Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it?

J Hepatol. 2022 Feb;76(2):458-463. doi: 10.1016/j.jhep.2021.09.029. Epub 2021 Oct 2.


Clinical and experimental advances related to the detection, magnitude and pathobiology of subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD), primarily observed in the presence of non-alcoholic steatohepatitis (NASH), prompt us to revisit current disease paradigms. Hepatic venous pressure gradient (HVPG) has been reported to underestimate portal pressure in NASH-related cirrhosis, while inaccuracy is more likely in non-cirrhotic livers, indicating a potential need for new and preferably non-invasive methods of measurement. Although clinically significant portal hypertension (HVPG ≥10 mmHg) retains its prognostic significance in NASH, subclinical portal hypertension (HVPG 6.0-9.5 mmHg) has been repeatedly detected in patients with NAFLD in the absence of cirrhosis or even significant fibrosis whereas the impact of these findings on disease outcomes remains unclear. Mechanocrine signalling pathways in various types of liver cell reveal a molecular basis for the adverse effects of subclinical portal hypertension and suggest a bidirectional relationship between portal pressure and fibrosis. These findings may guide efforts to improve risk assessment and identify novel therapeutic targets in NAFLD.

Keywords: hepatic vein catheterization; hepatic vein pressure gradient; mechanocrine signaling; nonalcoholic fatty liver disease; portal pressure gradient.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypertension, Portal / diagnosis*
  • Hypertension, Portal / physiopathology
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Prognosis
  • Severity of Illness Index
  • Weights and Measures / instrumentation*
  • Weights and Measures / standards