Forschungsgruppe - A. Berzigotti

Liver cirrhosis and chronic liver diseases

Berzigotti Annalisa, Principal Investigator,
Margini Cristina, MD


Invasive and non-invasive assessment of Liver Disease

Non-invasive diagnostic methods: an urgent clinical need

The onset of liver cirrhosis and portal hypertension are critical steps in the natural history of chronic liver disease, since they mark the progression to a stage in which all clinical complications of the disease (e.g. gastroesophageal varices bleeding, ascites, hepatic encephalopathy and hepatocellular carcinoma) are most likely to occur. An early diagnosis is then crucial for a correct management. Liver biopsy and measurement of the hepatic venous pressure gradient (HVPG) through liver vein catheterization remain the gold-standard methods to diagnose, respectively, cirrhosis and portal hypertension, and to provide a prognostic stratification in patients with cirrhosis. Endoscopy is needed to diagnose gastroesophageal varices in portal hypertensive patients, and was traditionally suggested in all patients diagnosed of cirrhosis.
All the above mentioned reference tests are invasive, expensive, and not available in all Centers. Therefore, non-invasive diagnostic methods to safely replace them are an urgent clinical need. Ultrasound and Doppler-ultrasound allow excluding non-cirrhotic causes of portal hypertension such as portal vein thrombosis and hepatic veins thrombosis, and should be performed as a first step examination. The presence of nodular liver surface is associated to cirrhosis with a high accuracy in the appropriate clinical setting, and porto-systemic collaterals on ultrasound holds a 100% specificity for the diagnosis of portal hypertension. Transient elastography (Fibroscan®) allow an accurate non-invasive assessment of liver fibrosis, and the test holds an accuracy >90% for the diagnosis of cirrhosis and portal hypertension. The combination of ultrasound and elastography provides a one-step non-invasive assessment able to reduce the need for invasive tests.

Newer elastographic methods such as acoustic radiation force impulse imaging (ARFI) and 2Dimensional-Real Time-Shear Wave Elastography (2D-RT-SWE) are embedded into ultrasound equipment and measurements of liver stiffness can be obtained under visual control. These methods are more applicable than transient elastography and have a similar accuracy for the diagnosis of cirrhosis and portal hypertension. The knowledge of the limitations and sources of false negative and false positive results of each method is needed for a correct interpretation of the results. Novel non-invasive tests, such as contrast-enhanced ultrasound, can lead to improvements in diagnosis of cirrhosis and portal hypertension. Innovation in ultrasound is needed to provide a complete evaluation of liver tissue such as fat content and inflammation.

Publications :
Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S, Peron JM, Selves J, Stefanescu H, Berzigotti A, Vinel JP, Bureau C. Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension.  Dig Liver Dis. 2015;47(5):411-6.

de Franchis R, Baveno VI Faculty (Berzigotti A). Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743-52.

Amat-Roldan I, Berzigotti A, Gilabert R, Bosch J. Assessment of Hepatic Vascular Network Connectivity by Automated Graph-Analysis of Dynamic Contrast-Enhanced Ultrasound to Evaluate Portal Hypertension in Patients with Cirrhosis: a Pilot Study. Radiology. 2015;277(1):268-76.

Procopet B*, Berzigotti A*, Abraldes JG, Turon F, Hernandez-Gea V, García-Pagán JC, Bosch J.  Real-time shear-wave elastography: applicability, reliability and accuracy for clinically significant portal hypertension.  J Hepatol. 2015;62(5):1068-75. * share first authorship.

Thiele M, Madsen BS, Procopet B, Hansen JF, Møller LS, Detlefsen S, Berzigotti A, Krag A. Reliability Criteria for Liver Stiffness Measurements with real-time 2D Shear Wave Elastography in different clinical scenarios of chronic liver disease. Ultraschall Med. Submitted.

Effects of obesity and lifestyle changes in cirrhosis

In the past liver cirrhosis was traditionally diagnosed in a late, decompensated phase in which malnutrition and sarcopenia are common. On the other hand, nowadays patients with cirrhosis are diagnosed earlier, in compensated, asymptomatic phase. In this stage of the disease the co-existence of obesity is common, and its impact on the natural history of cirrhosis is now matter of study. Obesity markedly increases the risk of clinical decompensation in patients with cirrhosis due to any cause. Furthermore, it is associated with a reduced response to non-selective beta-blockers for portal hypertension. Lifestyle changes including diet and exercise can improve obesity in patients with cirrhosis, are safe, and seem to induce a significant decrease of portal pressure. The mechanisms mediating these beneficial effects are unknown and will be object of future research.

Publications :
Berzigotti A, Garcia-Tsao G, Bosch J, Grace N, Burroughs A, Morillas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Groszmann RJ and the Portal Hypertension Collaborative Group. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology. 2011;54: 555-561. 

Berzigotti A, Abraldes JG. Impact of obesity and insulin-resistance on cirrhosis and portal hypertension. Gastroenterol Hepatol. 2013;36(8):527-33.

Berzigotti A, Villanueva C, Genescá J, Ardevol A, Augustín S, Calleja JL et al. Lifestyle intervention by a 16-week programme of supervised diet and physical exercise ameliorates portal hypertension in patients with cirrhosis and obesity: the SportDiet study. Hepatology 2014;60:253A.

Berzigotti A, Saran U, Dufour JF. Physical activity and liver diseases. Hepatology. 2016;63(3):1026-40.


 

Research Focus

Liver Cirrhosis
Portal Hypertension
Non-Invasive methods 
Acoustic Radiation Force Impulse Imaging 
2Dimensional-Real Time-Shear Wave Elastography
Contrast-Enhanced Ultrasound

Research ratios

Humans : Animals

88 : 5

Top Major MeSH Headings

Liver Cirrhosis
Hypertension, Portal
Esophageal and Gastric Varices
Treatment Outcome
Hemodynamics
Portal pressure
Elasticity Imaging Techniques
 

On-going Studies:

  • Prospective assessment of patients with cirrhosis (led by A. Berzigotti and G. Stirnimann)
  • Ultrasound biopsy for the assessment of steatosis, fibrosis and inflammation in chronic liver disease. UniBe-ID grant 2015. Coordinator: A. Berzigotti. Investigators: A. Berzigotti, M. Jaeger, M. Frenz, JF Dufour.

Collaborations

Prof. Fabio Piscaglia, University of Bologna, Italy

Prof. Jaime Bosch, University of Barcelona, Spain

Dr. Maja Thiele, Odense University, Denmark

Dr. Bogdan Procopet, University of Cluj-Napoca, Romania