Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: A retrospective clinical study

Journal Pre-proof Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: a retrospective clinical study

Jia Liu, Rui Dong, Gong Chen, Kuiran Dong, Shan Zheng PII:

S0022-3468(19)30566-4

DOI:

https://doi.org/10.1016/j.jpedsurg.2019.08.026

Reference:

YJPSU 59318

To appear in:

Journal of Pediatric Surgery

Received date:

6 August 2019

Accepted date:

24 August 2019

Please cite this article as: J. Liu, R. Dong, G. Chen, et al., Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: a retrospective clinical study, Journal of Pediatric Surgery(2019), https://doi.org/10.1016/ j.jpedsurg.2019.08.026

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© 2019 Published by Elsevier.

Journal Pre-proof Title: Risk Factors and Prognostic Effects of Cholangitis After Kasai Procedure in Biliary Atresia Patients: A Retrospective Clinical Study

Author names: Jia Liu, Rui Dong, Gong Chen, Kuiran Dong, Shan Zheng

Affiliations:

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Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, Shanghai, China

Professor Shan Zheng Department of Pediatric Surgery

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Children’s Hospital of Fudan University Shanghai Key Laboratory of Birth Defect

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Fax: +86 021 64931901

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399 Wan Yuan Road 201102, Shanghai, China

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Corresponding Author:

Telephone: +86 021 64931007 E-mail: [email protected].

Journal Pre-proof Abstract Purpose: Cholangitis after Kasai procedure has been previously shown to be related to poor prognosis in Biliary Atresia (BA). To investigate the risk factors and clinical outcomes of cholangitis, we did a retrospective study in post-Kasai BA patients. Methods: Two-year follow-up data of 180 type-III BA patients after Kasai procedure in 2016 in our hospital were analyzed, including 119 cholangitis patients (66.11%). Among the cholangitis group, patients were further divided into early vs late cholangitis and single vs recurrent cholangitis groups. Liver pathology, liver function, cholangitis occurrence and frequency, jaundice clearance, and survival rates were examined.

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Results: Higher gamma-glutamyl transferase levels before Kasai is a risk factor for cholangitis (p=0.0393). Older age and higher liver fibrosis score at Kasai are risk factors for recurrent cholangitis (p<0.05). Shorter prophylactic intravenous antibiotics usage may contribute to early cholangitis, which may lead to higher cholangitis frequency (p<0.0001). Recurrent cholangitis is associated with earlier cholangitis onsets (p<0.0001). Cholangitis patients have a relatively delayed jaundice clearance, while early and recurrent cholangitis may contribute to lower overall survival.

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Conclusions: Personalized treatment considering risk factors in individual BA patients is needed to prevent cholangitis, especially early onsets, and to improve postoperative outcomes.

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Level of Evidence: III

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Keywords: Cholangitis; Biliary atresia; Overall survival; Jaundice clearance

Journal Pre-proof Biliary Atresia (BA) is a devastating neonatal liver disease characterized by persistent jaundice, progressive biliary system obstruction and liver fibrosis[1]. Although Kasai hepatoportoenterostomy and other perioperative managements have improved the outcomes, many BA patients still need liver transplantation for long-term survival. Cholangitis is the most common complication in post-Kasai BA patients, with an incidence of 30% to 70%, and occurs most commonly in the first year especially first six months post Kasai[2].Several studies have demonstrated that cholangitis could be a risk factor for poor prognosis in post-Kasai BA patients[3, 4].

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The diagnosis of cholangitis is primarily based on clinical symptoms (unexplained fever, recurrent jaundice and acholic stools) and laboratory tests (increased bilirubin levels, elevated C-reactive protein (CRP) and elevated white blood cells (WBC) counts)[4].Though the etiology of cholangitis is still unclear, several hypotheses have been established, in which intestinal bacteria migration and immune inflammatory response may be the leading factors[5].

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Furthermore, cholangitis can affect bile drainage and lead to cholestasis, which may accelerate the progression of liver damage and fibrosis. The more episodes of cholangitis (considered as recurrent cholangitis) a patient experiences, the worse liver damage the patient may suffer from. Therefore, recurrent cholangitis is correlated with accelerated development of liver fibrosis and other severe complications[6, 7]. Early cholangitis is commonly defined as an onset within the first month post-Kasai and is considered to be an important marker for poor outcomes, including prolonged jaundice clearance and lower native liver survival[3, 8]. In this study, we assessed several preoperative factors and analyzed two-year outcomes for cholangitis patients post-Kasai procedure. We particularly focused on early and recurrent cholangitis, to investigate their risk factors and prognostic effects on BA patients.

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1. Methods 1.1 Patients’ information

This study enrolled type-III BA patients who underwent Kasai procedure during June to December 2016 in Children’s Hospital of Fudan University consecutively. The diagnoses of BA were based on clinical, cholangiogram and histological findings. Patients’ clinical data were retrospectively collected. Patients’ information included age and body weight at Kasai procedure, prophylactic intravenous antibiotic duration, hospital stay length, and methylprednisolone use. Written consents were obtained from all patients’ parents before surgery. This study was approved by the Ethics Committee at the Children’s Hospital of Fudan University. 1.2 Liver pathology and liver function tests Liver pathology and liver function tests were analyzed to assess the state of a patient’s liver. Liver tissue samples were taken during Kasai procedure and fixed in 10% neutral-buffered formalin, embedded in paraffin, and sectioned by 4μm. Hematoxylin and eosin (H&E) staining was used to assess the inflammation and Masson's trichrome staining was used to assess the fibrosis stage of a patient’s liver. Three experienced pathologists blinded to all specimens evaluated the stage of liver inflammation and fibrosis using a scoring system based on previous

Journal Pre-proof studies[9]. Liver function tests parameters included total bilirubin (TB), direct bilirubin (DB), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total bile acid (TBA) and albumin (Alb). 1.3 Clinical follow-ups and cholangitis

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All patients were followed up for at least two years or until they reached an end point (liver transplantation or death). Liver function tests were conducted before Kasai procedure; by the end of the first month, three months, six months and two years post-Kasai. Cholangitis occurrence and outcomes were recorded during the first six months of follow-ups. Cholangitis was defined as a combination of at least two of the following clinical findings: 1. unexplained fever over 38℃; 2. recurrence or exacerbation of clinical jaundice with increased bilirubin levels, or changes from yellow to acholic stools; 3. elevated C-reactive protein (CRP). The outcomes were assessed by jaundice clearance (total bilirubin ≤ 20 μmol/L, JC), overall survival (OS), nonicteric native liver survival (nNLS), liver transplantations (LTs) and death.

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Patients were basically divided into cholangitis and non-cholangitis groups depending on whether they had ever experienced any cholangitis episode during the first six months post-Kasai. In the cholangitis group, patients were further grouped according to the occurrence and frequency of cholangitis. For occurrence, early cholangitis group was defined as the first cholangitis onset occurring within the first month post-Kasai; while late cholangitis group was defined as the first cholangitis onset occurring later after the first month post-Kasai. For frequency, patients who experienced more than one episode of cholangitis were grouped to recurrent cholangitis group, while patients who experienced only one episode of cholangitis belonged to single cholangitis group. We compared patients’ information, liver pathology and liver function tests, cholangitis occurrence and frequency, and two-year outcomes between cholangitis and non-cholangitis, early and late cholangitis, and single and recurrent cholangitis groups. Adverse events were also recorded in all patients. Furthermore, we compared the OS and nNLS rates between non-cholangitis and cholangitis groups in patients who achieved earlier JC within the first six months post-Kasai. 1.4 Statistical analysis

Data were presented as mean ± standard error of the mean (SEM) or percentage. The Student’s t-test was used for comparisons between two groups. Chi-square (and Fisher’s exact) test was used for comparisons of cholangitis frequency. Kaplan-Meier analysis was used for survival curves in BA infants. A p-value of < 0.05 was considered statistically significant. All analyses were performed by GraphPad Prism 6 software.

2. Results 2.1 Study population We enrolled 180 BA patients altogether. There were a total of seven patients lost to follow up. Three patients were in the non-cholangitis group. Among the other four in cholangitis group, they can be divided into two in early cholangitis and two in late cholangitis group, or three in single cholangitis and one in recurrent cholangitis group. These seven patients were lost to follow-up

Journal Pre-proof after more than seven months post-Kasai. Therefore, patients’ information, liver pathology and liver function tests, cholangitis occurrence and frequency were analyzed in all 180 enrolled patients, while adverse events and two-year outcomes were analyzed in 173 patients (excluded patients who lost follow-ups). 2.2 Patients’ information

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Patients’ information before Kasai was analyzed and is displayed in Table 1, in which p < 0.05 can be considered as a risk factor. Among these factors, higher body weight before Kasai is a risk factor for cholangitis (p = 0.0005). Older age at Kasai is a risk factor for recurrent cholangitis (p = 0.0192). Patients with late cholangitis had a significant higher rate of methylprednisolone use compared to patients with early cholangitis (p = 0.0275), while early cholangitis patients had a shorter prophylactic intravenous antibiotics usage (Table 1). There was no significant difference between the groups with respect to hospital stay length.

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2.3 Liver pathology and liver function tests

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Liver H&E and Masson score at Kasai and liver function tests before Kasai procedure are displayed in Table 2. A higher Masson score at Kasai is a risk factor for recurrent cholangitis (p = 0.0095). A higher GGT level before Kasai is a risk factor for cholangitis (p = 0.0393). Late cholangitis patients had a significant higher AST level before surgery compared to early cholangitis patients (p = 0.0346). No other significant differences were found among H&E score or other liver function parameters among the groups (Table 2). 2.4 Cholangitis occurrence and frequency

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For the 180 BA patients, 66.11% (119/180) of them experienced cholangitis in the first six months post-Kasai and 33.89% (61/180) belonged to non-cholangitis group. Among these cholangitis patients, 48.74% (58/119) experienced early cholangitis and 51.26% (61/119) belonged to late cholangitis group; while 54.62% (65/119) experienced recurrent cholangitis and 45.38% (54/119) belonged to single cholangitis group. Compared with the late cholangitis group, patients with early cholangitis had a significant higher cholangitis frequency (2.57±0.19 vs. 1.62±0.12 times, p < 0.0001, Figure1-A). Compared with the single cholangitis group, patients with recurrent cholangitis had much earlier cholangitis onsets (first cholangitis episode started on day 29.57±3.29 vs. 71.63±6.82 post-Kasai, p < 0.0001, Figure1-B).

2.5 Patient outcomes Three adverse events (3.45%) were recorded in the non-cholangitis group, which are one gastrointestinal hemorrhage, one intestinal obstruction and one intestinal perforation. In the cholangitis group, there were altogether nine (7.83%) adverse events recorded. Looking into the subgroups, these nine can be divided into three gastrointestinal hemorrhage and two intestinal obstructions in early cholangitis group (8.93%); three gastrointestinal hemorrhage and one perforation in late cholangitis group (6.78%). Or three gastrointestinal hemorrhage and one perforation in single cholangitis group (7.84%); and three gastrointestinal hemorrhage and two obstructions in recurrent cholangitis group (7.81%). Patients with cholangitis, especially early and recurrent cholangitis, tend to have higher adverse event rates. However, no significance was found among these groups.

Journal Pre-proof In surviving patients after two years follow-ups, patients with cholangitis had a trend of higher JC, but the difference was not significant (Table 3). Non-cholangitis patients tend to have an earlier JC (Table 4). However, cholangitis patients had a significant higher two-year OS rate and a higher nNLS rate, while early cholangitis and recurrent cholangitis patients had relatively lower OS rates (Table 3; Figure 2-A-F). Furthermore, among the patients who achieved earlier JC within the first six months post-Kasai (19/58 in the non-cholangitis group and 66/115 in the cholangitis group), non-cholangitis patients had a significantly higher nNLS rate compared to the cholangitis patients (p = 0.0311).

3. Discussion

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In this retrospective study, we assessed several preoperative factors and analyzed two-year outcomes for cholangitis, based on a population of 180 type-III BA patients who underwent Kasai procedures in our hospital. To investigate the prognostic effects of different types of cholangitis which may be related to the etiology and pathology, we further examined early cholangitis and recurrent cholangitis, and patients with earlier JC as well.

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For preoperative factors, we found that older surgical age can be a risk factor for recurrent cholangitis. While higher body weight before Kasai, may also indicating an older surgical age, can be a risk factor for cholangitis. Though no study has demonstrated the relation between surgical age and cholangitis, an older age at Kasai usually indicates a potential for more severe liver damage and poor outcomes[10]. Meanwhile, the Masson score before Kasai, which can help to assess the patient’s liver fibrosis stage, was significantly higher in recurrent cholangitis, and also relatively higher in cholangitis and early cholangitis groups. Therefore, the patients with worse liver function status before Kasai tended to have a higher risk of cholangitis especially recurrent cholangitis. GGT is mostly produced by liver and biliary tract, which rises early and persists to be elevated when there is a liver damage. In our study, GGT level was significantly elevated in cholangitis patients, and was also higher in the early cholangitis and recurrent cholangitis groups. Our result is consistent with a previous study which indicated that the sensitivity of GGT can directly reflect worse liver function and be used to detect cholangitis[7]. We also assessed the occurrence and frequency of cholangitis. We chose the definition of early cholangitis as first onset within the first month post-Kasai in the present study. There were different definitions for early cholangitis, ranging from one month to one year post-Kasai, in which one month is more favorable and reasonable[3].The healing time of the anastomosis between hepatic hilum and intestine usually takes around one month, during which bacteria may be able to colonize[10]. Therefore, the mechanism and effect of early and late cholangitis may be different. After early onset of cholangitis, inflammatory and fibrous tissue may partially block the bile drainage, causing cholestasis and slowing down the healing process, resulting in poor prognosis[3]. The fibrous tissue around the anastomosis can also block or weaken the effect of antibiotics, which may lead to recurrent and intractable cholangitis in the future. However, when late cholangitis takes place, the anastomosis has already healed, which can avoid bile duct obstruction and provide better prognosis[5]. Several previous studies have demonstrated that early cholangitis is associated with adverse outcomes and recurrent cholangitis could lead to progressive liver failure and other severe complications[6, 7, 11]. In our study, we found that

Journal Pre-proof compared to the late cholangitis group, patients with early cholangitis experienced significantly more cholangitis episodes, while compared to the single cholangitis group, patients with recurrent cholangitis had a significantly earlier first cholangitis onset. Though not significant, early cholangitis and recurrent cholangitis groups tended to have shorter durations of intravenous antibiotics usage and suffered lower OS rates. Therefore, effective interventions are needed to prevent early onset of cholangitis, and lower the risk for recurrent cholangitis with poor outcomes in the future.

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Our results showed a trend that compared to non-cholangitis patients, cholangitis patients had a higher JC rate but a delayed JC time; and a lower rate of methylprednisolone use which was also found in early cholangitis and recurrent cholangitis groups. This is likely because that cholangitis usually occurs in the patients who had insufficient bile drainage after Kasai. In these patients, the insufficient bile drainage can cause cholestasis and provide the chance for bacterial colonization, leading to cholangitis onsets and eventually delayed JC time or JC rate [8]. However, in patients with satisfactory bile drainage, the inflammation and cholestasis can be alleviated and become a protective factor against cholangitis. Moreover, patients with no bile drainage or severe fibrous liver status are relatively resistant to cholangitis, without a precondition for bacterial colonization[4]. Methylprednisolone is usually used in patients who have continuous jaundice and acholic stools post-Kasai, which is supposed to relieve bile epithelium edema and establish good bile drainage[12]. The lower rate of methylprednisolone use in our cholangitis patients indicated that more patients in the cholangitis group established early bile drainage post-Kasai, to an either satisfactory or insufficient level. These results indicated that early bile drainage establishment can be a risk factor for cholangitis onset, while cholangitis may delay the JC time.

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When we examined the two-year outcomes, we found more adverse events in cholangitis patients, which was consistent with the progressive damage and complications associated with cholangitis. The nNLS rate and OS rate were higher and the LTs ratio was lower in cholangitis patients when we analyzed among all followed-up patients. However, among the non-cholangitis group, there were patients who never established bile drainage post-Kasai, thus accepted liver transplantation earlier or gave up due to other reasons. Previous studies have demonstrated that cholangitis can be a crucial factor for long-term prognosis in patients who have had successful bile flow restoration[3, 7]. After we excluded the patients without JC in the first six months post-Kasai, cholangitis patients had a significantly higher LTs ratio and significantly lower nNLS. Therefore, cholangitis can lead to poor prognosis in nonicteric patients post-Kasai, and longer follow-ups are needed to evaluate their long-term outcomes. In conclusion, we have found that worse liver status before surgery can be a risk factor for recurrent cholangitis in which preoperative GGT may indicating cholangitis onset. We also found that patients with early bile drainage post-Kasai are more vulnerable to cholangitis; early cholangitis and recurrent cholangitis are related to each other and can contribute to lower overall survival rates. Finally, we identified that cholangitis can cause poor prognosis in patients who have achieved earlier jaundice clearance. Therefore, based on these findings, personalized treatment considering risk factors in individual BA patients should be strongly considered to prevent cholangitis, especially early onsets and to improve postoperative outcomes.

Journal Pre-proof Acknowledgments This study was supported by the Shanghai Hospital Development Center (SHDC12014106), Shanghai Key Disciplines (no.2017ZZ02022), National Natural Science Foundation of China (no. 81370472, no. 81770519, no. 81771633, no. 81401243and no. 81500394), Shanghai Rising-Star Program (A type) (no. 15QA1400800), The Science Foundation of Shanghai Excellent Youth Scholars (no. 2017YQ042), and The Science Foundation of Shanghai (no. 16411952200, no. 16140902300 and no. 17411960600).

Declarations of interest

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None.

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References

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[1] Qiao G, Li L, Cheng W, et al. Conditional probability of survival in patients with biliary atresia after Kasai portoenterostomy: a Chinese population-based study. Journal of Pediatric Surgery,

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2015;50(8):1310-1315.

[2] Gunadi, Gunawan TA, Widiyanto G, et al. Liver transplant score for prediction of biliary atresia

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patients' survival following Kasai procedure. BMC Res Notes, 2018;11(1):p.381. [3] Jiang H, Gao PF, Chen HD, et al. The Prognostic Value of CD8(+) and CD45RO(+) T Cells

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Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation. J Korean Med Sci, 2018;33(30):p.e198. [4] Koga H, Wada M, Nakamura H, et al. Factors influencing jaundice-free survival with the native liver

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in post-portoenterostomy biliary atresia patients: results from a single institution. Journal of Pediatric Surgery, 2013;48(12):2368-2372.

[5] Ernest VHL, Saing H and Tam PK. Cholangitis after hepatic portoenterostomy for biliary atresia: a multivariate analysis of risk factors. J Pediatr, 2003;142(5):p.566-571. [6] Chen SY, Lin CC, Tsan YT, et al. Number of cholangitis episodes as a prognostic marker to predict timing of liver transplantation in biliary atresia patients after Kasai portoenterostomy. BMC Pediatr, 2018;18(1):p.119. [7] Li D, Wang P, He Y, et al. Intravenous immunoglobulin for the treatment of intractable cholangitis after Kasai portoenterostomy in biliary atresia patients. Pediatr Surg Int, 2018;34(4):p.399-404. [8] Nakajima H, Koga H, Okawada M, et al. Does time taken to achieve jaundice-clearance influence survival of the native liver in post-Kasai biliary atresia? World J Pediatr, 2018;14(2):p.191-196. [9] Moyer K, Kaimal V, Pacheco C, et al. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med, 2010;2(5):p.33.

Journal Pre-proof [10] Luo Y and Zheng S. Current concept about postoperative cholangitis in biliary atresia. World J Pediatr, 2008;4(1):p.14-9. [11] Hukkinen M, Kerola A, Lohi J, et al. Very low bilirubin after portoenterostomy improves survival of the native liver in patients with biliary atresia by deferring liver fibrogenesis. Surgery, 2018;9:35. [12] Chen Y, Nah SA, Chiang L, et al. Postoperative steroid therapy for biliary atresia: Systematic

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review and meta-analysis. J Pediatr Surg, 2015;50(9):p.1590-4.

Journal Pre-proof Table 1. Patient Information Cholang

P

Early-C

Late-Ch

P

Single-C

Recur-C

P

o

itis

value

ho

o

value

ho

ho

value

Kasai Age

62.43±2.

62.96±1.

0.856

62.50±2.

63.39±2.

0.799

58.48±2.

66.68±2.

0.019

(days)

27

75

6

38

58

9

41

42

2*

Body Weight at

4.51±0.0

4.97±0.0

0.000

5.03±0.1

4.90±0.1

0.420

4.81±0.1

5.10±0.1

0.068

Kasai (kg)

9

8

5*

2

0

6

0

1

5

ABX time

10.64±0.

10.48±0.

0.795

9.76±0.4

10.92±0.

0.093

10.96±0.

9.85±0.4

0.107

(days)

56

34

0

8

48

3

52

5

5

Hospital stay

15.85±0.

16.30±0.

0.260

16.72±0.

15.90±0.

0.078

16.10±0.

16.47±0.

0.428

(days)

33

23

1

36

29

1

32

33

9

75.41

71.43

0

0.027

62.07

80.33

5*

0.560 74.07

69.23

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olone use (%)

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0.570

Methylprednis

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Non-Ch

4

ABX, intravenous antibiotics usage before discharge from hospital. Non-Cho, patients without cholangitis during

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the first 6 month post-Kasai. Early-Cho, early cholangitis. Late-Cho, late cholangitis. Single-Cho, patients only

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experienced cholangitis once during the first 6 month post-Kasai. Recur-Cho, recurrent cholangitis. *, p < 0.05.

