Sequential Operation of Kasai Portoenterostomy and Liver Transplantation is Recommended in Biliary Atresia Children for Better Outcomes: A Propensity Score Matching Analysis

doi:10.21203/rs.3.rs-3564349/v1

Download PDF

Research Article

Sequential Operation of Kasai Portoenterostomy and Liver Transplantation is Recommended in Biliary Atresia Children for Better Outcomes: A Propensity Score Matching Analysis

https://doi.org/10.21203/rs.3.rs-3564349/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Kasai portoenterostomy (KPE) is widely accepted for biliary atresia (BA) when diagnosed timely. However, the outcomes for many patients were not satisfactory and required liver transplantation (LT) subsequently. The aim of our study was to determine whether KPE could improve the post-transplant outcomes of BA children.

Methods

In this retrospective cohort study from 2006 to 2019, 1647 BA children were included and divided into two cohorts: those who underwent primary liver transplantation (pLT) (n = 599) and those who received KPE followed by LT (n = 1048). Propensity score matching (PSM) was conducted in a 1:1 ratio to balance basic characteristics and minimize the selection bias.

Results

Of 954 recipients after PSM, pLT group (n = 477) showed poor survival rate than KPE + LT group (n = 477) (p < 0.001), with 1-year survival rate of 87.2% and 94.7%, 5-year survival rate of 82.4% and 91.9% respectively. 59.2% of deaths happened within post-operative day 90, especially the first month (41.7%) after LT. pLT group had a significant higher mortality rate than KPE + LT group (15.5% vs 6.1%, p < 0.001). Pulmonary infection and post-LT liver failure were leading causes of death in pLT group compared with KPE + LT group.

Conclusions

KPE could improve the post-transplant survival for BA children. If diagnosed within 3 months, it is advisable to try KPE before considering LT for BA children.

Biliary atresia

Primary liver transplantation

Kasai portoenterostomy

Biliary atresia (BA) is a congenital cholangiopathy characterized by obstruction of intrahepatic and extrahepatic bile ducts, resulting in neonatal cholestasis¹. The prevalence of BA is about 0.5 to 2.6 per 10,000 live births^2,3. Kasai portoenterostomy (KPE) was designed to construct Roux-en-Y biliary-enteric drainage to alleviate obstructive-type jaundice and prevent rapidly progressive sclerosing injury of liver, which should be performed within 3 months old. A high proportion of BA patients will still progress to end-stage cirrhosis after KPE, which is neither certain nor predictable³. For these BA patients, liver transplantation (LT) is the best choice. The indications include failure of hepatic portoenterostomy, malnutrition, recurrent cholangitis, symptomatic progressive portal hypertension⁴. On the other hand, for BA patients with late referral and delayed diagnosis, primary liver transplantation (pLT) is the only choice.

However, there is no consensus on the role of KPE in post-LT survival. In 2018, a study involving 626 BA patients concluded that patients underwent KPE before LT had higher long-term mortality than patients with pLT⁵. Considering high failure rate of KPE and advance in LT, they thought unsuccessful KPE was a temporizing treatment, which did not confer a survival advantage. Indeed, BA patients who performed Kasai surgery or not both constitutes a large proportion of cases when considering LT. Nevertheless, there were few studies focusing on the long-term prognosis difference between patients who underwent KPE before LT and those who did not. As advance in newborn screening and early diagnosis of BA⁶, as well as an enhanced understanding of the disease itself, it is common for parents to opt for their children to undergo LT directly after diagnosis⁷, which based on the considerations that children underwent KPE always suffer from complications such as post-operative abdominal adhesion, cholangitis or infection and may also have to undergo LT finally. It is a pity that recent studies have not addressed these issues and give them a better suggestion.

Here, we aimed to exam the association of KPE with post-LT prognosis for BA patients and assess whether BA patients benefit from KPE based on the large-scale follow-up data in our transplant center.

Study design

From 2006 to 2019, a total of 2080 pediatric recipients (< 18 years old) underwent LT at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Among them, 1647 were diagnosed with BA and included in this study. These patients were categorized into two cohorts based on whether or not they had a history of KPE before LT. The diagnosis of BA is confirmed through intraoperative cholangiography, liver histology combined biochemical tests and ultrasonography. Medical records in this study were obtained from the follow-up system at the Department of liver surgery, Renji Hospital. This study was approved by Renji Hospital Review Board.

Propensity score

To minimize differences in preoperative factors and operative variables between groups, propensity score matching (PSM) was used. BA patients from the pLT group were matched in a 1:1 ratio with participants from the KPE + pLT group based on all covariates listed in Table 1. These covariates include age, gender, body weight, blood type, common comorbidities, pre-LT examinations (TB, albumin, PT, INR), cytochrome P450 (CYP), blood flow of portal vein, PELD and Child-Pugh score, operation type, graft type, graft-to-recipient weight ratio (GRWR) and donor characteristics.

Table 1

Characteristics of pLT patients and KPE + LT patients
	Population before matching (n = 1647)			Population after matching (n = 954)
	pLT (n = 599)	KPE + LT (n = 1048)	p-value	pLT (n = 477)	KPE + LT (n = 477)	p-value
Age at LT, median (IQR), m	6.00 [5.00, 8.00]	8.00 [6.00, 14.00]	< 0.001	6.00 [5.00, 8.00]	7.00 [6.00, 9.00]	< 0.001
Male, n (%)	266 (44.4)	482 (46.0)	0.569	208 (43.6)	205 (43.0)	0.896
Body weight, median (IQR), kg	7.00 [6.30, 8.00]	7.50 [6.50, 9.20]	< 0.001	7.00 [6.30, 8.00]	7.20 [6.50, 8.20]	0.127
Blood type, n (%)			0.615			0.885
A	193 (32.2)	316 (30.2)		149 (31.2)	139 (29.1)
AB	49 (8.2)	89 (8.5)		34 (7.1)	38 (8.0)
B	159 (26.5)	308 (29.4)		133 (27.9)	134 (28.1)
O	198 (33.1)	335 (32.0)		161 (33.8)	166 (34.8)
Growth retardation, n (%)	356 (59.4)	681 (65.0)	0.029	282 (59.1)	293 (61.4)	0.508
Portal hypertension, n (%)	236 (39.4)	497 (47.4)	0.002	188 (39.4)	204 (42.8)	0.324
Gastrointestinal hemorrhage, n (%)	70 (11.7)	180 (17.2)	0.004	52 (10.9)	60 (12.6)	0.481
Cholangitis, n (%)	113 (18.9)	540 (51.5)	< 0.001	113 (23.7)	132 (27.7)	0.182
Ascites, n (%)	474 (79.1)	647 (61.7)	< 0.001	360 (75.5)	360 (75.5)	1
TB, median (IQR), mg/dL	17.90 [13.60, 23.55]	10.40 [3.30, 18.00]	< 0.001	16.50 [12.70, 21.40]	16.70 [11.00, 23.20]	0.861
Albumin, median (IQR), g/dL	3.33 [2.92, 3.77]	3.49 [3.12, 3.85]	< 0.001	3.35 [2.92, 3.78]	3.35 [3.04, 3.70]	0.668
PT, median (IQR), s	15.80 [13.20, 19.90]	14.35 [12.47,18.00]	< 0.001	15.50 [13.00, 19.30]	15.60 [13.40, 20.70]	0.171
INR, median (IQR)	1.38 [1.16, 1.74]	1.27 [1.10, 1.60]	< 0.001	1.36 [1.14, 1.67]	1.38 [1.16, 1.82]	0.088
CYP, n (%)			0.899			0.793
AA	50 (8.3)	92 (8.8)		40 (8.4)	42 (8.8)
AG	225 (37.6)	383 (36.5)		175 (36.7)	165 (34.6)
GG	324 (54.1)	573 (54.7)		262 (54.9)	270 (56.6)
Blood flow direction of portal vein, n (%)			< 0.001			0.611
Bidirectional	15 (2.5)	22 (2.1)		13 (2.7)	11 (2.3)
Ex-liver	146 (24.4)	169 (16.1)		109 (22.9)	98 (20.5)
Toward-liver	438 (73.1)	857 (81.8)		355 (74.4)	368 (77.1)
PELD	20.00 [15.00, 26.00]	15.00 [7.00, 22.00]	< 0.001	19.00 [15.00, 24.00]	19.00 [14.00, 26.00]	0.611
Child-Pugh	10.00 [9.00, 11.00]	9.00 [7.00, 10.00]	< 0.001	10.00 [8.00, 11.00]	9.00 [8.00, 11.00]	0.369
Operation type, n (%)			0.001			0.98
SLT	34 (5.7)	37 (3.5)		22 (4.6)	23 (4.8)
OLT	39 (6.5)	123 (11.7)		37 (7.8)	38 (8.0)
LDLT	526 (87.8)	888 (84.7)		418 (87.6)	416 (87.2)
Graft type, n (%)			< 0.001			0.46
Left lateral lobe	492 (82.1)	787 (75.1)		395 (82.8)	379 (79.5)
Reduced-size left lateral lobe	63 (10.5)	98 (9.4)		42 (8.8)	53 (11.1)
Enlarged left lateral lobe	0 (0.0)	8 (0.8)		0 (0.0)	0 (0.0)
Left hemi-liver	5 (0.8)	25 (2.4)		3 (0.6)	6 (1.3)
Right hemi-liver	0 (0.0)	5 (0.5)		0 (0.0)	0 (0.0)
Right posterior lobe	0 (0.0)	2 (0.2)		0 (0.0)	1 ()
Whole liver	39 (6.5)	123 (11.7)		37 (7.8)	38 (8.0)
GRWR, median (IQR), %	3.43 [2.85, 4.01]	3.24 [2.61, 3.87]	< 0.001	3.44 [2.84, 4.06]	3.38 [2.82, 3.94]	0.13
Donor
Age, median (IQR), y	29.00 [25.00, 34.00]	29.00 [25.00, 34.00]	0.614	29.00 [25.00, 34.00]	29.00 [26.00, 33.00]	0.675
Male, n (%)	255 (42.6)	480 (45.8)	0.224	203 (42.6)	206 (43.2)	0.896
Donor-recipient consistency, n (%)
Gender	304 (50.8)	506 (48.3)	0.361	238 (49.9)	250 (52.4)	0.476
CYP	338 (56.4)	616 (58.8)	0.38	277 (58.1)	279 (58.5)	0.948
Blood type¹	526 (87.8)	915 (87.3)	0.919	419 (87.9)	397 (83.3)	0.119
pLT, primary liver transplantation; KPE, Kasai portoenterostomy; IQR, interquartile range; LT, liver transplantation; TB, total bilirubin; PT, prothrombin time; INR, international normalized ratio; PELD, pediatric end-stage liver disease score; SLT, split liver transplantation; OLT, orthotopic liver transplantation; LDLT, living donor liver transplantation; GRWR, graft-to-recipient weight ratio;
Consistent blood types include compatible or identical ones.

Statistical Analysis

Median and interquartile range (IQR) were used to express continuous variables. Categorical variables were expressed with number and percent. The survival rate was calculated from the time of LT to the last follow-up. Survival curves were plotted by Kaplan-Meier analysis and comparison between groups was performed by log-rank test. The Kruskal-Wallis test was employed to analyze differences in continuous variables, while the Chi-Square test was used for categorical variables. Statistical analyses were carried out using SPSS (IBM, version 26) and R (R Foundation for Statistics Computing, version 3.6.3). Two-sided p-values were calculated, and p-value less than 0.05 was considered statistically significant.

Characteristics of BA patients with and without KPE

A total of 2080 pediatric recipients underwent LT at the Department of Liver Surgery of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January 1, 2006, and December 31, 2019. Out of these, 1647 cases diagnosed with BA were enrolled in our study (Fig. 1). Among them, 599 (36.4%) underwent pLT and 1048 (63.6%) received KPE before LT. For KPE + LT group, the median time of KPE was 60 days after birth. The median age at LT (8 months vs 6 months, p < 0.001) and body weight (7.5 kg vs 7 kg, p < 0.001) were higher in the KPE + LT group. The proportion of patients with growth retardation, portal hypertension, gastrointestinal hemorrhage and cholangitis was higher in the KPE + LT group compared to the pLT group before LT, while the pLT group had a higher prevalence of ascites than the KPE + LT group (Table 1). Additionally, serum biochemistry revealed higher levels of total bilirubin, prothrombin time, INR and lower albumin in the pLT group (Table 1). The median PELD score and Child-Pugh score were higher in the pLT group, indicating more severe liver impairment in BA children without KPE before LT.

To minimize differences in characteristics, PSM was performed with a 1:1 ratio. The baseline characteristics were comparable between the two matched groups, except that the age in KPE + LT group was 1 month older than the pLT group. Intraoperative variables, including the type of LT, graft type, GRWR, and donor factors were also comparable between the two groups (Table 1).

After PSM, a total of 954 children with BA were included for further analysis. Among them, 413 (43.3%) were male and 541 (56.7%) were female. The median age at LT was 7 months. Among these patients, 87.4% underwent living donor liver transplantation (LDLT), 7.9% underwent orthotopic liver transplantation (OLT), and 4.7% performed split liver transplantation (SLT). The median (IQR) weight of graft was 245 (215, 280) grams and the median (IQR) GRWR was 3.41(2.83, 4.00) %.

BA patients underwent KPE before LT had superior post-LT survival

We conducted Kaplan-Meier survival analysis to evaluate the long-term prognosis of the patients. Among BA patients with pLT, the survival rate was 88.5% at 1-year post-LT and 84.7% at 5 years post-LT. In contrast, BA patients who underwent KPE before LT showed a higher survival rate of 96.2% at 1-year post-LT and 93.4% at 5 years post-LT. After PSM, the analysis still revealed a significant difference in post-LT survival between the groups with or without KPE (p < 0.001). Specifically, the survival rate for the KPE + LT group was 94.8% at 1 year and 91.9% at 5 years, while it was 87.2% at 1 year and 82.4% at 5 years for the pLT group (Fig. 2).

Outcomes of LT recipients diagnosed with BA

Subsequently, we analyzed the outcomes of matched children with BA after LT (Table 2). After PSM, 86.8% BA patients were on tacrolimus therapy and 13.2% were on cyclosporine therapy. The death rate was significantly higher in the pLT group (15.5%; 74 out of 477) compared to the KPE + LT group (6.1%; 29 out of 477) (p < 0.001). There were no significant differences between the groups in terms of drug-induced liver injury (pLT 7.1% versus KPE + LT 7.1%), acute rejection (pLT 26.6% versus KPE + LT 28.7%), viral infection (HBV: pLT 4.0% versus KPE + LT 5.0%, EBV : pLT 56.6% versus KPE + LT 55.8%, CMV: pLT 29.1% versus KPE + LT 34.0%), vascular complications (portal vein complications: pLT 5.9% versus KPE + LT 3.6%, hepatic artery complications: pLT 1.7% versus KPE + LT 1.7%), respiratory complications (pLT 32.7% versus KPE + LT 29.1%), digestive complications (pLT 21.1% versus KPE + LT 25.7%), urinary complications (pLT 6.5% versus KPE + LT 4.2%) mental and neurological complications (pLT 1.0% versus KPE + LT 1.7%), hematological complications (pLT 9.9% versus KPE + LT 11.7%), skeletal complications (pLT 1.0% versus KPE + LT 2.9%), allergy-related complications (pLT 25.4% versus KPE + LT 26.4%), and post-transplant lymphoproliferative disorder (PTLD) (pLT 4.6% versus KPE + LT 5.2%). Therefore, except for mortality, the proportion of patients experiencing adverse events was similar in both groups.

