SEE ARTICLE ON PAGE 492 Mass vaccination campaigns against HBV and treatment of chronic HBV carriers with oral nucleos(t)ide analogues (NUCs) represent the pillars of World Health Organization campaigns aiming to curb life‐threatening complications of chronic hepatitis B (CHB), including HCC.[1] Over 250 million people worldwide remain persistently infected with HBV, and <3% of them are currently covered by NUC treatment.[2] This notion, coupled with the evidence that even lifelong NUC regimens may not eliminate the risk of HCC,[2] has prompted the assessment of additional strategies for cancer prevention. Particular attention in recent years has been given to largely prescribed over‐the‐counter (OTC) drugs that may possess anti‐HCC potential. In this context, aspirin at low doses—having platelet‐specific effects with minimal anti‐inflammatory or analgesic/antipyretic properties[3] and long assumed to reduce the risk of developing different solid tumors in humans[4,5]—has been shown to prevent and/or delay the onset of HCC in animal models of chronic HBV infection.[6,7] Mechanistically, the sustained inhibition of platelet function by low‐dose aspirin reduces the intrahepatic accumulation of pathogenic HBV‐specific cluster of differentiation 8–positive T cells that would otherwise trigger immunopathological responses leading to fibrosis, cirrhosis, and HCC.[6,7] These preclinical studies have been supported by epidemiological evidence that evaluated the risk of HCC in patients suffering from liver diseases, particularly chronic HBV and HBV infections. Indeed, most of these studies reported that regular and long‐term use of low‐dose aspirin is associated with reduced HCC incidence and mortality, with little or no excess risk of gastrointestinal bleeding.[8–18] Along these lines, in this issue of hepatology, Jang et al. conducted a record‐linkage cohort study of low‐dose aspirin and HCC among >300,000 Korean patients with CHB over a 10‐year period (2007–2017).[19] By defining patients treated with aspirin as those individuals receiving aspirin prescriptions for 90 or more consecutive days, the authors derived a propensity score–matched cohort of 19,003 pairs.[19] With a median follow‐up of 6.7 years, 2697 patients developed HCC, 1232 in the treated and 1465 in the untreated group.[19] The 10‐year cumulative incidence of HCC was 9.5% in the treated versus 11.3% in the untreated group, corresponding to an adjusted HR of 0.85 (95% CI, 0.78–0.92).[19] Aspirin use for 90 or more consecutive days was therefore inversely related to HCC, but there was no evidence of a duration–risk relationship. When the analysis was restricted to the 14,689 patients with CHB who had used aspirin for >1 year (and 14,689 untreated), the HR was 0.86 (95% CI 0.78–0.94).[19] A stratified analysis was also provided for patients without cirrhosis versus those with cirrhosis treated or not with aspirin. Among the patients without cirrhosis, 900 cases of HCC were registered in individuals who received aspirin treatment, while there were 1059 HCC cases in untreated individuals, corresponding to an HR of 0.87 (95% CI 0.79–0.95).[19] By contrast, there was no association with aspirin use and reduced HCC risk among patients with cirrhosis: 323 and 333 HCCs were observed in aspirin‐treated versus aspirin‐untreated individuals with cirrhosis, corresponding to an adjusted HR of 1.00 (95% CI 0.85–1.15).[19] The latter finding may depend on cirrhosis‐linked thrombocytopenia, which could have weakened the capacity of aspirin to inhibit platelet function.[19] However, the divergence of results between those without cirrhosis and patients with cirrhosis was of borderline significance (p for interaction = 0.04) and was less evident in a sensitivity analysis using a 1:3 (instead of a 1:1) propensity score–matched cohort, where the HR was 0.81 among those without cirrhosis and 0.94 among patients with cirrhosis.[19] Likewise, when liver disease–related mortality was considered, the overall HR was 0.80 (95% CI 0.71–0.90); the HR was lower among individuals without cirrhosis (0.84) versus those with cirrhosis (0.91), but the heterogeneity was not significant. Hence, it is plausible that a favorable effect of aspirin on HCC may be greater in patients without cirrhosis, but a similar effect cannot be excluded in patients with cirrhosis. A multivariate analysis on all cohorts—in addition to the propensity score–derived data sets—could provide more precise quantifications. Major bleeding was reported in 1738 patients (908 treated with aspirin, 830 untreated), corresponding to an overall adjusted HR of 1.09 (95% CI 0.99–1.07). The HR was apparently greater in patients with cirrhosis (1.15) than in those without cirrhosis (1.05), but, again, the heterogeneity was not significant.[19] The findings of this Korean report are consistent with those of two studies from Taiwan and Sweden, both of which used a similar record‐linkage design.[14,18] The inverse association between aspirin use and HCC risk, however, appears less strong in the Korean study. The multivariate HRs of HCC for aspirin‐treated versus aspirin‐untreated patients were 0.68 in the Taiwanese study of patients with CHB[14] and 0.69 in the Swedish study, which included patients chronically infected with HBV or HCV and used a standard full‐cohort analysis rather than a propensity score design.[18] At variance with the Korean report, the Swedish study also documented a strong inverse duration–risk relationship, with an HR of 0.57 for the use of aspirin at 5 years or more compared to its short‐term use (3 months–1 year).[18] All of these studies share similar strengths (i.e., cohort designs with defined measures of exposure and outcome, large sample sizes, and allowance for a considerable number of covariates). Aspirin is a widely available and cheap drug, and exposure information based on prescription record linkage does not necessarily include OTC sales. The possible bias introduced by OTC sales is, however, probably unrelated to HCC outcome and, if anything, should lead to an underestimate of the association. In keeping with this, findings from five cohort and case–control studies that were pooled in a meta‐analysis and that were based on aspirin exposure (where the information about exposure was collected at direct interview and, therefore, was not affected by bias) revealed that the overall pooled relative risk was 0.71 for HCC and 0.62 (95% CI 0.44–0.86) for all hepatobiliary cancers.[15] The implications from this Korean report must be taken with caution due to the limited strength of the association between aspirin use and HCC risk and the rather surprising absence of a duration–risk relationship. This is particularly difficult to interpret for a disease like CHB‐associated HCC, which normally develops after several decades of persistent, immune‐mediated liver injury.[20] However, the overall evidence now available from three record‐linkage reports[14,18,19] and five additional studies[15] allows us to confidently conclude that the regular use of low‐dose aspirin has a favorable effect on HCC risk in patients with CHB. Because this Korean study reported a moderate excess in the risk of bleeding as documented in the previous Taiwanese and Swedish studies[14,18] (on the order of 10%, not significant in each single study but similar across various populations), it remains to be debated whether it is now time to recommend aspirin treatment initiation in selected patient populations or whether it is better to wait for improved biomarkers predicting HCC risk and/or dedicated and randomized clinical trials. To the least, this additional study by Jang et al.[19] should encourage a discussion on the future of antiplatelet therapies in patients with CHB. CONFLICT OF INTEREST Dr. Guidotti is a member of the board of directors and stockholder at Genenta Science, is a member of the Scientific Advisory Board at Antios Therapeutics and Ananda Immunotherapies, and participates in advisory boards/consultancies at Gilead Sciences, Roche, Arbutus Biopharma, and Chroma Medicine. Dr. Colombo participates in advisory boards for Galapagos, Exelixis, and Target HCC.

Background: Psoriasis is a common, chronic, inflammatory, debilitating, systemic disease with a great impact on healthcare systems worldwide. As targeted therapies have transformed the therapeutic landscape, updated estimates of the Global Burden of Disease (GBD) imposed by psoriasis are necessary in order to evaluate the effects of past health care policies and to orient and inform new national and international healthcare strategies. Methods: Data were extracted from the GBD 2019 study, which collates a systematic review of relevant scientific literature, national surveys, claims data, and primary care sources on the prevalence of psoriasis. Prevalence data were combined with disability weight (DW) to yield years lived with disability (YLDs). Measures of burden at global, regional, and national levels were generated for incidence, prevalence, and YLDs, due to psoriatic disease. All measures were reported as absolute numbers, percentages, and crude and age-adjusted rates per 100,000 persons. In addition, psoriasis burden was assessed by socio-demographic index (SDI). Findings: According to the GBD 2019 methodology, there were 4,622,594 (95% uncertainty interval or UI 4,458,904–4,780,771) incident cases of psoriasis worldwide in 2019. The age-standardized incidence rate in 2019 was 57.8 (95% UI 55.8–59.7) per 100,000 people. With respect to 1990, this corresponded to a decrease of 20.0% (95% UI −20.2 to −19.8). By sex, the age-standardized incidence rate was similar between men [57.8 (95% UI 55.8–59.8) per 100,000 people] and women [(57.8 (95% UI 55.8–59.7) per 100,000 people]. With respect to 1990, this corresponded to a decrease by 19.5% (95% UI −19.8 to −19.2) and by 20.4% (95% UI −20.7 to −20.2) for men and women, respectively. The age-standardized incidence rate per 100,000 persons was found to vary widely across geographic locations. Regionally, high-income countries and territories had the highest age-standardized incidence rate of psoriasis [112.6 (95% UI 108.9–116.1)], followed by high-middle SDI countries [69.4 (95% UI 67.1–71.9)], while low SDI countries reported the lowest rate [38.1 (95% UI 36.8–39.5)]. Similar trends were detected for prevalence and YLDs. Conclusion: In general, psoriasis burden is greatest in the age group of 60–69 years, with a relatively similar burden among men and women. The burden is disproportionately greater in high-income and high SDI index countries of North America and Europe. With advances in psoriasis therapeutics, objective evaluation of psoriasis disease burden is critical to track the progress at the population level.

&#x0D; Luigi Mangiagalli (1850-1928) is a well known figure and a “founding father” of obstetrics and gynecology in Italy, but less recognized are the wide range implications of his work on a public health and social level. In fact, apart from its surgical, clinical and academic values, all the activities of Mangiagalli had a public health, and hence a political relevance. Thus, when at age 27 hewas named professor of Obstetrics and Gynecology in Sassari, Sardinia, he not only focused on the improvement of the local obstetrics clinic -when he arrived there were no beds and only a one broken forceps- and the control of puerperal infections, but also to the control of malaria and syphilis in pregnancy.&#x0D;

Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.

In the countries considered, predicted downward trends started later and were less marked than those in the European Union and the USA. Despite overall favorable predictions, colorectal cancer remains one of the major causes of cancer mortality.

ALcOHOL AND cANcER RIsk, wITH fOcus ON mODERATE DRINkERs Alcohol and cancer risk, with focus on moderate drinkers Carlo La Vecchia (1) , Claudio Pelucchi (2) A Alcohol substantially increases the risk of head and neck and oesophageal cancers.The risks are essentially due to total ethanol intake.Alcohol drinking has also been associated with primary liver cancer, with cancers of the large bowel in both sexes, of the female breast, and -at high doses only-of the pancreas [1].To evaluate the strength of the evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 18 known or potentially alcohol-related neoplasms, we performed a search of the epidemiological literature from 1966 to 2012 using major bibliographic data-bases.We fitted meta-regression models considering linear and non-linear effects of alcohol intake.We also investigated the effects of selected characteristics of the studies (e.g., allowance for tobacco) and of individuals included in the studies (e.g., gender, age, etc.), as possible sources of heterogeneity of the estimates.A total of approximately 600 studies including 200,000 cases were considered.Strong trends in risk were observed for cancers of the oral cavity, oesophagus and larynx, the strongest one being for oral cancer, with a relative risk (RR) around 5 for 50 g/day of alcohol.Direct relations were also observed for cancers of the colon and rectum, liver, breast, and (for high doses only) pancreas [2].We also specifically considered the association between light alcohol consumption and cancer risk for those sites for which there is sufficient or limited evidence for carcinogenicity of alcohol [1,3].Thus, we considered cancers of the upper digestive and respiratory tract (oral and pharyngeal cancer, esophageal squamous cell carcinoma -but not adenocarcinoma of the esophagus, that is not associated to alcohol drinking [4] -and laryngeal cancer), liver, colorectum, pancreas and breast.Quantification of the association between low doses of alcohol consumption and cancers known to be alcohol-related is particularly important, as it is still unclear

A primary challenge in single-cell RNA sequencing (scRNA-seq) studies comes from the massive amount of data and the excess noise level. To address this challenge, we introduce an analysis framework, named single-cell Decomposition using Hierarchical Autoencoder (scDHA), that reliably extracts representative information of each cell. The scDHA pipeline consists of two core modules. The first module is a non-negative kernel autoencoder able to remove genes or components that have insignificant contributions to the part-based representation of the data. The second module is a stacked Bayesian autoencoder that projects the data onto a low-dimensional space (compressed). To diminish the tendency to overfit of neural networks, we repeatedly perturb the compressed space to learn a more generalized representation of the data. In an extensive analysis, we demonstrate that scDHA outperforms state-of-the-art techniques in many research sub-fields of scRNA-seq analysis, including cell segregation through unsupervised learning, visualization of transcriptome landscape, cell classification, and pseudo-time inference.

This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.