Multidisciplinary treatment of hepatocellular carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part II - Non-surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC.

Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.

Meet-Test-Treat for HCV management: patients' and clinicians' preferences in hospital and drug addiction services in Italy.

BACKGROUND: It has been estimated that the incidence of chronic hepatitis C virus (HCV) will not decline over the next 10 years despite the improved efficacy of antiviral therapy because most patients remain undiagnosed and/or untreated. This study aimed to investigate the opinion of relevant target populations on the practicability, effectiveness and best modalities of the test-and-treat approach in the fight against HCV in Italy. METHODS: A survey was delivered to patients with HCV from the general population, patients from drug addiction services, hospital physicians and healthcare providers for drug addiction services. RESULTS: For both hospital clinicians and SerD HCPs, tolerability is shown as the most important feature of a suitable treatment. Time to treatment (the time from first contact to initiation of treatment) is deemed important to the success of the strategy by all actors. While a tolerable treatment was the main characteristic in a preferred care pathway for general patients, subjects from drug addiction services indicated that a complete Meet-Test-Treat pathway is delivered within the habitual care center as a main preference. This is also important for SerD HCPs who are a strong reference for their patients; hospital clinicians were less aware of the importance of the patient-HCP relationship in this process. CONCLUSION: The health system is bound to implement suitable pathways to facilitate HCV eradication. A Meet-Test-Treat program within the drug addiction services may provide good compliance from subjects mainly concerned with virus transmission.

Milestones to reach Hepatitis C Virus (HCV) elimination in Italy: From free-of-charge screening to regional roadmaps for an HCV-free nation.

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.

Estimation of the number of HCV-positive patients in Italy.

BACKGROUND: HCV is one of the main causes of cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation. AIM: The aim of this study was to estimate the number of living individuals diagnosed with hepatitis C in Italy. This study also aimed to stratify these subjects as diagnosed and cured, diagnosed awaiting a cure, and undiagnosed (individuals who were not diagnosed, living or lived with hepatitis C). METHODS: To quantify the number of ill patients in Italy, an inquiry was conducted based on questionnaires submitted to three nationally representative regions, namely, Campania, Lazio and Piemonte, as representatives of the three main areas of Italy (North, Centre and South regions). The data were collected through a questionnaire to acquire demographic and clinical information on patients in the participating hospitals. The questionnaires contained 6 questions on sex, age, region of residence, disease condition, type of exemption and category. The questionnaires were administered individually to consecutive patients through face-to-face interviews conducted by specialised personnel in each centre. Data were collected between September 2017 and January 2018. RESULTS: In total, 2,860 questionnaires were analysed. They were completed by the patients (55% male), who had an average age of 61 years (64 years for women and 59 years for men). In total, 54% of the sample declared that they were still infected with HCV (1,548 patients out of 2,860 respondents), while the remaining subjects declared that they had been cured. The inquiry showed that 46.6% of the sample had at least a 016 exemption (chronic hepatitis), while more than 51% (1,469 interviewed patients out of 2,860 respondents) had a different type of exemption. Only 2% of the respondents declared that they had no exemption. Assuming that the analysed sample is representative of the actual HCV-positive population in Italy and considering the number of 016 exempt patients in the regional data, the model estimates that there are 443,491 cured and HCV-positive living patients and 240,043 ill patients who have yet to be treated. CONCLUSIONS: Although this study has limitations, it represents a considerable improvement over the previously available studies. This study can help decision-makers implement more effective strategic planning to eliminate hepatitis C.

Point-of-care testing for hepatitis C virus infection at an Italian dental clinic: portrait of the pilot study population.

The dental clinic is an appropriate place to promote the prevention of hepatitis C virus (HCV) infection and fast access for care of HCV-positive subjects with new-generation anti-HCV drugs. This study aimed to determine the socio-demographic profile of subjects screened for HCV virus in a dental clinic to acquire useful information for future campaigns of prevention. An easy, free-of-charge, screen salivary test was offered to patients referred to the dental clinic of San Raffaele Scientific Research Hospital in Milan, Italy for dental procedures. These patients were also asked to complete an anonymous questionnaire on demographics and risk behaviours. A total of 1388 of 2097 (66.19%) questionnaires were evaluable. The demographics of the population responding to this initiative was primarily Italians citizen (96.47%), homogeneous gender distribution (55.55%), age over 50 (609 subjects; 43.88%), with high-level education and stable professional positions. 905 subjects (65.20%) were never tested for HCV before. The test showed positive reactivity in 22 cases (1.05%); of these, 21 subjects were known to be HCV-positive, and the test confirmed their status. One subject was newly diagnosed as HCV-positive. The percentage of subjects who were never tested for HCV infection appears too high (905 subjects, i.e., 65.20%), especially among subjects with high level of education and professions, and among adults over 40 or young people (18-25). The easy screening test in dental clinic can help raise awareness, promote early diagnosis and prevention, and provide a fast link to care for HCV infection.

