Research

10 pages, 1030 KiB

Open AccessArticle

Quality of Life Outcomes for Patients Who Underwent Conventional Resection and Liver Transplantation for Locally Advanced Hepatoblastoma

by Zishaan Farooqui, Michael Johnston, Emily Schepers, Nathalie Brewer, Stephen Hartman, Todd Jenkins, Alexander Bondoc, Ahna Pai, James Geller and Gregory M. Tiao

Children 2023, 10(5), 890; https://doi.org/10.3390/children10050890 - 16 May 2023

Cited by 1 | Viewed by 1225

Abstract

Hepatoblastoma is the most common malignant liver tumor of childhood, with liver transplant and extended resection used as surgical treatments for locally advanced tumors. Although each approach has well-described post-operative complications, quality-of-life outcomes have not been described following the two interventions. Long-term pediatric [...] Read more.

Hepatoblastoma is the most common malignant liver tumor of childhood, with liver transplant and extended resection used as surgical treatments for locally advanced tumors. Although each approach has well-described post-operative complications, quality-of-life outcomes have not been described following the two interventions. Long-term pediatric survivors of hepatoblastoma who underwent conventional liver resection or liver transplantation at a single institution from January 2000–December 2013 were recruited to complete quality-of-life surveys. Survey responses for the Pediatric Quality of Life Generic Core 4.0 (PedsQL, n = 30 patient and n = 31 parent surveys) and Pediatric Quality of Life Cancer Module 3.0 (PedsQL-Cancer, n = 29 patient and n = 31 parent surveys) were collected from patients and parents. The mean total patient-reported PedsQL score was 73.7, and the parent-reported score was 73.9. There were no significant differences in scores on the PedsQL between patients who underwent resection compared to those who underwent transplantation (p > 0.05 for all comparisons). On the PedsQL-Cancer module, procedural anxiety scores were significantly lower for patients who underwent resection as compared to transplant (M = 33.47 points less, CI [−60.41, −6.53], p-value 0.017). This cross-sectional study demonstrates that quality of life outcomes are overall similar among patients receiving transplants and resections. Patients who received a resection reported worse procedural anxiety. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

12 pages, 1314 KiB

Open AccessArticle

Identifying the Aetiology of Acute Liver Failure Is Crucial to Impact Positively on Outcome

by Angelo Di Giorgio, Silvia Gamba, Naire Sansotta, Emanuele Nicastro, Michele Colledan and Lorenzo D’Antiga

Children 2023, 10(4), 733; https://doi.org/10.3390/children10040733 - 16 Apr 2023

Cited by 3 | Viewed by 1720

Abstract

Management of children with acute liver failure is challenging. In this retrospective study, paediatric patients diagnosed with ALF at our centre, in the last 26 years, were divided into two groups (G1 = diagnosed from 1997 to 2009; G2 = from 2010 to [...] Read more.

Management of children with acute liver failure is challenging. In this retrospective study, paediatric patients diagnosed with ALF at our centre, in the last 26 years, were divided into two groups (G1 = diagnosed from 1997 to 2009; G2 = from 2010 to 2022) and compared to see whether they differed with regard to aetiologies, need for liver transplantation (LT), and outcome. A total of 90 children (median age 4.6 years, range 1.2–10.4; M/F = 43/47) were diagnosed with ALF, by autoimmune hepatitis (AIH) in 16 (18%), paracetamol overdose in 10 (11%), Wilson disease in 8 (9%), and other causes in 19 (21%); 37 (41%) had indeterminate ALF (ID-ALF). Comparing the two periods, the clinical features, aetiologies, and median peak values of INR [3.8 (2.9–4.8) in G1 vs. 3.2 (2.4–4.8) in G2] were similar (p > 0.05). The percentage of ID-ALF tended to be higher in G1 compared to G2 (50% vs. 32% in G2, p = 0.09). The overall percentage of patients diagnosed with Wilson disease, inborn errors of metabolism, neonatal hemochromatosis or viral infection was higher in G2 (34% vs. 13% in G1, p = 0.02). A total of 21/90 patients (23%; 5 with indeterminate ALF) were treated with steroids; 12 (14%) required extracorporeal liver support treatment. The need for LT was significantly higher in G1 compared to G2 (56% vs. 34%; p = 0.032). Among 37 children with ID-ALF, 6 (16%) developed aplastic anaemia (all in G2, p < 0.001). The survival rate at last follow up was of 94%. On a KM curve, the transplant-free survival was lower in G1 compared to G2. In conclusion, we report a lower need for LT in children diagnosed with PALF during the most recent period compared to the first era. This suggests improvements over time in the diagnosis and management of children with PALF. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

