Application of transjugular liver biopsy in pediatric living donor liver transplantation

Abstract

Objective

To evaluate the safety and diagnostic utility of transjugular liver biopsy (TJLB) in pediatric patients with contraindications to percutaneous biopsy after living donor liver transplantation (LDLT).

Methods

This was a single-center retrospective case series of 22 pediatric LDLT recipients (7 females) who underwent TJLB at Tianjin First Central Hospital between January 2021 and June 2024. Key cohort risks included preoperative coagulation dysfunction (INR > 1.5, n = 9), thrombocytopenia (platelet count < 50 × 10⁹/L, n = 7), and ascites (n = 12). Outcomes analyzed included technical/clinical success rates and postoperative complications.

Results

Technical and clinical success rates were both 100% (95% CI: 85.2%–100.0%). No severe complications occurred; only 1 case (4.5%, 95% CI: 0.1%–22.8%) of postoperative abdominal pain (managed with oral analgesics) was reported. All specimens were diagnostically adequate.

Conclusion

TJLB demonstrates encouraging safety and diagnostic value in this small single-center cohort of high-risk pediatric LDLT recipients with coagulopathy, thrombocytopenia, or ascites. It provides a reliable alternative for patients with percutaneous biopsy contraindications.

Introduction

In pediatric living donor liver transplantation, sampling of transplanted liver tissue is primarily used to assess graft function level and guide further treatment. Liver histopathological examination helps evaluate rejection, steatosis, vascular damage, ischemic bile duct injury or ischemia-reperfusion injury, and provides relevant information to help adjust immunosuppressive drug doses and formulate other protocols and treatment measures [1]. Methods for obtaining histopathological samples include percutaneous transhepatic and transjugular approaches. In liver transplant patients with coagulation abnormalities, thrombocytopenia, and ascites, percutaneous transhepatic biopsy is no longer the first choice due to increased bleeding risk. Therefore, transjugular liver biopsy (TJLB) provides a safe alternative with technical success rates reaching 87%-98% [2–7].

TJLB was first reported by Dotter in 1964 in animal experiments on dogs [8], and first applied clinically by Weiner and Hanafee in 1970 [9]. Pediatric patients after living donor liver transplantation require procedural liver biopsy. Most patients can complete biopsy through percutaneous transhepatic approach, but some patients have contraindications to percutaneous biopsy. The transjugular technique collects specimens through hepatic vein biopsy, effectively reducing bleeding risk, as bleeding is confined within liver tissue with lower risk of fatal hemorrhage. Previous studies have shown that TJLB has extremely high feasibility and good diagnostic accuracy in adult liver transplant patients and general liver disease patients [10–14]. However, for pediatric liver transplant patients, most undergo left lateral segment living donor liver transplantation, and due to the specificity of their vessels and liver, the safety and efficacy of TJLB have rarely been reported. This article explores the safety and efficacy of TJLB in pediatric liver transplant patients.

Materials and methods

General materials

This is a retrospective study. After explaining TJLB and its related risks, informed consent was obtained from children’s parents or guardians, and the ethical committee of Tianjin First Central Hospital exempted ethical review due to the retrospective nature.

All patients were on standardized immunosuppression regimens before TJLB, including tacrolimus-based (tacrolimus + mycophenolate mofetil ± prednisone) or cyclosporine-based (cyclosporine + mycophenolate mofetil ± prednisone) regimens, with drug doses adjusted to maintain therapeutic blood concentrations (tacrolimus: 5–10 ng/mL; cyclosporine: 100–200 ng/mL).

Inclusion criteria

All patients received left lateral segment (segments II–III) grafts from living donors; time from LDLT to TJLB ≥ 1 month (range: 1–24 months); patients with prior vascular (hepatic vein stenosis, portal vein thrombosis) or biliary (biliary stricture, bile leak) complications were not excluded but recorded separately.

