Journal of Internal Medicine Concepts & Practice >
Metabolic-associated non-cirrhotic portal hypertension: from preliminary recognition to precision management
Received date: 2026-02-27
Revised date: 2026-03-04
Accepted date: 2026-04-14
Online published: 2026-06-15
Copyright
Portal hypertension has often been regarded as a hallmark manifestation of cirrhosis, characterized by elevated pressure in the portal venous system and the establishment of collateral circulation. However, non-cirrhotic portal hypertension (NCPH) is not rare in clinical practice. Based on the different underlying pathogenetic mechanisms, NCPH can be classified into pre-hepatic, hepatic, and post-hepatic types, whose clinical features and management strategies differ significantly from those of cirrhosis-related portal hypertension. In recent years, a series of studies have demonstrated that metabolic associated fatty liver disease can induce liver sinusoidal endothelial dysfunction and intrahepatic vascular alterations, leading to a significant increase in portal pressure before the development of cirrhosis, thereby becoming an important cause of NCPH. This article summarizes the pathogenesis, clinical characteristics, diagnosis and differential diagnosis, therapeutic and management strategies, as well as future research directions, etc., aiming to enhance clinical physicians’ awareness of this disease and precision management capabilities for this disease.
ZHANG Lu , WANG Jian , LIN Yong . Metabolic-associated non-cirrhotic portal hypertension: from preliminary recognition to precision management[J]. Journal of Internal Medicine Concepts & Practice, 2026 , 21(02) : 171 -175 . DOI: 10.16138/j.1673-6087.2026.02.11
| [1] | Simonetto DA, Liu M, Kamath PS. Portal hypertension and related complications: diagnosis and management[J]. Mayo Clin Proc,2019,94(4):714-726. |
| [2] | 何福亮, 马琳, 李悦榕, 等. 非肝硬化性门脉高压的临床诊断[J]. 实用肝脏病杂志,2022,25(1):1-4. |
| He FL, Ma L, Li YR, et al. Non-cirrhotic portal hypertension: the highlight of its diagnosis[J]. J Prac Hepatol,2022,25(1):1-4. | |
| [3] | 张博静, 韩国宏, 樊代明. 非肝硬化性门静脉高压症的研究现状[J]. 临床肝胆病杂志,2016,32(2):245-249. |
| Zhang BJ, Han GH, Fan DM. Research advances in non-cirrhotic portal hypertension[J]. J Clin Hepatol,2016,32(2):245-249. | |
| [4] | De Gottardi A, Rautou PE, Schouten J, et al. Porto-sinusoidal vascular disease: proposal and description of a novel entity[J]. Lancet Gastroenterol Hepatol,2019,4(5):399-411. |
| [5] | Shukla A, Rockey DC, Kamath PS, et al. Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management[J]. Hepatol Int,2024,18(6):1684-1711. |
| [6] | Ryou M, Stylopoulos N, Baffy G. Nonalcoholic fatty liver disease and portal hypertension[J]. Explor Med,2020,1:149-169. |
| [7] | Hirayama AB, Taliberti IB, Oliveira CPMS, et al. Lipotoxicity plays a key role in the development of angiogenesis and microcirculatory modulation in MASLD spectrum[J]. Arq Gastroenterol,2025,62:e25053. |
| [8] | Seifalian AM, Chidambaram V, Rolles K, et al. In vivo demonstration of impaired microcirculation in steatotic human liver grafts[J]. Liver Transpl Surg,1998,4(1):71-77. |
| [9] | Seifalian AM, Piasecki C, Agarwal A, et al. The effect of graded steatosis on flow in the hepatic parenchymal microcirculation[J]. Transplantation,1999,68(6):780-784. |
| [10] | McCuskey RS, Ito Y, Robertson GR, et al. Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice[J]. Hepatology,2004,40(2):386-393. |
| [11] | Wang XK, Peng ZG. Targeting liver sinusoidal endothelial cells: an attractive therapeutic strategy to control inflammation in nonalcoholic fatty liver disease[J]. Front Pharmacol,2021,12:655557. |
| [12] | Minciuna I, Taru MG, Procopet B, et al. The interplay between liver sinusoidal endothelial cells, platelets, and neutrophil extracellular traps in the development and progression of metabolic dysfunction-associated steatotic liver disease[J]. J Clin Med,2024,13(5):1406. |