11 pages, 792 KiB

Open AccessArticle

Experience with the mTOR Inhibitor Everolimus in Pediatric Liver Graft Recipients

by Mathis Wehming, Dorothée Krebs-Schmitt, Andrea Briem-Richter, Bianca Hegen, Florian Brinkert, Lutz Fischer and Enke Grabhorn

Children 2023, 10(2), 367; https://doi.org/10.3390/children10020367 - 13 Feb 2023

Cited by 1 | Viewed by 1332

Abstract

Introduction: Immunosuppression after pediatric liver transplantation remains a major challenge. MTOR inhibitors provide a promising therapeutic approach in combination with reduced CNI after transplantation. However, there are still few data regarding their use in children. Patients: We analyzed 37 patients with a median [...] Read more.

Introduction: Immunosuppression after pediatric liver transplantation remains a major challenge. MTOR inhibitors provide a promising therapeutic approach in combination with reduced CNI after transplantation. However, there are still few data regarding their use in children. Patients: We analyzed 37 patients with a median age of 10 years, who received Everolimus for one or more of the following indications: I = chronic graft dysfunction (n = 22); II = progressive renal impairment (n = 5); III = non-tolerable side effects with previous immunosuppressive medication (n = 6); and IV = malignancies (n = 10). The median follow-up time was 36 months. Results: Patient survival was 97%, and graft survival 84%, respectively. Stabilization of graft function was observed in 59% in subgroup 1, with 18.2% ultimately requiring retransplantation. No patient in subgroup IV developed recurrence of his primary tumor or PTLD by the endpoint of the study. Side effects were observed in 67.5% of the study patients, with infections being the most frequent (n = 20; 54.1%). There were no relevant effects on growth and development. Conclusion: Everolimus seems to be a treatment option in selected pediatric liver graft recipients for whom other regimens are not suitable. Overall, the efficacy was good and the side effect profile appeared to be acceptable. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

15 pages, 582 KiB

Open AccessArticle

Long-Term Outcome Following Liver Transplantation for Primary Hepatic Tumors—A Single Centre Observational Study over 40 Years

by Christoph Leiskau, Norman Junge, Frauke E. Mutschler, Tobias Laue, Johanna Ohlendorf, Nicolas Richter, Florian W. R. Vondran, Eva-Doreen Pfister and Ulrich Baumann

Children 2023, 10(2), 202; https://doi.org/10.3390/children10020202 - 22 Jan 2023

Cited by 2 | Viewed by 1462

Abstract

The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe [...] Read more.

The incidence of pediatric liver tumors in general has been rising over the last years and so is the number of children undergoing liver transplantation for this indication. To contribute to the ongoing improvement of pre- and post-transplant care, we aim to describe outcome and risk factors in our patient cohort. We have compared characteristics and outcome for patients transplanted for hepatoblastoma to other liver malignancies in our center between 1983 and 2022 and analysed influential factors on tumor recurrence and mortality using nominal logistic regression analysis. Of 39 children (16 f) who had transplants for liver malignancy, 31 were diagnosed with hepatoblastoma. The proportion of malignant tumors in the transplant cohort rose from 1.9% (1983–1992) to 9.1% in the current decade (p < 0.0001). Hepatoblastoma patients were transplanted at a younger age and were more likely to have tumor extent beyond the liver. Post-transplant bile flow impairment requiring intervention was significantly higher compared to our total cohort (48 vs. 24%, p > 0.0001). Hearing loss was a common side effect of ototoxic chemotherapy in hepatoblastoma patients (48%). The most common maintenance immunosuppression were mTor-inhibitors. Risk factors for tumor recurrence in patients with hepatoblastoma were higher AFP before transplant (AFP_pre-LTX), a low ratio of AFP_max to AFP_pre-LTX and salvage transplantation. Liver malignancies represent a rising number of indications for liver transplantation in childhood. Primary tumor resection can spare a liver transplant with all its long-term complications, but in case of tumor recurrence, transplantation might have inferior outcome. The rate of acute biopsy-proven rejections and biliary complications in comparison to our total transplant cohort needs further investigations. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

