Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

BACKGROUND AND AIMPorto-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.METHODSThe study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021.RESULTS144 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).CONCLUSIONSPSVD 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.IMPACT AND IMPLICATIONSIn outpatient settings, it is common to encounter subjects with persistent and unexplained GGT elevation. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder (PSVD) among these subjects when they undergo liver biopsy. Male sex, liver stiffness measurement (LSM) < 10 kPa, and GGT < 200 IU/L predict this histological finding.These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension (PH). Additionally, the data may encourage further studies in the field of PSVD, particularly to define its clinical evolution in patients without signs of PH at diagnosis.