1. Age < 18 years old (pediatric population) who underwent living donor liver transplantation (LDLT) at our hospital;

2. Abnormal liver function (defined as at least one of the following: AST > 40 U/L, ALT > 40 U/L, total bilirubin > 20.5 µmol/L, or Child-Pugh score ≥ 7 points) requiring histological evaluation to guide clinical management;

3. Presence of contraindications to percutaneous liver biopsy (at least one of the following: ascites confirmed by ultrasound, coagulation dysfunction with INR > 1.5 or PT > 16 s, thrombocytopenia with platelet count < 50 × 10⁹/L);

4. Time from LDLT to TJLB ≥ 1 month (to avoid acute perioperative complications interfering with biopsy safety and pathological interpretation);

5. Hemodynamic stability (systolic blood pressure 90–140 mmHg, diastolic blood pressure 60–90 mmHg, heart rate 60–120 beats/min, no requirement for vasopressor support);

6. Complete clinical, laboratory, surgical, and pathological data available for analysis.

Child-Pugh scoring was adapted appropriately for pediatric patients: ① Ascites was graded based on ultrasound findings (mild: small amount without clinical symptoms; moderate: detectable with abdominal distension; severe: massive with respiratory compromise); ② Encephalopathy was assessed using age-specific neurocognitive markers (e.g., altered alertness, poor feeding in young children, academic or behavioral changes in older children) [15]; ③ Synthetic function (albumin, PT/INR) was interpreted using pediatric reference ranges. This adaptation aligns with previous studies applying Child-Pugh in post-transplant children to stratify liver function severity [16, 17].

Exclusion criteria

1. Age ≥ 18 years old;

2. No contraindications to percutaneous liver biopsy (normal coagulation function, no thrombocytopenia, no ascites);

3. Hemodynamic instability (shock, hypotension refractory to fluid resuscitation, or need for vasopressor/inotropic support);

4. Severe hepatic vein stenosis or occlusion confirmed by preoperative imaging (CT angiography or Doppler ultrasound);

5. Severe infection (sepsis, systemic inflammatory response syndrome) or active bleeding diathesis (e.g., hemophilia);

6. Allergy to contrast agents or local anesthetics used in the procedure;

7. Incomplete clinical or pathological data.

This study included 22 patients who met the above criteria and underwent TJLB at Tianjin First Central Hospital from January 2021 to December 2024. We reviewed electronic medical records and imaging data, and recorded laboratory values (including Hb, PT/INR, platelets, AST/ALT, total bilirubin, Child-Pugh score), surgical records (biopsy method, sampling vessel, puncture times), adequacy of biopsy samples in pathology reports, and intraoperative and postoperative complications.

From January 2021 to June 2024, a total of 156 pediatric patients underwent living donor liver transplantation (LDLT) in our hospital, among whom 68 patients developed abnormal liver function requiring histological evaluation to guide clinical management. Among these 68 patients, biopsy was performed via three routes: 22 patients (32.4%) underwent transjugular liver biopsy (TJLB, the study cohort), 41 patients (60.3%) underwent percutaneous liver biopsy (with no contraindications such as coagulation dysfunction, thrombocytopenia, or ascites), and 5 patients (7.3%) underwent surgical biopsy (due to concurrent intra-abdominal complications requiring laparotomy). Statistical analysis was conducted on the study cohort’s basic information, preoperative liver function (Child-Pugh score), coagulation function (PT/INR), platelet count, surgical success rate, and postoperative complications.

Peri-procedural correction strategies for coagulation/thrombocytopenia

To optimize procedural safety, standardized peri-procedural correction protocols were implemented based on preoperative coagulation function and platelet count, with no blood product or correction agent administered for ascites alone (ascites management focused on preoperative volume optimization via diuretics as needed): for thrombocytopenia correction, patients with preoperative platelet count < 50 × 10⁹/L (n = 4) received platelet transfusion 2–4 h before TJLB at a dose of 1 unit/10 kg body weight to target a platelet count ≥ 50 × 10⁹/L, while those with platelet count ≥ 50 × 10⁹/L (n = 18) did not receive platelet transfusion; for coagulation abnormality correction, patients with INR > 1.8 (n = 5) were administered preoperative fresh frozen plasma (FFP) at 10–15 mL/kg to target INR ≤ 1.8, no FFP was given to patients with INR ≤ 1.8 (n = 17), 3 patients with combined vitamin K deficiency (preoperative vitamin K level < 0.5 ng/mL) received 1–2 mg intramuscular vitamin K 24 h before the procedure, and cryoprecipitate was not used in any patient as fibrinogen levels were ≥ 1.5 g/L in all cases; for ascites management, ascites alone did not require blood product correction, while patients with massive ascites (n = 3, ascites volume > 500 mL via preoperative ultrasound assessment) received oral diuretics (spironolactone + furosemide) for 3–5 days preoperatively to reduce ascites volume and improve liver tissue sampling efficiency without affecting coagulation or platelet parameters. All patients underwent recheck of PT/INR and platelet count 1 h before TJLB to confirm target parameters were achieved, with no procedure delayed due to inadequate correction.

Transjugular liver biopsy procedure

Under general anesthesia, TJLB was performed by interventional radiologists with ≥ 5 years of specialized experience. Venous access site: The right internal jugular vein (20 cases) or left internal jugular vein (2 cases) was selected as the access site, with preference for the right side due to its anatomical straightness. Local anesthesia and puncture: After skin disinfection and draping, 2% lidocaine was used for local infiltration anesthesia. Under ultrasound guidance, a 21G trocar needle was used to puncture the target jugular vein via the Seldinger technique. Sheath/catheter system: A 0.018-inch hydrophilic guidewire was advanced under fluoroscopy, followed by placement of a 6 F introducer sheath; subsequent guidewire exchange allowed implantation of a 10 F dilator sheath to accommodate the biopsy system. A 260 cm stiff guidewire was positioned into the left hepatic vein (S3 segment), and the angiographic catheter was replaced with a 7 F dedicated biopsy sheath (LABS-100, COOK Medical, Bloomington, USA). Needle type and gauge: A coaxial 26G automated core biopsy needle (Quick-Core, Cook Medical) was used for tissue sampling, selected for its balance of tissue yield and minimal vascular injury in pediatric patients. Number of cores/passes policy: The standard strategy was 2–3 initial punctures; additional passes (maximum 1 extra pass, total ≤ 4) were performed only if the initial sample was deemed inadequate (tissue length < 1.0 cm or < 3 portal areas on gross inspection), to minimize bleeding risk. Fluoroscopy and radiation dose: All steps (guidewire/catheter positioning, needle puncture) were guided by low-dose fluoroscopy; the average fluoroscopy time was 3.2 ± 1.1 min, with a mean effective radiation dose of 0.12 ± 0.05 mSv, consistent with pediatric radiation protection guidelines. Venography steps: Two venographic evaluations were performed: ① Pre-biopsy: To confirm catheter positioning in the S3 segment hepatic vein and rule out vascular stenosis; ② Post-biopsy: To exclude contrast extravasation or active bleeding from the biopsy tract. Post-biopsy tract management: No additional tract embolization was required due to the low bleeding risk of hepatic vein punctures; post-biopsy venography confirmed no contrast leakage in all cases, and manual compression of the jugular access site (10 min) was performed before application of a pressure bandage. Immediate post-procedure monitoring pathway: Patients were monitored in the interventional recovery room for 30 min post-procedure, with continuous recording of oxygen saturation, heart rate, and blood pressure. Upon return to the ward, monitoring was intensified for 24 h: ① First 2 h: Vital signs (oxygen saturation, HR, BP) and puncture site inspection (swelling, bleeding) every 30 min; ② Subsequent 22 h: Vital signs and symptom assessment (abdominal pain, nausea, dyspnea) every 6 h; ③ Laboratory monitoring: Hemoglobin and hematocrit were measured at 2 h and 24 h postoperatively to rule out occult bleeding. Biopsy specimens were fixed in 10% neutral buffered formalin and sent for pathological examination immediately, with tissue length, number of portal and central veins, and final pathological results recorded based on pathology reports.

Adverse event assessment

Postoperative vital signs (oxygen saturation, heart rate, blood pressure, respiratory rate) were monitored initially every 30 min for 2 h, then every 6 h for 24 h (extended to 72 h if clinically indicated); adverse events and complications were classified and defined based on the Society of Interventional Radiology (SIR) Clinical Practice Guidelines [18] (a recognized interventional procedure standard) with procedure-specific supplements: major complications refer to events causing permanent morbidity, mortality, or requiring urgent intervention (surgical/interventional treatment or transfusion of > 4 units of blood products within 72 h), including fatal hemorrhage, hemobilia, severe vascular injury, symptomatic capsular perforation with intra-abdominal hemorrhage, and life-threatening arrhythmia; minor complications are self-limiting events requiring minimal intervention without permanent sequelae, including postoperative pain requiring analgesics, access-site complications (neck hematoma < 5 cm or ecchymosis), transient contrast extravasation, transient arrhythmia, and small asymptomatic pneumothorax < 15% of hemithorax; all suspected complications were confirmed by clinical assessment, laboratory tests (hemoglobin, hematocrit), and/or imaging (ultrasound, CT) as needed, with severity independently evaluated by two attending interventional radiologists and discrepancies resolved by consensus.

Operational definitions of key outcomes

Technical success is defined as the successful completion of the TJLB procedure, including ① successful puncture and cannulation of the target jugular vein (right/left internal jugular vein) via ultrasound-guided Seldinger technique, ② successful placement of the biopsy sheath into the predefined target hepatic vein (S3 segment), and ③ acquisition of at least one intact liver tissue core with grossly visible hepatic parenchyma (excluding fragmented or blood-clotted tissue); clinical success is defined as the achievement of the primary clinical goal of TJLB—obtaining liver tissue that enables a definitive pathological diagnosis to guide clinical management (e.g., adjusting immunosuppressive therapy, treating complications)—without the occurrence of major adverse events (classified per Society of Interventional Radiology standards [18], including fatal hemorrhage, need for emergency transfusion > 4 units of blood products, urgent surgical intervention, or significant vascular injury requiring interventional embolization) within 72 h post-procedure; report adequacy is defined based on pathological assessment criteria, including ① tissue length ≥ 1.0 cm (to ensure sufficient sampling of hepatic parenchyma), ② presence of ≥ 3 portal areas (each containing portal vein, hepatic artery, and bile duct) and ≥ 1 central venous area (to evaluate zonal hepatic pathology), and ③ absence of severe tissue artifact (e.g., extensive crush artifact, hemorrhage obscuring histological details) that impairs pathological interpretation, with specimens meeting all three criteria deemed adequate for reporting and those failing any criterion classified as inadequate.

Pathological diagnosis evaluation/reporting adequacy definition

Pathology reports covered portal tracts and central venous areas. Specimens with zero portal tracts and central venous areas were not statistically eligible. Specimens required for reporting were defined as those containing portal tracts, central venous areas, and deemed sufficient for diagnosis by pathologists. Additionally, for cases that could be retrospectively evaluated, we re-counted the number of portal tracts and assessed the diagnostic capability of TJLB. Additionally, for cases that could be retrospectively evaluated, we re-counted the number of portal areas and assessed the diagnostic capability of TJLB.

All biopsy specimens were independently reviewed by two attending pathologists specialized in hepatic pathology (with ≥ 8 years of experience). Discrepancies regarding adequacy were resolved by consensus. For retrospective verification, the number of portal areas and central venous areas was manually counted using digital pathological slides, and tissue length was measured with a calibrated ruler on formalin-fixed specimens before embedding. The diagnostic capability of TJLB was assessed based on whether the pathological report provided clear etiological information (e.g., rejection, ischemic-hypoxic change, biliary complication) to guide clinical decision-making.

Rejection was categorized and graded in accordance with the Banff Classification of Liver Allograft Pathology (2021 update) [19]: ① Acute cellular rejection (ACR) was defined by portal inflammation, endothelialitis, and bile duct injury, graded as mild (Banff grade 1), moderate (grade 2), or severe (grade 3); ② Antibody-mediated rejection (AMR) was diagnosed based on evidence of donor-specific antibodies (DSA) positivity plus histological features (capillary inflammation, C4d deposition); ③ Chronic rejection (CR) was characterized by ductopenia, arterial occlusion, and fibrosis, graded as early or established per Banff criteria. All rejection diagnoses and gradings were confirmed by two hepatic pathologists with consensus resolution of discrepancies.

Non-specific pathological changes were defined as histological findings that did not meet the diagnostic criteria for rejection, ischemic-hypoxic injury, biliary complications, or other specific etiologies. These changes included minimal lobular inflammation (≤ 2 foci of inflammatory cells per high-power field), slight sinusoidal dilation without necrosis, and no evidence of duct injury, endothelialitis, or fibrosis. Importantly, these findings were not attributed to sampling limitations (all specimens met adequacy criteria: tissue length ≥ 1.0 cm, ≥ 3 portal tracts, no severe artifacts).

Follow-up protocol

All patients were followed up post-TJLB to assess long-term outcomes. Follow-up was conducted via outpatient visits and telephone interviews, with surveillance intervals: 1 month, 3 months, 6 months, and 12 months post-TJLB, then annually thereafter. Outcomes were assessed by: ① Clinical evaluation (symptom inquiry, physical examination); ② Laboratory tests (liver function: AST/ALT, total bilirubin; coagulation function: PT/INR; platelet count); ③ Imaging examinations (abdominal ultrasound to assess graft morphology and exclude vascular/biliary complications) at 3 and 12 months post-TJLB.

Results

TJLB indications

Figure 1 shows the specific indications for patients selecting TJLB, which are fully aligned with the study narrative. The indications include four categories: ascites (12 cases, 54.5%), coagulation abnormalities (9 cases, 40.9%), thrombocytopenia (7 cases, 31.8%), and other contraindications to percutaneous liver biopsy (0 cases, 0.0%, including obesity and need for oral anticoagulants—these were predefined indications but not present in the enrolled cohort). The Venn diagram clearly presents the overlapping distribution of the three main indications: 4 cases (18.2%) with only coagulation abnormalities, 7 cases (31.8%) with only ascites, 6 cases (27.3%) with only thrombocytopenia, 4 cases (18.2%) with both coagulation abnormalities and ascites, 1 case (4.5%) with all three indications, and 0 cases (0.0%) with either coagulation abnormalities combined with thrombocytopenia or ascites combined with thrombocytopenia (totaling 5 cases with overlapping indications). All count and percentage data in the figure have been thoroughly verified to eliminate internal inconsistencies, and the total number of cases is consistent with the cohort size (22 patients), ensuring the reliability of descriptive reporting.

Fig. 1.

Causes in TJLB Patients. Note: TJLB, transjugular liver biopsy

Basic characteristics of patients undergoing TJLB

General characteristics of TJLB patients are shown in Table 1. This study included 22 patients, including 15 male children, with a mean age of 109 ± 56.6 months, with the youngest patient being only 38 months at the time of surgery. All patients had varying degrees of liver dysfunction, with significantly prolonged PT (mean ± SD: 18.6 ± 4.2 s, median [IQR]: 17.8 [16.3–20.5] seconds; longest PT: 34.5 s); international normalized ratio (INR) was significantly increased (mean ± SD: 1.7 ± 0.4, median [IQR]: 1.6 [1.5–1.9]; highest INR: 2.88); overall Child-Pugh score averaged 7.9 ± 1.6 (median [IQR]: 8.0 [7.0–9.0]; highest score: 13 points.

Table 1.

Characteristics of Patients Undergoing TJLB

Characteristic	Value
Age (months)	109 ± 56.6 (38–216)
Male, n (%)	15 (68.2%)
PT (seconds)	18.6 ± 4.2 (14.3–34.5)
INR	1.7 ± 0.4 (1.3–2.88)
Platelet count (×10⁹/L)	68.5 ± 32.4 (32–145)
Total bilirubin (µmol/L)	56.8 ± 42.1 (22.3–186.4)
Child-Pugh score	7.9 ± 1.6 (7–13)

TJLB transjugular liver biopsy, INR international normalized ratio

Sample quality and safety evaluation

Among all patients undergoing TJLB, the average number of punctures was 2.5 ± 0.6, the average sample length was 1.4 ± 0.3 cm, the average number of portal tracts was 5.3 ± 2.3, and the average number of central venous areas was 2.1 ± 1.2. All 22 specimens met the predefined adequacy criteria aligned with the primary diagnostic targets (post-transplant rejection, ischemic-hypoxic changes, biliary complications), with 100% of samples providing sufficient histological detail for definitive pathological diagnosis. Notably, 7 cases (31.8%) with suspected rejection were confirmed by identification of portal tract inflammation, endothelialitis, or ductopenia—findings directly dependent on adequate portal tract sampling—while 5 cases (22.7%) of ischemic-hypoxic changes were diagnosed via centrilobular necrosis or sinusoidal dilation, requiring intact central venous area evaluation. All samples met pathological diagnostic requirements, with both technical success rate and clinical success rate at 100% (95% CI: 85.2%–100.0%). Among 22 patients undergoing TJLB, only 1 case (4.5%, 95% CI: 0.1%–22.8%) experienced postoperative pain requiring local analgesic treatment, with no serious adverse events (0%, 95% CI: 0.0%–15.8%). Details are shown in Table 2.

Table 2.

Sample Quality and Adverse Events in TJLB Patients

Parameter	Value
Number of punctures	2.5 ± 0.6 (2–4)
Sample length (cm)	1.4 ± 0.3 (1.0–2.1)
Number of portal tracts	5.3 ± 2.3 (3–10)
Number of central venous areas	2.1 ± 1.2 (1–5)
Fluoroscopy time (minutes)	3.2 ± 1.1 (1.8–5.6)
Radiation dose (mSv)	0.12 ± 0.05 (0.06–0.23)

*Major adverse events: Adverse events prolonging hospitalization

**Minor adverse events: Adverse events not prolonging hospitalization

Diagnostic value of TJLB

In this study, all patients undergoing TJLB met pathological diagnostic requirements and further achieved clinical diagnostic purposes. Among the 22 patients, 7 cases were diagnosed with rejection (31.8%), including 5 cases of acute cellular rejection (ACR), 1 case of antibody-mediated rejection (AMR), and 1 case of chronic rejection (CR) (detailed in Table 3). The 5 ACR cases were graded per Banff criteria: 3 cases of mild (grade 1), 2 cases of moderate (grade 2); no severe ACR (grade 3) was identified. The AMR case was confirmed by positive DSA (anti-HLA-DR) and C4d deposition in portal capillaries. The CR case was classified as established, with ductopenia (portal tracts with bile ducts < 50%) and periportal fibrosis. Two cases showed non-specific pathological changes, with liver function gradually returning to normal during follow-up (median: 14 months, range: 8–22 months).

Table 3.

Pathological Diagnosis Results

Histological Diagnosis	Number of Cases (n, %)	Management Changes	Follow-up Outcome	Rejection Subtype/Grading (Banff 2021)
Acute cellular rejection	5 (22.7%)	Immunosuppression escalation (tacrolimus adjustment/mycophenolate mofetil + steroids)	Liver function normalized (4–8 weeks)	Mild (grade 1): 3 cases; Moderate (grade 2): 2 cases
Chronic rejection	2 (9.1%)	Switch to sirolimus + low-dose prednisone	Stable graft function (3 months)	DSA-positive (anti-HLA-DR) + C4d deposition
Ischemic-hypoxic changes	5 (22.7%)	Hemodynamic optimization + fluid balance adjustment	Resolution of centrilobular necrosis	Established (ductopenia + periportal fibrosis)
Biliary complications (ischemic-type)	3 (13.6%)	Biliary drainage/stenting + ursodeoxycholic acid	Decreased bilirubin levels
Sinusoidal obstruction syndrome	1 (4.5%)	Volume expansion + low-molecular-weight heparin	Radiological improvement (3 months)
Inflammatory infiltration	2 (9.1%)	Targeted antibiotic/anti-inflammatory therapy	Normalized inflammatory markers
Non-specific changes	2 (9.1%)	No targeted management; close follow-up	Spontaneous liver function normalization

TJLB transjugular liver biopsy

Table 4 summarizes the detailed correlation between each histological diagnosis and the corresponding clinical management adjustments, including specific immunosuppressive drug modifications, interventional procedures, and supportive therapies. Notably, 90.9% (20/22) of patients underwent targeted changes to their clinical management based on TJLB-derived pathological findings, highlighting the procedure’s direct clinical utility in guiding post-transplant care.

Table 4.

Correlation Between TJLB Histological Diagnoses and Clinical Management Changes

Histological Diagnosis	Number of Cases (n, %)	Management Changes
Acute cellular rejection	5 (22.7%)	Escalation of immunosuppression: Tacrolimus dosage adjustment (n = 3) or addition of mycophenolate mofetil (n = 2); pulsed steroid therapy (methylprednisolone, 10 mg/kg/day for 3 days) (n = 2)
Chronic rejection	2 (9.1%)	Switch from tacrolimus to sirolimus; addition of low-dose prednisone (0.5 mg/kg/day)
Ischemic-hypoxic changes	5 (22.7%)	Hemodynamic optimization: Adjustment of vasoactive agents (n = 3) and fluid balance (n = 5); oxygen supplementation (n = 2)
Biliary complications (ischemic-type biliary lesions)	3 (13.6%)	Interventional biliary drainage + stenting (n = 2); ursodeoxycholic acid (15 mg/kg/day) for cholestasis (n = 3)
Sinusoidal obstruction syndrome	1 (4.5%)	Supportive care: Volume expansion; low-molecular-weight heparin anticoagulation (1 mg/kg twice daily)
Inflammatory infiltration	2 (9.1%)	Targeted antibiotic therapy (for concurrent infection, n = 1); anti-inflammatory treatment (n = 1)
Non-specific changes	2 (9.1%)	No targeted management change; close follow-up (liver function normalized spontaneously within 4–8 weeks)
Total with management changes	20 (90.9%)	—
Total without management changes	2 (9.1%)	—

Discussion

In this study, all pediatric TJLB procedures were technically feasible, obtained good histological results, and helped clinicians obtain final clinical diagnoses. The most common TJLB cause was ascites (54.5%), with 9 patients having coagulation abnormalities (40.9%), thrombocytopenia (31.8%), and some patients having overlapping causes. The indications for pediatric TJLB are similar to those in adults [4]. Our study results show good TJLB safety, with no major adverse events occurring (0%, 95% CI: 0.0%–15.8%), and only 1 patient experiencing postoperative pain (4.5%, 95% CI: 0.1%–22.8%). Previous studies have shown that the risk of complications during TJLB is not affected by the number of punctures, severity of coagulopathy, or amount of ascites [16]. The study by Lal BB et al. [20] showed that no factor (INR/platelets/pass number/age/tissue size) could predict the risk of minor or major complications; this study also validated the safety and efficacy of TJLB in pediatric patients. Additionally, this study found no complications related to jugular vein puncture, such as neck hematoma, jugular vein injury/thrombosis, or pneumothorax, which may be related to ultrasound-guided puncture and adequate postoperative compression hemostasis.

In general pediatric liver disease patients, TJLB shows high technical success rates [21]. Unlike adults or general pediatric liver disease patients, hepatic vein or inferior vena cava anatomical variations related to liver transplant surgery and postoperative hepatic vein stenosis increase surgical difficulty. Compared to non-liver transplant patients, in patients receiving left lateral segment split liver transplantation, the liver consists only of segments II and III with smaller volume, further increasing surgical difficulty. According to Clark TW et al., pointing the biopsy needle straight down during TJLB puncture biopsy can obtain more satisfactory liver tissue [22]. Combined with our center’s previous experience, the angle between segment III branch hepatic vein and inferior vena cava is obtuse, making entry into the LABS-100 system easier. Therefore, we all selected segment III hepatic vein for puncture biopsy to increase biopsy tissue volume and pathological diagnostic accuracy. Studies of TJLB in pediatric liver disease patients show that the number of portal tracts is positively correlated with puncture tissue length, and pathologists generally recommend liver biopsy tissue > 15 mm (1.5 cm) to meet diagnostic needs [23, 24]. Among the 22 patients included in this study, the average number of portal tracts was 5.3 ± 2.3, with an average sample length of 1.4 ± 0.3 cm (equivalent to 14 mm), which is comparable to previous research results [15, 20] and exceeds the minimum requirement of ≥ 3 portal tracts for evaluating post-transplant rejection (per Banff Classification of Liver Allograft Pathology [19]). Importantly, while general pathology guidelines emphasize ≥ 10 portal tracts for accurate fibrosis staging [17, 25], this study’s primary diagnostic goal was not fibrosis assessment but identification of acute/chronic rejection, ischemic injury, and biliary complications—conditions that can be reliably diagnosed with fewer portal tracts due to their distinct, focal or zonal histological features. For example, acute cellular rejection is characterized by portal inflammation and endothelialitis, which are detectable even with 3–5 portal tracts [11, 26]; similarly, ischemic-hypoxic changes manifest as centrilobular necrosis, which is evaluable via central venous area sampling. All specimens in this study provided sufficient histological evidence to guide clinical management (e.g., adjusting immunosuppressive therapy for rejection, optimizing perfusion for ischemic injury), confirming that adequacy aligns with the intended diagnostic targets.