Point-of-care testing for hepatitis C virus infection at alternative and high-risk sites: an Italian pilot study in a dental clinic.

The Infectious Diseases Department and the Department of Dentistry of San Raffaele Scientific Institute in Milan conducted a screening and prevention program, the "EASY HCV-test Program," at a dental clinic to increase the identification of unrecognized infections. Using a cross-sectional community-based study design, hygienists in the dental clinic offered patients a hepatitis C virus (HCV) rapid salivary test (OraQuick ADVANCE® Rapid HCV Antibody Test) with pre- and post-test counseling prior to initiation of their oral hygiene routine. From April 2015 to November 2015, the EASY HCV test was offered to 2650 patients visiting the Center of Oral Health and Prevention at the Department of Dentistry at San Raffaele Hospital in Milan. Among them, 2077 eligible volunteers were tested. The test showed positive reactivity in 22 cases; of these, 21 subjects were known to suffer from HCV, and the test confirmed their status. One subject was newly diagnosed with HCV infection. The results of this study suggest EASY HCV test screening conducted in dental clinics may constitute an effective strategy for increasing HCV testing among people at risk for infection.

Primary Biliary Cholangitis: advances in management and treatment of the disease.

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting.

The societal burden of chronic liver diseases: results from the COME study.

OBJECTIVE: Chronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with CLDs at different stages and with different aetiologies. DESIGN: A cost-of-illness study was conducted. Direct costs, productivity loss and HRQoL were estimated in patients with chronic hepatitis, cirrhosis hepatocellular carcinoma (HCC) or where orthotopic liver transplantation (OLT) had been performed, for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, or in those with liver disease from other causes. Patients were retrospectively observed for 6 months. The societal perspective was adopted to calculate costs. RESULTS: In total, 1088 valid patients (median age=59.5 years, 60% men) were enrolled. 61% had chronic hepatitis, 20% cirrhosis, 8% HCC and 12% underwent OLT. HCV infection was identified in 52% and HBV infection in 29% of the patients. Adjusted mean direct costs increased from <€200/patient-month in HCV-infected patients with hepatitis to >€3000/patient-month in HBV infected patients with OLT. Antiviral treatment was the cost driver in patients with hepatitis, while hospital costs were the driver in the other subgroups. Absenteeism increased from HBV-infected patients with hepatitis (0.7 day/patient-month) to patients with OLT with other aetiologies (3.7 days/patient-month). HRQoL was on average more compromised in cirrhosis and patients with HCC, than in hepatitis and patients with OLT. HBV-infected patients generated higher direct costs, patients with other aetiologies generated the highest productivity loss and HCV-infected patients reported the worst HRQoL levels. CONCLUSIONS: The present study can be considered a benchmark for future research and to guide policies aimed at maximising the cost-effective of the interventions.

Comparing the performance of the standard EQ-5D 3L with the new version EQ-5D 5L in patients with chronic hepatic diseases.

PURPOSE: To assess the performance of the EQ-5D-5L version compared with the standard EQ-5D-3L in a clinical setting targeted at patients with chronic hepatic diseases (CHDs). METHODS: We introduced the 5L descriptive system into a cost-of-illness study involving patients with different CHDs. The patients completed a questionnaire including the two versions of the EQ-5D, together with other questions related to their condition. We tested the feasibility, the level of inconsistency, the redistribution properties among consistent responses, the ceiling effect, the discriminative power, and the convergent validity of the 5L compared with the 3L system. RESULTS: A total of 1,088 valid patients were recruited: 62% male, 19-89 (median = 59) years old. Patients had chronic hepatitis from HCV (31.8%) or HBV infections (29.3%) or other causes (7.8%), 20.4% had cirrhosis, 11.9% underwent liver transplantation, and 7.8% had hepatic carcinoma. Less than 1% of EQ-5D-5L were returned blank, and 1.6% or less of missing values were calculated on the dimensions of the partially completed questionnaires. The proportion and weight of inconsistent responses (i.e., 3L responses that were at least two levels away from the 5L responses) was 2.9% and 1.2 on average, respectively. Regarding redistribution, 57-65% of the patients answering level 2 with the 3L version redistributed their responses to levels 2 or 4 with the 5L version. A relative 7% reduction of the ceiling effect was found. Furthermore, the absolute informativity increased but the relative informativity slightly decreased in every domain, and the convergent validity with the VAS improved. CONCLUSIONS: In a clinical setting involving CHD patients, the EQ-5D-5L was shown to be feasible and with promising levels of performance. Our findings suggest that the 5L performs better in at least some of the properties analyzed, and encourage further research to also test other psychometric properties of this new version of the EQ-5D.