The Equitable Benefit Approach to guide the assessment of medical and psychosocial factors in liver transplant candidacy.

Lack of available organs poses a significant challenge in meeting the needs of patients with life-threatening liver disease who could benefit from liver transplantation (LT). Psychosocial vulnerability markers have been linked to post-transplant outcomes, raising questions about their use in patient selection. However, their incorporation into selection criteria raises concerns about health equity and potential discrimination. As a result, there is a pressing need to refine fair allocation systems that consider both clinical and psychosocial factors to ensure equitable access and optimize post-transplant outcomes. The Equitable Benefit Approach (EBA) proposed in this paper by the multidisciplinary group of clinical experts in LT from the Italian Society for the Study of the Liver seeks to address these concerns. It presents four procedural principles, the two allocative principles usually applied in transplantation (urgency and utility) and introduces a new one, the principle of health equity. The EBA aims to prioritize patients with the highest transplant benefit while addressing health inequalities. It emphasizes evidence-based decision-making and standardized assessment tools to reliably evaluate psychosocial risk factors. Implementing the EBA involves a multi-step process, including stakeholder engagement, prospective studies to validate its efficacy, development of institutional policies and algorithms, and ongoing monitoring and revision. By following these steps, health care providers can ensure that LT allocation decisions are transparent and responsive to evolving clinical and social contexts. Ultimately, the EBA should offer a comprehensive framework for fair patient selection in LT, considering both biomedical and psychosocial aspects.

Inequities in primary liver cancer in Europe: The state of play.

Given the increasing burden of liver cancer in Europe, it is crucial to investigate how social determinants of health (SDoH) affect liver cancer risk factors and access to care in order to improve health outcomes equitably. This paper summarises the available evidence on the differential distribution of liver cancer risk factors, incidence, and health outcomes in the European Economic Area and the United Kingdom from an SDoH perspective. Vulnerable and marginalised populations have low socio-economic and educational levels and are the most affected by liver cancer risk factors. Reasons for this include varied access to hepatitis B virus vaccination and limited access to viral hepatitis B and C screening, harm reduction, and treatment. Additionally, alcohol-related liver disease remains highly prevalent among individuals with low education, insecure employment, economic instability, migrants, and deprived populations. Moreover, significant variation exists across Europe in the proportion of adults with steatotic liver disease, overweight/obesity, and diabetes, based on geographical area, gender, socio-economic and educational background, and density of ultra-processed food outlets. Inequities in cirrhosis mortality rates have been reported, with the highest death rates among individuals living in socio-economically disadvantaged areas and those with lower educational levels. Furthermore, insufficient healthcare access for key populations with primary liver cancer is influenced by complex healthcare systems, stigmatisation, discrimination, low education, language barriers, and fear of disclosure. These challenges contribute to inequities in liver cancer care pathways. Future studies are needed to explore the different SDoH-interlinked effects on liver cancer incidence and outcomes in European countries. The ultimate goal is to develop evidence-based multilevel public health interventions that reduce the SDoH impact in precipitating and perpetuating the disproportionate burden of liver cancer in specific populations.

From Prioritization to Universal Treatment: Successes and Challenges of Hepatitis C Virus Elimination in Italy.

Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, €71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations.

Liver transplantation for severe alcoholic hepatitis: A multicenter Italian study.

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.

Factors Affecting Hesitancy to mRNA and Viral Vector COVID-19 Vaccines among College Students in Italy.

Vaccine hesitancy (VH) may be significant in jeopardizing efforts to mass containment of COVID-19. A cross-sectional survey was carried out on a sample of 2667 Italian college students, before the COVID-19 vaccines became available for this age group (from 7 May to 31 May 2021). An online survey was created to obtain information about socio-demographic, health-related, and psychological factors linked to mRNA and viral vector COVID-19 vaccines. Statistically significant higher VH (30.4%) and vaccine resistance (12.2%) rates were found for viral vector than mRNA COVID-19 vaccines (7.2% and 1.0%, respectively; p < 0.001). Factors related to viral vector VH were partially different from those related to mRNA VH. Students with greater endorsement on conspiracy statements and negative attitudes toward the vaccine had higher odds of being vaccine-hesitant or -resistant. Students who had received a previous COVID-19 test and who scored higher on the agreeableness personality dimension had lower odds to be vaccine-hesitant or -resistant. The willingness to choose the vaccine was related to the viral vector but not to the mRNA VH. Taking into consideration the factors involved in vaccine hesitancy/resistance in college students could represent a key public health strategy to increase vaccine coverage and reduce viral spreading.

Who Should Get COVID-19 Vaccine First? A Survey to Evaluate Hospital Workers' Opinion.

Prospective planning of COVID-19 vaccines allocation will be essential to maximize public health and societal benefits while preserving equity. Decisions about how to allocate limited supplies of vaccines need to be clear about the criteria used in setting priorities, with a specific commitment to transparency and communication. The aim of our study was to think through these competing demands, focusing on the opinion of healthcare workers (HCWs). The primary endpoint of the study was to assess the opinion of all the HCWs in a University based Italian Hospital about the fairest priority order to COVID 19 vaccines and to understand on which criteria the prioritization preferences of HCWs are implicitly based. The secondary endpoints were to assess whether HCWs approach differs from national guidelines and to assess the attitude of HCWs towards mandatory vaccination. An online survey accounting with multiple choice single answer questions and ranking questions was administered to all the HCWs of the University Hospital P. Giaccone of Palermo (Italy) and completed by a total of 465 participants. Almost all respondents confirmed the need for prioritization in COVID-19 vaccination for HCWs (n = 444; 95.5%), essential services and law enforcement (both n = 428; 92%). Clinically vulnerable individuals, HCWs and population over 65 years have been considered the first three groups to be involved in getting vaccination, being indicated as first position group by 26.5%, 32.5% and 21.9% of respondents, respectively. A large majority of respondents (85%) asked for a consistent, transparent and detailed order of priority at a national level. After adjusting for potential confounding due to sex and age, physicians have been found to be statistically significantly associated with the choice of mandatory vaccination (odds ratio (OR): 10.2; 95% confidence interval (CI) = 2.7-39.1) or with other strategies different from voluntary (OR = 7.2; 95% CI = 1.9-27.3). The broad consensus expressed by respondents towards mandatory vaccination for HCWs is extremely relevant at a time when vaccination hesitation is one of the biggest obstacles to achieving herd immunity. Data show a mismatch in the position attributed to long-term care residents compared to the position of absolute priority assigned by most of national distribution plans, impelling us to reflect on the issue of maximizing benefit from limited healthcare resources. Our findings clearly indicate a preference for COVID-19 frontline health professionals as the first tier of recipients, since they better meet all the criteria (higher risk, immediate system stability). As the guidelines are likely to directly affect a considerable number of citizens, our results call for policy interventions to inform people on the ethical rationale behind vaccine distribution decisions, to avoid resentment and feelings of unfairness.

Rationing in a Pandemic: Lessons from Italy.

In late February and early March 2020, Italy became the European epicenter of the COVID-19 pandemic. Despite increasingly stringent containment measures enforced by the government, the health system faced an enormous pressure, and extraordinary efforts were made in order to increase overall hospital beds' availability and especially ICU capacity. Nevertheless, the hardest-hit hospitals in Northern Italy experienced a shortage of ICU beds and resources that led to hard allocating choices. At the beginning of March 2020, the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) issued recommendations aimed at supporting physicians in prioritizing patients when the number of critically ill patients overwhelm the capacity of ICUs. One motivating concern for the SIAARTI guidance was that, if no balanced and consistent allocation procedures were applied to prioritize patients, there would be a concrete risk for unfair choices, and that the prevalent "first come, first served" principle would lead to many avoidable deaths. Among the drivers of decision for admission to ICUs, age, comorbidities, and preexisting functional status were included. The recommendations were criticized as ageist and potentially discriminatory against elderly patients. Looking forward to the next steps, the Italian experience can be relevant to other parts of the world that are yet to see a significant surge of COVID-19: the need for transparent triage criteria and commonly shared values give the Italian recommendations even greater legitimacy.

HCV Eradication: A Duty of the State, an Option for the Individual.

In recent years, the debate on ethical issues related to hepatitis C virus therapies has been focused on the problem of drug prices and access to therapies. Nonetheless, the goal of hepatitis C virus eradication set by the World Health Organization in 2016 is raising new ethical issues, since governments are faced with a new challenge: reaching through screening, diagnosis and treatment a large amount of subjects with undiagnosed hepatitis C infection. National governments, especially high-income countries with a Welfare State, are compelled to provide access to therapies, but also to involve those who are still unaware of their disease status.Since people cannot be forced but should be guided towards the choice of screening, diagnosis and treatment, three concepts will be instrumental in the success of any HCV elimination policy: involvement, communication and protection of vulnerable individuals.Given the importance of diagnosis and treatment both in terms of individual benefit and social benefit, while respecting individual freedom and autonomy, the government has a moral obligation to try to drive individuals on the path of therapy. Even if it fails to get a complete success, the hepatitis C virus eradication campaign will lead to a significant reduction in the incidence of the disease and it will convey a very important message: today more than ever public health interventions must be thought in a global perspective, far beyond the borders of National States.

[Access to hepatitis C treatment: a lesson for the future.] / Accesso alle terapie per l'HCV: una lezione per il futuro.

The new generation of direct acting antivirals (DAA) for the treatment of chronic hepatitis C virus infection has revolutionized the previous scenario and has put the institutions under test because of the high cost of therapies. An analysis of what has happened over the last three years, especially in Italy, helps us understand how price negotiation has been managed, and what criteria were chosen at first to allow limited access on the basis of the need of patient care. This allows to focus on some important issues and to identify the challenges ahead in the near future.

A return to humane medicine: Osler's legacy.

Sir William Osler is celebrated today not only for his contributions to the advancement of medical education, but also for the humanism he brought to the practice of medicine. He was a doctor whose bedside skills and manners were emulated, and can legitimately be called an infectious diseases specialist. Nonetheless, he was also a humanist in the broader sense of the term, a student of human affairs and human nature, who emphasised compassion for the individual. To what extent, if any, are today's challenges influenced by departures from the paradigms created by Osler? In this paper we sought to ascertain whether such a tradition is still relevant to current practice and may foster a new perspective. We analysed two features of Osler's legacy that may be useful to clinicians: the first is his vision of the patient-physician relationship; the second is his approach to humanities. William Osler saw medicine in its wider scope, with the right and duty to be concerned with the human condition as a whole. Indeed, his rounded concept of the medical profession as being engaged in helping and caring for the whole human being could help physicians build a more humanised medicine. Adopted in the age of evidence-based medicine, the Oslerian approach can enhance the relationship with patients and give physicians a role based on trust and authoritativeness rather than on authority.

Ethical assessment of hepatitis C virus treatment: The lesson from first generation protease inhibitors.

Since chronic hepatitis C has mostly become curable, issues concerning choice and allocation of treatment are of major concern. We assessed the foremost ethical issues in hepatitis C virus therapy with 1st generation protease inhibitors using the personalist ethical framework within the health technology assessment methodology. Our aim was to identify values at stake/in conflict and to support both the physicians' choices in hepatitis C therapy and social (macro-) allocation decision-making. The ethical assessment indicates that: (1) safety/effectiveness profile of treatment is guaranteed if its use is restricted to the patients subgroups who may benefit from it; (2) patients should be carefully informed, particularly on treatment deferral, and widespread information on these therapies should be implemented; (3) since treatment was proven to be cost-effective, its use is acceptable respecting resource macro-allocation. Concerning individual (micro-) location criteria: (a) criteria for eligibility to treatment should be clearly identified and updated periodically; (b) information on criteria for eligibility/deferral to treatment for specific patients' subgroups should be made widely known. Interferon-based regimens will disappear from use within the next year, with the introduction of highly effective/tolerable combination regimens of direct-acting antivirals, thus profoundly changing social choices. Nonetheless, our model could support future ethical assessment since the evaluation pertaining ethical domains remains generally applicable.

[BETWEEN HORROR AND SCIENCE: THE BIRTH OF A CABINET OF PATHOLOGICAL ANATHOMY AT THE UNIVERSITY OF PALERMO]. / TRA ORRORE E SCIENZA: LA NASCITA DEL GABINETTO DI ANATOMIA PATOLOGICA DELL'UNIVERSITÁ DI PALERMO.

This paper outlines the history of the Cabinet of Pathological Anathomy at the University of Palermo, describes rapidly its current status and analyzes the composition of its displays in 1859. It aims to highlight the analogies with other collections of a similar kind and to pinpoint potential actions to endorse and develop this important scientific asset.

[Hepatitis: a longstanding companion in human history]. / L'epatite: un compagno di lungo corso della storia umana.

Hepatitis has gone along with human history since its origins, due to its prompt identifiability linked to jaundice as a symptom. Written evidence of outbreaks of epidemic jaundice can be tracked back a few millenniums before Christ. Unavoidable confusion arises due to the overlap of different sources possibly linked to different aetiologies, identified over time as epidemic jaundice (HAV or HEV hepatitis?) and serum hepatitis (HBV or HCV hepatitis?). The journey that brought to recognize viruses as the main cause of jaundice was long and started midway during the last century, when the infectious hypothesis, which had taken place step by step, was finally confirmed by epidemiological investigations of an outbreak occurring in the US army in 1942, after a yellow fever immunization campaign. Further research identified two clinically different types of hepatitis, called for the first time hepatitis A and hepatitis B.