Forschungsgruppe - A. Berzigotti

Liver cirrhosis and chronic liver diseases

Berzigotti Annalisa, Principal Investigator,
Susana G. Rodrigues, MD
Yuly Mendoza, MD
Pompilia Radu, MD
Cristina Margini, MD
Tao Wan
Cong Wang

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.

Publications in this research line (past 2 years)


Publications :
Thiele M, Madsen BS, Procopet B, Hansen FJ, 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. 2017 Dec;38(6):648-654.

Berzigotti A. Non invasive Evaluation of Portal Hypertension using Ultrasound Elastography. J Hepatol. 2017 Aug;38(4):377-394.

Hari A, Nair HK, De Gottardi A, Baumgartner I, Dufour JF, Berzigotti ADiagnostic Hepatic Hemodynamic Techniques: Safety and Radiation Exposure. Liver Int. 2017 Jan;37(1):148-154.

Rodrigues SG, Maurer MH, Baumgartner I, De Gottardi A, Berzigotti A. Imaging and minimally invasive endovascular therapy in the management of portal vein thrombosis. Abdom Radiol (NY). 2018 Aug;43(8):1931-1946.

Simón-Talero M, Roccarina D, Martínez J, Lampichler K, Baiges A, Low G, Llop E, Praktikjo M, Maurer MH, Zipprich A, Triolo M, Vangrinsven G, Garcia-Martinez R, Dam A, Majumdar A, Picon C, Toth D, Darnell A, Abraldes JG, Lopez M, Kukuk G, Krag A, Bañares R, Laleman W, La Mura V, Ripoll C, Berzigotti A, et al. for the Baveno VI-SPSS group from the Baveno Cooperation       Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis. Gastroenterology 2018 May;154(6):1694-1705.

Margini C, Murgia G, Stirnimann G, De Gottardi A, Semmo N, Casu S, Bosch J, Dufour JF, Berzigotti A. Prognostic Significance of Controlled Attenuation Parameter in Patients With Compensated Advanced Chronic Liver Disease. Hepatol Commun. 2018 Jul 24;2(8):929-940.

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.

Publications in this research line (past 2 years)

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

Berzigotti A, Albillos A, Villanueva C, Genescá J, Ardevol A, Augustín S, Calleja JL, Bañares R, García-Pagán JC, Mesonero F, Bosch J, Ciberehd SportDiet Collaborative Group. Effects of an Intensive 16-week Lifestyle Intervention Program on Portal Hypertension in Patients with Cirrhosis and Obesity: the SportDiet Study. Hepatology. 2017 Apr;65(4):1293-1305.

European Association for the Study of the Liver (Berzigotti A  part of the guidelines panel). EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2018. Aug 22. pii: S0168-8278(18)32177-9. doi: 10.1016/j.jhep.2018.06.024. [Epub ahead of print]


Research Focus

Contrast-Enhanced Ultrasound
Portal hypertension
Liver cirrhosis

On-going Studies:

  • Conatus IDN-6556-14. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects with Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension. Recruitment closed in 2018, follow-up ongoing.
  • 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.

Main International Collaborations

Prof. Fabio Piscaglia, University of Bologna, Italy
Prof. Guadalupe Garcia-Tsao, Yale University, United States
Prof. Juan G. Abraldes, 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