G. Soardo | Università degli Studi di Udine / University of Udine (original) (raw)

Papers by G. Soardo

Research paper thumbnail of Increased burden of inherited IRF3 rare genetic variants in Europeans with severe NAFLD

Digestive and Liver Disease

Research paper thumbnail of HLA antigens in familial hyper-alphalipoproteinemia

Tissue Antigens, 1986

Tissue typing for HLA-A, B and C antigens was performed in 28 subjects belonging to a family in w... more Tissue typing for HLA-A, B and C antigens was performed in 28 subjects belonging to a family in which an inherited increase of high density lipoprotein cholesterol (HDL-C) is present. Nine subjects had definite hyper-alphalipoproteinemia (HDL-C greater than 80 mg/dl) and 3 "borderline" values (HDL-C greater than 70 mg/dl). There is not any linkage between the presence of HDL-C elevation and the HLA haplotypes.

Research paper thumbnail of Increase of serum alpha 1-acid glycoprotein despite the decline of liver synthetic function in cirrhotics with hepatocellular carcinoma

European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies, 1993

alpha 1-Acid glycoprotein, an acute phase reactant synthesised by the liver, has been reported to... more alpha 1-Acid glycoprotein, an acute phase reactant synthesised by the liver, has been reported to be increased in neoplastic conditions and reduced in chronic liver disease. We measured serum alpha 1-acid glycoprotein by a nephelometric method in 186 subjects (112 males, 74 females): 55 had mild chronic liver disease (chronic hepatitis and steatofibrosis), 45 cirrhosis, 38 hepatocellular carcinoma, 15 extra-hepatic malignant disease; 33 healthy subjects were used as controls. Analysis of variance demonstrated a significant variability among groups (F = 17.08, P = 0.0000). Higher concentrations of alpha 1-acid glycoprotein were detected in malignant extra-hepatic disease than in all other groups (P < 0.01); concentrations of alpha 1-acid glycoprotein were higher in hepatocellular carcinoma than in cirrhosis (P < 0.01). Multiple regression analysis by groups (dependent variable = alpha 1-acid glycoprotein; group 1 = mild chronic liver disease + cirrhosis; group 2 = hepatocellula...

Research paper thumbnail of Functional characterization of a novel genetic variant predisposing to hepatocellular carcinoma development in nonalcoholic fatty liver disease

Digestive and Liver Disease, 2018

Research paper thumbnail of Role of rare pathogenic mutations in the development of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

Digestive and Liver Disease

Research paper thumbnail of P.09.4 Evaluation of Prognostic Factors of Overall Survival and Progression-Free Survival in Patients with Hepatocellular Carcinoma (HCC)

Digestive and Liver Disease

Research paper thumbnail of Noninvasive risk stratification in nonalcoholic fatty liver disease: a polygenic risk score

Digestive and Liver Disease

Research paper thumbnail of TM6SF2/PNPLA3/MBOAT7 loss-of-function genetic variants impact on NAFLD development and progression both in patients and in in vitro models

