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The field of portal hypertension (PHT) faces many current challenges, regarding the variations in the etiology of cirrhosis. It also changes in the natural history of advanced chronic liver disease, once the etiological factors have been checked (i.e. patients’ sustained virological response after receiving antiviral treatment for HCV). This group of patients remain at high risk of developing PHT complications, but should we manage them differentially? Additionally, an improvement in diagnostic tools and awareness in the medical community have led to an increase in the identification of other etiologies of portal hypertension, other than cirrhosis, requiring specific approaches.