Research Article: Influence of hepatic fibrosis and inflammation: Correlation between histopathological changes and Gd-EOB-DTPA-enhanced MR imaging

Date Published: May 13, 2019

Publisher: Public Library of Science

Author(s): N. Verloh, U. Probst, K. Utpatel, F Zeman, F. Brennfleck, J. M. Werner, C. Fellner, C. Stroszczynski, M. Evert, P. Wiggermann, M. Haimerl, Pavel Strnad.


To evaluate the influence of an active inflammatory process in the liver on Gd-EOB-DTPA-enhanced MR imaging in patients with different degrees of fibrosis/cirrhosis.

Overall, a number of 91 patients (61 men and 30 women; mean age 58 years) were included in this retrospective study. The inclusion criteria for this study were Gd-EOB-DTPA-enhanced MRI of the liver and histopathological evaluation of fibrotic and inflammatory changes. T1-weighted VIBE sequences of the liver with fat suppression were evaluated to determine the relative signal change (RE) between native and hepatobiliary phase (20min). In simple and multiple linear regression analyses, the influence of liver fibrosis/cirrhosis (Ishak score) and the histopathological degree of hepatitis (Modified Hepatic Activity Index, mHAI) on RE were evaluated.

RE decreased significantly with increasing liver fibrosis/cirrhosis (p < 0.001) and inflammation (mHAI, p = 0.004). In particular, a correlation between RE and periportal or periseptal boundary zone hepatitis (moth feeding necrosis, mHAI A, p = 0.001) and portal inflammation (mHAI D, p < 0.001) was observed. In multiple linear regression analysis, both the degree of inflammation and the degree of fibrosis were significant predictors for RE (p < 0.01). The results of this study suggest that the MR-based hepatic enhancement index RE is not only influenced by the degree of fibrosis, but also by the degree of inflammation.

Partial Text

Inflammation is an immune-mediated reaction to infections and foreign bodies. It can be distinguished into acute and chronic inflammation, which differ in duration, onset, and outcome. While acute inflammation can be treated reversibly, recurrent acute inflammation due to persistent acute infection may lead to tissue injury and destruction. Thereof, fibrosis results as a consequence of the pathophysiological response following tissue injury. However, the distinction between physiology and pathology is blurry as the right degree of inflammation and repair can heal a wound and restore tissue integrity and function, whereas excessive, uncontrolled inflammation or repair mechanisms may lead to tissue dysfunction. Inflammation may induce hepatocellular damage which will activate and promote hepatic stellate cells and Kupffer cells and finally leads to an inflammatory and fibrogenic response [1–3]. Consequently, the enhanced inflammatory and immune-mediated responses will promote additional hepatocyte necrosis and apoptosis, which triggers further fibrogenic processes [4]. By intervening in the signaling pathways that influence myofibroblast apoptosis, hepatic stellate cell inactivation, and extracellular matrix degeneration, hepatic fibrosis can be prevented or even reversed, it is therefore important to recognise inflammatory processes as early as possible in order to be able to take appropriate countermeasures.

Inflammation and fibrosis are strongly associated: hepatic inflammation initiates fibrogenesis and maintains itself by promoting proinflammatory signaling molecule release and can occur at any stage of liver fibrosis/cirrhosis [1, 2]. To be able to initiate an adequate treatment as early as possible, researchers aim to distinguish inflammation and fibrosis in MR imaging approaches. Variable MR techniques were applied to evaluate the fibrotic and inflammation status of hepatic parenchyma [15]. Based on liver stiffness and damping ratio, assumptions of the NAFLD status and the distinction to initial liver fibrosis have been shown [16, 17]. Similarly, liver kinetics assessed in contrast-enhanced MR imaging as well as the apparent diffusion coefficient can indicate liver fibrosis and inflammation [18–22].