Digestive and Liver Disease

Background and aims The I148M PNPLA3, the rs641738 in MBOAT7/TMC4 locus and the E167K TM6SF2 poly... more Background and aims The I148M PNPLA3, the rs641738 in MBOAT7/TMC4 locus and the E167K TM6SF2 polymorphisms represent the main predisposing factors to non-alcoholic fatty liver disease (NAFLD) development and progression. We previously generated a full knockout of MBOAT7 in HepG2 cells (MBOAT7-/-), homozygous for the I148M PNPLA3. Therefore, we aimed to:1) investigate the synergic impact of the 3 at-risk variants on liver injury and hepatocellular carcinoma (HCC) in a large cohort of NAFLD patients;2) create in vitro models of genetic NAFLD by silencing TM6SF2 in both HepG2 and MBOAT7-/- cells. Methods NAFLD patients (n=1380) of whom 121 had HCC were stratified with a semi-quantitative score ranging from 0 to 3 according to the number of PNPLA3, TM6SF2 and MBOAT7 at-risk variants. TM6SF2 was silenced in HepG2 (TM6SF2-/-) and MBOAT7-/- (MBOAT7-/-TM6SF2-/-) through CRISPR/Cas9. Results In NAFLD patients, the additive weight of these mutations was associated with liver disease severity and increased risk to develop HCC. In HepG2 cells, TM6SF2 silencing altered lipid composition and induced the accumulation of micro-vesicular LDs, whereas the MBOAT7-/-TM6SF2-/- cells showed a mixed micro/macro pattern of LDs. TM6SF2 deletion strongly affected endoplasmic reticulum (ER) and mitochondria ultrastructures thus increasing ER/oxidative stress. Mitochondrial number raised in both TM6SF2-/- and MBOAT7-/-TM6SF2-/- models, suggesting an unbalancing in mitochondrial dynamics and the silencing of both MBOAT7 and TM6SF2 impaired mitochondrial activity with a shift towards anaerobic glycolysis. MBOAT7-/-TM6SF2-/- cells also showed the highest proliferation rate. Conclusions The co-presence of the 3 at-risk variants impacts on NAFLD course, in both patients and experimental models affecting LDs accumulation, mitochondrial functionality and metabolic reprogramming towards HCC.

Research paper thumbnail of Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

Disease Markers

Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver ... more Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P<0.001); Bonferroni’s test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (p<0.0 I) and mild chronic liver disease (p<0.0S J. Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reacti ve protein, alkaline phosphatase and al-fetoprotein as predictor variables was significant (multiple R= 0.7056, multiple R2= 0.4978, F= 15.36, P= <0.0001). The standardized regression coefficient...

Research paper thumbnail of In Silico Identification and in Vivo Validation of Non-Invasive Biomarkers for Liver Fibrosis

Journal of Hepatology, 2016

Research paper thumbnail of Real life of DAAs (direct antiviral agents) for HCV infection in Friuli Venezia Giulia: Who, why, what, how did we treat?

Digestive and Liver Disease, 2016

Research paper thumbnail of O071 : Telomerase reverse transcriptase mutations are associated with hepatocellular carcinoma in nash

Journal of Hepatology, 2015

O071 TELOMERASE REVERSE TRANSCRIPTASE MUTATIONS ARE ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN N... more O071 TELOMERASE REVERSE TRANSCRIPTASE MUTATIONS ARE ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN NASH B. Donati, E. Vanni, P. Dongiovanni, M. Iavarone, R. Rametta, C. Rosso, A. Carnelutti, S. Petta, A.L. Fracanzani, H.L. Reeves, J.F. Dofour, L. Miele, Q. Anstee, E. Bugianesi, G. Soardo, S. Fargion, L. Valenti. Pathophysiology and Transplantation, Universita degli Studi di Milano, Milano, Medical Sciences, University of Turin, Turin, Internal Medicine, Gastroenterology, Fondazione IRCCS Ca’ Granda, Milano, Internal Medicine, University of Udine, Udine, Gastroenterology, University of Palermo, Palermo, Italy; Medicine, Freeman Hospital, Newcastle Upon Tyne, United Kingdom; Clinical Research, University of Bern, Bern, Switzerland; Internal Medicine, Catholic University, Rome, Italy; Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom; Gastroenterology, University of Turin, Turin, Italy E-mail: donatibenedetta@gmail.com

Research paper thumbnail of Intra-abdominal penetration and pharmacodynamic exposure to fluconazole in three liver transplant patients with deep-seated candidiasis

The Journal of antimicrobial chemotherapy, 2014

Research paper thumbnail of Prediction of serum markers of fibrosis by levels of circulating intercellular adhesion molecule-1 in acute and chronic liver disease

Clinical Biochemistry, 1994

To clarify the link between cytotoxic damage to the hepatocyte and the development of fibrosis, w... more To clarify the link between cytotoxic damage to the hepatocyte and the development of fibrosis, we immunoenzymatically measured serum prolyl hydroxylase (hPH), type IV collagen (CL-IV) and circulating intercellular adhesion molecule-1 (clCAM-1). The population studied was comprised of 122 patients with liver disease (acute hepatitis; mild chronic liver disease; cirrhosis; hepatocellular carcinoma) and 33 patients with extrahepatic diseases. Similar patterns were observed for hPH, CL-IV, and clCAM-1, that were higher in patients with acute hepatitis and hepatocellular carcinoma than in those with mild chronic liver disease (Bonferroni&#39;s test for pairwise comparisons, p &lt; 0.01). Liver function tests and markers of fibrosis showed a strict correlation, which disappeared when the linear effect of clCAM-1 was removed. The ability to predict serum hPH and CL-IV from clCAM-1 might suggest the existence of a causal relationship between fibrosis and targeting of cytotoxic damage.

Research paper thumbnail of Metabolic Aspects and Mechanisms

High Blood Pressure & Cardiovascular Prevention, 2008

Introduction. To investigate the relationship of serum insulin (I), leptin (L) and adiponectin (A... more Introduction. To investigate the relationship of serum insulin (I), leptin (L) and adiponectin (A) levels and their changes over time to the incidence of hypertension (HT) in men. Methods. The study population was made of 479 adult untreated normotensive (NT) men (mean age 51.6, range 25-74 years) participating in the 1994-1995 examination of the Olivetti Heart Study, who were examined again in 2002-2004 (8-year average follow-up) and had serum I, L and A measured in both occasions. Incident HT in 2002-20004 was defined as a BP more than 140 and/or 90 mmHg or current pharmacological treatment. Results. Both at baseline and at follow-up examination I and L were positively related and A inversely related to SBP and DBP (p between <0.001 and 0.02). The subjects who developed HT (54%) were older, had higher BMI, I and L levels and lower levels of A at baseline compared with those who remained NT (p between 0.01 and <0.001). By logistic regression, after adjustment for age and baseline SBP, a 1-SD positive difference in log transformed values of basal I, L or A level was associated with 22% higher (p=0.044), 30% higher (p=0.015) and 20% lower rate (p=0.029) of incident HT, respectively. Upon further adjustment for baseline BMI or waist circumference, the association was maintained only for baseline A (p=0.03). The changes occurred during the follow-up period in BMI (p<0.001), waist (p<0.001), I (p=0.01 5) and L (p=0.018) were also associated with higher rates, whereas the changes in A (p=0.10) with lower rates of incident HT, upon adjustment for age, baseline SBP and baseline level (rank) of the respective variables. Conclusions. In this adult male population, baseline insulin and leptin levels and their changes over time were associated with higher rates and adiponectin levels with lower rate of incident HT, independently of age and baseline BP levels. Adiponectin maintained its long-term influence on risk of HT also after adjustment for BMI or abdominal adiposity.

Research paper thumbnail of Henoch-Schonlein purpura in a patient with diabetic nephropathy and vascular complications

Nephrology Dialysis Transplantation, 2005

Research paper thumbnail of Elevated adiponectin levels in heavy drinkers are related to liver disease severity: Effects of alcohol withdrawal

Digestive and Liver Disease, 2008

Research paper thumbnail of Fluoxetine Disposition in Patients with Chronic Hepatitis C Treated with Interferon-α

Clinical Pharmacokinetics, 2010

Background and Objectives: Combination therapy with interferon-a and ribavirin is considered the ... more Background and Objectives: Combination therapy with interferon-a and ribavirin is considered the treatment of choice for chronic hepatitis C. However, interferon-a may induce severe depression. It has been suggested that interferon-a is able to modify cytochrome P450 (CYP) 1A2 and 2D6 activity. We therefore decided to study the effects of the interferon-a-2b pegylated derivative on fluoxetine disposition in patients receiving combination chemotherapy for chronic hepatitis C. Methods: After approval by the institutional ethics committee, 20 adult patients with chronic hepatitis C, but with no history of other liver diseases, were prospectively admitted to the study, which included phenotyping by means of a dextromethorphan test and evaluation of fluoxetine and norfluoxetine pharmacokinetic parameters (the area under the serum concentration-time curve, maximum serum concentration, time to reach the maximum serum concentration and terminal elimination half-life) before and after 2 months of continuous peginterferon-a-2b therapy. Results: The only statistically significant difference we observed was a significant reduction in the terminal elimination half-life of fluoxetine (from 47.30 to 33.23 hours; p = 0.014) after peginterferon-a-2b treatment. Conclusion: These data suggest that interferon-a may induce, rather than inhibit, the biotransformation of fluoxetine.

Research paper thumbnail of Circulating standard CD44 isoform in patients with liver disease: Relationship with other soluble adhesion molecules and evaluation of diagnostic usefulness

Clinical Biochemistry, 1997

To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. We studied 142 sub... more To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. We studied 142 subjects (90 male, 52 female): 14 had acute hepatitis (AH); 45, noncirrhotic chronic liver disease (CLD); 34, cirrhosis; 35 had extrahepatic diseases (EHD); and 14 were healthy controls. sCD44, soluble intercellular adhesion molecule-1 (slCAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured immunoenzymatically. Patients with AH or cirrhosis had higher sCD44 in comparison to CLD, EHD, and controls (p &lt; 0.01). On univariate analysis, sCD44 was associated with sVCAM-1, sICAM-1, bilirubin, cholinesterase, aspartate aminotransferase, and alkaline phosphatase (p &lt; 0.001). By stepwise discriminant analysis, a set of variables, including sCD44 and sVCAM-1, were entered into a model that allocated correctly 79% of observations (p &lt; 0.0001). However, when adhesion molecules were excluded, the model could still allocate correctly 72% of observations. Although sCD44 concentration increases during severe acute or chronic liver disease, its measurement adds little to the clinical information provided by traditional liver biochemistry.

Research paper thumbnail of Blood lipids of patients with chronic hepatitis: differences related to viral etiology

Clinica Chimica Acta, 1997

Research paper thumbnail of Increased burden of inherited IRF3 rare genetic variants in Europeans with severe NAFLD

Digestive and Liver Disease

Research paper thumbnail of HLA antigens in familial hyper-alphalipoproteinemia

Tissue Antigens, 1986

Tissue typing for HLA-A, B and C antigens was performed in 28 subjects belonging to a family in w... more Tissue typing for HLA-A, B and C antigens was performed in 28 subjects belonging to a family in which an inherited increase of high density lipoprotein cholesterol (HDL-C) is present. Nine subjects had definite hyper-alphalipoproteinemia (HDL-C greater than 80 mg/dl) and 3 "borderline" values (HDL-C greater than 70 mg/dl). There is not any linkage between the presence of HDL-C elevation and the HLA haplotypes.

Research paper thumbnail of Increase of serum alpha 1-acid glycoprotein despite the decline of liver synthetic function in cirrhotics with hepatocellular carcinoma

European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies, 1993

alpha 1-Acid glycoprotein, an acute phase reactant synthesised by the liver, has been reported to... more alpha 1-Acid glycoprotein, an acute phase reactant synthesised by the liver, has been reported to be increased in neoplastic conditions and reduced in chronic liver disease. We measured serum alpha 1-acid glycoprotein by a nephelometric method in 186 subjects (112 males, 74 females): 55 had mild chronic liver disease (chronic hepatitis and steatofibrosis), 45 cirrhosis, 38 hepatocellular carcinoma, 15 extra-hepatic malignant disease; 33 healthy subjects were used as controls. Analysis of variance demonstrated a significant variability among groups (F = 17.08, P = 0.0000). Higher concentrations of alpha 1-acid glycoprotein were detected in malignant extra-hepatic disease than in all other groups (P < 0.01); concentrations of alpha 1-acid glycoprotein were higher in hepatocellular carcinoma than in cirrhosis (P < 0.01). Multiple regression analysis by groups (dependent variable = alpha 1-acid glycoprotein; group 1 = mild chronic liver disease + cirrhosis; group 2 = hepatocellula...

Research paper thumbnail of Functional characterization of a novel genetic variant predisposing to hepatocellular carcinoma development in nonalcoholic fatty liver disease

Digestive and Liver Disease, 2018

Research paper thumbnail of Role of rare pathogenic mutations in the development of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

Digestive and Liver Disease

Research paper thumbnail of P.09.4 Evaluation of Prognostic Factors of Overall Survival and Progression-Free Survival in Patients with Hepatocellular Carcinoma (HCC)

Digestive and Liver Disease

Research paper thumbnail of Noninvasive risk stratification in nonalcoholic fatty liver disease: a polygenic risk score

Digestive and Liver Disease

Research paper thumbnail of TM6SF2/PNPLA3/MBOAT7 loss-of-function genetic variants impact on NAFLD development and progression both in patients and in in vitro models

Digestive and Liver Disease

Background and aims The I148M PNPLA3, the rs641738 in MBOAT7/TMC4 locus and the E167K TM6SF2 poly... more Background and aims The I148M PNPLA3, the rs641738 in MBOAT7/TMC4 locus and the E167K TM6SF2 polymorphisms represent the main predisposing factors to non-alcoholic fatty liver disease (NAFLD) development and progression. We previously generated a full knockout of MBOAT7 in HepG2 cells (MBOAT7-/-), homozygous for the I148M PNPLA3. Therefore, we aimed to:1) investigate the synergic impact of the 3 at-risk variants on liver injury and hepatocellular carcinoma (HCC) in a large cohort of NAFLD patients;2) create in vitro models of genetic NAFLD by silencing TM6SF2 in both HepG2 and MBOAT7-/- cells. Methods NAFLD patients (n=1380) of whom 121 had HCC were stratified with a semi-quantitative score ranging from 0 to 3 according to the number of PNPLA3, TM6SF2 and MBOAT7 at-risk variants. TM6SF2 was silenced in HepG2 (TM6SF2-/-) and MBOAT7-/- (MBOAT7-/-TM6SF2-/-) through CRISPR/Cas9. Results In NAFLD patients, the additive weight of these mutations was associated with liver disease severity and increased risk to develop HCC. In HepG2 cells, TM6SF2 silencing altered lipid composition and induced the accumulation of micro-vesicular LDs, whereas the MBOAT7-/-TM6SF2-/- cells showed a mixed micro/macro pattern of LDs. TM6SF2 deletion strongly affected endoplasmic reticulum (ER) and mitochondria ultrastructures thus increasing ER/oxidative stress. Mitochondrial number raised in both TM6SF2-/- and MBOAT7-/-TM6SF2-/- models, suggesting an unbalancing in mitochondrial dynamics and the silencing of both MBOAT7 and TM6SF2 impaired mitochondrial activity with a shift towards anaerobic glycolysis. MBOAT7-/-TM6SF2-/- cells also showed the highest proliferation rate. Conclusions The co-presence of the 3 at-risk variants impacts on NAFLD course, in both patients and experimental models affecting LDs accumulation, mitochondrial functionality and metabolic reprogramming towards HCC.

Research paper thumbnail of Increased Serum Phospholipase A2 Activity in Advanced Chronic Liver Disease as an Expression of the Acute Phase Response

Disease Markers

Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver ... more Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were f1uorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOV A demonstrated a significant difference among groups (F= 4.53, P<0.001); Bonferroni’s test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (p<0.0 I) and mild chronic liver disease (p<0.0S J. Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reacti ve protein, alkaline phosphatase and al-fetoprotein as predictor variables was significant (multiple R= 0.7056, multiple R2= 0.4978, F= 15.36, P= <0.0001). The standardized regression coefficient...

Research paper thumbnail of In Silico Identification and in Vivo Validation of Non-Invasive Biomarkers for Liver Fibrosis

Journal of Hepatology, 2016

Research paper thumbnail of Real life of DAAs (direct antiviral agents) for HCV infection in Friuli Venezia Giulia: Who, why, what, how did we treat?

