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Endoscopy 04/2012; 44 Suppl 2 UCTN:E88-9. · 5.21 Impact Factor
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F. Piscaglia,
A. Gianstefani,
M. Ravaioli,
R. Golfieri,
A. Cappelli,
E. Giampalma,
E. Sagrini,
G. Imbriaco,
A.D. Pinna,
L. Bolondi, [......],
M. Del Gaudio,
G. Ercolani,
G.L. Grazi,
M. Lenzi,
S. Leoni, G. Mazzella,
M.C. Morelli,
M. Tame,
G. Verucchi,
M. Vivarelli
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ABSTRACT: Malignant portal vein thrombosis is a contraindication for liver transplantation. Patients with cirrhosis and early hepatocellular carcinoma (HCC) may have either malignant or benign (fibrin clot) portal vein thrombosis. The aim of this study was to assess prospectively whether well-defined diagnostic criteria would enable the nature of portal vein thrombosis to be established in patients with HCC under consideration for liver transplantation. Benign portal vein thrombosis was diagnosed by the application of the following criteria: lack of vascularization of the thrombus on contrast-enhanced ultrasound and on computed tomography or magnetic resonance imaging, absence of mass-forming features of the thrombus, absence of disruption of the walls of veins, and, if uncertainty persisted, biopsy of the thrombus for histological examination. Patients who did not fulfill the criteria for benign thrombosis were not placed on the transplantation list. In this study, all patients evaluated at our center during 20
Liver Transplantation. 01/2010; 16:658-667.
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ABSTRACT: We prospectively compared gadoliniumenhanced magnetic resonance imaging (dynamic MRI), superparamagnetic iron oxide (SPIO) (ferucarbotran) MRI and multidetector-row computed tomography (MDCT) and the combination of dynamic MRI plus MDCT vs. dynamic MRI plus SPIO-MRI (double-contrast MRI: DC-MRI) for the detection of small (<or=3 cm) hepatocellular carcinomas (HCCs).
Sixty-three patients with liver cirrhosis and suspicious nodules detected during ultrasound (US) surveillance underwent DC-MRI in the same imaging session and MDCT within 15 days. The final diagnosis was established at pathology on the explanted liver (n=10), resection (n=6) and biopsy (n=38) specimens or at 2-years' follow-up (n=9).
One hundred and twenty-three nodules were detected: 87 were confirmed HCCs in 54 patients. The accuracy of SPIO-MRI and dynamic MRI were similar, both being superior to MDCT. Dynamic MRI demonstrated the highest sensitivity (83.9%; p<0.001). especially for lesions <1 cm (90.6%) - coupled with a lower specificity (36.1%) than SPIO-MRI, particularly in subcentimeter lesions (28.6%). SPIO-MRI demonstrated the highest sensitivity for nodules >1 cm and the highest specificity (83.3%) superior to dynamic MRI (p<0.0001). In the per-lesion analysis, SPIO-MRI demonstrated a positive predictive value higher than dynamic MRI (p=0.0059) and than both the combinations dynamic MRI/MDCT and DC-MRI (p=0.0021 and p=0.0087, respectively). DC-MRI showed the highest sensitivity (97.7%) and accuracy (78.9%), detecting hypovascular and atypical HCCs >1 cm. Furthermore its per-patient negative predictive value was the highest (100%), and significantly higher than all the other methods.
DC-MRI is the most sensitive and accurate method and can be confidently used as a single-step procedure for the detection of small HCCs, with the exception of lesions <1 cm.
La radiologia medica 08/2009; 114(8):1239-66. · 1.44 Impact Factor
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ABSTRACT: Gemfibrozil, like clofibrate, is effective in lowering both serum cholesterol and triglycerides and in increasing high-density lipoproteins. The information available about its effects on biliary lipids is still limited, and conflicting results have been reported. In this study we evaluated the effect of gemfibrozil (1.2g/day) and clofibrate (2.0g/day), in a single-blind crossover design for 6 weeks with a 4-week washout period, on the biliary cholesterol saturation index (SI) in stimulated hepatic bile and on the hepatic secretion rate of biliary lipids in patients with hyper-lipidemia. Clofibrate increased cholesterol SI (from 1.70 ± 0.14 to 2.05 ± 0.24), whereas gemfibrozil decreased it (from 1.70 ± 0.14 to 1.54 ± 0.16). The results were not statistically significant. The hepatic secretion rate of cholesterol was significantly (p < 0.04) increased by clofibrate therapy, whereas it was significantly (p < 0.04) decreased after gemfibrozil; a significant (p < 0.04) decrease in the hepatic secretion rate of bile acids, bile acid pool size, and bile acid fecal excretion (p < 0.04) was also found after gemfibrozil administration. Gemfibrozil interferes extensively with bile acid metabolism, but it does not increase biliary cholesterol secretion, as clofibrate does. These results suggest that gemfibrozil does not seem to increase the risk of gallstone formation in patients with hyperlipidemia.
