FUNDENI HBFG Hepato-Biliary Focus Group (HBFG) - Fundeni Clinical Institute

HBFG is a multidisciplinary team with a special interest in clinical and basic research of hepato-biliary diseases activating in Fundeni Clinical Institute, having as a main aim to improve the quality of care and long term outcomes of our patients. The team involves gastroenterology and hepatology specialists, surgeons, oncologists, radiology specialists, anaesthesiologists, pathologists and biologists (see the most prominent members in the RoALD leaders). All activity (clinical/research/academic/publishing) is reflected in the CVs of the main leaders included on the webpage of RoALD.

Regarding clinical research our main interests reside in: chronic viral hepatitis and the eradication of HCV, new therapies for HBV/HDV chronic hepatitis, non-invasive evaluation of chronic liver diseases, improving screening and prevention of hepatocellular carcinoma (HCC), management of hepatocellular carcinoma (all treatment modalities) in a multidisciplinary approach, autoimmune liver disorders, Wilson disease as well as other rare diseases with liver involvement, non-alcoholic liver diseases, acute on chronic liver failure, liver transplantation and pre- and post-transplant management of these complex patients, therapeutic endoscopy pre- and post-transplantation.

The clinical hepatology studies ongoing in the Gastroenterology and Hepatology Department of Fundeni Clinical Institute will be mentioned on the dedicated webpage of RoALD. Past clinical hepatology studies performed in our Hepatology Department are over 20.

Regarding public health interventions our centre is leading public health projects and collaborating with health policy makers to prevent and mitigate the burden of liver disease in Romania by prevention, improving screening and early diagnosis in liver disease and making therapies more affordable. In this regard out intervention are focused on

• screening for HCV infected individuals in high risk groups and general population in order to link them to care and eliminate hepatitis C as major public health threat and leading cause for liver cirrhosis, HCC and liver transplantation in Romania
• early identification of HCC by improving screening
• policy strategies in order to reduce alcohol consumption, obesity and NAFLD as emerging leading causes of liver diseases
• education of general population on a healthy lifestyle for the liver, on how to prevent liver diseases and when to address to specialty care
• promote a healthy lifestyle to maintain liver health.

Regarding basic research our main interests reside in:

• identification of new serological and genetic markers with diagnostic and prognostic significance in hepatocellular carcinoma;
• diagnosis and disease monitoring of patients with non-alcoholic steatohepatitis and metabolic liver diseases (hemochromatosis, Wilson’s disease) by integrating in the diagnostic and follow-up algorithm of new molecular and genetic biomarkers, next generation sequencing for genetic mutation screening in Wilson’s Disease, investigation of molecular markers that predict NASH in the post liver transplant setting, the investigation of donor specific antibodies and the significance in predicting long-term complications following liver transplantation;
• cell culture experiments involving standard cell lines and primary cells to investigate novel mechanisms of liver diseases, primary cells isolations for in vitro studies (e.g. hepatocytes isolations, primary digestive epithelial cells/stem cells isolations);
• studies on ectopic gene expression, generation of personalized cell lines, using induced pluripotent stem cells for genetic and personalized pharmacological studies (basic research is conducted in the Centre of Excellence for Translational Medicine, http://cemt.icfundeni.ro/index.php/acasa).

Some of these topics were investigated in our previous research hepatology projects:

• HEPASIST Project
  • Has implemented a pilot study for computerised management of the waiting list for liver transplantation, that allows the prospective monitoring of patients listed for liver transplantation and real time sorting of transplant priorities according to current guidelines, based on disease severity.
• PROSONOHEP Project
  • Has implemented a pilot study for noninvasive sono-elastographic evaluation of small hepatocellular carcinoma nodules in liver cirrhosis.
• BAROFAT Research Grant
  • The Project has included patients with morbid obesity that underwent bariatric surgery and has registered antromometric modifications, liver function biochemistry, imaging, non-invasive biomarkers of liver disease, serological pro-inflammatory profiles, liver histology and specific immunohistochemistry, at baseline and at 6 months after surgery. There have been investigated predictive factors for postoperative evolution with the aim of developing new non-invasive methods for assessment of advanced liver disease (NASH, advanced fibrosis, cirrhosis) that can be used in the postoperative setting.
• GENOWIL Research Grant
  • The aim of the project was to investigate the genotype of Romanian patients diagnosed with Wilson’s Disease and the correlations with disease phenotype. The Project has provided for the first time information on H1069Q SNP allelic frequency in our population. There has been established a long term collaboration with UniKlinikum Muenster that currently supports whole gene sequencing of ATP7B gene, for the complete evaluation of the mutational profile of Romanian patients, that will allow in the future a better genetic diagnosis in our population.
• PNCDI2 125/2011 Research Grant (Project Leader)
  • The project has systematically evaluated in patients with hepatocellular carcinoma, the expression of genetic markers specific to stem/progenitor cells genes (KRT19, EPCAM, CD133, CD90, CD44, SOX9, TERT, LGR5, LGR6, OCT4, SOX2, NANOG etc). It has been investigated the prognostic utility of these markers for tumor recurrence, with the goal of developing new predictive tools that could improve patients survival after surgery by stratifying the risk of recurrence.
• APOHEPI Research Grant (TE 120/2018)
  • The Project evaluated for the first time in the LT recipients the association between the SNP in TBX21 gene (rs4794067) and in CYP3A5 gene (rs776746) and occurrence of fibrosis and steatosis after LT, as well as with the level of immunosuppression
  • Effects on hepatocyte apoptosis of different immunosuppression agents were also investigated; mycophenolate mofetil based immunosuppressive regimens proved to have a favourable anti-apoptotic profile in vitro, in human cirrhotic hepatocytes cultures, as suggested by cytometry and gene expression studies, supporting its use in case of LT recipients at high risk for liver graft fibrosis

Current ongoing hepatology projects in Fundeni Clinical Institute are the following:

• National POCU Programmes for Continuing Medical Education on chronic hepatitis coordinated by Fundeni Clinical Institute:
• LIVE(Ro)1 Project: “Continuing Medical Education Programme for medical personnel in Romania for the setup of population-based screening for chronic infection with HBV/HCV/ HDV” (Project Manager SL Dr. Laura Simona Diaconu, see for more description the specific Grants webpage)
• LIVE(Ro)2 SUD Project: “Regional Programme of Prevention, Screening and Diagnosis of patients with chronic hepatic diseases secondary to viral hepatitis B/D and C”(Project Manager Prof.Dr. Liliana Simona Gheorghe, see for more information the specific Grants webpage)
• DIACURE (Fundeni Clinical Institute is partner in this project coordinated by “Titu Maiorescu” University): The project is aimed at transdifferentiation of hepatic cells to beta pancreatic cells, by ectopic expression of specific transcription factors. The project opens new perspectives for autologous cell therapy in diabetes mellitus.