Table 2

Outcomes of pLT and KPE + LT patients
Outcomes, n (%)	Total (n = 954)	pLT (n = 477)	KPE + LT (n = 477)	p-value
Death	103 (10.8)	74 (15.5)	29 (6.1)	< 0.001
Immunosuppressant				0.214
tacrolimus	828 (86.8)	421 (88.3)	407 (85.3)
Cyclosporine	126 (13.2)	56 (11.7)	70 (14.7)
Drug-induced liver injury	68 (7.1)	34 (7.1)	34 (7.1)	1
Acute rejection ^a	264 (27.7)	127 (26.6)	137 (28.7)	0.515
Infection
HBV	43 (4.5)	19 (4.0)	24 (5.0)	0.532
EBV	536 (56.2)	270 (56.6)	266 (55.8)	0.845
CMV	301 (31.6)	139 (29.1)	162 (34.0)	0.125
Vascular Complications
Portal vein	45 (4.7)	28 (5.9)	17 (3.6)	0.127
Hepatic artery	16 (1.7)	8 (1.7)	8 (1.7)	1
Respiratory complications	295 (30.9)	156 (32.7)	139 (29.1)	0.262
Digestive complications	224 (23.5)	101 (21.1)	123 (25.7)	0.321
Urinary complications	51 (5.3)	31 (6.5)	20 (4.2)	0.15
Mental and neurological complications	13 (1.4)	5 (1.0)	8 (1.7)	0.576
Hematological complications	103 (10.8)	47 (9.9)	56 (11.7)	0.404
Skeletal complications	19 (2.0)	5 (1.0)	14 (2.9)	0.064
Allergy or Urticaria	247 (25.9)	121 (25.4)	126 (26.4)	0.767
PTLD	47 (4.9)	22 (4.6)	25 (5.2)	0.765
HBV, hepatitis B virus; EBV, Epstein-Barr virus; CMV, cytomegalovirus; PTLD, post-transplant lymphoproliferative disorder
^a acute rejection within post-operative day 90

Among the 1647 BA patients who underwent LT, a total of 130 deaths (7.9%) were recorded. After PSM, there were 103 cases of death. It was observed that the majority of deaths occurred within the first year after LT, with a particularly high proportion in the first month (Fig. 3), accounting for 41.7% of all deaths after LT. The proportion of deaths occurring within the first 90 days post-LT was 59.2%.

The leading causes of death among patients after PSM were pulmonary infection (n = 38) and liver failure (n = 19), which also remained the leading causes in the entire cohort of 1647 BA patients. Other causes of death included abdominal infection (n = 9), vascular complications (n = 7), biliary complications (n = 3), PTLD (n = 5) and a few causes attributed to accidents (n = 6) or unknown reasons (n = 15). When comparing the KPE + LT group to the pLT group, it was found that deaths due to pulmonary infection (p = 0.047) and liver failure (p = 0.003) were higher in the pLT group (Table 3).

Table 3

Causes of post-LT death for BA children after PSM.
	Total (n = 103)	pLT (n = 74)	Kasai + LT (n = 29)	p-value
Pulmonary infection, n (%)	38 (36.9)	25 (33.8)	13 (44.8)	0.047
Abdominal infection, n (%)	9 (8.7)	5 (6.8)	4 (13.8)	1.000
Liver failure, n (%)	19 (18.4)	16 (21.6)	3 (10.3)	0.003
Portal vein thrombosis, n (%)	6 (5.8)	5 (6.8)	1 (3.4)	0.219
Hepatic arterial thrombosis, n (%)	1 (1.0)	1 (1.4)	0 (0.0)	0.500
Biliary complication, n (%)	3 (2.9)	2 (2.7)	1 (3.4)	1.000
PTLD, n (%)	5 (4.9)	5 (6.8)	0 (0.0)	0.073
Bleeding, n (%)	1 (1.0)	1 (1.4)	0 (0.0)	0.500
Accident, n (%)	6 (5.8)	4 (5.4)	2 (6.9)	0.682
Unknown, n (%)	15 (14.6)	10 (13.5)	5 (17.2)	0.193
PTLD, post-transplant lymphoproliferative disorder

Trends in BA mortality after LT

In assessing the temporal trends in BA mortality after LT, we evaluated the proportion of deaths in the total number of LTs performed each year. Our study revealed a decrease in the percentage of deaths among LT cases over the years, coinciding with a soaring increase in the number of transplantations (Fig. 3B). Since 2017, our transplant center has been performing over 400 pediatric LTs annually, and the BA mortality rate among LT patients has remained below 3% based on the most recent four-year data. in the pLT group, the percentage of deaths decreased from 15.9% during the period of 2006–2010 to 2.7% during 2016–2019. Notably, patients who had undergone previous KPE treatment consistently exhibited better outcomes, with the mortality rate declining from 7.8–0.6%.