11 pages, 1062 KiB

Open AccessArticle

Diagnosing Acute Cellular Rejection after Paediatric Liver Transplantation—Is There Room for Interleukin Profiles?

by Imeke Goldschmidt, Evgeny Chichelnitskiy, Nicole Rübsamen, Veronika K. Jaeger, André Karch, Lorenzo D’Antiga, Angelo Di Giorgio, Emanuele Nicastro, Deirdre A. Kelly, Valerie McLin, Simona Korff, Dominique Debray, Muriel Girard, Loreto Hierro, Maja Klaudel-Dreszler, Malgorzata Markiewicz-Kijewska, Christine Falk and Ulrich Baumann

Children 2023, 10(1), 128; https://doi.org/10.3390/children10010128 - 07 Jan 2023

Cited by 1 | Viewed by 1498

Abstract

Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in [...] Read more.

Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR. Methods: A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7–427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5–17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis. Results: TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7. Conclusion: Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

14 pages, 1256 KiB

Open AccessArticle

Intra-Abdominal Hypertension and Compartment Syndrome after Pediatric Liver Transplantation: Incidence, Risk Factors and Outcome

by Norman Junge, Annika Artmann, Nicolas Richter, Florian W. R. Vondran, Dietmar Böthig, Michael Sasse, Harald Köditz, Ulrich Baumann, Philipp Beerbaum and Torsten Kaussen

Children 2022, 9(12), 1993; https://doi.org/10.3390/children9121993 - 18 Dec 2022

Viewed by 1493

Abstract

In pediatric liver transplantation (pLT), the risk for the manifestation and relevance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is high. This observational study aimed to evaluate the incidence, relevance and risk factors for IAH and ACS by monitoring the intra-abdominal [...] Read more.

In pediatric liver transplantation (pLT), the risk for the manifestation and relevance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is high. This observational study aimed to evaluate the incidence, relevance and risk factors for IAH and ACS by monitoring the intra-abdominal pressure (IAP), macro- and microcirculation (near-infrared spectroscopy (NIRS)), clinical and laboratory status and outcomes of 27 patients (16 female) after pLT (median age at pLT 35 months). Of the patients, 85% developed an elevated IAP, most of them mild. However, 17% achieved IAH° 3, 13% achieved IAH° 4 and 63% developed ACS. A multiple linear regression analysis identified aortal hepatic artery anastomosis and cold ischemia time (CIT) as risk factors for increased IAP and longer CIT and staged abdominal wall closure for ACS. ACS patients had significantly longer mechanical ventilation (p = 0.004) and LOS-PICU (p = 0.003). No significant correlation between NIRS or biliary complications and IAH or ACS could be shown. IAH and ACS after pLT were frequent. NIRS or grade of IAH alone should not be used for monitoring. A longer CIT is an important risk factor for higher IAP and ACS. Therefore, approaches such as the ex vivo machine perfusion of donor organs, reducing CIT effects on them, have great potential. Our study provides important basics for studying such approaches. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

9 pages, 759 KiB

Open AccessArticle

Hepatitis A Immunity and Paediatric Liver Transplantation—A Single-Centre Analysis

by Tobias Laue, Johanna Ohlendorf, Christoph Leiskau and Ulrich Baumann

Children 2022, 9(12), 1953; https://doi.org/10.3390/children9121953 - 12 Dec 2022

Viewed by 1327

Abstract

Following paediatric solid organ liver transplantation, risk of infection is high, both in the short and long term. Even though an infection with hepatitis A virus (HAV) is often asymptomatic and self-limited in children, some case studies describe severe cases leading to death. [...] Read more.

