∆4-3-oxo-5ß-reductase deficiency: favorable outcome in 16 patients treated with cholic acid.

BACKGROUND: Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3ß-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5ß-reductase (Δ4-3-oxo-R) deficiency. METHODS: Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. RESULTS: First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1-159) and serum liver tests normalized in all within 6-12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1-24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. CONCLUSIONS: Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.

Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children.

PURPOSE: To evaluate the effect of probe-induced abdominal compression of split liver transplants (SLT) in children on 2D-shear wave elastography (SWE) values. MATERIALS AND METHODS: Data from 11 children (4.7 ±â€Š4.8 years) who had undergone SLT and SWE were evaluated retrospectively. Elastograms were obtained with probes placed in an epigastric, midline position on the abdominal wall, with no and slight compression, using convex and linear transducers. For each identically positioned probe and condition, 12 serial elastograms were obtained and the SLT diameter was measured. Liver stiffness and degree of SLT compression were compared. RESULTS: Slight probe pressure resulted in SLT compression, with a shorter distance between the cutis and the posterior margin of the liver transplant than in the measurement with no pressure (curved array, 5.0 ±â€Š1.1 vs. 5.9 ±â€Š1.3 cm, mean compression 15 %±â€Š8 %; linear array, 4.7 ±â€Š0.9 vs. 5.3 ±â€Š1.0 cm, mean compression 12 %±â€Š8 %; both p < 0.0001). The median liver stiffness was significantly greater with slight pressure than with no pressure (curved transducer, 13.38 ±â€Š3.0 vs. 7.02 ±â€Š1.7 kPa, p < 0.0001; linear transducer, 18.53 ±â€Š7.1 vs. 9.03 ±â€Š1.5 kPa, p = 0.0003). CONCLUSION: Slight abdominal compression can significantly increase SWE values in children with left-lateral SLT. To obtain meaningful results and reduce operator dependency in free-hand examinations, probe pressure must be controlled carefully. KEY POINTS: · Probe-induced compression can increase elastography values in split liver transplants in children. · In free-hand examination, probe pressure must be controlled carefully. · Pressure loading can be determined indirectly by the anteroposterior transplant diameter. CITATION FORMAT: · Groth M, Fischer L, Herden U et al. Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children. Fortschr Röntgenstr 2023; 195: 905 - 912.

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation.

BACKGROUND: In a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort. AIM: To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients. METHODS: We performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication. RESULTS: DSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development. CONCLUSION: DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.

Tissue inhibitor of metalloproteinase 1 and AST-to-Platelet Ratio Index as noninvasive biomarkers predict allograft fibrosis after pediatric liver transplantation.

BACKGROUND: Assessing liver fibrosis in patients after liver transplantation is still largely dependent on liver biopsy. Especially in children, noninvasive methods are of utmost importance. We evaluated tissue inhibitor of metalloproteinase 1 (TIMP1) and AST-to-Platelet Ratio Index (APRI) and their potential as serum biomarkers to predict liver allograft fibrosis (LAF) in a pediatric cohort. METHODS: In this retrospective, observational study, we analyzed 91 protocol liver biopsy specimens from 73 children after pediatric liver transplantation (PLT) and compared histological stage of liver fibrosis using LAF Score (LAFSc) and Ishak Score (IshakSc) to TIMP1-serum concentration and APRI using ROC analysis. RESULTS: In our cohort, TIMP1 and APRI reliably predict LAF. Depending on the histological scoring system, cutoff values for TIMP1 were 328 ng/mL (IshakSc ≥ IV) and 351 ng/mL (LAFSc ≥ 5) with AUC of 0.86 and 0.98. The cutoff for APRI was 0.8 with AUC of 0.87 (IshakSc ≥ IV) and 0.94 (LAFSc ≥ 5). Using LAFSc, TIMP1 and APRI showed excellent diagnostic accuracy to detect severe LAF (LAFSc ≥ 5) with PPV of ≥ 90% and NPV of 100%. CONCLUSION: TIMP1 and APRI are accurate biomarkers to predict severe LAF in children. The use of TIMP1 and APRI will not replace but complement liver biopsies after PLT to further improve our understanding of each individual patient.