Key points for pediatric TJLB procedures: (1) Because children are small and have thin internal jugular veins, and some children have internal jugular vein occlusion due to long-term central venous catheter placement in the right internal jugular vein, all punctures should be performed under ultrasound guidance. (2) Because all children underwent living donor left lateral segment liver transplantation, some children have straight hepatic vein courses, making entry into the LABS system difficult. This can be resolved through the following methods: ① Control breathing through anesthesia to put the child in maximum inspiratory phase, then introduce the liver puncture kit; ② Introduce a 5 F angiographic catheter into the liver puncture kit, first introduce the angiographic catheter into the hepatic vein, then introduce the liver puncture kit along the angiographic catheter; ③ If the above methods still fail, adjust the angle of the liver puncture kit externally, though the disadvantage is increased friction between the biopsy needle and puncture kit, reduced tissue cutting force, and poor puncture tissue integrity. (3) Children’s livers are small, and there are no pediatric-specific biopsy kits. Attention should be paid to the position of the liver puncture kit, with general insertion depth 4–6 cm from the inferior vena cava. Preoperative CT scanning should be performed to observe the distance and direction between hepatic veins and portal vein system and liver edge. Avoid puncturing portal veins or hepatic arteries and puncturing out of liver edge; ultrasound guidance would be even better. (4) There is no consensus on the rotation direction of the liver puncture kit, mainly based on tissue thickness anterior and posterior to the hepatic vein (greater than 3 cm). (5) After biopsy, perform angiography again to observe for contrast extravasation and hepatic artery or other vessel visualization.

In adults or general pediatric liver disease patients, TJLB is most commonly used to diagnose diffuse liver diseases such as viral hepatitis, autoimmune hepatitis, and cirrhosis [17, 23, 24]. TJLB can also be safely used to diagnose rejection after pediatric liver transplantation [15, 27]. Studies have shown that for patients with early acute rejection, portal areas obtained from one or two punctures can meet pathological diagnostic requirements [26]. In our study, we found that pathological results after liver transplantation were mostly related to rejection, including ischemic-hypoxic changes and biliary complications caused by rejection. Additionally, 2 patients showed non-specific changes in pathological examination, with liver function gradually returning to normal during long-term follow-up.

This study has certain limitations, with a small number of pediatric patients. For TJLB, there are only a few domestic reports [28, 29] applying it to adult liver disease biopsy, with no studies confirming its safety and efficacy in domestic pediatric liver transplant patients. Our next step will be to conduct a comparative study of percutaneous liver biopsy and TJLB to further confirm the application value of TJLB after liver transplantation, and to further increase case numbers to optimize data distribution.

Conclusion

TJLB can be safely and effectively applied in patients with abnormal liver function after living donor liver transplantation, especially in patients with various contraindications to percutaneous liver biopsy. TJLB can better help clinicians establish diagnoses.

Authors’ contributions

(1), Xunjin Zeng, Haijun Gao and Guang Chen conceiving and designing the study; (2), Xunjin Zeng, Mengyao Zhang, Mei Wu, Hao Wang and Yilong Jiao collecting the data; (3), Xunjin Zeng, Mengyao Zhang, Mei Wu, Hao Wang and Yilong Jiao analyzing and interpreting the data; (4), Xunjin Zeng writing the manuscript; (5), Haijun Gao and Guang Chen providing critical revisions that are important for the intellectual content; (6), All authors approving the final version of the manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the declaration of Helsinki. This is a retrospective study. After explaining TJLB and its related risks, informed consent was obtained from children’s parents or guardians. Thus, the ethical committee of Tianjin First Central Hospital has exempted ethical review.

Consent for publication

The written informed consent was obtained from children’s parents or guardians.

Competing interests

The authors declare no competing interests.