07/2009; 25(12):1227-1234.
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M Montagnani,
A Marangoni,
A Roda,
F Azzaroli, G Mazzella,
E Roda,
M Tsivian,
F Neri,
M Jovani,
M Giandinoto,
A Caponi,
R Aldini
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ABSTRACT: Intestinal bile acid absorption is mediated by a sodium-dependent transporter located in the brush border apical membrane of ileocytes. The transmembrane topology and the role of individual amino acid residues in the bile acid transport process have been investigated by means of various experimental approaches, leading to multiple hypotheses. We raised a monoclonal antibody against a segment of the transporter comprising vicinal cysteine residues, in order to evaluate its functional role. A 14 amino acid peptide, corresponding to amino acids 104-117 of the transporter, was synthesized, and a monoclonal anti-peptide antibody was raised. In vitro uptake-inhibition studies in the presence of the monoclonal anti-peptide antibody were performed using ileal brush border membrane vesicles. Rabbit ileum was perfused in vivo with 5 mM taurocholic acid in the presence of the monoclonal antibody, and bile acid absorption inhibition was evaluated. The anti-peptide monoclonal antibody significantly reduced the in vitro uptake and in vivo absorption of taurocholic acid. The present data demonstrate the functional relevance of the 104-117 peptide segment and report the generation of a novel antibody against the apical sodium-dependent bile acid transporter (ASBT) that may be used as a therapeutic agent in hypercholesterolemia and in cholestatic pruritus.
Molecular Pharmaceutics 05/2009; 6(3):1012-8. · 4.78 Impact Factor
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D. FESTI,
F. MONTI,
S. CASANOVA,
T. LIVRAGHI,
R. FRABBONI,
C. A. ROVERSI,
D. BERTOLI,
G. BORELLI, G. MAZZELLA,
F. BAZZOLI,
R. ALDINI,
L. BARBARA,
E. RODA
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ABSTRACT: The local and systemic effects, as well as the repair mechanisms, of sterile absolute ethyl alcohol injection were evaluated at a range of doses (0.1–2.0 mL/kg body weight) in rabbit liver in order to confirm the feasibility and safety of local treatment of tumours in man. Saline injection was used in the control animals. The animals were killed at varying intervals (range: 1–30 days after injection), and the liver was studied by gross and microscopic examination. The ethyl alcohol injection was well tolerated and did not induce significant systemic side-effects. All doses could induce necrosis and none proved to be lethal. The alcohol injection produced an area of coagulation necrosis, the size of which appeared to be dose-related, and which was surrounded by granulation tissue, gradually repairing the necrotic lesion; the adjacent tissue was intact, or had signs of mild steatosis. However, at higher doses (1.0 and 2.0 mL/kg bodyweight), necrotic lesions were observed in the liver both near and remote from the site of injection. Fine needle percutaneous alcohol injection is effective in producing necrotic lesions which appear to be dose-related; at higher doses, however, an unpredictable intrahepatic diffusion may occur.
Journal of Gastroenterology and Hepatology 06/2008; 5(4):402 - 406. · 2.87 Impact Factor
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A Floreani,
I Carderi,
D Paternoster,
G Soardo,
F Azzaroli,
W Esposito,
M Montagnani,
D Marchesoni,
A Variola,
E Rosa Rizzotto,
C Braghin, G Mazzella
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ABSTRACT: Intrahepatic cholestasis of pregnancy is a multifactorial disorder of pregnancy associated with a genetic background.
To evaluate the genetic contribution of ABCB4, MDR3 gene in the development of intrahepatic cholestasis of pregnancy in a large cohort of Italian subjects.
