Raffaele Romito

Azienda Ospedaliero Universitaria Maggiore della Carita

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Vincenzo Mazzaferro

Fondazione IRCCS Istituto Nazionale dei Tumori

Enrico Regalia

Fondazione IRCCS Istituto Nazionale dei Tumori

Andrea Pulvirenti

University of Modena and Reggio Emilia

Jorgelina Coppa

Fondazione IRCCS Istituto Nazionale dei Tumori

Alfonso Marchianò

Fondazione IRCCS Istituto Nazionale dei Tumori

M Schiavo

University of Chieti-Pescara

Carlo Sposito

Fondazione IRCCS Istituto Nazionale dei Tumori

Carlo Spreafico

Fondazione IRCCS Istituto Nazionale dei Tumori

Tiziana Camerini

Fondazione IRCCS Istituto Nazionale dei Tumori

Luca Portigliotti

Azienda Ospedaliero Universitaria Maggiore della Carita

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384

Istituti di Ricovero e Cura a Carattere Scientifico

185

University of Milan

142

Ospedale Maggiore

University of Naples Federico II

Fondazione IRCCS Istituto Nazionale dei Tumori

Sapienza University of Rome

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

University of Bologna

University of Turin

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8Experience with liver transplantation for hepatocellular carcinoma in cirrhosis

Liver Transplantation (2000)

Jorgelina Coppa Enrico Regalia Andrea Pulvirenti S Andreola Raffaele Romito

Milan criteria

10.1016/s1527-6465(05)80037-1

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Citations (0)

Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion

Journal of Hepatology (2018)

Carlo Spreafico Carlo Sposito Marta Vaiani Tommaso Cascella Sherrie Bhoori

10.1016/j.jhep.2017.12.026

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Citations (127)

Amino Acid Kinetics During the Anhepatic Phase of Liver Transplantation

Diabetes (2002)

Alberto Battezzati Andrea Caumo A Fattorini Lucia Piceni Sereni Jorgelina Coppa

Alanine and glutamine are interorgan nitrogen/carbon carriers for ureagenesis and gluconeogenesis, which are mainly but not necessarily only hepatic. The liver is central to alanine and glutamine metabolism, but most organs can produce and use them. We studied amino acid kinetics after liver removal to depict initial events of liver failure and to provide a model to study extrahepatic gluconeogenesis and nitrogen disposal in humans. We measured amino acid kinetics with [5,5,5-2H3]leucine and [3-13C]alanine or [1,2-13C2]glutamine tracers in 21 subjects during and after the anhepatic phase of liver transplantation: 12 were at 7 months posttransplantation, and 7 were healthy control subjects. Anhepatic leucine kinetics, including proteolysis, was unchanged. Alanine plasma and whole-body contents increased 3× and 2×, with a halved metabolic clearance and a doubled production, 2% greater than disposal. Free whole-body glutamine decreased 25% but increased 50% in plasma. Glutamine clearance was halved, and the production decreased by 25%, still 2% greater than disposal. Liver replacement decreased alanine and glutamine concentrations, leaving leucine unchanged. Liver removal caused doubled alanine fluxes, minor changes in glutamine, and no changes in leucine. The initial events after liver removal are an accumulation of three-carbon compounds, an acceleration of alanine turnover, and limited nitrogen storage in alanine and glutamine.

Alanine

Gluconeogenesis

10.2337/diabetes.51.6.1690

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Citations (11)

Resection versus transplantation for liver metastases from neuroendocrine tumors

Transplantation Proceedings (2001)

Jorgelina Coppa Andrea Pulvirenti M Schiavo Raffaele Romito Paola Collini

10.1016/s0041-1345(00)02586-0

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Citations (101)

Prevention of recurrent hepatitis C after liver transplantation with early interferon and ribavirin treatment

Transplantation Proceedings (2001)

Vincenzo Mazzaferro A. Tagger M Schiavo Enrico Regalia Andrea Pulvirenti

Hepatitis C

10.1016/s0041-1345(00)02508-2

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Citations (130)

Percutaneous Transhepatic Biliary Drainage in the Management of Postsurgical Biliary Leaks in Patients with Nondilated Intrahepatic Bile Ducts

CardioVascular and Interventional Radiology (2006)

G. Cozzi A Severini Enrico Civelli M Milella Andrea Pulvirenti

Biliary fistula

Intrahepatic bile ducts

Biliary Drainage

Biliary sludge

10.1007/s00270-005-0102-4

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Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation

Frontiers in Medicine (2021)

Elena Grossini Divya Praveen Garhwal Giuseppe Calamita Raffaele Romito Cristina Rigamonti

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Huh7.5 cells/primary human hepatocytes were exposed to plasma from 12 NAFLD patients and 12 healthy subjects and specific assays were performed to examine viability, H 2 O 2 and mitochondrial reactive oxygen species (ROS) release, mitochondrial membrane potential and triglycerides content. The involvement of NLRP3 inflammasome and of signaling related to peroxisome-proliferator-activating-ligand-receptor-γ (PPARγ), sterol-regulatory-element-binding-protein-1c (SREBP-1c), nuclear-factor-kappa-light-chain-enhancer of activated B cells (NF-kB), and NADPH oxidase 2 (NOX2) was evaluated by repeating the experiments in the presence of NLRP3 inflammasome blocker, MCC950, and through Western blot. The results obtained shown that plasma of NAFLD patients was able to reduce cell viability and mitochondrial membrane potential by about 48 and 24% ( p < 0.05), and to increase H 2 O 2 , mitochondrial ROS, and triglycerides content by about 42, 19, and 16% ( p < 0.05), respectively. An increased expression of SREBP-1c, PPARγ, NF-kB and NOX2 of about 51, 121, 63, and 46%, respectively, was observed ( p < 0.05), as well. Those effects were reduced by the use of MCC950. Thus, in hepatocytes, exposure to plasma from NAFLD patients induces a NAFLD-like phenotype by interference with NLRP3-inflammasome pathways and the activation of intracellular signaling related to SREBP-1c, PPARγ, NF-kB and NOX2.

Viability assay

10.3389/fmed.2021.693997

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Citations (14)

Multicentre evaluation of case volume in minimally invasive hepatectomy

British journal of surgery (2019)

Luca Viganò Matteo Cimino Luca Aldrighetti Alessandro Ferrero Umberto Cillo

Abstract Background Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. Methods Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). Results A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). Conclusion A volume–outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

10.1002/bjs.11369

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Citations (20)

Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis

Hepatology (2006)

Vincenzo Mazzaferro Raffaele Romito Marcello Schiavo Luigi Mariani Tiziana Camerini

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA–positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]–negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc–positive) groups, then randomized to IFN-α (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence ( P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09–0.9; P = .04). In conclusion , IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment.

Hepatitis C

10.1002/hep.21415

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Citations (365)

Nonhepatic glucose production in humans

AJP Endocrinology and Metabolism (2004)

Alberto Battezzati Andrea Caumo Francesca Martino Lucia Piceni Sereni Jorgelina Coppa

Extrahepatic glucose release was evaluated during the anhepatic phase of liver transplantation in 14 recipients for localized hepatocarcinoma with mild or absent cirrhosis, who received a bolus of [6,6- 2 H 2 ]glucose and l-[3- 13 C]alanine or l-[1,2- 13 C 2 ]glutamine to measure glucose kinetics and to prove whether gluconeogenesis occurred from alanine and glutamine. Twelve were studied again 7 mo thereafter along with seven healthy subjects. At the beginning of the anhepatic phase, plasma glucose was increased and then declined by 15%/h. The right kidney released glucose, with an arteriovenous gradient of -3.7 mg/dl. Arterial and portal glucose concentrations were similar. The glucose clearance was 25% reduced, but glucose uptake was similar to that of the control groups. Glucose production was 9.5 ± 0.9 μmol·kg -1 · min -1 , 30% less than in controls. Glucose became enriched with 13 C from alanine and especially glutamine, proving the extrahepatic gluconeogenesis. The gluconeogenic precursors alanine, glutamine, lactate, pyruvate, and glycerol, insulin, and the counterregulatory hormones epinephrine, cortisol, growth hormone, and glucagon were increased severalfold. Extrahepatic organs synthesize glucose at a rate similar to that of postabsorptive healthy subjects when hepatic production is absent, and gluconeogenic precursors and counterregulatory hormones are markedly increased. The kidney is the main, but possibly not the unique, source of extrahepatic glucose production.

Gluconeogenesis

Alanine

Bolus (digestion)

10.1152/ajpendo.00486.2002

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Citations (71)