Digestive and Liver Disease, 2016

Research paper thumbnail of O071 : Telomerase reverse transcriptase mutations are associated with hepatocellular carcinoma in nash

Journal of Hepatology, 2015

O071 TELOMERASE REVERSE TRANSCRIPTASE MUTATIONS ARE ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN N... more O071 TELOMERASE REVERSE TRANSCRIPTASE MUTATIONS ARE ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN NASH B. Donati, E. Vanni, P. Dongiovanni, M. Iavarone, R. Rametta, C. Rosso, A. Carnelutti, S. Petta, A.L. Fracanzani, H.L. Reeves, J.F. Dofour, L. Miele, Q. Anstee, E. Bugianesi, G. Soardo, S. Fargion, L. Valenti. Pathophysiology and Transplantation, Universita degli Studi di Milano, Milano, Medical Sciences, University of Turin, Turin, Internal Medicine, Gastroenterology, Fondazione IRCCS Ca’ Granda, Milano, Internal Medicine, University of Udine, Udine, Gastroenterology, University of Palermo, Palermo, Italy; Medicine, Freeman Hospital, Newcastle Upon Tyne, United Kingdom; Clinical Research, University of Bern, Bern, Switzerland; Internal Medicine, Catholic University, Rome, Italy; Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom; Gastroenterology, University of Turin, Turin, Italy E-mail: donatibenedetta@gmail.com

Research paper thumbnail of Intra-abdominal penetration and pharmacodynamic exposure to fluconazole in three liver transplant patients with deep-seated candidiasis

The Journal of antimicrobial chemotherapy, 2014

Research paper thumbnail of Prediction of serum markers of fibrosis by levels of circulating intercellular adhesion molecule-1 in acute and chronic liver disease

Clinical Biochemistry, 1994

To clarify the link between cytotoxic damage to the hepatocyte and the development of fibrosis, w... more To clarify the link between cytotoxic damage to the hepatocyte and the development of fibrosis, we immunoenzymatically measured serum prolyl hydroxylase (hPH), type IV collagen (CL-IV) and circulating intercellular adhesion molecule-1 (clCAM-1). The population studied was comprised of 122 patients with liver disease (acute hepatitis; mild chronic liver disease; cirrhosis; hepatocellular carcinoma) and 33 patients with extrahepatic diseases. Similar patterns were observed for hPH, CL-IV, and clCAM-1, that were higher in patients with acute hepatitis and hepatocellular carcinoma than in those with mild chronic liver disease (Bonferroni&#39;s test for pairwise comparisons, p &lt; 0.01). Liver function tests and markers of fibrosis showed a strict correlation, which disappeared when the linear effect of clCAM-1 was removed. The ability to predict serum hPH and CL-IV from clCAM-1 might suggest the existence of a causal relationship between fibrosis and targeting of cytotoxic damage.

Research paper thumbnail of Metabolic Aspects and Mechanisms

High Blood Pressure & Cardiovascular Prevention, 2008

Introduction. To investigate the relationship of serum insulin (I), leptin (L) and adiponectin (A... more Introduction. To investigate the relationship of serum insulin (I), leptin (L) and adiponectin (A) levels and their changes over time to the incidence of hypertension (HT) in men. Methods. The study population was made of 479 adult untreated normotensive (NT) men (mean age 51.6, range 25-74 years) participating in the 1994-1995 examination of the Olivetti Heart Study, who were examined again in 2002-2004 (8-year average follow-up) and had serum I, L and A measured in both occasions. Incident HT in 2002-20004 was defined as a BP more than 140 and/or 90 mmHg or current pharmacological treatment. Results. Both at baseline and at follow-up examination I and L were positively related and A inversely related to SBP and DBP (p between <0.001 and 0.02). The subjects who developed HT (54%) were older, had higher BMI, I and L levels and lower levels of A at baseline compared with those who remained NT (p between 0.01 and <0.001). By logistic regression, after adjustment for age and baseline SBP, a 1-SD positive difference in log transformed values of basal I, L or A level was associated with 22% higher (p=0.044), 30% higher (p=0.015) and 20% lower rate (p=0.029) of incident HT, respectively. Upon further adjustment for baseline BMI or waist circumference, the association was maintained only for baseline A (p=0.03). The changes occurred during the follow-up period in BMI (p<0.001), waist (p<0.001), I (p=0.01 5) and L (p=0.018) were also associated with higher rates, whereas the changes in A (p=0.10) with lower rates of incident HT, upon adjustment for age, baseline SBP and baseline level (rank) of the respective variables. Conclusions. In this adult male population, baseline insulin and leptin levels and their changes over time were associated with higher rates and adiponectin levels with lower rate of incident HT, independently of age and baseline BP levels. Adiponectin maintained its long-term influence on risk of HT also after adjustment for BMI or abdominal adiposity.

Research paper thumbnail of Henoch-Schonlein purpura in a patient with diabetic nephropathy and vascular complications

Nephrology Dialysis Transplantation, 2005

Research paper thumbnail of Elevated adiponectin levels in heavy drinkers are related to liver disease severity: Effects of alcohol withdrawal

Digestive and Liver Disease, 2008

Research paper thumbnail of Fluoxetine Disposition in Patients with Chronic Hepatitis C Treated with Interferon-α

Clinical Pharmacokinetics, 2010

Background and Objectives: Combination therapy with interferon-a and ribavirin is considered the ... more Background and Objectives: Combination therapy with interferon-a and ribavirin is considered the treatment of choice for chronic hepatitis C. However, interferon-a may induce severe depression. It has been suggested that interferon-a is able to modify cytochrome P450 (CYP) 1A2 and 2D6 activity. We therefore decided to study the effects of the interferon-a-2b pegylated derivative on fluoxetine disposition in patients receiving combination chemotherapy for chronic hepatitis C. Methods: After approval by the institutional ethics committee, 20 adult patients with chronic hepatitis C, but with no history of other liver diseases, were prospectively admitted to the study, which included phenotyping by means of a dextromethorphan test and evaluation of fluoxetine and norfluoxetine pharmacokinetic parameters (the area under the serum concentration-time curve, maximum serum concentration, time to reach the maximum serum concentration and terminal elimination half-life) before and after 2 months of continuous peginterferon-a-2b therapy. Results: The only statistically significant difference we observed was a significant reduction in the terminal elimination half-life of fluoxetine (from 47.30 to 33.23 hours; p = 0.014) after peginterferon-a-2b treatment. Conclusion: These data suggest that interferon-a may induce, rather than inhibit, the biotransformation of fluoxetine.

Research paper thumbnail of Circulating standard CD44 isoform in patients with liver disease: Relationship with other soluble adhesion molecules and evaluation of diagnostic usefulness

Clinical Biochemistry, 1997

To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. We studied 142 sub... more To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. We studied 142 subjects (90 male, 52 female): 14 had acute hepatitis (AH); 45, noncirrhotic chronic liver disease (CLD); 34, cirrhosis; 35 had extrahepatic diseases (EHD); and 14 were healthy controls. sCD44, soluble intercellular adhesion molecule-1 (slCAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured immunoenzymatically. Patients with AH or cirrhosis had higher sCD44 in comparison to CLD, EHD, and controls (p &lt; 0.01). On univariate analysis, sCD44 was associated with sVCAM-1, sICAM-1, bilirubin, cholinesterase, aspartate aminotransferase, and alkaline phosphatase (p &lt; 0.001). By stepwise discriminant analysis, a set of variables, including sCD44 and sVCAM-1, were entered into a model that allocated correctly 79% of observations (p &lt; 0.0001). However, when adhesion molecules were excluded, the model could still allocate correctly 72% of observations. Although sCD44 concentration increases during severe acute or chronic liver disease, its measurement adds little to the clinical information provided by traditional liver biochemistry.

Research paper thumbnail of Blood lipids of patients with chronic hepatitis: differences related to viral etiology

Clinica Chimica Acta, 1997