| [13] | Baffy G, Bosch J. Overlooked subclinical portal hypertension in non-cirrhotic NAFLD:is it real and how to measure it?[J]. J Hepatol,2022,76(2):458-463. |
| [14] | Hilscher MB, Sehrawat T, Arab JP, et al. Mechanical stretch increases expression of cxcl1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthrombi, and promote portal hypertension[J]. Gastroenterology,2019,157(1):193-209. |
| [15] | Sun X, Harris EN. New aspects of hepatic endothelial cells in physiology and nonalcoholic fatty liver disease[J]. Am J Physiol Cell Physiol,2020,318(6):C1200-C1213. |
| [16] | Zadorozhna M, Di Gioia S, Conese M, et al. Neovascularization is a key feature of liver fibrosis progression: anti-angiogenesis as an innovative way of liver fibrosis treatment[J]. Mol Biol Rep,2020,47(3):2279-2288. |
| [17] | Ucar F, Sezer S, Erdogan S, et al. The relationship between oxidative stress and nonalcoholic fatty liver disease: its effects on the development of nonalcoholic steatohepatitis[J]. Redox Rep,2013,18(4):127-133. |
| [18] | Li Y, Yang P, Ye J, et al. Updated mechanisms of MASLD pathogenesis [J/OL]. Lipids Health Dis, 2024, 23(1):117[2024-04-22]. https://link.springer.com/article/10.1186/s12944-024-02108-x. |
| [19] | Iwakiri Y, Trebicka J. Portal hypertension in cirrhosis: pathophysiological mechanisms and therapy[J]. JHEP Rep,2021,3(4):100316. |
| [20] | Zhao F, Ding J, Cui J, et al. Platelet activation is upregulated in cirrhotic patients with portal vein thrombosis[J]. Thromb Haemost,2024,124(8):739-752. |
| [21] | Baffy G. Potential mechanisms linking gut microbiota and portal hypertension[J]. Liver Int,2019,39(4):598-609. |
| [22] | Maruyama H, Kobayashi K, Kiyono S, et al. Interrelationship between insulin resistance and portal haemodynamic abnormality in cirrhosis[J]. Int J Med Sci,2017,14(3):240-245. |
| [23] | European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)[J]. J Hepatol,2024,81(3):492-542. |
| [24] | Bao J, Zhao Y, Xu X, et al. Advances in the use of metformin for liver disease[J]. Curr Med Chem,2025,32(18):3591-3605. |
| [25] | Jang H, Kim Y, Lee DH, et al. Outcomes of various classes of oral antidiabetic drugs on nonalcoholic fatty liver disease[J]. JAMA Intern Med,2024,184(4):375-383. |
| [26] | Nevola R, Epifani R, Imbriani S, et al. GLP-1 receptor agonists in non-alcoholic fatty liver disease: current evidence and future perspectives[J]. Int J Mol Sci,2023,24(2):1703. |
| [27] | Brusilovskaya K, K?nigshofer P, Schwabl P, et al. Vascular targets for the treatment of portal hypertension[J]. Semin Liver Dis,2019,39(4):483-501. |
| [28] | Gracia-Sancho J, Maeso-Díaz R, Fernández-Iglesias A, et al. New cellular and molecular targets for the treatment of portal hypertension[J]. Hepatol Int,2015,9(2):183-191. |
| [29] | Schwabl P, Hambruch E, Seeland BA, et al. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction[J]. J Hepatol,2017,66(4):724-733. |
| [30] | Fernandez M, Vizzutti F, Garcia-Pagan JC, et al. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice[J]. Gastroenterology,2004,126(3):886-894. |
| [31] | Shepherd AI, Wilkerson DP, Fulford J, et al. Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial[J]. Am J Physiol Gastrointest Liver Physiol,2016,311(3):G356-364. |
| [32] | Owen NE, Williams TL, Maguire JJ, et al. Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein[J]. Biosci Rep,2024,44(7):BSR20240528. |
| [33] | Deibert P, Schumacher YO, Ruecker G, et al. Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver — results of a pilot study[J]. Aliment Pharmacol Ther,2006,23(1):121-128. |
| [34] | 孙成林, 王冰琼, 孙亚朦, 等. 肝硬化门静脉高压的无创诊断及预后评估新进展[J]. 肝脏,2025,30(6):756-758. |
| Sun CL, Wang BQ, Sun YM, et al. Recent advances in non-invasive diagnosis and prognosis assessment of cirrhotic portal hypertension[J]. Chinese Hepatology,2025,30(6):756-758. |
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