Publications by authors named "Angelo Iacobellis"

20 Publications

  • Page 1 of 1

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression.

Br J Cancer 2021 Jul 6;125(2):190-199. Epub 2021 Apr 6.

Medical Oncology, Saint-Louis Hospital & Paris 7 University, Paris, France.

Background: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression.

Methods: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b ('3 + 3' design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2).

Results: In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5-74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%).

Conclusions: Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit-risk balance in sorafenib pretreated aHCC with MET overexpression.

Trial Registration: ClinicalTrials.gov: NCT02115373.
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http://dx.doi.org/10.1038/s41416-021-01334-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292404PMC
July 2021

Procedure-related bleeding risk in patients with cirrhosis and severe thrombocytopenia.

Eur J Clin Invest 2021 Jun 26;51(6):e13508. Epub 2021 Feb 26.

I Clinica Medica, Sapienza University of Rome, Rome, Italy.

Background: Gaps of knowledge still exist about the potential association between severe thrombocytopenia and increased risk of procedure-associated bleeding in patients with liver disease.

Methods: In this narrative review, we aimed at examining the association between procedure-related bleeding risk and platelet count in patients with cirrhosis and severe thrombocytopenia in various settings. We updated to 2020 a previously conducted literature search using MEDLINE/PubMed and EMBASE. The search string included clinical studies, adult patients with chronic liver disease and thrombocytopenia undergoing invasive procedures, any interventions and comparators, and haemorrhagic events of any severity as outcome.

Results: The literature search identified 1276 unique publications, and 15 studies met the inclusion criteria and were analysed together with those identified by the previous search. Most of the new studies included in our analysis did not assess the association between post-procedural bleeding risk and platelet count alone in patients with chronic liver disease. Furthermore, some results could have been biased by prophylactic platelet transfusions. A few studies found that severe thrombocytopenia may be predictive of bleeding following percutaneous liver biopsy, dental extractions, percutaneous ablation of liver tumours and endoscopic polypectomy.

Conclusions: Currently available literature cannot support definitive conclusions about the appropriate target platelet counts to improve the risk of bleeding in cirrhotic patients who underwent invasive procedures; moreover, it showed enormous variability in the use of prophylactic platelet transfusions.
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http://dx.doi.org/10.1111/eci.13508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244048PMC
June 2021

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L-PLUS 2).

Hepatology 2019 10 15;70(4):1336-1348. Epub 2019 Mar 15.

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 10 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 10 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 10 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.
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http://dx.doi.org/10.1002/hep.30561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849531PMC
October 2019

Optimization of direct anti-viral agent treatment schedule: Focus on HCV genotype 3.

United European Gastroenterol J 2018 Mar 20;6(2):225-237. Epub 2017 Jun 20.

Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background And Aim: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option.

Methods: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs.

Results: A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir ± ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors.The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir.

Conclusions: Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-to-treat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.
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http://dx.doi.org/10.1177/2050640617717158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833227PMC
March 2018

Hepatitis C Virus Clearance in Older Adults.

J Am Geriatr Soc 2018 01 14;66(1):85-91. Epub 2017 Nov 14.

Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy.

Objectives: To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy.

Participants: Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis).

Measurements: We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered.

Results: Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5-23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk.

Conclusion: In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.
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http://dx.doi.org/10.1111/jgs.15140DOI Listing
January 2018

Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia.

Eur J Intern Med 2017 Mar 15;38:79-82. Epub 2016 Dec 15.

Division of Gastroenterology, "Casa Sollievo Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background: In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy.

Patients: In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations. PLT and/or fresh-frozen plasma (FFP) units were infused at the discretion of the attending physician, and the occurrence of post-procedural bleeding was related to pre-and post-infusion results.

Results: 852 Procedures were carried out in 363 cirrhotics sub-grouped according to the Child-Pugh-Turcotte (CPT) classification (class A/B/C: 124/154/85). The infusion of PLT and/or FFP improved only marginally circulating PLT counts and INR values. Ten post-procedural bleeds occurred in the whole case series, i.e. 1 episode every 85 procedures or every 36 patients. Post-procedural bleeding was unrelated to the PLT counts, to the degree of INR abnormalities, nor to the CPT classes, but was more frequent in patients who underwent repeated investigations. In the 10 patients with the most profound alterations in PLT and/or INR values, no post-procedural bleeding occurred.

Conclusions: In cirrhotic patients with low PLT and/or abnormal INR values undergoing invasive investigations, post-procedural bleeding was rare and unpredicted by PLT counts or abnormal INR values. In particular, the recommendation to infuse platelets when counts are <50×10/L is not substantiated by this case series of cirrhotic patients.
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http://dx.doi.org/10.1016/j.ejim.2016.11.007DOI Listing
March 2017

Efficacy and Safety of Long-Term Administration of Tapentadol in Relieving Chronic Pancreatitis Pain.

Pain Med 2017 04;18(4):815-817

Division of GastroenterologyGeriatric Unit & Gerontology-Geriatrics Research LaboratoryDepartment of Anesthesiology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.

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http://dx.doi.org/10.1093/pm/pnw220DOI Listing
April 2017

Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience.

World J Hepatol 2016 Aug;8(22):949-56

Luigi Elio Adinolfi, Barbara Guerrera, Internal Medicine Unit, Second University of Naples, 80125 Marcianise, Italy.

Aim: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings.

Methods: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL).

Results: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age.

Conclusion: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.
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http://dx.doi.org/10.4254/wjh.v8.i22.949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976214PMC
August 2016

Feasibility of pegylated interferon and ribavirin in hepatitis C-related cirrhosis with neutropenia or thrombocytopenia.

Dig Liver Dis 2014 Jul 25;46(7):621-4. Epub 2014 Mar 25.

Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo 71013, Italy.

Aim: To investigate the feasibility of pegylated interferon plus ribavirin treatment in cirrhotic patients who presented with, or developed while on-treatment, platelet counts ≤ 80,000/μL and/or neutrophil counts ≤ 1,500/μL.

Methods: A retrospective analysis of prospectively gathered data on 123 cirrhotic patients treated with pegylated interferon and ribavirin. Adverse effects and haematological changes were monitored: bleeding and infectious events were registered and related to platelet and absolute neutrophil counts.

Results: Among the 58 patients (47.2%) with nadir platelets ≤ 50,000/μL during therapy, 6 (10.3%) experienced a bleeding episode; of the remaining 65 patients with platelets constantly >50,000/μL, 3 (4.6%) bled. Of the 11 bleedings, 3 manifested during an infection, while patients had platelets >50,000/μL. Nadir neutrophils ≤ 750/μL occurred in 45 patients (38.2%) during treatment, and 14 of them (29.8%) had an infectious event. Infections were also documented in 18 of the 76 patients (23.7%) with neutrophils constantly >750/μL.

Conclusions: The study reveals the feasibility of treating cirrhotic patients with cytopenia with pegylated interferon and ribavirin, as bleeding or infectious events under therapy were unrelated to platelet and neutrophil counts. Withdrawal of therapy or variations in the pre-assigned dosages of either pegylated interferon or ribavirin owing to abnormally low haematological parameters seems to no longer be tenable.
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http://dx.doi.org/10.1016/j.dld.2014.02.001DOI Listing
July 2014

Long-term outcome after antiviral therapy of patients with hepatitis C virus infection and decompensated cirrhosis.

Clin Gastroenterol Hepatol 2011 Mar 17;9(3):249-53. Epub 2010 Nov 17.

Division of Gastroenterology and Digestive Endoscopy, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background & Aims: We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection.

Methods: Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3-78 months).

Results: Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48-59 months) and 73 months among those who did achieve SVRs (95% CI, 67-80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0-16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV.

Conclusions: Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.
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http://dx.doi.org/10.1016/j.cgh.2010.10.036DOI Listing
March 2011

The intelligent, painless, "germ-free" colonoscopy: A Columbus' egg for increasing population adherence to colorectal cancer screening?

Dig Liver Dis 2010 Dec 4;42(12):839-43. Epub 2010 Aug 4.

Division of Gastroenterology and Digestive Endoscopy, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy.

Colorectal cancer (CRC) represents a major cause of morbidity and mortality. Although it is widely accepted that CRC screening in average risk populations lowers CRC incidence and mortality, a disappointedly low adherence rate to both faecal occult blood testing and colonoscopy-based screening programs has been observed in Italy and in other European countries. Main reasons for the low acceptance of colonoscopy-based CRC screening has been ascribed to lack of recommendations given by general practitioners, fear of discomfort or complications, embarrassment, and avoidance of unpleasant preparation. New advances in endoscopic technology such as colon capsule and robotic colonoscopy might represent the ideal tool for CRC screening since they reduce or eliminate procedure-related pain and discomfort. Moreover, no disinfection between procedures is required. Motion of the new probes along the gastrointestinal tract is achieved either in passive modality by utilizing the gut peristalsis (colon capsule) or in active "intelligent" modality by means of computer-assisted propulsion (robotic colonoscopy). In this review, the preliminary clinical results obtained with the new devices are summarized. It is expected that the new instruments will be soon available in clinical practice with the hope of increasing adherence to CRC screening programs.
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http://dx.doi.org/10.1016/j.dld.2010.06.007DOI Listing
December 2010

Effect of the BioEnterics intragastric balloon on weight, insulin resistance, and liver steatosis in obese patients.

Gastrointest Endosc 2010 May 27;71(6):927-33. Epub 2009 Oct 27.

Division of Gastroenterology and Endoscopic Unit, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background: In obese patients, positioning of the BioEnterics intragastric balloon (BIB) proved beneficial for weight loss, but the effect of the device on ameliorating some components of the metabolic syndrome associated with obesity remains uncertain.

Objective: To evaluate the effectiveness of BIB insertion on weight control and amelioration of components of the metabolic syndrome.

Design: A prospective intervention study performed at baseline, 6 months after BIB insertion, and after a mean (standard deviation [SD]) of 21 (3) months (range 14-26) of follow-up.

Setting: Division of Gastroenterology and Endoscopic Unit, "Casa Sollievo della Sofferenza" Hospital.

Patients: One hundred thirty obese patients with a mean (SD) weight of 118 (24) kg and mean (SD) body mass index (BMI) of 43 (8) kg/m(2).

Interventions: Positioning of BIB.

Main Outcome Measurements: Anthropometric and laboratory parameters.

Results: Overall, the mean (SD) weight and BMI decreased by 13.2 (8.2) kg and 5.1 (3.2) kg/m(2), respectively, compared with baseline. The mean glycemia, insulinemia, Homeostasis Model Assessment index, triglyceridemia, and alanine aminotransferase levels were significantly reduced. In the 91 responders (BMI decrease of > or = 3.5 kg/m(2)), the mean (SD) weight and BMI decreased by 16.4 (6.3) kg and 6.4 (2.3) kg/m(2), respectively, and severe liver steatosis decreased from 52% to 4% (P < .0001). On multivariate analysis, severe steatosis and the Homeostasis Model Assessment index were predictive of the response to BIB: odds ratios of 6.71 (95% CI, 2.23-20.19) and 3.18 (95% CI, 1.20-8.42). After a median follow-up of 22 months after BIB removal, 50% of responders maintained or continued to lose weight.

Limitations: No sham-treated patients were included as comparative controls.

Conclusions: Treatment was effective in inducing weight loss, improving liver steatosis, and restoring some components of the metabolic syndrome.
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http://dx.doi.org/10.1016/j.gie.2009.06.036DOI Listing
May 2010

Antiviral therapy in compensated and decompensated cirrhotic patients with chronic HCV infection.

Expert Opin Pharmacother 2009 Aug;10(12):1929-38

'Casa Sollievo Sofferenza' Hospital, Division of Gastroenterology, IRCCS, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy.

Liver cirrhosis secondary to HCV infection is a chronic disorder that carries high morbidity and mortality. Approved antiviral treatment for this condition at present includes peginterferon in combination with ribavirin. Treatment is only recommended for a well-compensated liver cirrhosis, whereas antiviral therapy is commonly not implemented in cirrhotics with signs of liver decompensation, over the concern that the use of peginterferon and ribavirin might expose patients to severe treatment-related side effects. This review focuses on data available to support both efficacy and safety of antiviral therapy in both compensated and decompensated cirrhotic patients.
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http://dx.doi.org/10.1517/14656560903066811DOI Listing
August 2009

Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition.

World J Gastroenterol 2008 Nov;14(42):6467-72

"Casa Sollievo della Sofferenza" Hospital, IRCCS, viale Cappuccini 1, San Giovanni Rotondo 71013, Italy.

The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (Child-Pugh-Turcotte score >= 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving.
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http://dx.doi.org/10.3748/wjg.14.6467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773331PMC
November 2008

Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis.

Gastrointest Endosc 2007 Apr;65(4):624-32

Division of Gastroenterology, Casa Sollievo Sofferenza and De Bellis Hospitals, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy.

Background: The prophylactic use of somatostatin or gabexate in patients undergoing ERCP is still controversial.

Objective: Our purpose was to update the meta-analysis on somatostatin (SS, 16 studies) or gabexate mesylate (GM, 9 studies) prophylaxis of post-ERCP pancreatitis and to run sensitivity analyses by subgrouping trials according to schedules of drug administration.

Main Outcome Measurements: Post-ERCP acute pancreatitis, hyperamylasemia, and pain.

Results: Heterogeneity was present among selected studies, which appeared eliminated when only 9 high-quality trials on SS and 5 randomized studies on GM were considered. After data were pooled from SS trials, pancreatitis occurred in 7.3% of controls versus 5.3% of treated patients, a nonsignificant effect (odds ratio [OR] = 0.73; 95% CI 0.54-1.006). The funnel plot showed asymmetry with a negative slope (P = .05). The meta-analysis produced negative results for either short- (<6 hours) or long-term (> or =12 hours) SS infusion, whereas a bolus injection proved effective (OR = 0.271; 95% CI 0.138-0.536), with a pooled absolute risk reduction of 8.2% (95% CI 4.4-12.0%). Postprocedural hyperamylasemia, but not pain, was significantly reduced (OR = 0.67, 95% CI 0.57-0.81). In controls and patients treated with GM, pancreatitis developed in 5.7% versus 4.8%, hyperamylasemia in 40.6% versus 36.9%, and pain in 1.7% versus 8.9%. All pooled ORs were nonsignificant: P = .34, .17, and .19, respectively. The meta-analysis produced no significant effect for either short-term (<6 hours) or long-term (>12 hours) GM administration.

Conclusion: Short- or long-term infusion of SS or GM proved ineffective in reducing post-ERCP pancreatitis and pain. The beneficial effect of SS on postprocedural hyperamylasemia seems of marginal significance. When given as a bolus injection, SS maintains its promise in this field, but additional data are needed.
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http://dx.doi.org/10.1016/j.gie.2006.10.030DOI Listing
April 2007

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis.

World J Gastroenterol 2006 Dec;12(48):7821-5

Division of Gastroenterology, Hospital Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.

Aim: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD).

Methods: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT).

Results: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21).

Conclusion: BMI helps identify children with NASH who might have fibrotic deposition in the liver.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087549PMC
http://dx.doi.org/10.3748/wjg.v12.i48.7821DOI Listing
December 2006

Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study.

J Hepatol 2007 Feb 20;46(2):206-12. Epub 2006 Oct 20.

Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.

Background/aim: To evaluate long-term outcomes in decompensated HCV-related cirrhotic patients treated with antiviral therapy.

Methods: Of 129 eligible patients, 66 received peginterferon alfa-2b and ribavirin for 24 weeks, and 63 were controls. Survival and recurrence of liver failure events after therapy were main outcomes.

Results: Therapy was tolerated by 27 patients, dose reduced in 26 for toxicity, and discontinued in 13 for intolerance. End-of-therapy and sustained virological response (SVR) rates were 82.6% and 43.5% for HCV 2/3 patients, and 30.2% and 7.0% for HCV 1/4 patients. During therapy, odds ratios for severe infections or deaths due to infection were 2.95 (95% C.I. 0.93-9.3) and 1.97 (95% C.I. 0.40-9.51) in treated patients as compared with controls. During a follow-up of 30 months off-therapy, decompensated events occurred in 52, 33, and 3 of controls, non-responders, and SVR patients. Odds ratios for ascites, encephalopathy, and oesophageal bleeding in treated patients significantly decreased as compared with controls. Annualized incidence of death was 2.34, 1.91, and 0 per 1000 patient-years, respectively, in controls, non-responders, and SVR patients. Survival curves showed early separation of SVR patients from both non-responders and controls at approximately 6 months.

Conclusions: In decompensated cirrhotics, HCV clearance by therapy is life-saving and reduces disease progression.
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http://dx.doi.org/10.1016/j.jhep.2006.08.020DOI Listing
February 2007
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