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BACKGROUND & AIMS: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. METHODS: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. RESULTS: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). CONCLUSIONS: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.
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Carcinoma Hepatocelular , Hepatitis D Crónica , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Italia/epidemiología , Hepatitis D Crónica/complicaciones , Anciano , Virus de la Hepatitis Delta/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Estudios Retrospectivos , Anticuerpos Antihepatitis/sangre , Hepatitis B Crónica/complicaciones , AdultoRESUMEN
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort. METHODS: We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC. RESULTS: MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). CONCLUSIONS: The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Hypercoagulability and hypofibrinolysis in acutely decompensated cirrhosis (AD) may be implicated in disease progression and haemostatic complications. We conducted a prospective study to: (1) characterise haemostatic alterations in AD; (2) evaluate whether such alterations can predict acute-on-chronic liver failure (ACLF) and bleeding/thrombosis. METHODS: Hospitalised individuals with AD were prospectively recruited and underwent an extensive haemostatic profiling including coagulation factors, thrombomodulin-modified thrombin generation assay with evaluation of endogenous thrombin potential (ETP; marker for plasmatic hypercoagulability), fibrinolytic factors, and plasmin-antiplasmin complex (fibrinolysis activation marker). Inflammation severity was assessed by C-reactive protein (CRP). In part 1 of the study, we compared haemostasis in AD vs. controls (stable decompensated and compensated cirrhosis). In part 2 of the study, we prospectively followed individuals with AD for 1 year and investigated predictors of ACLF and bleeding/thrombosis. RESULTS: A total of 169 individuals with AD were recruited (median model for end-stage liver disease score 20; CLIF-C AD 54). Compared with controls, AD was associated with more pronounced hypercoagulability (ETP: 871 vs. 750 vs. 605 nmol/L per min; p <0.0001), without differences in fibrinolysis activation. During follow-up, 55 individuals developed ACLF. CLIF-C AD, CRP, and Child-Pugh were independently associated with ACLF. A predictive model combining these variables (Padua model) accurately identified individuals at higher risk of ACLF (AUROC 0.857; 95% CI 0.798-0.915; sensitivity 74.5%, specificity 83.3%). Notably, CRP and progression to ACLF, but not baseline coagulopathy, were associated with bleeding (n = 11); CRP and antifibrinolytic factor PAI-1 >50 ng/ml were associated with thrombosis (n = 14). The prognostic value of the Padua model was validated in an independent, bicentric European cohort (N = 301). CONCLUSIONS: Inflammation severity, and not coagulopathy, is the most important predictor of ACLF and bleeding in AD. The Padua model can be used to identify individuals with AD at risk of ACLF. IMPACT AND IMPLICATIONS: A better understanding of haemostasis in individuals with acutely decompensated cirrhosis may help to identify those at higher risk of progression and complications. In this prospective study, we found no significant association between alterations of haemostasis and cirrhosis progression, indicating that the assessment of haemostatic alterations is not useful to identify those at risk. However, we found that C-reactive protein (a simple blood test that reflects severity of inflammation) and severity of chronic liver disease itself (as assessed by specific scores) were associated with cirrhosis progression and development of bleeding complications. Therefore, we developed a simple predictive model - based on C-reactive protein and liver disease scores - that, if validated by independent studies, could be used in clinical practice to assist physicians in identifying individuals with decompensated cirrhosis at higher risk of disease progression and death (i.e. in whom to consider an expedited evaluation for liver transplantation).
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Insuficiencia Hepática Crónica Agudizada , Trastornos de la Coagulación Sanguínea , Enfermedad Hepática en Estado Terminal , Hemostáticos , Trombofilia , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/etiología , Estudios Prospectivos , Trombina , Enfermedad Hepática en Estado Terminal/complicaciones , Proteína C-Reactiva , Índice de Severidad de la Enfermedad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Inflamación/complicaciones , Pronóstico , Trastornos de la Coagulación Sanguínea/complicaciones , Hemorragia , Progresión de la EnfermedadRESUMEN
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non-transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. METHODS: From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up-to-seven criteria were compared between patients with HCC <4 and ≥4 cm. RESULTS: During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up-to-seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence-free survival and overall survival. HCC size ≥4 cm and high alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up-to-seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non-transplantable recurrence. CONCLUSIONS: Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long-term survival. Non-transplantable recurrence is predicted by HCC size and AFP levels, among pre-operatively available variables. High-risk patients could be considered for frontline LT or listed for transplantation even before recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Neoplasias Hepáticas/patología , alfa-Fetoproteínas , Recurrencia Local de Neoplasia/patología , Hepatectomía/métodos , Estudios RetrospectivosRESUMEN
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the "primum movens" of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sorafenib/uso terapéuticoRESUMEN
OBJECTIVE: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5âyears OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5âyears were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Estadificación de Neoplasias , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Estudios Retrospectivos , Sorafenib/uso terapéutico , Resultado del TratamientoRESUMEN
Venous thrombosis is a frequent complication in cancer and is associated with high morbidity and mortality. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related death worldwide, and it is associated with preexisting cirrhosis in 90% of cases. Patients with cirrhosis acquire complex alterations in their haemostatic system that may predispose them to bleed or thrombotic complications. There is growing evidence that HCC may tilt the haemostatic equilibrium in cirrhosis towards hypercoagulability, thus increasing the risk of venous thrombosis. Previously described mechanisms of HCC-driven thrombophilia include thrombocytosis and increased platelet activation/function, increased fibrinogen concentration/polymerization, enhanced thrombin generation, hypofibrinolysis, and release of tissue factor-expressing microvesicles. Nevertheless, there are currently no specific guidelines on risk stratification and management of thromboprophylaxis in patients with cirrhosis and HCC. Our review endeavours to summarize the latest findings on epidemiology, risk factors and pathogenesis of non-malignant venous thrombosis in patients with cirrhosis and HCC, and provide evidence in support of tailored management of thrombotic risk in these patients.
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Carcinoma Hepatocelular , Hemostáticos , Neoplasias Hepáticas , Trombofilia , Trombosis , Tromboembolia Venosa , Trombosis de la Vena , Anticoagulantes/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Hemostáticos/uso terapéutico , Humanos , Cirrosis Hepática/patología , Neoplasias Hepáticas/tratamiento farmacológico , Trombosis/etiología , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/tratamiento farmacológico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiologíaRESUMEN
BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Hepatectomía , Humanos , Italia , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
Machine learning has recently been proposed as a useful tool in many fields of Medicine, with the aim of increasing diagnostic and prognostic accuracy. Models based on machine learning have been introduced in the setting of solid organ transplantation too, where prognosis depends on a complex, multidimensional and nonlinear relationship between variables pertaining to the donor, the recipient and the surgical procedure. In the setting of liver transplantation, machine learning models have been developed to predict pretransplant survival in patients with cirrhosis, to assess the best donor-to-recipient match during allocation processes, and to foresee postoperative complications and outcomes. This is a narrative review on the role of machine learning in the field of liver transplantation, highlighting strengths and pitfalls, and future perspectives.
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Trasplante de Hígado , Humanos , Cirrosis Hepática , Aprendizaje Automático , Pronóstico , Donantes de TejidosRESUMEN
Gastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice.
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The systemic treatment of hepatocellular carcinoma (HCC) is changing rapidly. After a decade of tyrosine kinase inhibitors (TKIs), as the only therapeutic option for the treatment of advanced HCC, in the last few years several phase III trials demonstrated the efficacy of immune checkpoint inhibitors (ICIs). The combination of the anti-PD-L1 atezolizumab and the anti-vascular endothelial growth factor (VEGF) bevacizumab demonstrated the superiority over sorafenib and currently represents the standard of care treatment for advanced HCC. In addition, the combination of durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) proved to be superior to sorafenib, and in the same trial durvalumab monotherapy showed non-inferiority compared to sorafenib. However, early reports suggest an influence of HCC etiology in modulating the response to these drugs. In particular, a lower effectiveness of ICIs has been suggested in patients with non-viral HCC (in particular non-alcoholic fatty liver disease). Nevertheless, randomized controlled trials available to date have not been stratified for etiology and data suggesting a possible impact of etiology in the outcome of patients managed with ICIs derive from subgroup not pre-specified analyses. In this review, we aim to examine the potential impact of HCC etiology on the response to immunotherapy regimens for HCC.
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Carcinoma Hepatocelular , Enfermedades del Sistema Digestivo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , Sorafenib , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , InmunoterapiaRESUMEN
BACKGROUND: The 2022 Barcelona Clinic Liver Cancer (BCLC) algorithm does not recommend liver resection (LR) in BCLC A patients with oligo-nodular (two or three nodules ≤3â cm) hepatocellular carcinoma (HCC). This sharply contrasts with the therapeutic hierarchy concept, implying a precise treatment order exists within each BCLC stage. This study aimed to compare the outcomes of LR versus radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) in BCLC A patients. METHODS: A meta-analysis adhering to PRISMA guidelines and the Cochrane Handbook was performed. All RCT, cohort and case-control studies that compared LR versus RFA or TACE in oligo-nodular BCLC A HCC published between January 2000 and October 2023 were comprehensively searched on PubMed, Embase, the Cochrane Library and China Biology Medicine databases. Primary outcomes were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Risk ratio (RR) was computed as a measure of treatment effect (OS and DFS benefit) to calculate common and random effects estimates for meta-analyses with binary outcome data. RESULTS: 2601 patients from 14 included studies were analysed (LR = 1227, RFA = 686, TACE = 688). There was a significant 3- and 5-year OS benefit of LR over TACE (RR = 0.55, 95% c.i. 0.44 to 0.69, P < 0.001 and RR 0.57, 95% c.i. 0.36 to 0.90, P = 0.030, respectively), while there was no significant 3- and 5-year OS benefit of LR over RFA (RR = 0.78, 95% c.i. 0.37 to 1.62, P = 0.452 and RR 0.74, 95% c.i. 0.50 to 1.09, P = 0.103, respectively). However, a significant 3- and 5-year DFS benefit of LR over RFA was found (RR = 0.70, 95% c.i. 0.54 to 0.93, P = 0.020 and RR 0.82, 95% c.i. 0.72 to 0.95, P = 0.015, respectively). A single study comparing LR and TACE regarding DFS showed a significant superiority of LR. The Newcastle-Ottawa Scale quality of studies was high in eight (57%) and moderate in six (43%). CONCLUSIONS: In BCLC A oligo-nodular HCC patients, LR should be preferred to RFA or TACE (therapeutic hierarchy concept). Additional comparative cohort studies are urgently needed to increase the certainty of this evidence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Supervivencia sin EnfermedadRESUMEN
Background: Gastroesophageal reflux disease (GERD) is a challenging condition that involves different physicians, such as general practitioners (GPs), gastroenterologists, and ears, nose and throat (ENT) specialists. A common approach consists of proton-pump inhibitors (PPIs) administration. Adjunctive pharmacological treatment may have a role in the management of non-responders to PPIs. Objectives: We aimed to survey GPs and different medical specialists to investigate the medical approaches to patients reporting GERD symptoms. In addition, we examined the use of adjunctive pharmacological treatments in patients with GERD symptoms who do not respond to PPIs. Design: Retrospective observational study. Methods: A survey was conducted among a large sample of gastroenterologists, GPs, and ENT specialists. Symptoms were divided into typical and extraesophageal, and their severity and impact on quality of life were explored with the GERD Impact Scale and with Reflux Symptom Index (RSI). All therapies administered usually for GERD were investigated. Results: A total of 6211 patients were analyzed in this survey. Patients with typical symptoms were 53.5%, while those with extraesophageal symptoms were 46.5%. The latter were more frequently reported by ENT patients (53.6%, p < 0.0001). The GSI was higher in patients followed by gastroenterologists (9 points) and GPs (9 points) than ENT specialists (8 points), but the RSI was higher in the ENT group (14.3 ± 6.93) than in GPs and gastroenterologist groups (10.36 ± 6.36 and 10.81 ± 7.30, p < 0.0001). Chest pain had the highest negative impact on quality of life (p < 0.0001). Of the 3025 patients who used PPIs, non-responders showed a lower GSI when treated with a combination of adjunctive pharmacological treatments and bioadhesive compounds, than with single-component drugs. Conclusion: Patients with GERD referred to a gastroenterologist had more severe disease and poorer quality of life. The combination of adjunctive pharmacological treatments and bioadhesive compounds seems to be effective in the management of PPI refractory patients.
Gastroesophageal reflux disease management: real-world perspectives from Italian gastroenterologists, primary care physicians and ENT specialists Gastroesophageal reflux disease (GERD) is a prevalent and chronic condition that affects millions of individuals worldwide, causing significant discomfort and impacting their overall quality of life. In the comprehensive management of GERD, a collaborative approach involving different physicians is essential to address the various aspects of this complex condition. Given the wide range of diagnostic and therapeutic possibilities in clinical practice, we aimed to investigate how GERD is managed in clinical practice by general practitioners and different medical specialists, including gastroenterologists and ears, nose, and throat (ENT) specialists. A total of 6,211 observations were carried out from a survey. The severity and impact of GERD on quality-of-life was higher in patients followed by gastroenterologists and general practitioners than ENT specialists. Non-cardiac chest pain had the highest negative impact on quality-of-life. Of the 3,025 patients who used PPIs, non-responders showed an improved quality of life when treated with a combination of adjunctive pharmacological treatments and bio adhesive compounds.
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MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.
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Introduction: Psychosocial pre-transplant evaluation in patients undergoing liver transplantation (LT) could help identify those patients at higher risk of pharmacological non-adherence, organ rejection, and mortality. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated tool for assessing LT candidates' psychosocial well-being. Data on the ability of the SIPAT evaluation to predict post-transplant outcomes are sparse. Material and Methods: clinical and psychosocial data from a sample of 134 candidates for LT were analyzed. Moreover, the association between pre-transplant psychosocial evaluation and post-transplant clinical outcomes, including organ rejection, mortality, and immunosuppressant drug adherence, was calculated. Results: At the pre-transplant evaluation, patients who showed high SIPAT scores (77, 57%) also had more liver disease assessed by model for end-stage liver disease (MELD; F = 5.04; p < 0.05), alcoholic etiology (F = 35.80; p < 0.001), encephalopathy (F = 5.02; p < 0.05), and portal hypertension (F = 7.45; p < 0.01). Of the 51 transplant patients, those who had a high pre-transplant SIPAT score showed lower post-transplant immunosuppressive adherence, linked to more frequent immunological events. Conclusions: Patients with an alcoholic etiology of liver disease and more severe liver dysfunction are likelier to not adhere to medical prescriptions following transplantation. Current data suggests that this specific group of patients could benefit from early psychological pre-habilitation before undergoing liver transplantation.
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BACKGROUND AND AIMS: The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. METHOD: Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. RESULTS: In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9-9.6) vs. 3.9 (2.6-5.2) months (p<0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2-17.8) vs.3.0 (2.2-3.8) months (p<0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). CONCLUSION: C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis.
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Importance: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. Objective: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. Design, Setting, and Participants: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. Interventions: LR, PRFA, or TACE. Main Outcomes and Measures: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. Results: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. Conclusions and Relevance: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.
RESUMEN
In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with hepatocellular carcinoma (HCC). Following the positive results of the IMbrave150 trial, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) became the standard of care frontline treatment for patients with advanced stage HCC. Several other trials evaluated immunotherapy in HCC, demonstrating that ICIs-based regimens are currently the most effective treatment strategies and expanding the therapeutic possibilities. Despite the unprecedent rates of objective tumor response, not all patients benefit from treatment with ICIs. Therefore, in order to select the appropriate therapy as well as to correctly allocate medical resources and avoid unnecessary treatment-related toxicities, there is great interest in identifying the predictive biomarkers of response or resistance to immunotherapy-based regimens. Immune classes of HCC, genomic signatures, anti-drug antibodies, and patient-related factors (e.g., etiology of liver disease, gut microbiota diversity) have been associated to the response to ICIs, but none of the proposed biomarkers have been translated into clinical practice so far. Considering the crucial importance of this topic, in this review we aim to summarize the available data on tumor and clinical features associated with the response or resistance of HCC to immunotherapies.