Hypergammaglobulinemia before Starting DAA Therapy Is A Strong Predictor of Disease Progression in Cirrhotic Patients Even after HCV Clearance

The predictive factors of long-term clinical benefits in patients with hepatitis C virus (HCV)—related liver cirrhosis after Direct Antiviral Agents (DAA) treatment are still undefined. The aim of this study was to identify any predictors of liver failure, hepatocellular carcinoma (HCC) and/or death in patients with compensated liver cirrhosis who achieved the sustained virological response (SVR). To this purpose, 324 consecutive cirrhotic patients who started DAA treatment from 1 April 2015 to 31 December 2016 were retrospectively analyzed. All patients were followed up for a median time of 63 months (range 19–77) through clinical/biochemical/instrumental examinations performed at baseline and after stopping the DAA treatment. At the end of the evaluation, 230 (71%) individuals showed stable clinical liver disease over time, 43 (13.3%) developed HCC, and 24 (7.4%) developed hepatic decompensation without HCC. Overall, 49 (15,1%) patients died. Multivariate regression analysis showed that hepatic decompensation was significantly associated with at baseline older age, higher liver stiffness, higher spleen longitudinal size values and hypergammaglobulinemia (p = 0.003, p = 0.005, p = 0.001, p = 0.029, respectively). HCC development was significantly associated with hypergammaglobulinemia (p p p = 0.007, respectively). Finally, survival analysis confirmed that patients with gamma globulin levels ≥ 1.8 gr/dl had a significantly higher risk of death compared to those with gamma globulin levels p < 0.001). In conclusion, hypergammaglobulinemia before starting DAA therapy represents a strong predictor of hepatic decompensation, HCC and death in cirrhotic patients even after HCV clearance

Monofocal hepatocellular carcinoma: how much does size matter?

none88mixedPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐Baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, VeronicaPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, Veronic

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material depriva- tion (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treat- ments progressively decreased as the SMD worsened. Consequently, overall survival was bet- ter in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs

Background &amp; Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006–2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006–2010; 2011–2015; 2016–2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions: In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and Implications: Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients’ eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance