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Mario Rizzetto

Publications and source records attributed to Mario Rizzetto.

At least 55 records · Page 3Linked to original sources
PubMed2004

Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma.

AIM: Only a minority of patients carrying a defined viral aetiologic agent develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism underlying the worsening is still undefined. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and HCC and recently, more Helicobacter species (Helicobacter spp.) have been detected in the liver of patients suffering from cholestatic diseases and HCC arising from non-cirrhotic liver. We investigated whether Helicobacter spp. sequences could be detected in the liver of patients with cirrhosis and HCC compared to subjects with metastasis to liver from colon cancer. METHODS: Twenty-three liver samples from patients operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis and 6 from patients with resected metastases from colorectal cancer, were tested by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter genus using specific primers. DNA sequencing and cag A gene analysis were also performed. RESULTS: Genomic sequences of Helicobacter spp. were found in 17 of 20 (85%) liver samples from patients with HCC and in 2 of 6 samples from patients with liver metastasis. In three samples of the first group the result was uncertain. H pylori was revealed in 16 out of 17 positive samples and Helicobacter pullorum in the other. CONCLUSION: Helicobacter spp., carcinogenic in mice, were found at a higher frequency in the liver of patients with HCV-related cirrhosis and HCC than those in patients without primary liver disease.

Carcinoma, Hepatocellular↗
PubMed2004

Identification of HBV DNA sequences that are predictive of response to lamivudine therapy.

Numerous studies have shown that resistance to long-term lamivudine therapy occurs in as many as (2/3) of hepatitis B virus (HBV) chronic carriers. Additional studies have shown that reversion of HBV mutations in the precore/core promoter region conferring an HBeAg-negative phenotype/genotype can occur in up to 30% of lamivudine-treated patients. In this study, sequences of the HBV polymerase and precore/core coding regions in 26 HBV-infected patients (24 with HBeAg-negative virus infection, 25 genotype D, 1 genotype A) treated for 27 to 53 months with lamivudine were analyzed to determine the relationship between pretreatment HBV DNA sequence patterns and long-term treatment response, and the effect of therapy on the status of HBV precore mutations. Reversions of precore mutations A1762T/G1764A and G1896A were observed in 29% and 25% of patients, respectively, but none became HBeAg-positive. These data are consistent with previously published reversion frequencies for 2 other groups of lamivudine-treated patients. Two naturally-occurring DNA polymorphisms at aa91 and aa256 of the HBV polymerase were observed in the pretreatment serum samples, which correlated with extended treatment failure. In conclusion, reversion of mutations conferring an HBeAg-negative phenotype occur relatively frequently under lamivudine therapy. Furthermore, at least in HBeAg-negative patients infected predominantly with HBV genotype D, specific viral DNA sequences which are present before therapy appear to be useful as predictors of long-term response to lamivudine treatment.

Adult↗
PubMed2004

Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver.

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21- 2.58; P =.0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33-0.87; P =.0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD.

Adult↗
PubMed2004

Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine.

The effect of lamivudine treatment on the outcome of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis is unclear. In a retrospective multicenter study, we have analyzed the virological events observed during lamivudine therapy in patients with HBeAg-negative chronic hepatitis and evaluated the correlation between virological response and clinical outcomes. Among 656 patients (mean age 49.1 years) included in the database, 54% had chronic hepatitis, 30% had Child-Turcotte-Pugh (CTP) A cirrhosis, and 16% had CTP B/C cirrhosis. On therapy (median 22 months, range 1-66), a virological response was obtained in 616 patients (93.9%). The rate of maintained virological response was 39% after 4 years. During follow-up, 47 (7.2%) patients underwent liver transplantation, liver disease worsened in 31 (4.7%), hepatocellular carcinoma (HCC) developed in 31 (4.7%), and 24 patients (3.6%) died of liver-related causes. Patients who had cirrhosis and who maintained virological response were less likely than those with viral breakthrough to develop HCC (P <.001) and disease worsening (P <.001). Survival was better in CTP A patients with cirrhosis and maintained virological response (P =.01 by rank test). Multivariate analysis revealed that presence of cirrhosis and viral breakthrough were independently related to mortality and development of HCC. In conclusion, lamivudine is highly effective in reducing viral load in HBeAg-negative patients. After 4 years of therapy, 39% of patients maintain a virological and biochemical response. Loss of virological response may lead to clinical deterioration in patients with cirrhosis.

Adult↗
PubMed2004

Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation.