Following paediatric solid organ liver transplantation, risk of infection is high, both in the short and long term. Even though an infection with hepatitis A virus (HAV) is often asymptomatic and self-limited in children, some case studies describe severe cases leading to death. Vaccinations offer simple, safe and cheap protection. However, data on vaccination rates against hepatitis A in children with liver disease are scarce. Moreover, the vaccine is only approved from the age of one year old. At the same time, up to 30% of children with liver disease are transplanted within the first year of life, so the window of opportunity for vaccination is limited. This retrospective, observational, single-centre study examines the HAV immunity in paediatric liver transplant recipients before and after the first year of transplantation. Vaccination records of 229 of 279 (82.1%) children transplanted between January 2003 and June 2021 were analysed. Of 139 eligible children aged ≥ 1 year old, only 58 (41.7%) were vaccinated at least with one HAV dose prior to transplantation. In addition, seven patients received the vaccine below one year of age. After one or two doses, 38.5% or 90.6% of 65 patients were anti-HAV-IgG positive, respectively. This percentage remained stable up to the first annual check-up. For children vaccinated only once, a shorter interval from vaccination to transplantation is a risk factor for lack of immunity. Thus, HAV immunisation should be started earlier in liver transplant candidates to improve immunity in this high-risk group. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

9 pages, 411 KiB

Open AccessFeature PaperArticle

Accumulation of Postoperative Unexpected Events Assessed by the Comprehensive Complication Index^® as Prognostic Outcome Parameters for Kasai Procedure

by Omid Madadi-Sanjani, Julia Brendel, Marie Uecker, Eva-Doreen Pfister, Ulrich Baumann, Johanna Ohlendorf and Joachim F. Kuebler

Children 2022, 9(10), 1590; https://doi.org/10.3390/children9101590 - 20 Oct 2022

Viewed by 1332

Abstract

Introduction The Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI^®) is a validated metric in adult surgery for the analysis of complications and morbidity in surgical patients. We [...] Read more.

Introduction The Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI^®) is a validated metric in adult surgery for the analysis of complications and morbidity in surgical patients. We aimed to analyze the CCI^® for the first time in BA infants and to correlate its association with outcomes. Material and Methods We conducted a retrospective review of medical records of infants with type III BA undergoing the Kasai procedure between January 2011 and December 2021 at our institution. All unexpected events were ranked according to the Clavien–Dindo classification, and the CCI^® per patient was subsequently calculated. Clavien–Dindo grades, individual events, CCI^®, and total event numbers per patient were correlated with one- and two-year outcomes post-surgery. Results A total of 131 events were identified in 101 patients (ranging 0–11 per patient). Forty-four Grade I (33.6%), 67 Grade II (51.1%), 18 Grade III (13.7%), and two sentinel events [>Grade IV] (1.5%) were documented according to Clavien–Dindo, including one death in a cardiac-associated BA patient. None of the complications significantly correlated with a poor outcome. Sixty-three (62.4%) CCI^® scores were calculated (range 0–100). The mean CCI^® score during the in-patient treatment post-surgery was significantly higher in patients with a poorer outcome than patients with native liver survival at one- and two-year follow-up (22.7 ± 21.7 vs. 13.2 ± 18.1; p = 0.02). Conclusion Not the severity of complications, but the accumulation of numerous events related to Kasai procedure were associated with a poorer outcome. Therefore, the CCI^® is an excellent instrument for the postoperative morbidity assessment of BA patients. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

12 pages, 890 KiB

Open AccessArticle

Long-Term Survival and Kidney Function in Pediatric Patients Following Liver Transplantation: A 15-Year Retrospective Cohort Study

by Rin Son, Sung Yun Suh, Yoon Sook Cho and Sandy Jeong Rhie

Children 2022, 9(10), 1544; https://doi.org/10.3390/children9101544 - 12 Oct 2022

Viewed by 1391

Abstract

Long-term preservation of kidney function after liver transplantation (LT) has not been well studied. We thus evaluated the rates of kidney function preservation and long-term survival after pediatric LT. We also investigated the risk factors associated with the progression of chronic kidney disease [...] Read more.

