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Table 3 Liver disease and need for liver transplantation in early and late nitisinone-treated TYR1 patients

From: Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review

Study Study design Participants Outcome Age at last follow-up /
study end date
Birmingham study
Bartlett 2014 [17] Cohort
(prospective data collection)
N=38
No NTBC: n=7
NTBC: n=31
Age at presentation:
<2 months: n=11
2-6 months: n=11
>6 months: n=9
OLT   
<2 months: 0/11 NR
2-6 months: 3/11 (27%) NR
>6 months: 4/9 (44%) NR
No NTBC: 6/7 (86%) NR
  (p=0.004 vs 7/31 with NTBC)  
Median age at NTBC start
No OLT: 52 (range 2-990) days;
OLT: 428 (range 86-821) days. (p=0.004)
 
McKiernan 2015 [14] Cohort
(sibling-controlled,
retrospective data collection)
N=17
Pre-clinically diagnosed: n=12
Clinically diagnosed siblings: n=5
OLT   
Pre-clinically: 0/12 3-12.5 years;
Clinically: 1/5 (20%) 10-19 years or death at 1.5 and 7 months, respectively
Liver disease   
Pre-clinically 0/12 3-12.5 years;
Clinically 2/3 (67%) surviving patients 10-19 years
Québec study
Larochelle 2012 [10] Cohort
(Before 1994 retrospective, thereafter prospective
data collection)
N=78
NTBC introduced
≤30 days: n=24
>30 days: n=26
No NTBC: n=28
UI   
≤30 days: 0/24 5-11 years;
>30 days: 7/26 (27%) 9-19 years or OLT/death at 2-8 years;
No NTBC: 20/28 (71%) OLT/death at 0.5-10 years
p < 0.001, ≤30 days vs No NTBC (Chi square test); p < 0.001, >30 days vs No NTBC (Chi square test); p = 0.010, ≤30 vs >30 days (Fisher exact test)a  
Simoncelli 2015 [11] Cohort
(Retrospective data collection)
N=95
<4 weeks: n=41
≥4 weeks: n=26
No NTBC: n=28
Supersedes Larochelle et al. [10]
OLT   
<4 weeks: 0/41 IQR 3.4-8.5 years
≥4 weeks: 7/26 (27%) IQR 12.6-15.0 years
No NTBC: 20/28 (71%) IQR 16.3-21.7 years
(p<0.001, Fisher exact test) (p<0.001, Kruskal-Wallis test)
International cohort
Mayorandan 2014 [18] International cohort
(retrospective data collection via questionnaire)
N=168 included in study.
N=148 NTBC-treated patients included in analysis.
NTBC start:
<1 month: n=37
1-6 months: n=45
7-12 months: n=20
>12 months: n=46
OLT OR (95%CI)  
>12 months: 12.7 (1.5-103)b NR
Acute liver disease   
<1 month: 0/37 NR
7-12 months: 3/20 (15%)* NR
Liver cancer OR (95%CI)  
>12 months: 12.7 (1.5-103)b NR
Liver cirrhosis OR (95%CI)  
7-12 months: 41.6 (2.2-779.9)b NR
>12 months: 40.5 (2.3-704.1)b NR
Hepatomegaly OR (95%CI)  
1-6 months: 3.3 (0.9-11.3)b NR
7-12 months: 4.4 (1.1-17.7)b NR
>12 months: 3.9 (1.1-13.3)b NR
Odds/rates for not presented late-treated groups were not significantly different compared to early NTBC (<1 month).  
  1. aBased on our analysis of data presented in the paper by Larochelle et al. [10] using Fisher exact test. b <1 month: OR = 1. * p <0.05 vs <1 month
  2. CI confidence interval, IQR interquartile range, NR not reported, NTBC nitisinone, OLT orthotopic liver transplantation, OR odds ratio