilirubin 0.5 mg/dl; ALT 20 U/L; AST 54 U/l; GGT 62 U/l), this improvement was sustained when further tested aged 18 months and 2 years ( Figure 3).
Alanine transaminase (ALT) of Case 3.. This demonstrated abnormal levels before starting ursodeoxycholic acid (UDCA) that normalized following initiation of UDCA. Dotted line signifies normal value (less than 50 units/L)
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f4
After commencing UDCA, the persistently elevated ALT levels returned to normal range (ALT 48 U/l, RR<50 U/l) and this has been maintained for over 2 and a half years ( Figure 4).
NIH scoring in Case 3.. (
a) Total NIH score (without hearing and auditory brainstem response) for Case 3. Time of ursodeoxycholic acid (UDCA) commencement (6.67 yrs) marked on graph. (
b) NIH severity scale scores in the four key domains (Ambulation, Fine motor, Swallow and Cognition) for Case 3, both before and after commencement of UDCA.
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f5
Ambulation, by only a single point ( Figures 5a and b). At 8 years 4 months he was enrolled on the VTS-270 clinical study .