A functional view of the progression of liver disease would hold that etiologic agents of disease initiate damage and injury, which is sequentially followed by inflammation, fibrosis, and hepatic impairment with concomitant alteration of the portal circulation. DSI encompasses changes in both hepatic function and the altered portal circulation and is a proximal surrogate for liver-related outcomes. Because DSI and HVPG both focus on changes to the portal circulation, DSI could be viewed as potentially a noninvasive alternative to HVPG. Unlike HVPG and MELD, which only measure impairment and track changes in advanced stages of disease, DSI measures hepatic impairment over the entire spectrum of disease from F0 to F4 and through clinical stages of cirrhosis.