Felix Piecha

Arterial pressure suffices to increase liver stiffness

Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood.

Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification

BACKGROUND & AIMS Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort. RESULTS A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71-0.83 and AUC ≥S2 = 0.78; 0.72-0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4-6) for detoxification, CAP decreased by 32 ± 47 dB/m (p <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obese patients with body mass index ≥30 kg/m2 had a significantly higher CAP, which did not decrease significantly during detoxification. CONCLUSIONS CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal. LAY SUMMARY CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

Pharmacological decrease of liver stiffness is pressure-related and predicts long-term clinical outcome

Liver stiffness (LS) as measured by transient elastography is increasingly used to noninvasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, nitric oxide donors, and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n = 38 cirrhotic patients. In the animal model, cirrhosis induction resulted in a significant increase of LS and PP. After losartan or NO application, a LS decrease of 25% was strongly correlated with a concomitant decrease of mean arterial pressure (MAP) and PP. In contrast, acute propranolol administration decreased heart rate but not MAP resulting in stable LS. In the human cohort, most patients ( n = 25, 66%) showed a LS decrease after propranolol treatment initiation which significantly correlated to HVPG ( r = 0.518, P < 0.01) but was not accompanied by statistically significant changes in transaminases or model of end-stage liver disease (MELD). On multivariate analysis, patients with decreasing LS on propranolol had a decreased risk for experiencing a transplantation or death than patients with increasing LS irrespective of HVPG. In conclusion, LS changes after pharmacological interventions are influenced by hemodynamic effects on arterial and portal pressure. In humans, a LS decrease may be predictive of improved outcome irrespective of MELD scores and may serve as an additional follow-up tool in the future. NEW & NOTEWORTHY Liver stiffness (LS) is efficiently modulated by changes in portal venous and systemic pressures in an animal model of liver cirrhosis irrespective of baseline LS and portal pressure values. In humans, most patients show a decrease in LS after propranolol treatment initiation without statistically significant changes in transaminases or model of end-stage liver disease (MELD) scores. A decrease in LS may be associated with improved outcome and thus another valuable tool in the follow-up of patients after propranolol treatment initiation.

P0518 : Arterial pressure suffices to increase liver stiffness independent of central venous pressure

etiologies in which TE measurements were made either with the M (3.5MHz) probe or with XL (2.5MHz) between January 2012 and October 2014. In patients in which reliable measurements could not be obtained by M probe, XL measurements were performed in the same session. In each patient 10 valid LSM were acquired with each probe, a median was calculated expressed in kiloPascals (kPa). Reliable measurements were defined as: median value of 10 valid LSM with a success rate (SR) ≥60% and an interquartile range interval (IQR) <30%. Unreliable TE measurement were considered the following situations: fewer than 10 valid shots; SR <60% and/or IQR ≥30%. Results: A total of 2046 patients were examined, 1156 (56.5%) overweight and 890 (43.5%) obese. In the 1156 overweight patients reliable LSM were obtained in 979 (84.7%) cases: in 729 (63.1%) by the standard M probe and in 250 (21.6%) by the XL probe. In the 890 obese patients, reliable measurements were obtained in 744 patients (83.6%), in 165 (18.5%) by the M probe, and in 522 (58.6%) by using the XL probe. Thus, by using both probes, reliable measurements were obtained in 1723 (84.2%) of the 2046 examined cases. Conclusions: By using both M and XL probes, reliable LSM by TE can be obtained in the majority of the obese and overweight patients (84.2%).