In our study, after minimizing characteristic biases through PSM, we observed that BA children with KPE had a better survival rate compared to those without. There were no statistically significant differences in other post-transplant adverse events between the two groups. Notably, the mortality rates attributed to pulmonary infection and post-LT liver failure were lower in the KPE + LT group than that in the pLT group. Nearly 60% of deaths occurred within 3 months after LT. Overall, these findings emphasize the protective effect of KPE on the prognosis of BA patients after LT.

KPE and LT are crucial treatments for children with BA. Portoenterostomy, introduced in the 1950s by Kasai⁸, involves several steps to clear jaundice and restore liver function, including confirmation by exploration and cholangiography, dissection and transection of porta hepatis, construction of a Roux-en-Y jejunal drainage⁹. Early successful KPE is associated with higher survival rates for the native liver^10,11. However, the rate of complete jaundice removal after KPE was 36.2% (242 in 668) in France¹¹, which was more inferior in less experienced centers. LT is suitable for BA patients who have not benefit from KPE.

There was argument regarding the association of KPE with post-LT survival. Researchers analyzing data from the OSHPD in California found that salvage LT after KPE had a higher risk of mortality compared with pLT^5,7. In contrast, our records, which included more BA patients, showed that the survival rate of the KPE + LT group was higher than the pLT group both before and after PSM. In China and throughout Asia, the operation types of LT differ from those in western countries¹². The majority of pediatric patients undergo LDLT, which accounted for over 85% cases in our center. In contrast, only 11.1% pediatric candidates underwent LDLT in 2019 according to OPTN/SRTR data¹³. Given that LDLT eliminates the need to wait for an allograft, it reduces the mortality rate between KPE and LT. Recipients with LDLT have an excellent prognosis than those who undergo deceased donor transplant. On the other side, it should be noted that palliative KPE will increase patients’ age at LT¹⁴, which can impact post-LT survival according to our data and other reported multivariable analyses among LT recipients with BA¹⁵. Taken together, sequential operation of KPE and LT itself is the optimal choice for BA patients.

In this study, the leading cause of death was pulmonary infection, which accounted fot more than 30% of all causes of death, consistent with other studies¹⁶. However, the incidence of infection was remarkedly reduced in BA patients who underwent KPE. This may be attributed to differences in anti-infective capabilities. The immune system is not fully developed at birth and undergoes compositional changes in immune cells early in life¹⁷. Evidence suggests that the first 100 days after birth are critical for immune development and can be influenced by environmental exposures¹⁸. Since KPE is usually performed during this period, we hypothesize that it may impact immune system development. Additionally, the nutritional status of children can affect their relative risk of mortality^19,20. Low weight compared to peers is associated with a higher risk of mortality due to respiratory infections²¹. Although the mean weight was matched between the two groups in this study, the mean age of the KPE + LT group was one month older than the pLT group. More detailed indicators, such as upper limb fat, should be considered for further evaluation.

There were some limitations of in this study. Given that it is a retrospective study, some details such as immune cell subpopulations and indicators of nutritional status except for height and weight were not available. Future prospective multicenter studies should consider more risk factors.

Overall, in this study we highlighted that for BA patients who underwent KPE followed by LT had improved long-term survival, offering valuable insights for improving prognosis in BA patients.

Author contributions

Guangxiang Gu and Qiang Xia designed the study. Chen Chen, Tao Zhou, Zhifeng Xi, Yengfeng Lu, Jianjun Zhang and Guangxiang Gu conducted the study procedures and collected data. Chen Chen and Tao Zhou wrote the manuscript. All authors approved the final version to be published.

Acknowledgements

The authors wish to acknowledge all the staff who participated in the pediatric liver transplantation in our center. This study was approved by Renji Hospital Review Board. There are no conflicts of interest to declare.

Funding

This work was sponsored by Frontiers Science Center for Shanghai Municipality (2022ZZ01016).

Data Availability Statement

The data used in this study are available upon request.

