Hepatic congestion plays a role in liver stiffness
Authors: Nora Frulio, Hervé Laumonier, Charles Balabaud, Hervé Trillaud, Paulette Bioulac-Sage
Journal: Hepatology (2009)

We read with interest the letter written by Lebray et al.,1 who reported that hepatic congestion can considerably increase hepatic elastometry, as measured by Fibroscan, to values that are unambiguously diagnostic for liver cirrhosis. We recently made the same observation,2 and we would like to present more information on this topic. We had the opportunity to study, before resection, liver stiffness in various subtypes of hepatocellular adenomas (HCAs).3 In HCAs, fibrosis is usually absent. Indeed, hepatocyte nuclear factor 1α–mutated HCAs (HNF1α HCAs) are often steatotic, whereas inflammatory hepatocellular adenomas (IHCAs) often present congestion, with sinusoidal dilatation as the initial step and passage of red blood cells in the space of Disse as the second step. Liver stiffness was measured by the acoustic radiation force impulse method (Siemens S2000).4 The standard ultrasonographic probe offered elastography with a flexible metering box (2 × 1 cm2) at various depths (up to 5.5 cm), allowing the examination of specific areas, such as those within and outside tumors. The speed of the shear wave (m/s) was expressed as a median of 10 measurements.5 Elasticity could also be expressed in kilopascals with the Young formula [elasticity = 3ρv2, where ρ is the density and v is the speed of the shear wave (m/s)]. The interquartile range/median (IQR/M) ratio was then calculated. In the first case (HNF1α HCA), which was entirely and massively steatotic (Fig. 1A), the median speed was 1.05 m/s (3.34 kPa), and the IQR/M ratio was 0.18; in the second case (HNF1α HCA), which was mildly steatotic with sinusoidal dilatation (Fig. 1B), the median speed was 1.5 m/s (6.78 kPa), and the IQR/M ratio was 0.49; and in the third case (IHCA), which presented sinusoidal dilatation and major hepatic congestion (Fig. 1C), the speed was 3.17 (30.15 kPa), and the IQR/M ratio was 0.83. The median speed in the nontumoral liver [normal histology in cases 1 and 2 and mild steatosis (<5%) in case 3] was 1.28 (4.95 kPa), 1.2 (4.32 kPa), and 0.86 m/s (2.21 kPa) with IQR/M ratios of 0.14, 0.08, and 0.33, respectively. Hepatocyte nuclear factor 1α–mutated hepatocellular adenomas (HCAs) are shown for (A) case 1 and (B) case 2 with liver fatty acid–binding protein (LFABP) staining. There was an absence of LFABP labeling in the HCA nodule (N) in comparison with the nontumoral tissue (NT). There was major steatosis in case 1 and very mild steatosis in case 2 plus sinusoidal dilatation (shown by the circle). (C) An inflammatory hepatocellular adenoma (IHCA) is shown for case 3 with C-reactive protein staining. Strong staining was limited to the IHCA nodule (N). An area of hepatic congestion (shown by the circle) can be seen with extravasation of red blood cells in the space of Disse. These results indicate that (1) the speed measured in the nontumoral liver with the acoustic radiation force impulse method was in the range obtained with transient elastography, (2) massive steatosis does not increase stiffness, and (3) sinusoidal dilatation and hepatic congestion appear to play a major role in tissue elasticity. Hepatic congestion (case 3) in an IHCA is not homogeneously distributed, as reflected by the high IQR/M value. The rationale that the velocity of the elastic shear wave that propagates through the underlying liver tissue is directly related to tissue stiffness, which is considered an index of the amount of fibrotic tissue,6 is, however, too restrictive. The impact of confounding factors, particularly necro-inflammatory activity7, 8 and intrahepatic cholestasis,9 that may occur during the hepatitic process have been recently emphasized. Congestive hepatopathy, a key factor in the pathobiology of cirrhosis, is now another factor to consider.10 Passive liver congestion1 should also be taken into account in the presence of overt or subclinical heart failure in elderly patients. More generally, these factors should also be considered in patients with features of metabolic syndrome, for whom cardiovascular disease and nonalcoholic fatty liver disease may be present together. Nora Frulio*, Hervé Laumonier*, Charles Balabaud , Hervé Trillaud*, Paulette Bioulac-Sage §, * Department of Radiology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France, Department of Hepatology Hôpital St. André, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France, Institut National de la Santé et de la Recherche Médicale Unité 889, Université Bordeaux 2, Bordeaux, France, § Department of Pathology, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.