- Email: [email protected]
Sofosbuvir plus ribavirin in HCV-infected cirrhotic patients awaiting liver transplantation: preliminary data from a single-centre experience
Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
F-26
F-27
ENOS DYSFUNCTION IN STEATOSIS AND STEATOHEPATITIS
SOFOSBUVIR PLUS RIBAVIRIN IN HCV-INFECTED CIRRHOTIC PATIENTS AWAITING LIVER TRANSPLANTATION: PRELIMINARY DATA FROM A SINGLE-CENTRE EXPERIENCE
M. Masarone 1 , A. Carrizzo 2 , A. Federico 3 , V. Rosato 4 , E. Claar 5 , C. Vecchione 6 , M. Persico 1 1
Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy 2 Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli (IS), Italy 3 Gastroenterology Division - Second University of Naples, Italy 4 Internal Medicine and Hepatology Department, Second University of Naples, Italy 5 Internal Medicine Department, Hepatology Unit, Ospedale Evangelico Villa Betania, Naples, Italy 6 Department of Medicine and Surgery, University of Salerno, Salerno, Italy
Background: Non-Alcoholic-Fatty-Liver (NAFLD/NASH) has been associated to cardiometabolic syndrome that is a risk factor for cardiovascular diseases (CVD). The basis of CVD is oxidative stress. Endothelial Nitric-Oxide-Synthase (eNOS) dysfunction has been widely involved in oxidative stress and CVD. Although NAFLD/NASH and CVD are associated to the same factors, NAFLD/NASH represents itself an independent CVD risk-factor. Even diabetics show higher rates of CVD if they have NASH. eNOS derangement has been demonstrated in animal experimental models of NAFLD/NASH. Although clinical and “sublinical” markers (i.e.“intima-media-thickness”) seem to have confirmed this suspicion, nevertheless, no experimental studies on humans have directly demonstrated that eNOS dysfunction is associated with NAFLD/NASH. Aim: to directly demonstrate eNOS derangement in NAFLD/NASH. Patients and methods: 18 patients (13 M,5F), coming in our department of Internal Medicine for NAFLD/NASH, were consecutively enrolled. Every patient underwent a clinical evaluation and a liver biopsy after informed consent. Patients were divided in two groups according to the presence of NAFLD or NASH. We measured eNOS function by evaluating the vasorelaxation activity induced on isolated-mice-vessels by platelet-rich-plasma of peripheral blood, and by immunoblot-assays for platelet-derived eNOS (p-eNOS). Collected data were compared to those from an age-, sex-matched group of healthy volunteers from a local blood bank. All subjects were non-smokers and had no active CVD. Results:Of the 18 pts, 7 (38,8%) had NAFLD and 11 (61,7%) had NASH at the liver biopsy. No statistically significant differences were found between the two groups and controls for age, sex, BMI, ALT, hypertension, diabetes, dyslipidaemia, obesity and metabolic syndrome. Vascular reactivity curves demonstrated a reduced activity of eNOS in patients with NAFLD/NASH in respect to controls(p < 0.005). Moreover, immunoblot-assays for p-eNOS demonstrated a significantly lower expression in NAFLD/NASH patients in respect to controls (p < 0.007). Conclusions: we directly demonstrated that eNOS function is reduced in NAFLD/NASH. Endothelial dysfunction may be considered as one of the pathophysiological mechanisms of liver damage in NAFLD/NASH. http://dx.doi.org/10.1016/j.dld.2015.01.120
e55
S. Martini 1 , S. Strona 1 , D. Arese 1 , M. Sacco 1 , R. Romagnoli 2 , F. Tandoi 2 , A. Ottobrelli 1 , M.R. Torrani-Cerenzia 1 , F. Balzola 1 , M. Salizzoni 2 , M. Rizzetto 1 1 Gastrohepatology Unit, Department of Medical Sciences, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy 2 Liver Transplant Centre, General Surgery Unit, Department of Surgical Sciences, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