Journal Pre-proof Table 2. Liver Pathology and Liver Function Tests Non-Cho

H&E

1.78±0.11

Cholangit

P

Early-Ch

is

value

o

1.60±0.08

0.193

1.61±0.10

score Masso

Late-Cho

1.60±0.12

8 1.85±0.10

1.97±0.08

n score

P

Single-Ch

Recur-Ch

P

value

o

o

value

0.976

1.53±0.13

1.66±0.09

0.391

0

0.379

2.07±0.09

1.87±0.12

0.192

4

3 1.74±0.12

2.14±0.10

9

0.009 5*

147.5±4.4

155.1±3.8

0.232

149.4±5.0

160.7±5.8

0.146

154.4±5.7

155.6±5.2

0.879

(μmol/

9

6

0

0

4

2

8

4

4

DB

95.52±2.8

100.4±2.3

0.211

96.47±3.0

104.3±3.5

99.31±3.5

101.2±3.2

0.693

(μmol/

2

6

8

7

3

6

1

1

4

ALT

96.72±8.4

96.53±5.6

0.984

89.58±6.8

103.5±8.8

0.216

105.2±10.

89.73±5.5

0.170

(U/L)

5

0

1

3

4

1

52

9

9

AST

146.5±10.

155.5±9.3

0.553

135.8±9.8

175.3±15.

0.034

173.1±17.

141.8±9.2

0.097

(U/L)

85

7

7

4

62

6*

63

3

1

GGT

577.6±63.

767.4±56.

0.039

795.9±70.

739.4±89.

0.621

652.8±82.

858.4±76.

0.072

(U/L)

19

84

3*

30

51

2

88

53

3

TBA

151.7±7.4

149.9±4.7

152.7±6.0

147.0±7.2

145.6±6.8

153.2±6.4

(μmol/

5

0

0

7

3

6

na

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re

-p

L)

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0.827 2

L)

0.098

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L)

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TB

0.549 8

0.422 2

Alb

39.13±0.4

39.06±0.3

0.905

39.04±0.5

39.09±0.4

0.932

39.29±0.4

38.88±0.4

0.529

(g/L)

5

2

9

0

1

9

5

5

2

TB, total bilirubin. DB, direct bilirubin. ALT, alanine transaminase. AST, aspartate transaminase. GGT, gammaglutamyl transpeptidase. TBA, total bile acid. Alb, albumin. *, p < 0.05.

Journal Pre-proof Table 3. Two-Year Follow-Up Outcomes

Jaundice

Non-Ch

Cholangi

P

Early-C

Late-Ch

P

Single-C

Recur-C

P

o

tis

value

ho

o

value

ho

ho

value

50.00

67.74

0.099

70.45

65.31

0.595

66.67

68.63

0.840

9

Clearance rate

9

5

(%) Jaundice Clearance

time

3.05±0.

4.10±0.4

0.211

3.55±0.

4.63±0.

0.205

4.25±0.6

3.97±0.5

0.746

55

2

6

56

63

3

7

5

1

42.11

30.11

0.187

27.27

32.65

0.572

33.33

27.45

0.650

0

nNLS rate (%)

0.050

OS rate (%)

3

7

0.934

37.93

53.91

4

55.36

65.52

80.00

0.048

78.57

re

0*

ro

tion (%)

54.24

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Liver-transplanta

of

(m)

83.05

0.969

0

54.90

54.69

1

0.511

82.35

79.69

0.738

9

4

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(%), overall survival rate. *, p < 0.05.

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Jaundice Clearance time (m), calculated by months. nNLS rate (%), nonicteric native-liver survival rate. OS rate

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Table 4. Two-year follow-up outcomes for patients with JC before six months post-Kasai Cholangitis

P value

Jaundice Clearance time (m)

2.53±0.23

2.89±0.17

0.2917

Liver-transplantation (%)

0

16.67

0.1131

nNLS rate (%)

100.0

78.13

0.0311*

OS rate (%)

100.0

95.31

0.3415

of

Non-Cho

JC, jaundice clearance. nNLS rate (%) and OS rate (%), calculated in patients who achieved jaundice clearance

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lP

re

-p

ro

within the first six months post-Kasai. *, p < 0.05.

Figure 1

Figure 2