Ali S, Nisar A, Zhang A, Nagamani S, Aceves-Ewing NM, Rawls B, Quan T, Enns G, Goss J, Leung DH, Shneider BL, Jain S, Hazard FK, Schady D, Burrage LC. Prevalence of fibrosis in hepatic explants and biopsies from individuals with urea cycle disorders. Mol Genet Metab. 2025 Aug;145(4):109175. doi: 10.1016/j.ymgme.2025.109175. Epub 2025 Jun 13. PMID: 40540899; PMCID: PMC12573283.
In this study, researchers looked at liver samples from 66 people with different types of UCD who had either a liver transplant or a biopsy. The goal was to find out how often liver scarring (fibrosis) and fat buildup (steatosis) happen in these patients. The group included children and adults, from newborns to age 41, and covered several UCD types like OTCD, ASLD, ASS1D, CPS1D, and ARG1D. Researchers also checked if routine blood tests or imaging could predict liver problems. This is the first large study to measure these issues in UCD patients in a systematic way.
Key Takeaways
Fibrosis is Common in ASLD: About 23% of all patients had significant liver scarring, but in ASLD, it was much higher—80% (12 out of 15 people). This included children as young as 8 months old, showing that scarring can start early.
Other UCD Types Show Lower Rates: Only 10% of males with OTCD and 20% of those with ARG1D had significant fibrosis. No cases of severe scarring were found in ASS1D or CPS1D patients.
Fat in the Liver (Steatosis): Fat buildup was seen in 18% of patients. It was most common in ASLD and ARG1D and often appeared alongside fibrosis. Severe fat buildup was rare.
Routine Tests Did Not Predict Scarring: Blood tests like AST and ALT and imaging like ultrasound did not reliably show who had serious liver scarring. Some patients with severe fibrosis had only mild lab changes.
No Tumors Found, but Glycogen Was High: No liver tumors were detected in any sample. Almost all samples showed extra glycogen in the liver cells, which is typical in UCD.
Why This Matters
This research shows that liver problems are more likely to develop in the ASLD population, and may start very early. Knowing this helps patients and doctors understand the importance of monitoring liver health as part of UCD care.
Ali S, Nisar A, Zhang A, Nagamani S, Aceves-Ewing NM, Rawls B, Quan T, Enns G, Goss J, Leung DH, Shneider BL, Jain S, Hazard FK, Schady D, Burrage LC. Prevalence of fibrosis in hepatic explants and biopsies from individuals with urea cycle disorders. Mol Genet Metab. 2025 Aug;145(4):109175. doi: 10.1016/j.ymgme.2025.109175. Epub 2025 Jun 13. PMID: 40540899; PMCID: PMC12573283.
