Background & AimsEtiologic factor removal (ER) drives recompensation and improves portal hypertension in cirrhosis. Esophageal varices (EV) and portosystemic shunts (PSS) have been found in patients despite hepatic vein pressure gradient (HVPG) dropping below 10mmHg after ER, questioning HVPG accuracy in reflecting true portal pressure in the setting of ER. We aim to evaluate the correlation of HVPG with direct portal pressure (DPP) in patients with persistence of EV after ER despite HVPG < 10mmHg. MethodsBicentric "proof of concept" study evaluating HVPG and ultrasound guided percutaneous DPP in patients with HCV or alcohol related cirrhosis with persistent varices, and HVPG<10mmHg after at least 5 years of ER. Results7 patients with HCV and 3 with alcohol-related cirrhosis with persistent varices, and HVPG <10mmHg after at least 5 years of ER were included. At evaluation, all patients had a patent portal vein and were compensated. Median platelet counts were 129.5 (95-145) 10ˆ9/ml, and LSM 16.15 (14.4-22.3) kPa. In 5 patients, EV remained the same size (2 large and 3 small), and 5 downsized to small after ER. Wedge hepatic vein pressure [Median 19 (16.5-20) mmHg] and portal pressure [Median 18 (15-19.5) mmHg] had an excellent correlation (R =0.93, p<0.0001). Portal pressure gradient (PPG) confirmed the absence of clinically significant portal hypertension as identified by HVPG across all the patients. ConclusionHVPG accurately reflects PPG in the context of HCV and alcohol-related cirrhosis regression. After ER, EV may persist despite HVPG <10mmHg. The benefit of prophylaxis in patients with EV and HVPG <10mmHg is unknown. Future studies with clinical endpoints are needed to validate our findings. Impact and implicationsDespite a favorable evolution after removal of the etiological factor, varices persist in some patients and there is a lack of concise guidelines for the evaluation and management of portal hypertension in this population. Our research underscores the persistence of varices in absence of clinically significant portal hypertension, and significantly, demonstrates the accuracy of hepatic venous pressure gradient (HVPG) in reflecting portal vein pressure in this specific patient group. These findings emphasize the crucial role of HVPG in the assessment of portal hypertension after etiological factor removal and lay the groundwork for further investigation into clinical outcomes and the necessity of non-selective beta-blockers (NSBB) in individuals with persistent varices after the removal of etiologic factor.