Wang J, Xu Y, Chen Z, et al. Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia. Cell. 2020;183(7):1867-1883.e1826.
Sanchez-Valle A, Kassira N, Varela V, Radu S, Paidas C, Kirby RJAip. Biliary Atresia: Epidemiology, Genetics, Clinical Update, and Public Health Perspective. 2017;64(1):285-305.
Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet (London, England). 2009;374(9702):1704-1713.
Sundaram SS, Mack CL, Feldman AG, Sokol RJ. Biliary atresia: Indications and timing of liver transplantation and optimization of pretransplant care. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2017;23(1):96-109.
LeeVan E, Matsuoka L, Cao S, Groshen S, Alexopoulos S. Biliary-Enteric Drainage vs Primary Liver Transplant as Initial Treatment for Children With Biliary Atresia. JAMA surgery. 2019;154(1):26-32.
Harpavat S, Garcia-Prats JA, Anaya C, et al. Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements. Jama. 2020;323(12):1141-1150.
Alexopoulos SP, Merrill M, Kin C, et al. The impact of hepatic portoenterostomy on liver transplantation for the treatment of biliary atresia: early failure adversely affects outcome. Pediatr Transplant. 2012;16(4):373-378.
Oi R, Kasai M, Takahashi T. Intrahepatic biliary obstruction in congenital bile duct atresia. The Tohoku journal of experimental medicine. 1969;99(2):129-149.
Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007;46(2):566-581.
Okubo R, Nio M, Sasaki H. Impacts of Early Kasai Portoenterostomy on Short-Term and Long-Term Outcomes of Biliary Atresia. Hepatology communications. 2021;5(2):234-243.
Serinet MO, Broué P, Jacquemin E, et al. Management of patients with biliary atresia in France: results of a decentralized policy 1986-2002. Hepatology. 2006;44(1):75-84.
Chen CL, Kabiling CS, Concejero AM. Why does living donor liver transplantation flourish in Asia? Nat Rev Gastroenterol Hepatol. 2013;10(12):746-751.
Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2019 Annual Data Report: Liver. Am J Transplant. 2021;21 Suppl 2:208-315.
Yang J, Gao W, Zhan J, Feng J. Kasai procedure improves nutritional status and decreases transplantation-associated complications. Pediatric surgery international. 2018;34(4):387-393.
Diem HV, Evrard V, Vinh HT, et al. Pediatric liver transplantation for biliary atresia: results of primary grafts in 328 recipients. Transplantation. 2003;75(10):1692-1697.
Anderson CD, Turmelle YP, Lowell JA, et al. The effect of recipient-specific surgical issues on outcome of liver transplantation in biliary atresia. Am J Transplant. 2008;8(6):1197-1204.
Olin A, Henckel E, Chen Y, et al. Stereotypic Immune System Development in Newborn Children. Cell. 2018;174(5):1277-1292.e1214.
Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Science translational medicine. 2015;7(307):307ra152.
Schroeder DG, Brown KH. Nutritional status as a predictor of child survival: summarizing the association and quantifying its global impact. Bulletin of the World Health Organization. 1994;72(4):569-579.
Karunaratne R, Sturgeon JP, Patel R, Prendergast AJ. Predictors of inpatient mortality among children hospitalized for severe acute malnutrition: a systematic review and meta-analysis. The American journal of clinical nutrition. 2020;112(4):1069-1079.
Victora CG, Smith PG, Barros FC, Vaughan JP, Fuchs SC. Risk factors for deaths due to respiratory infections among Brazilian infants. International journal of epidemiology. 1989;18(4):918-925.

Supplements.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

Sequential Operation of Kasai Portoenterostomy and Liver Transplantation is Recommended in Biliary Atresia Children for Better Outcomes: A Propensity Score Matching Analysis

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Methods

Study design

Propensity score

Statistical Analysis

Results

Characteristics of BA patients with and without KPE

BA patients underwent KPE before LT had superior post-LT survival

Outcomes of LT recipients diagnosed with BA

Trends in BA mortality after LT

Discussion

Declarations

Author contributions

Acknowledgements

Funding

Data Availability Statement

References

Supplementary Files

Status:

Version 1