Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis

BACKGROUND &amp; AIMS: Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse.METHODS: Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and MetaAnalyses guidelines.RESULTS: Thirty-six studies met the inclusion criteria for meta-analysis. The median follow-up time was 40.8 months. Fifty-two percent of patients were classified as having type 1 AIP. The pooled estimate of relapse rate was 33% (95% CI, 30%-37%). A higher proportion of patients with type 1 AIP had a relapse compared with patients with type 2 AIP (37.5% vs 15.9%; P &lt;.001). We found significant heterogeneity among studies (P &lt;.01). Long-term maintenance therapy with steroids and study quality were associated independently with AIP relapse, after we adjusted for year of publication by multivariate meta-regression.CONCLUSIONS: In a systematic review and meta-analysis, we found that a large proportion of patients with AIP treated successfully with steroid induction therapy had a relapse (33%)-particularly patients with type 1 AIP (37%). Maintenance steroid therapy lasting longer than 1 year could reduce risk of relapse. However, the data characterizing relapse rates are of limited quality, indicating the need for randomized controlled trials and new immunosuppressive drugs

Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of inhospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. Discrimination and calibration were assessed by the area under the receiver operating characteristic curve (AUC) and by Brier score in both the derivation and validation cohorts. Seven variables were independent risk factors for in-hospital mortality: age (Hazard Ratio [HR] 1.08, 95% Confidence Interval [CI] 1.07\u20131.09), male sex (HR 1.62, 95%CI 1.30\u20132.00), duration of symptoms before hospital admission &lt;10 days (HR 1.72, 95%CI 1.39\u20132.12), diabetes (HR 1.21, 95% CI 1.02\u20131.45), coronary heart disease (HR 1.40 95% CI 1.09\u20131.80), chronic liver disease (HR 1.78, 95%CI 1.16\u20132.72), and lactate dehydrogenase levels at admission (HR 1.0003, 95%CI 1.0002\u20131.0005). The AUC was 0.822 (95%CI 0.722\u20130.922) in the derivation cohort and 0.820 (95%CI 0.724\u20130.920) in the validation cohort with good calibration. The prediction rule is freely available as a web-app (COVID-CALC: https://sites.google.com/community. unipa.it/covid-19riskpredictions/c19-rp). Conclusions A validated simple clinical prediction rule can promptly and accurately assess the risk for inhospital mortality, improving triage and the management of patients with COVID-1

Aminopyrine Breath Test Predict Liver-related Events and Death in HCV-related Cirrhosis on SVR after DAA Therapy

In patients with HCV-related advanced cirrhosis, the effects of SVR by DAAs on decompensation and liver deaths is 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

Are radiological endpoints surrogate outcomes of overall survival in hepatocellular carcinoma treated with transarterial chemoembolization?

Background&amp; Aims: Time to progression (TTP) and progression-free survival (PFS) are commonly used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of TTP and PFS with overall survival (OS) in studies of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (u-HCC) by innovative methods. Methods: A search of databases for studies of TACE for u-HCC reporting both OS and TTP or PFS was performed. Individual patient data were extracted from TTP/PFS and OS Kaplan-Meier curves of TACE arms. Pooled median TTP and OS were obtained from random-effect model. The surrogate relationships of hazard ratios (HRs) and median TTP for OS were evaluated by the coefficient of determination R2. Results: We identified 13 studies comparing TACE vs systemic therapy or vs TACE plus systemic therapy and including 1932 TACE-treated patients. Pooled median OS was 11.2&nbsp;months (95% confidence interval [95%CI] 7.9-17.8), and pooled median TTP was 5.4&nbsp;months (95%CI 3.8-8.0). Heterogeneity among studies was highly significant for both outcomes. The correlation between HR TTP and HR OS was moderate (R2&nbsp;=&nbsp;0.65. 95%CI 0.08-0.81). R2 value was 0.04 (95%CI 0.00-0.35) between median TTP and median OS. Conclusion: In studies of TACE for u-HCC, the surrogate relationship of radiology-based endpoints with OS is moderate. Multiple endpoints including hepatic decompensation, macrovascular invasion and extrahepatic spread are needed for future trials comparing systemic therapies or combination of TACE with systemic therapies vs TACE alone

Fibronectin type III domain-containing protein 5 rs3480 A>G polymorphism, irisin, and liver fibrosis in patients with Nonalcoholic fatty liver disease

Contrasting data have been reported on the role of irisin, a novel myokine encoded by the FNDC5 gene, in NAFLD pathogenesis. We tested in patients with suspected NASH the association of FNDC5 variants, hepatic expression and circulating irisin with liver damage(F2-F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models

Erratum to: Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study (Scientific Reports, (2018), 8, 1, (12624), 10.1038/s41598-018-29311-y)

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study

Binge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126 participants; 1278 reported at least one episode BD in the last year and 715 in the last month. A diagnosis of AUD was made in 165 adolescents. The prevalence of AUD was higher in adolescents that reported BD behavior than in those that did not report BD (11.6% vs 0.9%, respectively; p &lt; 0.0001). Logistic regression showed a positive relationship between a diagnosis of AUD and BD behavior (OR 9.6; 95% CI 4.7\u201322\ub79; p &lt; 0.0001). In conclusion alcohol consumption with the pattern of BD among adolescents is highly related to development of AUD

Practice guidelines for the treatment of hepatitis C: recommendations from an AISF/SIMIT/SIMAST Expert Opinion Meeting

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies

The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Background & Aims: Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15\ua0years. Methods: Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000\u20132004, 2005\u20132009 and 2010\u20132014). Results: The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of \u201cmetabolic\u201d hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. Conclusions: During the last 15\ua0years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments