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Background and Aims: Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta‐analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg‐negative anti‐HBc‐positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments. Approach and Results: Studies were identified through literature search until October 2022. Pooled estimates were obtained using random‐effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg‐negative anti‐HBc‐positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti‐HBc positive. HBVr was 4% (95% CI 3%–6%) in HBsAg‐negative anti‐HBc‐positive patients, with a significantly high heterogeneity (I2 69%; p <.01). The number‐needed‐to‐treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune‐mediated diseases. Net benefit was small for monoclonal antibodies. Conclusions: Our DCA in HBsAg‐negative anti‐HBc‐positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune‐mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower. [ABSTRACT FROM AUTHOR]

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. 44.4months, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Reviews of patients with chronic non-cirrhotic liver disease (69.1%) or those with compensated cirrhosis (54.5%) were limited, while 74.55% of centres continued on-site follow-up for patients with decompensated cirrhosis. In 21/52 (40.4%) cases, inpatients wards had reduced beds available for non-COVID19 patients, while in 12/52 (23.1%) cases, the wards were completely dedicated to the assistance of COVID19 patients, similar to what happened during the first wave (40.9% I P i = .97 and 33.3% I P i = .17 respectively; Figure 1). Keywords: cirrhosis; COVID19; HCC; liver transplant; SARS-CoV-2 EN cirrhosis COVID19 HCC liver transplant SARS-CoV-2 2228 2232 5 08/18/21 20210901 NES 210901 Abbreviations COVID19 Coronavirus disease 19 HCC hepatocellular carcinoma SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely limited the clinical activity of most hospitals around the world. Cirrhosis, COVID19, HCC, liver transplant, SARS-CoV-2. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Metabolic disorders are well‐known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0‐1, 2 and 3‐5 metabolic features. Results: As compared with patients with 0‐1 metabolic features, patients with 3‐5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child‐Pugh class A [P = .007] and MELD < 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco‐regional therapies for BCLC stage B patients with 3‐5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead‐time adjusted survival. Conclusions: Our "real world" study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival. [ABSTRACT FROM AUTHOR]

Background & Aims Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus ( HCV)-related hepatocellular carcinoma ( HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals ( DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Methods Studies reporting time-dependent outcomes ( HCC recurrence or death) after potentially curative treatment of HCV-related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival. Results Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6 months and 47.0% at 2 years. Pooled estimates of actuarial survival rates were 79.8% at 3 years and 58.6% at 5 years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, lower serum albumin, randomized controlled trial study design and follow-up were independently associated with higher recurrence risk, whereas tumour size and alpha-foetoprotein levels were associated with higher mortality. Conclusions This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus ( HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV-related HCC ( HCV- HCC) in a wide time range in Italy. Methods Multicentre retrospective study including 3695 patients prospectively recruited by the ITA. LI. CA group. Patients were classified into three subgroups according to aetiology (Group A[ GA], pure HCV; Group B[ GB], HCV + cofactors; and Group C[ GC], non- HCV) and in 5 time cohorts (5 years each), according to the year of diagnosis. Age, gender, Child-Pugh score, modality of diagnosis, stage, presence of thrombosis/metastases, type of treatment and survival were analysed. Results A total of 1801 GA patients, 445 GB and 1333 GC were recruited. The number of GA patients peaked in the 1996-2000, gradually dropping thereafter ( P < 0.0001), as observed for GB ( P < 0.0001). Age at diagnosis increased ( P < 0.0001), while percentage of patients diagnosed during surveillance and stage improved only in GA ( P = 0.02 and P = 0.003 respectively). The survival significantly increased over time particularly in GA (median 37 months) and was longer in GA than in GB and GC ( P < 0.0001). Conclusions The prevalence of HCC- HCV is decreasing in Italy since 2001. HCV- HCC patients are older, more frequently diagnosed under surveillance and in an earlier stage. HCC survival improved in the last 15 years and is significantly higher in patients with HCV- HCC. We therefore expect a further drop in both incidence and mortality for HCV- HCC in the years to come. [ABSTRACT FROM AUTHOR]