1. STEATO-HEPATITIS IN OBESE PATIENTS SUBMITTED TO BARIATRIC SURGERY (BS): UTILITY OF CONTRAST-ENHANCED US WITH TIME- INTENSITY CURVES (CEUS-TIS) FOR DIAGNOSIS: INITIAL EXPERIENCE Francesco Giangregorio*, Edoardo Baldini &, Adriano Zangrandi £, Carlo Paties £, Fabio Fornari*, Patrizio Capelli &, *Gastroenterology Department, Guglielmo da Saliceto Hospital, Piacenza, Italy & Surgery Department, Guglielmo da Saliceto Hospital, Piacenza, Italy £ Pathology Department, Guglielmo da Saliceto Hospital, Piacenza, Italy Francesco Giangregorio*, Edoardo Baldini &, Adriano Zangrandi £, Carlo Paties £, Fabio Fornari*, Patrizio Capelli &, *Gastroenterology Department, Guglielmo da Saliceto Hospital, Piacenza, Italy & Surgery Department, Guglielmo da Saliceto Hospital, Piacenza, Italy £ Pathology Department, Guglielmo da Saliceto Hospital, Piacenza, Italy

2. INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum that ranges from simple steatosis to non-alcoholic steatohepatitis (NASH)[1].1 It ’ s important establishing the diagnosis of NASH, both for prognosis and for indentifying potential candidates for future treatment protocols[2].2 Surgeons ’ evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease[3, 4].34 1.Miele L, Forgione A, Hernandez AP, Gabrieli ML, Vero V, Di RP, Greco AV, Gasbarrini G, Gasbarrini A, Grieco A: The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis. EurRevMedPharmacolSci 2005, 9(5):273-277. 2.Vuppalanchi R, Chalasani N: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2009, 49(1):306-317. 3.Charlton MR: Fibrosing NASH: On Being a Blind Man in a Dark Room Looking for a Black Cat (That Isn’t There). Gastroenterology 2011, 140(1):25-28. 4.Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP: Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007, 102(2):399-408 Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum that ranges from simple steatosis to non-alcoholic steatohepatitis (NASH)[1].1 It ’ s important establishing the diagnosis of NASH, both for prognosis and for indentifying potential candidates for future treatment protocols[2].2 Surgeons ’ evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease[3, 4].34 1.Miele L, Forgione A, Hernandez AP, Gabrieli ML, Vero V, Di RP, Greco AV, Gasbarrini G, Gasbarrini A, Grieco A: The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis. EurRevMedPharmacolSci 2005, 9(5):273-277. 2.Vuppalanchi R, Chalasani N: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2009, 49(1):306-317. 3.Charlton MR: Fibrosing NASH: On Being a Blind Man in a Dark Room Looking for a Black Cat (That Isn’t There). Gastroenterology 2011, 140(1):25-28. 4.Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP: Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007, 102(2):399-408

3. AIM Aim of the study was to understand if clinical data, blood examination, conventional US, colordoppler examination of splanchnic vasa or contrast-enhanced US with time-intensity curves studies were able to detect differences between simple steatosis from NASH.

4. MATERIALS from September 2010 to April 2012 we studied 75 morbidly obese patients (MOP), submitted to laparoscopic bariatric surgery (66 females; 9 males; mean age: 43,6 Y, range: 21-61; mean BMI 45,4 kg/m 2 ; all HBV and HCV negative patients). We collected clinical data, blood examinations, and the day before surgery patients were submitted to: – conventional US – colordoppler evaluation of Portal System – contrast-enhanced US with time intensity curves off-line elaborated with QONTRAST software (Bracco, Italy) from September 2010 to April 2012 we studied 75 morbidly obese patients (MOP), submitted to laparoscopic bariatric surgery (66 females; 9 males; mean age: 43,6 Y, range: 21-61; mean BMI 45,4 kg/m 2 ; all HBV and HCV negative patients). We collected clinical data, blood examinations, and the day before surgery patients were submitted to: – conventional US – colordoppler evaluation of Portal System – contrast-enhanced US with time intensity curves off-line elaborated with QONTRAST software (Bracco, Italy)

5. MATERIALS Clinical data: hepatomegaly Biochemical data: SGOT, SGPT, cholesterol, triglycerides, TSH Clinical data: hepatomegaly Biochemical data: SGOT, SGPT, cholesterol, triglycerides, TSH

6. MATERIALS conventional US (hepatomegaly, irregular margins, steatosis, splenomegaly) colordoppler evaluation of Portal System (Portal vein diameter, mean blood flow velocity, hepatic and splenic artery resistence index) contrast-enhanced US with time intensity curves off-line elaborated with QONTRAST software (Bracco, Italy) ) (CEUS-TIS); time to peak (TTP); peak% (P%); red blood volume (RBV) and flow (RBF); mean time to transit (MTT)). conventional US (hepatomegaly, irregular margins, steatosis, splenomegaly) colordoppler evaluation of Portal System (Portal vein diameter, mean blood flow velocity, hepatic and splenic artery resistence index) contrast-enhanced US with time intensity curves off-line elaborated with QONTRAST software (Bracco, Italy) ) (CEUS-TIS); time to peak (TTP); peak% (P%); red blood volume (RBV) and flow (RBF); mean time to transit (MTT)).

7. 77

8. 88 Portal Vein Hepatic Vein Hepatic arterySplenic artery

9. 9 arterial phaseportal phase late phase

10. 10

11. METHODS Liver biopsy was performed during bariatric surgery. Clinical, ultrasonographic, colordoppler and CEUS-TIS data were compared to hystology; sensitivity (sens), specificity(spec), diagnostic accuracy(DA), positive predictive (PPV) and negative predictive value (NPV) were calculated; comparison among data were performed with receiver operating curves (ROC) (spss version 18); Z test was calculated to evaluate statistical significance among AUC-ROC (p 1.96) Liver biopsy was performed during bariatric surgery. Clinical, ultrasonographic, colordoppler and CEUS-TIS data were compared to hystology; sensitivity (sens), specificity(spec), diagnostic accuracy(DA), positive predictive (PPV) and negative predictive value (NPV) were calculated; comparison among data were performed with receiver operating curves (ROC) (spss version 18); Z test was calculated to evaluate statistical significance among AUC-ROC (p 1.96)

12. 12 RESULTS: data Hystologic diagnosis: ① 57 non pathological normal:12 steatosis: 45 (30 initial, 15 overt steatosis) ② 18 pathological 12 initial steatohepatitis 6 overt hepatitis

13. 13 RESULTS: data

14. RESULTS: statistical analysis

15. 15 RESULTS: auc ROC

16. SUMMARY Clinical and ultrasonographic criteria are not useful for discriminating simple steatosis from steato-hepatitis in obese patients. Only CEUS –TIS may help to establishing the diagnosis of NASH in a non-invasive way Clinical and ultrasonographic criteria are not useful for discriminating simple steatosis from steato-hepatitis in obese patients. Only CEUS –TIS may help to establishing the diagnosis of NASH in a non-invasive way

17. 17 Grazie dell ’ attenzione!!!