Research group - A. Berzigotti

Liver cirrhosis and chronic liver diseases

Berzigotti Annalisa, Principal Investigator
Yuly Mendoza, MD
Chiara Becchetti, MD
Élise Vuille-Lessard, MD
Cristina Margini, MD
Tao Wan, PhD
Cong Wang, PhD
Ahmed Y. Elmahdy, 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. Our group substantially contributed to establish that 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.

Recently, we also started investigating in a translational research project funded by the SNF how the stiffness of extracellular matrix impacts on the biology of liver cells, hypothesizing that the modulation of the mechanical properties of liver tissue could constitute a novel therapeutic target in patients with cirrhosis.

Publications in this research line

 

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. Our group described that obesity markedly increases the risk of clinical decompensation in patients with cirrhosis due to any cause. We also demonstrated that 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 at our center. We are currently investigating reliable and simple markers of prognosis in patients with advanced chronic liver diseases, obesity and obesity-associated comorbidity, as well as how adipopenia and sarcopenia and their management impact the prognosis of patients with portal hypertension.

Publications in this research line

Main International Collaborations
 
Baveno Cooperation: large international group collaborating in the setting of portal hypertension
EFSUMB collaborative network: large international group collaborating in the setting of elastography and contrast-enhanced ultrasound
Prof. Fabio Piscaglia, University of Bologna, Italy
Prof. Guadalupe Garcia-Tsao, Yale University, United States
Prof. Juan G. Abraldes, University of Alberta, Canada
Prof. Puneeta Tandon, University of Alberta, Canada

Dr. M. Ángeles Garcia-Criado, Hospital Clinic, University of Barcelona, Spain 
Dr. Maja Thiele, Odense University, Denmark 
Dr. Bogdan Procopet, University of Cluj-Napoca, Romania 
Dr. Giovanna Ferraioli, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy 
Prof. Ivica Grgurevic, University of Zagreb, Croatia 
Prof. Manuela Merli, University of Rome, Italy 
Prof. Giada Sebastiani, University of Montreal, Canada 
Prof. Erica Villa, University of Modena, Italy 
Prof. Salvatore Petta, University of Palermo, Italy

Research Focus

Ultrasound
Elastography
Contrast-Enhanced Ultrasound
Portal hypertension
Liver cirrhosis
Obesity
Lifestyle Changes
Liver stiffness on liver biology (translational research)

On-going Studies:

  • Combination of Simple Non-Invasive Tests in Chronic Liver Disease to Improve a Stage-Targeted Risk Stratification and Outcome Prediction (KEK-Nr. 2018-00487).
  • Body Composition and prognosis in advanced chronic liver disease (KEK-Nr. 2017-00957).
  • Effect of direct acting antiviral drugs on the occurrence of intra- and extra-hepatic malignancies in patients with chronic hepatitis C. Swiss Cancer Research KFS-4131-02-2017. Granted 198’000 CHF for 36 months (01.07.2017-31.08.2020) (KEK-Nr. 2018-00727).
  • Contrast-enhanced ultrasound evaluation of focal liver lesions in patients with cirrhosis or other risk factors for developing HCC. Multicentric study performed in US and Europe, funded by the National Institute of Health (NIH), US. Recruitment will likely start in January 2019. 
  • Inhibition of the stiffness-derived molecular axis to improve liver cirrhosis and portal hypertension. Swiss National Science Foundation. 320030_189252 (Berzigotti& Gracia-Sancho PI). 01.11.2019-31.10.2022.