Link between persistent, unexplained gammaGT elevation and Porto-Sinusoidal Vascular Disorder

BACKGROUND AND AIM: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension (PH). Liver biopsy (LB) is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyl transferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. METHODS: The study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021. RESULTS: 144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only twelve (8.3%) had liver stiffness measurements (LSM) >10 kPa, 7 (4.8%) had ultrasound PH evidence. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%). Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio, OR = 2.60, 95% confidence interval, CI: 1.13-5.99), LSM < 10 kPa (OR = 11.05, 95% CI: 2.16-56.66) and GGT < 200 U/L (OR = 2.69, 95% CI: 1.22-5.98). CONCLUSIONS: PSVD was the main cause of persistent and unexplained elevation of GGT. Male sex, LSM < 10kPa and GGT < 200U/l were associated with PSVD. These findings highlight the role of LB in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation.