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In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care. Digestive diseases were the first or second cause of hospitalizations in Italy in 1999–2009, with more than 1,500,000 admissions/year; however only 5–9% of these admissions was in specialized Gastroenterology units. Reported data show a better outcome in Gastroenterology Units than in non-specialized units: shorter average length of stay, in particular for admissions with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days); better case mix (higher average diagnosis-related groups weight in Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery units); lower inappropriateness of admissions (16–25% versus 29–87%); lower in-hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was 2.3% in Gastroenterology units versus 4.0% in others. The present document summarizes the scientific societies’ official report, which constitutes the “White paper of Italian Gastroenterology”

In rats with experimental liver cirrhosis, the kidney contains reduced amounts of membrane-bound CaRs (calcium-sensing receptors), and the specific stimulation of CaRs causes the generation of PGE2 (prostaglandin E2), renal vasodilation and increased natriuresis. CaR content and function in the liver of cirrhotic rats are unknown. To assess the activity of this Ca2+-dependent vasomotor system, we evaluated the effects of intravenous administration of PolyAg (poly-L-arginine), a selective CaR agonist, on hormonal status, portal haemodynamics, MAP (mean arterial pressure) in rats with liver cirrhosis induced by chronic CCl4 (carbon tetrachloride) administration. Two groups of eight control rats received intravenously 1 ml of 5% (w/v) glucose solution alone or containing 0.5 mg of PolyAg; two groups of ten cirrhotic rats were administered vehicle or PolyAg. Compared with controls, at baseline cirrhotic rats showed higher portal pressure (P

Preascitic cirrhosis is characterised by subtle renal sodium retention. Calcium inhibits Na(+)-K(+)-2Cl(-) cotransport in the Henle's loop and could potentially correct sodium-handling abnormalities at that site.To investigate the effects of calcium infusion on sodium handling in 10 patients with preascitic cirrhosis and nine healthy controls after 1 week of sodium loading of 200 mmol sodium/day.All patients underwent a 3 h supine determination of inulin, para-aminohippurate, lithium and free-water clearances, absolute and fractional excretions of sodium, potassium and calcium and plasma concentrations of renin, aldosterone, norepinephrine and vasopressin. The same were repeated over a further 3 h supine period including 60 min intravenous infusion of 33 mg/min calcium gluconate.After sodium loading, the 24 h urinary sodium excretion in patients with cirrhosis was lower than that in controls (p0.03). Calcium infusion significantly decreased plasma norepinephrine levels (p0.03), and induced greater increases in fractional delivery of sodium to the Henle's loop (p0.5) in those with cirrhosis than in controls. This was associated with a decreased fractional reabsorption of sodium beyond the proximal tubule (p0.03), resulting in greater urinary volume, sodium excretion and free-water clearance in those with cirrhosis than in controls (all with p0.05). Because the aldosterone-driven potassium secretion, as assessed by the computation of tubular-capillary gradient of [K(+)] in the collecting duct, was similar in the two groups and unaffected by calcium, sodium retention must have occurred in the Henle's loop in those with cirrhosis.Calcium is natriuretic in patients with preascitic cirrhosis; it also decreases norepinephrine release, which could be responsible for decreased reabsorption of sodium in the Henle's loop.

Catecholamines trigger proximal tubular fluid retention and reduce renal excretion of solute-free water. In advanced cirrhosis, non-osmotic hypersecretion of vasopressin (antidiuretic hormone or ADH) is considered the cause of dilutional hyponatraemia, but ADH V2 receptor antagonists are not beneficial in long-term treatment of ascites. To test the hypothesis that water retention in experimental ascitic cirrhosis might depend primarily on adrenergic hyper-function, hormonal status, renal function and tubular free-water reabsorption (TFWR) were assessed in six groups of rats with ascitic cirrhosis: rats with cirrhosis due to 13-week CCl4 (carbon tetrachloride) administration (group G1); cirrhotic rats receiving daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K+-canrenoate) from the 11th to the 13th week of CCl4 (G2), diuretics associated with guanfacine oral prodrug (α2A-adrenergic receptor agonist and sympatholytic agent) at 2 (G3), 7 (G4) or 10 (G5) mg/kg, or with SSP-004240F1 (V2 receptor antagonist) at 1 mg/kg (G6). Natriuresis was lower in G1 than in G2, G4 and G6 (all P

Background and aim. In preascitic cirrhosis increased sodium retention occurs in kidney distal tubule in spite of normal aldosterone plasma levels. No clearance technique can dissect the respective contribution to sodium retention exerted by Henle's loop, distal convoluted tubule and collecting duct, so we evaluated proximal and distal tubular sodium handling in preascites during two manoeuvres that temporarily increase aldosterone secretion. Methods. Ten patients with compensated cirrhosis and nine controls were studied in recumbency, during standing and after dopamine receptor blockade with metoclopramide through: 4 h renal clearances of sodium, potassium, lithium and creatinine; plasma levels of active renin and aldosterone. Results. Whilst comparable in recumbency, aldosterone levels significantly rose during standing and after metoclopramide in both groups. In patients, dopaminergic blockade caused a fall of distal sodium delivery (P

Background and aims. Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human–environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm. Patients and methods. Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66 ± 11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65 ± 11 years); Healthy controls (238 patients, M/F 117/121, mean age 63 ± 10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion. Results. No statistically significant differences in the genotype distribution among Control and Adenoma groups (p = 0.93), Control and Carcinoma groups (p = 0.52), and Adenoma and Carcinoma groups (p = 0.53) were observed. Conclusion. There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.

Background & Aims Sympathetic nervous system (SNS) activation decreases response to diuretics, but both α1-adrenoceptor agonists and sympatholytic α2-adrenoceptor agonists are recommended in the management of ascitic cirrhosis. We intend to compare the effects of increasing doses of clonidine (α2-agonist) vs. midodrine (α1-agonist) in advanced cirrhosis. Methods Renal function, mean arterial pressure (MAP), and hormonal status were measured in rats with ascitic cirrhosis due to 13-week CCl4 administration (groups G1-G5), in control rats (Gc), and in rats with ascitic cirrhosis untreated (G6) or treated with daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K+-canrenoate during the 11th–13th weeks of CCl4) (G7). G1–G5 cirrhotic rats received daily, during the 11th–13th CCl4 weeks: clonidine 0.3 μg only (G1), diuretics + clonidine 0.2 (G2), 0.5 (G3) or 1 μg (G4), and diuretics + midodrine 1 mg/kg b.w. (G5). Results Cirrhotic rats in G1 or G2 had higher glomerular filtration rate, renal plasma flow and natriuresis than cirrhotic rats treated with diuretics (G7) (all P

OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 ± 11.8 vs 3.5 ± 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = −0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.

In normal humans, plasma dopamine levels rise during head-out water immersion or saline intravenous infusion. Dopamine inhibits NA+,K+-ATPase activity in the proximal tubule and blunts aldosterone secretion leading to increased diuresis and natriuresis. The aim of this study is to evaluate the role of endogenous dopaminergic activity in the intrarenal sodium handling in patients with compensated liver cirrhosis. We studied nine healthy controls and 12 patients with Child-Pugh A cirrhosis during a normosodic diet for (1) dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min after intravenous metoclopramide administration; (2) basal plasma levels of active renin and aldosterone; (3) 4-hr renal clearance of lithium (an index of fluid delivery to the distal tubule), creatinine, sodium, and potassium, first without and then with dopaminergic blockade with intravenous metoclopramide. The patients displayed greater endogenous dopaminergic activity, evidenced by higher incremental aldosterone responses compared with controls (+30 min: 160.2 ± 68.8 vs 83.6 ± 35.2 pg/ml, P < 0.01; +60 min: 140.5 ± 80.3 vs 36.8 ± 39.1 pg/ml, P < 0.01, respectively). In spite of this, patients and controls did not show significantly different basal aldosterone plasma levels, delivery of sodium to the distal nephron, or urinary excretion of sodium. In both groups the dopaminergic blockade with metoclopramide determined no change in sodium and potassium urinary excretion, but it caused a fall of the fluid and sodium delivery from the proximal tubule to the distal nephron among the patients (from 30.7 ± 9.3 to 14.4 ± 4.5 ml/min, P < 0.001; and from 4.25 ± 1.30 to 2.00 ± 0.64 meq/min, P < 0.001, respectively). In this group the natriuresis was maintained due to a reduction of the reabsorbed fraction of the distal sodium delivery (from 97.5 ± 1.9% to 89.8 ± 12.4%, P < 0.05). In conclusions, compensated cirrhotic patients display an increased endogenous dopaminergic activity compared with controls. This function is critical in maintaining the delivery of sodium to the distal nephron.

Background The activity of epithelial lactase ( LCT ) associates with a polymorphism 13910 bp upstream the LCT -encoding gene ( LCT-13910C > T ). The relationship between LCT-13910C > T polymorphism and risk for colorectal cancer is unclear. Aims We examined the relationship between the LCT-13910C > T polymorphism causing lactose intolerance and risk for colorectal cancer/polyps onset in the Italian population. Patients and methods 793 subjects (306 with colorectal cancer, 176 with polyps and 311 controls) were genotyped for the LCT-13910C > T variant by TaqMan real time-PCR. Results Lactose malabsorption linked to the CC genotype did not associate with an increased risk for either colorectal cancer (OR = 1.041; 95% CI = 0.751–1.442; p = 0.868) or polyps (OR = 0.927; 95% CI = 0.630–1.363; p = 0.769). There was no association with colorectal cancer/polyps site. 60% of the subjects overall bore the CC genotype. Conclusion In the Italian population the LCT-13910C > T polymorphism is not associated to the risk for colorectal cancer or polyps.

Background In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites. Aim To compare clonidine (aspecific α2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites. Methods and Results Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6). Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance). In comparison with G4, the addition of clonidine (G5) or guanfacine (G6) to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels. Conclusions α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time.

AIM: To compare the rates of success and complications of two different methods of access into the common bile duct (CBD). METHODS: Between October 2007 and November 2008, 173 consecutive patients (71 men, 102 women, mean age 68.6 years) requiring endoscopic retrograde cannulation of the papilla and endoscopic treatment were studied. In the first 88 patients CBD cannulation was performed through supra-papillary fistulotomy (group F); in the following 85 patients standard cannulation was performed through the Oddi sphincter (group S). Indications for the procedure were: choledocholithiasis, biliary obstruction, postoperative leak, sclerosing cholangitis, and Mirizzi’s syndrome. RESULTS: Deep CBD cannulation was successful in 85/88 patients (96.5%) in group F vs 60/85 patients (70.6%) in group S (P < 0.0001). The remaining 25 group S patients in whom cannulation failed were shifted to fistulotomy. Fistulotomy was successful in 21/25 patients (84%). As for complications, hyperamilasemia occurred in 7 (7.9%) group F patients vs 7 (8.2%) group S patients (P = NS); mild pancreatitis in 1 (1.1%) group F patient vs 5 (5.8%) group S patients (P = NS); bleeding in 3 (3.4%) group F patients vs 3 (3.5%) group S patients (P = NS). CONCLUSION: Needle-knife fistulotomy should represent either the first approach to therapeutic cannulation or rescue therapy after unsuccessful standard cannulation.

Extracellular Ca(++) activates cell membrane calcium-sensing receptors (CaRs), leading to renal tubule production of prostaglandins E(2) (PGE(2)), which decrease both sodium reabsorption in the thick ascending limb of Henle's loop and free-water reabsorption in collecting ducts.To assess the activity of this diuretic system in experimental cirrhosis, we evaluated renal function, hormonal status, PGE(2) urinary excretion, and renal tissue concentrations of Na(+)-K(+)-2Cl(-) co-transporters (BSC-1) and CaRs in three groups of rats: one group of controls receiving 5% glucose solution (vehicle) intravenously and two groups of rats with CCl(4)-induced preascitic cirrhosis receiving either vehicle or 0.5mg i.v. Poly-l-Arginine (PolyAg), a CaR-selective agonist.Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (p0.05). Western blot analysis revealed reduced CaRs and increased BSC-1 protein content in kidneys of cirrhotic rats compared with controls (all p0.01). PolyAg-treated cirrhotic rats had their urine and sodium excretion returned to normal; PolyAg also increased renal plasma flow, PGE(2) urinary excretion, and free-water clearance in cirrhotic rats (all p0.01 v. untreated cirrhotic animals).In preascitic cirrhosis, sodium retention may be linked to down-regulation of renal CaRs and up-regulation of tubular sodium-retaining channels. Calcimimetic drugs normalize preascitic sodium retention.

P0206 PREVENTION OF BLEEDING FOLLOWING INVASIVE PROCEDURES IN CIRRHOTIC PATIENTS: A SINGLE CENTER EXPERIENCE F. Invernizzi, G. Tosetti, V. La Mura, A. Aghemo, M. Primignani, A. Sanvgiovanni, M.F. Donato, A. Nicolini, M. Iavarone, M. Colombo. Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Universita degli Studi di Milano, Division of Radiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy E-mail: massimo.colombo@unimi.it

Background: Carcinoid tumors are rare but considered to be one of the commonest tumors in the appendix. Their incidence has been shown to vary in different studies. Aims, setting & design: This seminal study was carried out to determine the incidence and clinico-pathological profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Emirate of Sharjah. Material and methods: The study included the retrospective data of 964 patients operated for clinically suspected appendicitis, the resected specimens of whom were received in the Pathology laboratory of Al-Qasmi hospital Sharjah from January 2010 to December 2010. Results: Out of the 964 patients 9 (0.93%) were found to have appendiceal carcinoids. The mean age was 28.7 years with a male to female ratio of 2 :1. Eight tumors were located near the tip of appendix with mean diameter of 3.3 mm. All tumors were found to be positive for chromogranin A, synaptophysin and neuron-specific enolase on immunohistochemistry (IHC). None of the patients had recurrence or any reportable complications in the short follow up period (12–26 months). Conclusions: Our study found higher incidence of appendiceal carcinoids in patients undergoing emergency appendectomy for acute appendicitis in Emirate of Sharjah compared to two previous studies from the same geographical region. Moreover, tumors were found more commonly in young males in contrary to previous studies and all the tumors were positive for common neuroendocrine markers.

117 GENE DELIVERY OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE-1 REDUCES PORTAL PRESSURE IN BILE DUCT-LIGATED RATS G. Mehta, V. Sharma, A. Habtesion, V. Balasubramaniyan, N.A. Davies, R. Jalan, V.S. Budhram-Mahadeo, R.P. Mookerjee. UCL Institute of Hepatology, Royal Free Hospital, Royal Free Hampstead NHS Trust and UCL, Medical Molecular Biology Unit, Rayne Institute, UCL, London, UK E-mail: gautam.mehta@ucl.ac.uk

Extracellular Ca stimulates membrane-bound calcium-sensing receptors (CaRs). In turn, CaRs stimulation leads to PGE2-mediated decrease in protein content of Na-K-2Cl co-transporters (BSC-1) in the thick ascending limb (TAL) of Henle’s loop and of aquaporin 2 (AQP2) water channels in collecting ducts. Parathyroid hormone (PTH) increases CaRs expression and, consequently, decreases BSC-1 and AQP2 content. To assess this Ca-dependent diuretic system in preascitic cirrhosis we evaluated renal function, hormonal status, PGE2 urinary excretion, renal content of BSC-1 and CaRs in three groups of rats: one group of controls receiving s.c. 5% glucose solution and two groups of rats with CCl4-induced preascitic cirrhosis receiving either glucose solution or five s.c. doses of 10 mcg/kg PTH (one dose every 12h) prior to study. The amount of fluid administered to each group was the same. Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (P < 0.05); western blot analysis revealed reduced CaRs and increased BSC-1 protein content in cirrhotic rat kidneys (all P < 0.01). PTH-treated cirrhotic rats had urine and sodium excretion normalized; s.c. PTH increased also renal plasma flow, PGE2 urinary excretion, free-water clearance, reduced BSC-1 and augmented CaRs content in cirrhotic rat kidneys (all P < 0.01 v. untreated cirrhosis). In conclusion, in preascitic cirrhosis sodium retention is linked to downregulation of renal CaRs and upregulation of tubular Na-K-2Cl co-transporters. PTH returns these biomolecular alterations and sodium and urine excretions to normality. Therefore, exaggerated sodium reabsorption in Henle’s loop is largely responsible for sodium retention in preascitic cirrhosis.

s A.I.S.F. Annual Meeting (Rome, February 25th−26th, 2010) / Digestive and Liver Disease 42 Suppl. 1 (2010) S1–S51 S17 T.N.6 INTRAHEPATIC RENIN-ANGIOTENSIN SYSTEM AND LIVER CIRRHOSIS: AN UPDATED REAPPRAISAL G. Sansoe1, M. Aragno2, C. Tomasinelli2, R. Mastrocola2, M. Parola2. Division of Gastroenterology, Gradenigo Hospital, Torino, Italy.; Department of Experimental Medicine and Oncology, University of Torino, Italy The concentrations of angiotensin II are 100-fold higher in renal, hepatic and myocardial tissue fluids than in the systemic circulation, due to local production of this hormone. 90% of this huge amount of tissue angiotensin II is not produced by ACE. Instead, angiotensin II in the above organs is produced by means of chymase (a membrane-bound enzyme) from circulating angiotensin I [1]. Another newly described enzyme (ACE2) degrades angiotensin II (composed of 8 aminoacids) into angiotensin-(1−7). Angiotensin II is a vasoconstrictor and stimulates fibrogenesis, but angiotensin-(1−7) is a strong vasodilator and inhibits fibrogenesis [2]. Moreover, chymase generates also endothelin-1 from precursors (big-endothelin and endothelin1−31) and activates TGF-beta. Both endothelin-1 and TGFbeta are fibrogenic agents in the cirrhotic liver. This study aims at evaluating the content of chymase, ACE and ACE2 inside the livers of normal rats (n = 5) and rats with CCl4-induced liver cirrhosis (n = 5) by means of quantitative western blotting. Normal and cirrhotic liver slices were also submitted to immuno-histochemistry studies in order to identify the location of these enzymes. Finally, normal and cirrhotic liver samples were studied by means of HPLC in order to determine tissue fluid concentrations of angiotensin II and angiotensin-(1−7). In cirrhotic liver samples we found out a marked over-expression of chymase and ACE (all P< 0.01) and, to a lesser extent, also of ACE2 (P< 0.05). In normal liver, concentrations of angiotensin II and angiotensin-(1−7) were similar (below 50 pg/ml); conversely, cirrhotic liver tissue showed increased concentrations of angiotensin II (1400±380 pg/ml) and of angiotensin-(1−7) (260±110 pg/ml). In other words, in cirrhotic liver the ratio between angiotensin II and angiotensin-(1−7) was five times higher than in control liver, arguably contributing to fibrogenesis. The reason for a preferential production of tissue angiotensin II inside the cirrhotic liver is the concurrently increased content of ACE and chymase, with respect to a smaller over-expression of the sole ACE2. These data indicate modulation of the chymase/ACE2 system seems promising in order to alter the process of fibrogenesis in chronic liver diseases.