This study represents an extension of a previous multicentre-prospective study including three Italian referral centres. In all, we enrolled 96 women at the 3rd trimester of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes by standard procedures. Polymerase chain reaction was used to amplify exon 14, 15 and 16 of MDR3 gene.
We found 3 non-synonymous heterozygous mutations in exon 14 (E528D, R549H, G536A), 1 in exon 15 (R590Q) and 2 in exon 16 (R652G, T6671). MDR3 gene variants in exons 14, 15 and 16 occurred in 7/96 of pregnant mothers with intrahepatic cholestasis of pregnancy (7.2%), and in none of 96 pregnant controls matched for age and parity. All seven patients had normal gamma-glutamyl transpeptidase, normal bilirubin, but high levels of both alanine transferase and serum bile acids. One had cholesterol biliary lithiasis. The outcome of pregnancy was normal in four cases (with vaginal delivery), while there was one fetal distress.
MDR3 mutations are responsible for the development of intrahepatic cholestasis of pregnancy in only a small percentage of Italian women. Further genetic studies are warranted, however, to clarify the role of different mutations in intrahepatic cholestasis of pregnancy.
Digestive and Liver Disease 06/2008; 40(5):366-70. · 3.05 Impact Factor
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F Lodato,
S Berardi,
A Gramenzi, G Mazzella,
M Lenzi,
M C Morelli,
M R Tame,
F Piscaglia,
P Andreone,
G Ballardini, [......],
M Del Gaudio,
G Ercolani,
G L Grazi,
W Grigioni,
S Lorenzini,
A D Pinna,
M Ravaioli,
E Roda,
C Sama,
M Vivarelli
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ABSTRACT: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates.
To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response.
Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 micro/kg/week plus RBV 8-10 mg/kg/day for 24 weeks. Those with 'early virological response at week 24' (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C).
Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02-106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR.
Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with > or =2 log10 drop in HCV-RNA at week 24.
Alimentary Pharmacology & Therapeutics 06/2008; 28(4):450-7. · 3.77 Impact Factor
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ABSTRACT: Liver cirrhosis complications in pregnant women are frequent and death rate secondary to variceal bleeding is relevant. Both sclerotherapy and banding ligation seem to be safe procedures in pregnancy; when bleeding is not arrested endoscopically an emergency transjugular intrahepatic portosystemic shunt should be considered, but data regarding pregnant cirrhotic women are scarce. We describe the case of a pregnant woman at 14 weeks of gestation who underwent management of acute variceal bleeding by transjugular intrahepatic portosystemic shunt. Transjugular intrahepatic portosystemic shunt may represent a rescue treatment for failed attempts of band ligation or sclerotherapy.
Digestive and Liver Disease 06/2008; 40(5):387-90. · 3.05 Impact Factor
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F Azzaroli,
A Mennone,
V Feletti,
P Simoni,
E Baglivo,
M Montagnani,
N Rizzo,
G Pelusi,
D DE Aloysio,
F Lodato,
D Festi,
A Colecchia,
E Roda,
J L Boyer, G Mazzella
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ABSTRACT: The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined.
To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta.
Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data.
Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups.
Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.
Alimentary Pharmacology & Therapeutics 10/2007; 26(8):1139-46. · 3.77 Impact Factor
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S Berardi,
F Lodato,
A Gramenzi,
A D'Errico,
M Lenzi,
A Bontadini,
M C Morelli,
M R Tamè,
F Piscaglia,
M Biselli,
C Sama, G Mazzella,
A D Pinna,
G Grazi,
M Bernardi,
P Andreone
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ABSTRACT: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients.
9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied.
In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths).
De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.
Gut 03/2007; 56(2):237-42. · 10.11 Impact Factor
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ABSTRACT: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR).
After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR.
OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t(1/2)) than CTR (P < 0.0044) at baseline; after UDCA, t(1/2) significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR.
The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.
World Journal of Gastroenterology 10/2006; 12(33):5336-43. · 2.47 Impact Factor
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F Azzaroli,
A Colecchia,
A Colecchi,
F Lodato,
D Trerè,
M L Bacchi Reggiani,
D Festi,
G M Prati,
E Accogli,
S Casanova,
M Derenzini,
E Roda, G Mazzella
[show abstract]
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ABSTRACT: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved.
To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma.
One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months.
Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index.
The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.
Alimentary Pharmacology & Therapeutics 08/2006; 24(1):129-36. · 3.77 Impact Factor
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A Floreani,
I Carderi,
D Paternoster,
G Soardo,
F Azzaroli,
W Esposito,
A Variola,
A M Tommasi,
D Marchesoni,
C Braghin, G Mazzella
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ABSTRACT: The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified.
To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects.
We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit.
Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third.
These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.
Alimentary Pharmacology & Therapeutics 07/2006; 23(11):1649-53. · 3.77 Impact Factor
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F Lodato,
F Azzaroli,
S Brillanti,
A Colecchia,
M R Tamé,
M Montagnani,
R Muratori,
S Giovanelli,
V Feletti,
M L Bacchi Reggiani,
E Roda, G Mazzella
[show abstract]
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ABSTRACT: Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 21% (9 [corrected] of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.
Journal of Viral Hepatitis 10/2005; 12(5):536-42. · 4.09 Impact Factor
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D Festi,
S Capodicasa,
L Sandri,
L Colaiocco-Ferrante,
T Staniscia,
E Vitacolonna,
A Vestito,
P Simoni, G Mazzella,
P Portincasa,
E Roda,
A Colecchia
[show abstract]
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ABSTRACT: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.
One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.
Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.
Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.
World Journal of Gastroenterology 02/2005; 11(1):142-8. · 2.47 Impact Factor
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ABSTRACT: Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.
World Journal of Gastroenterology 02/2004; 10(1):12-6. · 2.47 Impact Factor
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ABSTRACT: Cholesterolosis of the gallbladder consists in an accumulation of cholesterol esters and triglycerides in the macrophages at gallbladder wall level and may be either diffuse or polypoid in form. A prevalence of 4-8% has been reported, particularly in the male sex; results concerning a relationship between cholesterolosis and lifestyle are controversial (alcohol intake, smoking habit), as well as the clinical and laboratory parameters, such as serum cholesterol and body mass index. Even more controversial is the relationship with gallstones which has been associated with the presence of cholesterol polyps only in a few surgical series. An increase in the activity of the cholesterol ester enzyme has been observed, in cholesterolosis patients, at gallbladder mucosa level which has led to the hypothesis of an increase in cholesterol ester deposit at this level; the hypothesis of an alteration in bile composition, in these patients, still remains to be elucidated. Ultrasonography is a sensitive tool in the diagnosis of cholesterolosis even if the use of echoendoscopy is becoming increasingly important in the differential diagnosis between benign and malignant polypoid lesions. Even if, in a few series, patients with polyps present a clinical pattern characterized by specific biliary symptoms, both in our experience and in that of others, symptoms are aspecific, the frequency of dyspeptic symptoms being comparable to that in the general population. The natural history of this lesion is, in general, benign and for polyps with size ranging from 6 mm to 10 mm a yearly follow-up with ultrasonography is advisable.
Minerva gastroenterologica e dietologica 10/2003; 49(3):217-24.
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ABSTRACT: Functional gastrointestinal disorders can be defined as 'a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities'. Motor disorders are considered to be one of the pathogenetic mechanisms of these symptoms; in fact, it has been hypothesized that the smooth muscle of the whole gastrointestinal tract could be involved. Gallbladder motility has been evaluated in patients with dysmotility-like dyspepsia, irritable bowel syndrome and biliary disorders without gallstones; results of these observations are often inconclusive, conflicting and not always useful from a clinical point of view. The aim of this review is to explore the relationship between gallbladder motility and functional gastrointestinal disorders from pathogenetic and physiopathological points of view, and also to define the possible impact of these observations on clinical practice.
Digestive and Liver Disease 08/2003; 35 Suppl 3:S30-4. · 3.05 Impact Factor
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C Mazzeo,
F Azzaroli,
S Giovanelli,
A Dormi,
D Festi,
A Colecchia,
A Miracolo,
P Natale,
G Nigro,
A Alberti,
E Roda, G Mazzella
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ABSTRACT: Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy.
Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects.
For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses.
In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.
Gut 07/2003; 52(7):1030-4. · 10.11 Impact Factor