Long-term preservation of kidney function after liver transplantation (LT) has not been well studied. We thus evaluated the rates of kidney function preservation and long-term survival after pediatric LT. We also investigated the risk factors associated with the progression of chronic kidney disease (CKD). We conducted a retrospective study of 184 pediatric patients who had undergone LT from 2003 to 2018 at a university hospital. We collected demographics, primary indications for LT, liver disease scores, renal function test results, immunosuppressive drug prescriptions, and diagnosis of post-LT complications. The 15-year survival rate was 90.8%. Furthermore, the rate of kidney function preservation at 14 years post-LT in patients at high risk of renal disease was 79.3%, and that in those with less risk of kidney diseases was 96.0%. Arterial hypertension was an independent risk factor associated with CKD progression. However, when arterial hypertension was excluded, the use of cyclosporine and liver disease with renal involvement were risk factors for CKD progression. We found that kidney function after pediatric LT was well preserved. We encourage the early detection of underlying kidney involvement, routine monitoring of renal function for high-risk patients, active control of hypertension, and appropriate immunosuppressive regimens for pediatric patients with LT. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Figure 1

12 pages, 829 KiB

Open AccessArticle

Ultrasound Shear Wave Elastography, Shear Wave Dispersion and Attenuation Imaging of Pediatric Liver Disease with Histological Correlation

by Ivan Cetinic, Charlotte de Lange, Yvonne Simrén, Nils Ekvall, Maja Östling, Liselotte Stén, Håkan Boström, Kerstin Lagerstrand and Hanna Hebelka

Children 2022, 9(5), 692; https://doi.org/10.3390/children9050692 - 09 May 2022

Cited by 8 | Viewed by 2210

Abstract

Aim: To evaluate the feasibility of multiple ultrasound markers for the non-invasive characterization of fibrosis, inflammation and steatosis in the liver in pediatric patients. Materials and methods: The quantitative ultrasound measures shear wave elastography (SWE), shear wave dispersion (SWD) and attenuation imaging (ATI) [...] Read more.

Aim: To evaluate the feasibility of multiple ultrasound markers for the non-invasive characterization of fibrosis, inflammation and steatosis in the liver in pediatric patients. Materials and methods: The quantitative ultrasound measures shear wave elastography (SWE), shear wave dispersion (SWD) and attenuation imaging (ATI) were compared and correlated with percutaneous liver biopsies and corresponding measures in a control cohort. Results: The median age of the 32 patients was 12.1 years (range 0.1–17.9), and that of the 15 controls was 11.8 years (range: 2.6–16.6). Results: There was a significant difference in SWE values between histologic grades of fibrosis (p = 0.003), with a positive correlation according to the grade (r = 0.7; p < 0.0001). Overall, a difference in SWD values between grades of inflammation was found (p = 0.009) but with a lack of correlation (r = 0.1; p = 0.67). Comparing inflammation grades 0–1 (median:13.6 m/s kHz [min; max; 8.4; 17.5]) versus grades 2–3 (16.3 m/s kHz [14.6; 24.2]) showed significant differences between the groups (p = 0.003). In the 30 individuals with a steatosis score of 0, ATI was measured in 23 cases with a median value of 0.56 dB/cm/MHz. Conclusion: Comprehensive ultrasound analysis was feasible to apply in children and has the potential to reflect the various components of liver affection non-invasively. Larger studies are necessary to conclude to what extent these image-based markers can classify the grade of fibrosis, inflammation and steatosis. Full article

(This article belongs to the Special Issue Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Pediatric Hepatology and Liver Transplantation—How Can We Further Improve?

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (10 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI