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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
Advances in the surgical and systemic therapeutic landscape of hepatocellular carcinoma have increased the complexity of patient management. A dynamic adaptation of the available staging-based algorithms is required to allow flexible therapeutic allocation. In particular, real-world hepatocellular carcinoma management increasingly relies on factors independent of oncological staging, including patients' frailty, comorbid burden, critical tumour location, multiple liver functional parameters, and specific technical contraindications impacting the delivery of treatment and resource availability. In this Policy Review we critically appraise how treatment allocation strictly based on pretreatment staging features has shifted towards a more personalised treatment approach, in which expert tumour boards assume a central role. We propose an evidence-based framework for hepatocellular carcinoma treatment based on the novel concept of multiparametric therapeutic hierarchy, in which different therapeutic options are ordered according to their survival benefit (ie, from surgery to systemic therapy). Moreover, we introduce the concept of converse therapeutic hierarchy, in which therapies are ordered according to their conversion abilities or adjuvant abilities (ie, from systemic therapy to surgery).
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patologíaRESUMEN
Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin-sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.
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Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , InsulinaRESUMEN
AIM: To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. METHODS: A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. RESULTS: A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). CONCLUSIONS: Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , IncidenciaRESUMEN
Despite the institution of an interdisciplinary Inflammatory Bowel Disease (IBD) centre is encouraged, how it may improve patient care is still unknown. In a 5-year period following organisation of an IBD centre, hospitalisations per patient/year decreased (0.41-0.17) and patients on biologics increased (7.7%-26.7%). Total number of hospitalisations (-18.4%) and length of hospitalisation (-29.4%) improved compared with a preceding 5-year period. These findings suggest that institution of an interdisciplinary IBD centre is associated with improved healthcare utilisation.
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BACKGROUND AND AIMS: Treatment of de novo malignancies and recurrent hepatocellular carcinoma with immune checkpoint inhibitors (ICI) in liver transplant recipients (LT) is an attractive strategy that is infrequently pursued because of the lack of strong evidence regarding their safety and efficacy. In this systematic review with pooled analysis, we aimed to assess safety and efficacy of ICI therapy following LT. METHODS: We performed a systematic search of case reports and series published until January 2022. We included 31 publications reporting a total of 52 patients treated with ICIs after LT and assessed in a pooled analysis the risk of graft rejection and the outcome of ICI therapy. RESULTS: Acute graft rejection occurred in 15 patients (28.8%) and 7 patients (13.4% of the total cohort) died because of graft loss. Rejection was associated with shorter overall survival (OS) (17.2 months, confidence interval [CI] 12.1-22.2 vs. 3.5 months, CI 1.6-5.4, p < 0.001). Disease control rate was 44.2% (n = 23), and in these patients, OS was longer than in non-responders (26.4 months, CI 20.8-32.0 vs. 3.4 months, CI 2.1-4.7, p < 0.001). CONCLUSIONS: Observational, off-label experience suggests that treatment with ICI for advanced malignancies in LT recipients might not be discarded a priori. This notwithstanding, ICI treatment in these patients is associated with a substantial risk of graft rejection and mortality. Prospective studies are needed to provide adequate safety and efficacy figures of ICI treatment in this fragile population.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Neoplasias Hepáticas/cirugíaRESUMEN
BACKGROUND & AIMS: Patients with cirrhosis are considered in a haemostatic balance, though weaker than in normal subjects. In these patients, however, the use of pharmacological prophylaxis for venous thromboembolism (VTE) remains controversial. Therefore, in this study, we aimed to assess the safety and efficacy of VTE prophylaxis in patients with cirrhosis. METHODS: We conducted a systematic review of studies reporting the occurrence of bleeding and VTE events in patients with cirrhosis, and controls, undergoing VTE prophylaxis. Meta-regression analysis was conducted to further explore the determinants of heterogeneity in the study of the occurrence of either bleeding or VTE events. RESULTS: In a total of 10 studies, including 5712 patients, of which 2330 undergoing VTE prophylaxis, bleeding (n = 5513) and VTE events occurred in 8.2% and 2.8% patients respectively. A total of 2963 and 3162 patients were included from low-risk of bias studies in bleeding and VTE analysis respectively: while administration of VTE prophylaxis did not seem to reduce VTE (OR = 1.07, CI 0.39-2.96, p = .89), importantly prophylaxis was not associated with increased bleeding risk (OR = 0.56, CI 0.20-1.59, p = .27). Meta-regression analysis showed that no parameter significantly influenced the heterogeneity of data regarding bleeding or VTE events. CONCLUSIONS: In patients with cirrhosis, current evidence is insufficient to advise for or against the use of VTE prophylaxis, mainly due to lack of quality and homogeneity of available data. However, its use does not appear to be associated with a significant bleeding risk. Adequately designed studies are required to provide a measure of its overall utility.
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Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
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
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic that encompasses three distinct clinical phenotypes: uncomplicated fatty liver, nonalcoholic steatohepatitis (NASH) and NASH-related cirrhosis with its complications, including hepatocellular carcinoma. To date, no pharmacological treatments have been approved and lifestyle modifications including reduced caloric intake targeting a 7%-10% weight loss from baseline assessment represent the standard approach. Mediterranean diet has been recommended as the best dietary pattern since it is easy to follow and, independently of caloric intake its nutritional components have beneficial metabolic effects that not only improve steatosis but also risk factors for cardiovascular events, the leading cause of morbidity/mortality in individuals with NAFLD. Other dietary patterns such as ketogenic diet and Dietary Approach to Stop Hypertension (DASH) diet can be used in patients with NAFLD. Recently, intermittent fasting diets have gained popularity among healthy individuals and have been proposed as a safe and effective treatment for the metabolic syndrome in experimental and in a few human studies. In this narrative review, we aim to summarize the evidence for the available dietary approaches for patients with NAFLD.
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Enfermedad del Hígado Graso no Alcohólico/dietoterapia , HumanosRESUMEN
Hepatocellular carcinoma (HCC) is a common complication in patients with chronic liver disease and leads to significant morbidity and mortality. Liver disease and liver cancer are preventable by mitigating and managing common risk factors, including chronic hepatitis B and C infection, alcohol use, diabetes, obesity and other components of the metabolic syndrome. The management of patients with HCC requires treatment of the malignancy and adequate control of the underlying liver disease, as preserving liver function is critical for successful cancer treatment and may have a relevant prognostic role independent of HCC management. Hepatologists are the ideal providers to guide the care of patients with HCC as they are trained to identify patients at risk, apply appropriate surveillance strategies, assess and improve residual liver function, evaluate candidacy for transplant, provide longitudinal care to optimize and preserve liver function during and after HCC treatment, survey for cancer recurrence and manage its risk factors, and prevent and treat decompensating events. We highlight the need for a team-based holistic approach to the patient with liver disease and HCC and identify necessary gaps in current care and knowledge.
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Carcinoma Hepatocelular , Gastroenterólogos , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Recurrencia Local de Neoplasia , Hepatitis B Crónica/complicaciones , Factores de Riesgo , Cirrosis Hepática/complicacionesRESUMEN
The growing diffusion of digitalisation and informatics has promoted the creation and analysis of large databases able to provide solid information. Analyses of "big data" generated by real-world practice are particularly useful for knowing incidence and mortality, disparities, temporal trends of diseases, identifying risk factors, predicting future scenarios, obtaining inputs for cost-effectiveness and treatment benefit modelling, designing new studies, and monitoring rare diseases. Although randomised controlled trials (RCTs) represent the gold-standard for generating evidence about new diagnostic, preventive or therapeutic procedures, their results should be integrated with real-world data to personalise patient management. Indeed, a substantial proportion of patients observed in field-practice have characteristics that prevent the access to RCTs or, when included, form sub-groups too small to provide robust post-hoc analyses. Furthermore, as RCTs are resource-consuming and designed to maximize the probability of success, they are generally performed in expert centres of high-income areas, excluding economically-deprived regions which could complementarily contribute to the medical progress as huge sources of real-world data. These considerations fuelled the creation in 1998 of the Italian Liver Cancer (ITA.LI.CA) consortium, with the aim to merge data of patients with hepatocellular carcinoma (HCC) managed in several centres. This cooperation permitted to analyse a multicentre, large cohort of HCC patients. Since then, the ITA.LI.CA group has progressively expanded to currently include 24 centres, and its database counts more than 9,000 patients. This article describes the history of the ITA.LI.CA consortium and presents its scientific production whose results greatly contributed to the incessant improvement of HCC management.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Estudios de Cohortes , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Estudios Multicéntricos como Asunto , Factores de RiesgoRESUMEN
BACKGROUND: Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). Unfortunately, the long-term use of HBIG presents high costs. Therefore, the use of prophylaxis based only on nucleos(t)ide analogues (NUC) has been recently postulated. The present meta-analysis aimed to evaluate the impact of HBIG ± NUC vs HBIG alone or NUC alone in post-LT HBV recurrence prophylaxis. MATERIALS AND METHODS: A systematic literature search was performed using PubMed and Cochrane databases. The primary outcome investigated was the HBV recurrence after LT. Three analyses were done comparing the effect of (a) HBIG + NUC vs HBIG alone; (b) HBIG+NUC vs NUC alone; and (c) HBIG alone vs NUC alone. Sub-analyses were also performed investigating the effect of low and high genetic barrierto-recurrence NUC. RESULTS: Fifty-one studies were included. The summary OR (95%CI) showed a decreased risk with the combination of HBIG + NUC vs HBIG alone for HBV recurrence, being 0.36 (95% CI = 0.22-0.61; P < .001). HBIG + NUC combined treatment reduced HBV reappearance respect to NUC alone (OR = 0.22; 95% CI = 0.16-0.30; P < .0001). Similarly, HBIG alone was significantly better than NUC alone in preventing HBV recurrence (OR = 0.20; 95% CI = 0.09-0.44; P < .0001). CONCLUSIONS: Prophylaxis with HBIG is relevant in preventing post-LT HBV recurrence. Its combination with NUC gives the best results in terms of protection. The present results should be considered in light of the fact that also old studies based on lamivudine use were included. Studies exploring in detail high genetic barrier-to-recurrence NUC and protocols with definite use of HBIG are needed.
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Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Inmunoglobulinas/uso terapéutico , Trasplante de Hígado , Nucleósidos/uso terapéutico , Quimioterapia Combinada , Hepatitis B/prevención & control , Humanos , Recurrencia , Prevención SecundariaRESUMEN
BACKGROUND AND AIMS: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. METHODS: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. RESULTS: MaVI prevalence was 11.1%, and median survival of these patients was 6.0 months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). CONCLUSIONS: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Venas Mesentéricas/patología , Vena Porta/patología , Técnicas de Ablación , Anciano , Antineoplásicos/uso terapéutico , Ascitis , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , Enfermedad Hepática en Estado Terminal , Femenino , Hepatectomía , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Italia , Hepatopatías Alcohólicas/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Gravedad del Paciente , Pronóstico , Sistema de Registros , Sorafenib/uso terapéutico , Tasa de Supervivencia , Carga TumoralRESUMEN
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
BACKGROUND AND AIMS: Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. METHODS: Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). RESULTS: The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of 'metabolic' and 'metabolic + alcohol' HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. CONCLUSIONS: During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Italia/epidemiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
Wilson's disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end-stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19-60 years]; median Model for End-Stage Liver Disease score at LT, 27 [6-49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1- and 5-year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post-LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.
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Enfermedad Hepática en Estado Terminal , Degeneración Hepatolenticular , Trasplante de Hígado , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Degeneración Hepatolenticular/cirugía , Humanos , Italia/epidemiología , Trasplante de Hígado/efectos adversos , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.
Asunto(s)
Antivirales/uso terapéutico , Várices Esofágicas y Gástricas/patología , Hepatitis C Crónica/tratamiento farmacológico , Hipertensión Portal/fisiopatología , Cirrosis Hepática/fisiopatología , Anciano , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad , Endoscopía del Sistema Digestivo , Várices Esofágicas y Gástricas/sangre , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Femenino , Humanos , Hipertensión Portal/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Recuento de Plaquetas , Índice de Severidad de la Enfermedad , Bazo/patología , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13 C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. METHODS: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation - defined as Child A6 (N = 22, 44%) or previous decompensation (N = 7, 14%) - or Child B cirrhosis (N = 21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12 weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. RESULTS: Aminopyrine breath test was available for all 50 patients at baseline. The 120' cumulative dose was directly associated at regression analysis only with albumin levels (P = .001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2 months (range 12.2-32.1 months). Lower É ABT - defined as changes of 120' cumulative dose from FUW12 to baseline - (HR 0.97, 95% CI 0.94-0.99; P = .02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P = .03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of É ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P < .001). CONCLUSIONS: In patients with advanced HCV cirrhosis who achieve SVR with DAA, É ABT assists in assessing the residual likelihood of liver-related events and deaths after viral cure.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Aminopirina/uso terapéutico , Antivirales/uso terapéutico , Pruebas Respiratorias , Niño , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.