Living donor liver transplantation (LDLT) is becoming a widespread procedure. However, the risk of surgical and medical complications in healthy donors is still a major concern. Hypercoagulability contributes to thromboembolic complications after surgery, but alterations of hemostasis after liver resection are difficult to predict. This study aims to define the perioperative coagulation profile of living liver donors by the use of both routine tests and thromboelastogram (TEG). Ten subjects undergoing right hepatectomy for LDLT were studied. A complete coagulation screening was performed before operation. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), and TEG at the beginning and at the end of surgery, and on days 1, 3, 5, and 10 after operation, while the donors were under low molecular weight heparin (LMWH) prophylaxis. At preoperative screening, no subject showed evidence of a prothrombotic state. In all cases, TEG was normal at the beginning of surgery. In the postoperative period, despite decreased platelet counts, increased PT-INR, and normal aPTT values, TEG evidenced the progressive development of hypercoagulability in 4 subjects on day 5 and in 6 subjects on day 10. One donor with a definitely hypercoagulable TEG on day 5 experienced deep venous thrombosis (DVT) on day 8, which was resolved with therapeutic doses of LMWH. In conclusion, despite routine tests suggesting hypocoagulability and LMWH prophylaxis, TEG monitoring showed the unexpected occurrence of hypercoagulability in the majority of the subjects after hepatectomy for LDLT. TEG monitoring could be useful in the perioperative management of donors to guide antithrombotic treatment and increase the safety of the procedure.

Adult↗
PubMed2004

Occult hepatitis B virus infection in HBsAg negative patients undergoing liver transplantation: clinical significance.

Occult Hepatitis B virus (o-HBV) infection has been reported in HB surface antigen (HBsAg)-negative liver donors whose risk of transmitting HBV justifies a specific prophylaxis in liver recipients. The clinical significance of o-HBV infection in HBsAg-negative recipients and their need for prophylaxis is unknown. Liver samples collected during surgery from 23 HBsAg-negative patients (9 liver donors and 14 recipients) and 20 HBsAg-positive recipients (controls) were studied by polymerase chain reaction with an independent set of primers mapping the core and surface HBV genes. Intrahepatic HBV DNA was detected as core and surface genes in all the HBsAg-positive recipients, in none of the HBsAg-negative donors and in 9/14 (64%) of the HBsAg-negative recipients (2 HCV negative, 7 HCV positive). The intrahepatic amount of HBV was significantly lower in HBsAg-negative than in HBsAg-positive livers (median values 1.36 Log(10)/microg DNA vs. 3.66 Logs, p<0.0001, core gene, and 1.13 vs. 6.21 Logs p<0.0001, surface gene). No HBV DNA was detected in plasma from o-HBV recipients; one of them tested positive in lymphocytes. No correlation was found between o-HBV and serologic markers of previous HBV exposure, response to vaccination, acute rejection, hepatitis D and G virus-infections. None of o-HBV carriers experienced a de novo hepatitis B after transplantation (median follow-up: 477 days). Occult HBV is frequent in HBsAg-negative liver recipients. It is not associated with increased episodes of acute rejection, coinfection with hepatotropic viruses, different responses to HBV vaccination, or the development of de-novo hepatitis B. In o-HBV infection a particular virus-host interaction can explain the low intrahepatic HBV content and the lack of extrahepatic HBV replication, thus justifying the low risk of hepatitis B reactivation, in absence of specific prophylaxis, once the recipient liver is removed.

Adult↗
PubMed2004

Non-alcoholic steatohepatitis in patients cared in metabolic units.

The clinical significance of liver disease is frequently underestimated in patients with metabolic disorders. In patients followed up in a metabolic unit for diabetes, obesity or hyperlipidemia (n=147), we studied the prevalence and the severity of liver disease, and its relationship with the metabolic syndrome (MS). Cases cared for in a liver unit (n=179) were used as controls. Patients in the metabolic series were older and had a higher prevalence of coronary heart disease. Criteria for the metabolic syndrome were fulfilled in 64% and 22% of cases, respectively (P<0.0001). Liver biopsy was obtained in 44 and 66% of cases. Metabolic patients had a more severe steatosis score (P<0.0001), whereas the scores of fibrosis and necroinflammation were less severe (P=0.0059 and 0.0007, respectively). Histological criteria for non-alcoholic steatohepatitis (NASH) were present in 82% of metabolic cases and 68% cases in the liver series (P=0.057). Liver disease in patients routinely cared for in metabolic units is similar to that observed in patients cared for in liver units, and potentially may progress to terminal liver failure. Liver biopsy is recommended for diagnostic and prognostic purposes, as well as for testing treatment effects in controlled trials.

Adult↗
PubMed2004

Inappropriately low angiotensin II generation: a factor determining reduced kidney function and survival in patients with decompensated cirrhosis.

BACKGROUND/AIMS: Angiotensin II contributes to the post-glomerular arteriolar vasoconstriction which maintains the glomerular filtration rate (GFR) in renal hypoperfusion. To explore whether depressed angiotensin II generation, due to reduced angiotensinogen production or low angiotensin-converting enzyme (ACE) levels, could impair kidney function in advanced cirrhosis. METHODS: We studied and prospectively followed up 21 diuretic-free ascitic cirrhotic patients, through these determinations: plasma levels of active renin (AR), renin activity (PRA), angiotensin II, ACE and aldosterone; renal clearances of sodium, inulin and para-aminohippurate; antipyrine clearance. Fifteen healthy subjects were also studied. RESULTS: GFR distribution was bimodal, 10 patients had low GFR values (l-GFR group) and 11 had normal-GFR values (n-GFR group) (below and above 105 ml/min per 1.73 m(2) body surface area). Antipyrine clearance and Child-Pugh score did not differ in the two patient groups. l-GFR group had higher AR and PRA values, lower ACE levels and a significantly higher AR/Angiotensin II ratio than n-GFR group (all P<0.01). All 21 patients showed increased values of the AR/PRA ratio, i.e. subnormal angiotensinogen levels (P<0.03). The 18-month survival rates of l-GFR and n-GFR groups were 20 and 81% (P<0.02). CONCLUSIONS: Low-GFR cirrhotic patients had a worse survival rate associated with more severe contraction of the effective arterial blood volume, higher AR/Angiotensin II ratio and lower ACE levels.

Adult↗
PubMed2004

Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures.

BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic challenge. Metal stents occasionally have been used, but results have been disappointing. The present study assessed the safety and the efficacy of temporary placement of the new expandable polyester silicone-covered stent for management of problematic esophageal strictures. METHODS: Fifteen patients with benign esophageal strictures were treated by temporary (6 weeks) placement of an expandable polyester silicone-covered stent. All patients had previously been treated, unsuccessfully, by repetitive endoscopic dilation. RESULTS: Stent placement was successful in all patients. There was no procedure-related complication. Dilation with over-the-guidewire polyvinyl dilators was required before stent placement. With the stent in situ, dysphagia completely resolved in all patients. Six weeks after placement, one stent was found to have migrated into the stomach. In the remaining patients, the stent was easily removed with a foreign body forceps. The pretreatment dysphagia score was 3 (range 2-4); the post-treatment score was 1 (range 0-1) (p < 0.0005). Long-term resolution (mean follow-up 22.7 [2.6] months) of the stricture was achieved in 12 patients (80%). The treatment failed in 3 patients, all of whom continue to require periodic dilation. CONCLUSIONS: In patients with benign esophageal strictures refractory to conventional dilation, temporary placement of a removable expandable polyester silicone-covered stent may lead to long-term relief of dysphagia with minimal morbidity.

Adult↗
PubMed2004

Prevalence of non-organ-specific autoantibodies in patients suffering from duodenal ulcer with and without Helicobacter pylori infection.

Autoimmunity, a feature of chronic infection by Helicobacter pylori, is first directed against gastric cells but is also associated with extragastric diseases. The aim of the present work was to look for the influence of the infection on induction of non-organ-specific autoantibodies (NOSAs). We compared 49 patients (28 males and 21 females; age range, 36-72 years; mean, 61 +/- 4.6 years) suffering from duodenal ulcer and H. pylori infection (Group A) to 38 subjects (20 male, 18 female; age range, 40-78 years; mean, 63 +/- 3.8 years) affected by duodenal ulcer related to the assumption of nonsteroidal antiinflammatory drugs (Group B). H. pylori infection was diagnosed by histology, 13C-urea breath test, and serum IgG antibodies. Autoimmunitary pattern was demonstrated by the presence of NOSAs in serum. Antinuclear (ANA), anti-smooth muscle (SMA), and anti-liver/kidney microsomal-1 (LKM-1) antibodies were present in 5 of 49 (10.2%), 2 of 49 (4%), and 0 Group A patients, respectively. In Group B, ANA was present in 3 of 38 (7.9%), SMA in 3 of 38 (7.9%), and anti-LKM-1 in 0 patients. The difference was not statistically significant. In this population, H. pylori infection is not associated with an increased prevalence of NOSAs.

Adult↗
PubMed2004

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. METHODS: This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan-Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. RESULTS: The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. CONCLUSIONS: The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.

Adult↗
PubMed2004

Ectopic liver and hepatocarcinogenesis: report of three cases with four years' follow-up.

Hepatocellular carcinoma (HCC) may arise in ectopic livers, which are autonomous islands of normal liver parenchyma located in the abdomen or thorax. The majority of HCCs in ectopic livers are reported in oriental patients. We describe here three new cases of HCC in Caucasian patients. The clinical presentation varied from dull epigastric pain in one patient, to abrupt onset with signs and symptoms of acute abdomen caused by intra-abdominal bleeding in another patient, to an unexplained progressive increase of alpha-fetoprotein serum levels in a third patient. None had risk factors for HCC or liver disease. One of the patients developed HCC at age 34 years; she is the youngest patient ever described to develop HCC in ectopic liver. Our data further strengthen the hypothesis that ectopic livers are particularly predisposed to developing HCC. The patients were followed up for 4 years after surgery: two remain free of disease, suggesting that the unique localisation and growth pattern may render these tumours particularly susceptible to curative resection.

Adult↗
PubMed2003

Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Adefovir dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials. METHODS: We randomly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen (HBeAg) to receive either 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner. The primary end point was histologic improvement. RESULTS: At week 48, 64 percent of patients who had base-line liver-biopsy specimens available in the adefovir dipivoxil group had improvement in histologic liver abnormalities (77 of 121), as compared with 33 percent of patients in the placebo group (19 of 57, P<0.001). Serum hepatitis B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group (63 of 123) and in 0 percent of those in the placebo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA levels was greater with adefovir dipivoxil treatment than with placebo (3.91 vs. 1.35 log copies per milliliter, P<0.001). Alanine aminotransferase levels had normalized at week 48 in 72 percent of patients receiving adefovir dipivoxil (84 of 116), as compared with 29 percent of those receiving placebo (17 of 59, P<0.001). No HBV polymerase mutations associated with resistance to adefovir were identified. The safety profile of adefovir dipivoxil was similar to that of placebo. CONCLUSIONS: In patients with HBeAg-negative chronic hepatitis B, 48 weeks of adefovir dipivoxil treatment resulted in significant histologic, virologic, and biochemical improvement, with an adverse-event profile similar to that of placebo. There was no evidence of the emergence of adefovir-resistant HBV polymerase mutations.

Adenine↗
PubMed2003

Helicobacter pylori seroprevalence in patients with cirrhosis of the liver and hepatocellular carcinoma.

BACKGROUND: Infection by Helicobacter hepaticus causes chronic hepatitis and hepatocellular carcinoma (HCC) in mice, and Helicobacter pylori (H. pylori) genomic sequences have been demonstrated in the liver of patients with HCC. H. pylori infection reportedly occurs with high frequency in patients with cirrhosis but none of the studies has investigated it in subjects with cirrhosis and superimposed HCC. In this case-control study, we searched for the seroprevalence of H. pylori infection in patients with HCC. PATIENTS AND METHOD: Forty-six patients (30 males, 16 females, mean age 69 years) with HCC and hepatitis C virus (HCV)-related cirrhosis were compared to 46 sex and age (+/-1 year) matched patients presenting consecutively to the Emergency Department of Molinette Hospital of Torino. All subjects were tested for presence in serum of IgG antibodies against H. pylori and the result was analyzed using the chi-square test. RESULTS: H. pylori seropositivity was more prevalent among patients with HCC (36/46, 78.2%) than in controls (25/46, 54%) (P<0.05) (OR 3.02, 95% confidence interval ). Twenty-five out of 30 (83.3%) male patients showed seropositivity at a variance with 16/30 (53%) in the controls (P<0.05); 11 out of 16 (68.7%) female patients were seropositive versus 9 out of 16 (56.2%) control subjects (P=n.s.). CONCLUSION: Seroprevalence of antibodies to H. pylori was found to be higher in patients with HCC than in controls.

Aged↗
PubMed2003

Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study.

BACKGROUND/AIMS: The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. METHODS: Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40-120 mg/day (15 patients) for 2 months. RESULTS: Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median -19.5%, range -11/-31% vs. -4.8%, +2.5/-10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P<0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P<0.0001 vs. basal). CONCLUSIONS: Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.

Adult↗