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Article ; Online: Portosystemic Shunt Embolization and Recurrent Ascites: A Single-Center Case Series.

Privitera, Graziella / Figorilli, Francesco / Jalan, Rajiv / Mehta, Gautam

2018 Volume 155, Issue 5, Page(s) 1649–1650

MeSH term(s)	Ascites ; Embolization, Therapeutic ; Humans ; Hypertension, Portal ; Portasystemic Shunt, Transjugular Intrahepatic ; Treatment Outcome
Language	English
Publishing date	2018-08-15
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2018.06.092
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Article: An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature.

Privitera, Graziella / Meli, Giovanni

Gastroenterology and hepatology from bed to bench

2016 Volume 9, Issue 4, Page(s) 335–339

Abstract: Chronic anemia is common in liver cirrhosis. In this setting, the pathogenesis of anemia is complex and multifactorial. Spur cell anemia is a serious disorder in cirrhotic patients and is associated with poor prognosis. Liver transplantation constitutes ... ...

Abstract	Chronic anemia is common in liver cirrhosis. In this setting, the pathogenesis of anemia is complex and multifactorial. Spur cell anemia is a serious disorder in cirrhotic patients and is associated with poor prognosis. Liver transplantation constitutes the only therapeutic tool. We report a case with severe spur cell anemia in alcoholic liver cirrhosis. In the attempt to investigate the origin of the disorder, we have evaluated the lipoprotein profile and found a significant reduction of apolipoprotein AI and HDL
Language	English
Publishing date	2016-11-15
Publishing country	Iran
Document type	Case Reports
ZDB-ID	2569124-7
ISSN	2008-4234 ; 2008-2258
ISSN (online)	2008-4234
ISSN	2008-2258
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Article ; Online: Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

Privitera, Graziella / Spadaro, Luisa / Marchisello, Simona / Fede, Giuseppe / Purrello, Francesco

Digestive diseases and sciences

2018 Volume 63, Issue 1, Page(s) 16–26

Abstract: Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver ... ...

Abstract	Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.
MeSH term(s)	Hepatitis C/complications ; Humans ; Lipoproteins/blood ; Liver Cirrhosis/blood ; Liver Cirrhosis/etiology ; Liver Cirrhosis, Alcoholic/blood
Chemical Substances	Lipoproteins
Language	English
Publishing date	2018-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-017-4862-x
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Article: Cardiovascular dysfunction in patients with liver cirrhosis.

Fede, Giuseppe / Privitera, Graziella / Tomaselli, Tania / Spadaro, Luisa / Purrello, Francesco

Annals of gastroenterology

2015 Volume 28, Issue 1, Page(s) 31–40

Abstract: Hyperdynamic syndrome is a well-known clinical condition found in patients with cirrhosis and portal hypertension, characterized by increased heart rate and cardiac output, and reduced systemic vascular resistance and arterial blood pressure. The leading ...

Abstract	Hyperdynamic syndrome is a well-known clinical condition found in patients with cirrhosis and portal hypertension, characterized by increased heart rate and cardiac output, and reduced systemic vascular resistance and arterial blood pressure. The leading cause of hyperdynamic circulation in cirrhotic patients is peripheral and splanchnic vasodilatation, due to an increased production/activity of vasodilator factors and decreased vascular reactivity to vasoconstrictors. The term "cirrhotic cardiomyopathy" describes impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in patients with cirrhosis without known cardiac disease. Underlying circulatory and cardiac dysfunctions are the main determinant in the development of hepatorenal syndrome in advanced cirrhosis. Moreover, the clinical consequences of cirrhosis-related cardiovascular dysfunction are evident during and after liver transplantation, and after transjugular intrahepatic portosystemic shunt insertion. Cardiovascular complications following these procedures are common, with pulmonary edema being the most common complication. Other complications include overt heart failure, arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus formation. This review discusses the circulatory and cardiovascular dysfunctions in cirrhosis, examining the pathophysiologic and clinical implications in light of the most recent published literature.
Language	English
Publishing date	2015-01-21
Publishing country	Greece
Document type	Review
ZDB-ID	2032850-3
ISSN	1108-7471
ISSN	1108-7471
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Article: Direct oral anticoagulant treatment of deep vein thrombosis reduces IL-6 expression in peripheral mono-nuclear blood cells.

Candido, Saverio / Lumera, Giovanni / Barcellona, Giuliana / Vetri, Davide / Tumino, Elda / Platania, Ingrid / Frazzetto, Evelise / Privitera, Graziella / Incognito, Carmela / Gaudio, Agostino / Signorelli, Salvatore Santo

Experimental and therapeutic medicine

2020 Volume 20, Issue 6, Page(s) 237

Abstract: Multiple factors play a pathophysiologic role for the venous thromboembolism (VTE) as a multi-factorial disease. Inflammation might play a peculiar role in shifting towards a pro-thrombotic state. Anticoagulant drugs are the first cure line for VTE. The ... ...

Abstract	Multiple factors play a pathophysiologic role for the venous thromboembolism (VTE) as a multi-factorial disease. Inflammation might play a peculiar role in shifting towards a pro-thrombotic state. Anticoagulant drugs are the first cure line for VTE. The low-molecular-weight heparins (LMWH) show anti-coagulant capability as well as reducing levels of inflammatory factors, including interleukin (IL)-6. The direct oral anticoagulants (DOACs) have shown efficacy in threating VTE, additionally to the anti-activated factor X these drugs seem able to reduce the abnormal release of pro-inflammatory agents. The present study evaluated the capability of DOACs in reducing plasma level of IL-6 in patients suffered from deep vein thrombosis (DVT) of the lower limbs. Our results showed reduced IL-6 expression levels in the peripheral lymphocytes of DVT compared to controls (fold-change, 2.8; P<0.05). We postulate that lowered IL-6 expression in the lymphocytes of DVT patients may mediate the anti-inflammatory action of DOACs. The present study is the first evidence concerning the anti-inflammatory properties of DOACs in specific setting of VTE patients such as DVT.
Language	English
Publishing date	2020-10-21
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2020.9367
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Article ; Online: Emerging hepatic syndromes: pathophysiology, diagnosis and treatment.

Bertino, Gaetano / Privitera, Graziella / Purrello, Francesco / Demma, Shirin / Crisafulli, Emanuele / Spadaro, Luisa / Koukias, Nikolaos / Tsochatzis, Emmanuel A

Internal and emergency medicine

2016 Volume 11, Issue 7, Page(s) 905–916

Abstract: Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic ... ...

Abstract	Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions.
MeSH term(s)	Acute Kidney Injury/etiology ; Adrenal Insufficiency/complications ; Adrenal Insufficiency/etiology ; Ascites/complications ; Ascites/etiology ; Creatinine/urine ; Evidence-Based Medicine/methods ; Hepatorenal Syndrome/complications ; Hepatorenal Syndrome/etiology ; Hepatorenal Syndrome/physiopathology ; Humans ; Hypertension, Portal/complications ; Hypertension, Portal/physiopathology ; Liver Cirrhosis/complications ; Liver Cirrhosis/etiology ; Liver Cirrhosis/physiopathology ; Liver Transplantation ; Lypressin/analogs & derivatives ; Lypressin/pharmacology ; Lypressin/therapeutic use ; Midodrine/pharmacology ; Midodrine/therapeutic use ; Norepinephrine/pharmacology ; Norepinephrine/therapeutic use ; Octreotide/pharmacology ; Octreotide/therapeutic use ; Plasma Substitutes/pharmacology ; Plasma Substitutes/therapeutic use ; Portasystemic Shunt, Transjugular Intrahepatic ; Serum Albumin/pharmacology ; Serum Albumin/therapeutic use ; Vasodilator Agents/pharmacology ; Vasodilator Agents/therapeutic use ; Vasopressins/pharmacology ; Vasopressins/therapeutic use
Chemical Substances	Plasma Substitutes ; Serum Albumin ; Vasodilator Agents ; Vasopressins (11000-17-2) ; Lypressin (50-57-7) ; Midodrine (6YE7PBM15H) ; terlipressin (7Z5X49W53P) ; Creatinine (AYI8EX34EU) ; Octreotide (RWM8CCW8GP) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2016-10
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2454173-4
ISSN	1970-9366 ; 1828-0447
ISSN (online)	1970-9366
ISSN	1828-0447
DOI	10.1007/s11739-016-1478-7
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Article ; Online: Hepatic insulin resistance in NAFLD: relationship with markers of atherosclerosis and metabolic syndrome components.

Privitera, Graziella / Spadaro, Luisa / Alagona, Corradina / Calanna, Salvatore / Piro, Salvatore / Rabuazzo, Agata Maria / Purrello, Francesco

Acta diabetologica

2016 Volume 53, Issue 3, Page(s) 449–459

Abstract: Aims: Fat accumulation in the liver and in the muscle results in hepatic and muscle insulin resistance and has been associated with increased cardiovascular risk. It is unclear whether the individual role of hepatic and muscle insulin resistance in the ... ...

Abstract	Aims: Fat accumulation in the liver and in the muscle results in hepatic and muscle insulin resistance and has been associated with increased cardiovascular risk. It is unclear whether the individual role of hepatic and muscle insulin resistance in the onset of dyslipidaemia is observed in nonalcoholic fatty liver disease (NAFLD) patients and whether this association is mediated through traditional risk factors. The aim of this study was to assess hepatic and muscle insulin resistance in NAFLD and its relationship with carotid artery intima-media thickness (IMT) and the apoB/apoAI ratio as markers of atherosclerosis. Methods: We studied 132 patients with a non-invasive diagnosis of NAFLD stratified into two groups according to the severity of steatosis at ultrasound scan. In all subjects, we measured hepatic insulin resistance (H-IR) and muscle insulin sensitivity index (MISI) by oral glucose tolerance test as proposed by DeFronzo, IMT, apoB/apoAI and the components of the metabolic syndrome (MS) as defined by ATP III. Results: H-IR was significantly higher in moderate/severe steatosis than in the mild steatosis group (p < 0.0001). By contrast, MISI did not differ between the two groups. There was a significant correlation between H-IR, MISI and all of the components of MS. H-IR was significantly correlated with carotid IMT (r = 0.35; p < 0.0001) and the apoB/apoAI ratio (r = 0.43; p < 0.0001). Otherwise, a significant correlation was observed only between MISI and apoB/apoAI ratio. Multivariate analysis revealed that H-IR is related to early markers of atherosclerosis independent of MS components. Conclusions: In our study population, NAFLD was positively associated with carotid IMT, and this association is independent of MS components, but strictly related to H-IR that might contribute to the development of atherosclerosis through an impairment of the lipid profile in terms of the apoB/apoAI ratio. By contrast, no significant relation was observed between MISI and carotid IMT.
MeSH term(s)	Adolescent ; Adult ; Aged ; Apolipoprotein A-I/blood ; Biomarkers/blood ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/epidemiology ; Female ; Humans ; Insulin Resistance ; Liver/metabolism ; Male ; Metabolic Syndrome/blood ; Metabolic Syndrome/epidemiology ; Middle Aged ; Non-alcoholic Fatty Liver Disease/blood ; Non-alcoholic Fatty Liver Disease/epidemiology
Chemical Substances	APOA1 protein, human ; Apolipoprotein A-I ; Biomarkers
Language	English
Publishing date	2016-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1097676-0
ISSN	1432-5233 ; 0940-5429
ISSN (online)	1432-5233
ISSN	0940-5429
DOI	10.1007/s00592-015-0816-y
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Article ; Online: Diabetes increases renovascular impedance in patients with liver cirrhosis.

Spadaro, Luisa / Privitera, Graziella / Fede, Giuseppe / Magliocco, Orazio / Russello, Maurizio / Piro, Salvatore / Rabuazzo, Agata Maria / Purrello, Francesco

Internal and emergency medicine

2015 Volume 10, Issue 6, Page(s) 703–709

Abstract: Renal failure is a common complication of cirrhosis and is associated with poor prognosis. Several reports have demonstrated the clinical utility of renal resistive indices in the assessment of renal function in cirrhosis patients. It is unknown whether ... ...

Abstract	Renal failure is a common complication of cirrhosis and is associated with poor prognosis. Several reports have demonstrated the clinical utility of renal resistive indices in the assessment of renal function in cirrhosis patients. It is unknown whether the occurrence of diabetes affects renal haemodynamic indices in patients with cirrhosis. Therefore, the aim of our study was to compare renal Doppler indices in cirrhotic patients with and without type 2 diabetes mellitus (T2DM) and in diabetics without cirrhosis, and to relate the Doppler parameters to albuminuria. We evaluated 89 consecutive patients with normal renal functioning, including 37 with cirrhosis and T2DM (CD-Group), 41 with cirrhosis without diabetes (C-Group) and 11 with diabetes without cirrhosis (D-Group). The kidney pulsatility index (PI) and resistance index (RI) were measured by Doppler ultrasound. Renal function was expressed as the estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula. Microalbuminuria (µAlb) was also evaluated. No significant differences were observed with respect to age, the Child-Pugh class or the serum creatinine level. The eGFR was mildly reduced in the CD-Group compared with the C-Group and D-Group, and µAlb was present in 24.4 % of the patients in the CD-Group and in 9 % of those in the D-Group. The PI and RI were significantly increased in the CD-Group and D-Group compared with the C-Group. Both the PI and RI were significantly associated with µAlb independent of age and Child-Pugh class. The novel finding of this study was that T2DM potentially impairs renal haemodynamics in patients with cirrhosis.
MeSH term(s)	Aged ; Creatinine/analysis ; Creatinine/blood ; Diabetes Mellitus, Type 2/complications ; Female ; Humans ; Kidney/physiopathology ; Liver Cirrhosis/complications ; Liver Cirrhosis/physiopathology ; Male ; Middle Aged ; Renal Insufficiency/diagnosis ; Renal Insufficiency/etiology ; Vascular Resistance/physiology
Chemical Substances	Creatinine (AYI8EX34EU)
Language	English
Publishing date	2015-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2454173-4
ISSN	1970-9366 ; 1828-0447
ISSN (online)	1970-9366
ISSN	1828-0447
DOI	10.1007/s11739-015-1235-3
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Article ; Online: Hypothalamus-pituitary dysfunction is common in patients with stable cirrhosis and abnormal low dose synacthen test.

Fede, Giuseppe / Spadaro, Luisa / Privitera, Graziella / Tomaselli, Tania / Bouloux, Pierre-Marc / Purrello, Francesco / Burroughs, Andrew Kenneth

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2015 Volume 47, Issue 12, Page(s) 1047–1051

Abstract: Background: Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal ... ...

Abstract	Background: Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics. Methods: Prospective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal. Results: 46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198 nmol/L; p=0.02). Using ROC curve basal cortisol <254 nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p=0.001) with good accuracy (sensitivity 67%, specificity 81%). Conclusion: A delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment.
MeSH term(s)	Adrenal Insufficiency/blood ; Adult ; Aged ; Aged, 80 and over ; Cosyntropin/blood ; Female ; Humans ; Hydrocortisone/blood ; Hypothalamo-Hypophyseal System/physiopathology ; Liver Cirrhosis/physiopathology ; Male ; Middle Aged ; Pituitary-Adrenal System/physiopathology ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity
Chemical Substances	Cosyntropin (16960-16-0) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2015-12
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2015.08.006
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Article ; Online: Serum coding and non-coding RNAs as biomarkers of NAFLD and fibrosis severity.

Liver international : official journal of the International Association for the Study of the Liver

2019 Volume 39, Issue 9, Page(s) 1742–1754

Abstract: Background & aims: In patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non-alcoholic steatohepatitis (NASH) and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non-coding ... ...

Abstract	Background & aims: In patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non-alcoholic steatohepatitis (NASH) and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non-coding RNAs in serum samples of biopsy-diagnosed mild and severe NAFLD patients with respect to controls and to each other. Methods: We first performed a whole transcriptome analysis through microarray (n = 12: four Control: CTRL; four mild NAFLD: NAS ≤ 4 F0; four severe NAFLD NAS ≥ 5 F3), followed by validation of selected transcripts through real-time PCRs in an independent internal cohort of 88 subjects (63 NAFLD, 25 CTRL) and in an external cohort of 50 NAFLD patients. A similar analysis was also performed on liver biopsies and HepG2 cells exposed to oleate:palmitate or only palmitate (cellular model of NAFL/NASH) at intracellular/extracellular levels. Transcript correlation with histological/clinical data was also analysed. Results: We identified several differentially expressed coding/non-coding RNAs in each group of the study cohort. We validated the up-regulation of UBE2V1, BNIP3L mRNAs, RP11-128N14.5 lncRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with NAS ≥ 5 (vs NAS ≤ 4) and the up-regulation of HBA2 mRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with Fibrosis stages = 3-4 (vs F = 0-2). In in vitro models: UBE2V1, RP11-128N14.5 and TGFB2/TGFB2-OT1 had an increasing expression trend ranging from CTRL to oleate:palmitate or only palmitate-treated cells both at intracellular and extracellular level, while BNIP3L was up-regulated only at extracellular level. UBE2V1, RP11-128N14.5, TGFB2/TGFB2-OT1 and HBA2 up-regulation was also observed at histological level. UBE2V1, RP11-128N14.5, BNIP3L and TGFB2/TGFB2-OT1 correlated with histological/biochemical data. Combinations of TGFB2/TGFB2-OT1 + Fibrosis Index based on the four factors (FIB-4) showed an Area Under the Curve (AUC) of 0.891 (P = 3.00E-06) or TGFB2/TGFB2-OT1 + Fibroscan (AUC = 0.892, P = 2.00E-06) improved the detection of F = 3-4 with respect to F = 0-2 fibrosis stages. Conclusions: We identified specific serum coding/non-coding RNA profiles in severe and mild NAFLD patients that possibly mirror the molecular mechanisms underlying NAFLD progression towards NASH/fibrosis. TGFB2/TGFB2-OT1 detection improves FIB-4/Fibroscan diagnostic performance for advanced fibrosis discrimination.
MeSH term(s)	Adult ; Biomarkers/blood ; Biopsy ; Cohort Studies ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Liver/enzymology ; Liver/pathology ; Liver Cirrhosis/blood ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/pathology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/blood ; Non-alcoholic Fatty Liver Disease/diagnosis ; Non-alcoholic Fatty Liver Disease/pathology ; Predictive Value of Tests ; RNA, Untranslated/blood ; ROC Curve ; Severity of Illness Index
Chemical Substances	Biomarkers ; RNA, Untranslated
Language	English
Publishing date	2019-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.14167
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