Background and aims: Clearance of HCV infection before liver transplantation (LT) prevents recurrence after LT. We evaluated safety and efficacy of antiviral therapy (Tx) with sofosbuvir (SOF) plus ribavirin (RBV) in HCV-infected cirrhotic patients (pts) before LT. Methods: Since June 2014 to date we enrolled 24 HCV cirrhotic pts with HCC within Milan criteria (15 pts) and/or decompensated liver disease. Median MELD 13 (range 7-19); Child-Pugh score B 71% and C 17%; 83% male, mean age 55.4 years, mean BMI 25.8. Mean baseline HCVRNA 6.17 log10 IU/mL (4.91- 7.11 log10 IU/mL); GT1b 55%, GT1a 4%, GT2 4%, GT3 29%, GT4 8%; IL28CC 20%; 63% experienced. Planned treatment: SOF 400 mg/die (compassionate use) and RBV (weight-based) for 48 weeks or until LT. Results: Antiviral treatment resulted in rapid suppression of circulating virus (median decrease HCVRNA: 3.27 log10 IU/mL after 1 week of Tx); 10/20 pts (50%) at week 4, 14/14 week 8, 10/10 week 12 and 7/7 week 16 on Tx were HCVRNA negative. No serious adverse events were observed. RBV reduction and/or epoetin administration was required in 25% of pts and 3 were hospitalized due to complications of liver disease. Of the 7 pts transplanted until now, 4 had HCVRNA < 15 IU/mL for a median of 62 days (31-91) and discontinued antiviral Tx at LT. All those 4 pts are currently HCVRNA negative after a median follow-up post-LT of 45 days (16-69). 2 pts underwent LT while still being HCVRNA positive after less than 4 weeks of Tx, and the last one was transplanted 3 days ago having HCVRNA <15 IU/mL since 5 days. Conclusion. Tx with SOF plus RBV induces rapid HCV clearance and is well tolerated in cirrhotic pts awaiting LT. Preliminary postLT SVR4 is promising in pts undergoing LT after at least 1 month from viral clearance. http://dx.doi.org/10.1016/j.dld.2015.01.121
F-26
F-27
ENOS DYSFUNCTION IN STEATOSIS AND STEATOHEPATITIS
SOFOSBUVIR PLUS RIBAVIRIN IN HCV-INFECTED CIRRHOTIC PATIENTS AWAITING LIVER TRANSPLANTATION: PRELIMINARY DATA FROM A SINGLE-CENTRE EXPERIENCE
M. Masarone 1 , A. Carrizzo 2 , A. Federico 3 , V. Rosato 4 , E. Claar 5 , C. Vecchione 6 , M. Persico 1 1
Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy 2 Vascular Physiopathology Unit IRCCS, INM Neuromed, Pozzilli (IS), Italy 3 Gastroenterology Division - Second University of Naples, Italy 4 Internal Medicine and Hepatology Department, Second University of Naples, Italy 5 Internal Medicine Department, Hepatology Unit, Ospedale Evangelico Villa Betania, Naples, Italy 6 Department of Medicine and Surgery, University of Salerno, Salerno, Italy
Background: Non-Alcoholic-Fatty-Liver (NAFLD/NASH) has been associated to cardiometabolic syndrome that is a risk factor for cardiovascular diseases (CVD). The basis of CVD is oxidative stress. Endothelial Nitric-Oxide-Synthase (eNOS) dysfunction has been widely involved in oxidative stress and CVD. Although NAFLD/NASH and CVD are associated to the same factors, NAFLD/NASH represents itself an independent CVD risk-factor. Even diabetics show higher rates of CVD if they have NASH. eNOS derangement has been demonstrated in animal experimental models of NAFLD/NASH. Although clinical and “sublinical” markers (i.e.“intima-media-thickness”) seem to have confirmed this suspicion, nevertheless, no experimental studies on humans have directly demonstrated that eNOS dysfunction is associated with NAFLD/NASH. Aim: to directly demonstrate eNOS derangement in NAFLD/NASH. Patients and methods: 18 patients (13 M,5F), coming in our department of Internal Medicine for NAFLD/NASH, were consecutively enrolled. Every patient underwent a clinical evaluation and a liver biopsy after informed consent. Patients were divided in two groups according to the presence of NAFLD or NASH. We measured eNOS function by evaluating the vasorelaxation activity induced on isolated-mice-vessels by platelet-rich-plasma of peripheral blood, and by immunoblot-assays for platelet-derived eNOS (p-eNOS). Collected data were compared to those from an age-, sex-matched group of healthy volunteers from a local blood bank. All subjects were non-smokers and had no active CVD. Results:Of the 18 pts, 7 (38,8%) had NAFLD and 11 (61,7%) had NASH at the liver biopsy. No statistically significant differences were found between the two groups and controls for age, sex, BMI, ALT, hypertension, diabetes, dyslipidaemia, obesity and metabolic syndrome. Vascular reactivity curves demonstrated a reduced activity of eNOS in patients with NAFLD/NASH in respect to controls(p < 0.005). Moreover, immunoblot-assays for p-eNOS demonstrated a significantly lower expression in NAFLD/NASH patients in respect to controls (p < 0.007). Conclusions: we directly demonstrated that eNOS function is reduced in NAFLD/NASH. Endothelial dysfunction may be considered as one of the pathophysiological mechanisms of liver damage in NAFLD/NASH. http://dx.doi.org/10.1016/j.dld.2015.01.120
e55
S. Martini 1 , S. Strona 1 , D. Arese 1 , M. Sacco 1 , R. Romagnoli 2 , F. Tandoi 2 , A. Ottobrelli 1 , M.R. Torrani-Cerenzia 1 , F. Balzola 1 , M. Salizzoni 2 , M. Rizzetto 1 1 Gastrohepatology Unit, Department of Medical Sciences, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy 2 Liver Transplant Centre, General Surgery Unit, Department of Surgical Sciences, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
Background and aims: Clearance of HCV infection before liver transplantation (LT) prevents recurrence after LT. We evaluated safety and efficacy of antiviral therapy (Tx) with sofosbuvir (SOF) plus ribavirin (RBV) in HCV-infected cirrhotic patients (pts) before LT. Methods: Since June 2014 to date we enrolled 24 HCV cirrhotic pts with HCC within Milan criteria (15 pts) and/or decompensated liver disease. Median MELD 13 (range 7-19); Child-Pugh score B 71% and C 17%; 83% male, mean age 55.4 years, mean BMI 25.8. Mean baseline HCVRNA 6.17 log10 IU/mL (4.91- 7.11 log10 IU/mL); GT1b 55%, GT1a 4%, GT2 4%, GT3 29%, GT4 8%; IL28CC 20%; 63% experienced. Planned treatment: SOF 400 mg/die (compassionate use) and RBV (weight-based) for 48 weeks or until LT. Results: Antiviral treatment resulted in rapid suppression of circulating virus (median decrease HCVRNA: 3.27 log10 IU/mL after 1 week of Tx); 10/20 pts (50%) at week 4, 14/14 week 8, 10/10 week 12 and 7/7 week 16 on Tx were HCVRNA negative. No serious adverse events were observed. RBV reduction and/or epoetin administration was required in 25% of pts and 3 were hospitalized due to complications of liver disease. Of the 7 pts transplanted until now, 4 had HCVRNA < 15 IU/mL for a median of 62 days (31-91) and discontinued antiviral Tx at LT. All those 4 pts are currently HCVRNA negative after a median follow-up post-LT of 45 days (16-69). 2 pts underwent LT while still being HCVRNA positive after less than 4 weeks of Tx, and the last one was transplanted 3 days ago having HCVRNA <15 IU/mL since 5 days. Conclusion. Tx with SOF plus RBV induces rapid HCV clearance and is well tolerated in cirrhotic pts awaiting LT. Preliminary postLT SVR4 is promising in pts undergoing LT after at least 1 month from viral clearance. http://dx.doi.org/10.1016/j.dld.2015.01.121