Assessing ChatGPT's Potential in HIV Prevention Communication: A Comprehensive Evaluation of Accuracy, Completeness, and Inclusivity.

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.

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.

Safety and efficacy of molnupiravir in SARS-CoV-2-infected patients: A real-life experience.

Since the start of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several treatments have been proposed to cure coronavirus disease 2019 (COVID-19) and prevent it. Molnupiravir is a ribonucleoside prodrug of N-hydroxycytidine with an in vitro and in vivo activity against SARS-CoV-2. We conducted a retrospective cohort study that included all people treated with molnupiravir between January 10, 2022, and March 31, 2022, at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, to patients with recent symptom onset (≤5 days), no need for oxygen supplementation, and with a high risk of disease progression for the presence of chronic diseases. We included 192 people with a mean age of 70.4 ± 15.4 years, with 144 (75%) patients over 60 years. During the follow-up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological disease, having dyspnea at the onset of the symptoms, and acquiring SARS-CoV-2 infection during hospital admission were associated with an increased risk of progression. In contrast, an early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption. Our study shows that monlupiravir confirmed its efficacy and safety in a real-life cohort that included a high percentage of elderly people with a high comorbidity burden.

Optimizing diagnostic algorithms to advance Hepatitis C elimination in Italy: A cost effectiveness evaluation.

OBJECTIVES: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection. METHODS: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969-1989 over a 10-year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV-Ab) detection followed by HCV-RNA or HCV core antigen (HCV-Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients' drop-off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratios (ICER). RESULTS: The reference option was Rapid HCV-Ab followed by second sample HCV-Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV-RNA reflex testing which produced a high cost-effective ICER (€891/QALY). Reflex testing (same sample-single visit) vs two patients' visits algorithms, yielded the highest QALYs and high cost-effective ICERs (€566 and €635/QALY for HCV-Ag and HCV-RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations. CONCLUSIONS: Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions.

BACKGROUND: Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. METHODS: A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0-F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic). RESULTS: By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54-0.82%), of which 300,171 (0.50%; 95% CI: 0.4-0.6%) were stage F0-F3. Considering all individuals with HCV in stage F0-F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0-F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36-0.55%), Central 24.1% (0.61%; 95% CI: 0.48-0.74%), South 23.2% (0.50%; 95% CI: 0.4-0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39-0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0-F3). Undiagnosed individuals (F0-F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0-F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values. CONCLUSION: This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

HCV spread among female incarcerated population and treatment pathways to viral elimination in Italian prison settings: clinical perspectives and medico legal aspects.

BACKGROUND: Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided. METHODS: Incarcerated women from 4 Italian regions' penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test®) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan®, based on physicians' decision. Treatment prescription followed national protocols. RESULTS: We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value < 0.001). Of them, the 75.5% of patients had active infection, the most frequent genotype was 3a (50%). Among them, 4 (16.6%) and 6 (25%) had psychosis or alcohol abuse history. The 62.5%, 25% and 12.5% had low, intermediate, and advanced fibrosis, respectively. Out of the 24 HCV-RNA positive patients, the 75% underwent to DAAs treatment. The sustained virological response (SVR12) was achieved in 88.8% of cases. When evaluating the influence of quick diagnosis and staging methods vs standard phlebotomy and fibroscan® on SVR12, FIB-4 use showed higher performance for retainment in treatment during prison staying (p = 0.015), while the use of quick saliva test had no influence on the outcome (p = 0.22). CONCLUSION: HCV seroprevalence and active infections are very high among incarcerated women. More tailored interventions should be focused on HCV diagnosis and treatment in female prison population. The use of quick staging methods (FIB-4) is useful to increase SVR12 achievement without delays caused by the fibroscan® awaiting.

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study.

BACKGROUND: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. RESULTS: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7-18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). CONCLUSIONS: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions.

Low influenza vaccination coverage in subjects with liver cirrhosis. An alert waiting for winter season 2020-2021 during the COVID-19 pandemic.

We have evaluated flu vaccine coverage and variables associated with the lack of vaccination in cirrhotic subjects with particular attention to the cirrhosis etiology. Cirrhotic subjects consecutively referring to eight Italian centers were prospectively enrolled for a 6-month period in 2019. Subjects were asked if they had received a flu vaccine in the last 12 months. Multiple logistic regression analysis was performed to identify independent predictors of lack of vaccination. A total of 818 cases were recruited. The overall vaccine coverage was 39.6% (26.9% in those younger than 65 years and 51.9% in those older than 64 years; p < 0.001). Age < 65 years (odds ratio [OR] = 2.38; 95% confidence interval [CI] = 1.68-3.36), alcoholic etiology (OR = 2.40; 95% CI = 1.49-3.85), birth abroad (OR = 2.7; 95% CI = 1.10-6.61), and residence in South/Sardinia island (OR = 1.66; 95% CI = 1.14-2.42) all resulted independent predictors of the likelihood of lack of vaccination. The lack of information regarding the vaccine as the reason for no vaccination was reported by 71.4% of foreigners and by 34.7% of natives (p < 0.001). In conclusion, much work still should be done to improve coverage among groups at higher risk of lack of vaccination identified in this survey. The ongoing SARS-CoV-2 pandemic may represent one more alert for improving seasonal flu vaccine coverage to avoid further stress to the National Health System.

The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID-19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in-hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID-19) admitted to three COVID-19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91-1.64 vs 1.67; IQR: 1.38-1.97, P = .002) whilst there were no significant between-group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603-0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan-Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05-5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in-hospital mortality in COVID-19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.

Feasibility and efficacy of 8 week Glecaprevir/Pibrentasvir to treat incarcerated viraemic HCV patients: A case-control study.

Inmates have higher HCV prevalence than general population, representing a fundamental step towards HCV eradication. Our aim was to compare 8-week glecaprevir/pibrentasvir treatment in a case-control study between incarcerated and free patients. Eleven Italian prisons and six outpatient clinics were involved. Patients were matched for sex, risk factors, METAVIR grade, HIV and HBV co-infections. About 131 incarcerated (Group A) and 131 free patients (Group B) were included. Mean age was 43.0 ± 9.6 years and 42.8 ± 9.9 in Group A and B, respectively (P = .74). SVR rates were 96.2% and 99.2% in Group A and Group B respectively (P = .21). Five drop-outs occurred in Group A, one in Group B. Incarceration, being PWIDs and OST were not associated with SVR reductions (CI 95%). In conclusion, imprisonment does not influence unplanned interruptions or SVR rates when receiving short-term therapies. Short schedules with pangenotypic regimens could be a good approach to hard-to-reach populations, such as incarcerated patients.

Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C.

AIM: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). METHODS: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. RESULTS: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P < .001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P < .001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P = .04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P = .002). CONCLUSIONS: In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natural NS5A-RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.

Chronic hepatitis B virus infection in Italy during the twenty-first century: an updated survey in 2019.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25-5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02-2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9-4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Mood Reactive Disorders among COVID-19 Inpatients: Experience from a Monocentric Cohort.

OBJECTIVE: We aimed to investigate the presence and severity of depressive symptoms among coronavirus disease 2019 (COVID-19) inpatients and any possible changes after their discharge. SUBJECT AND METHODS: We collected data of patients admitted to the Infectious Disease Unit in Sassari, Italy, for COVID-19, from March 8 to May 8, 2020. The Beck Depression Inventory-II (BDI-II) was performed 1 week after admission (T0) and 1 week after discharge (T1). The cutoff point chosen to define the clinical significance of depressive symptoms was 20 (at least moderate). RESULTS: Forty-eight subjects were included. Mean age was 64.3 ± 17.6 years, and 32 (66.7%) were male. Most frequent comorbidities were cardiovascular diseases (19; 39.6%) and hypertension (17; 35.4%). When performing BDI-II at T0, 21 (43.7%) patients reported depressive symptoms at T0, according to the chosen cutoff point (BDI-II = 20). Eight (16.7%) patients had minimal symptoms. Mild mood disturbance and moderate and severe depressive symptoms were found in 24 (50%), 14 (29.2%), and 2 (4.2%) patients, respectively, at T0. The comparison of the BDI-II questionnaire at T0 with T1 showed a significant improvement in the total score (p < 0.0001), as well as in 4 out of the 5 selected questions of interest (p < 0.05). Univariate analysis showed that kidney failure and the death of a roommate were significantly associated with severity of mood disorders. CONCLUSION: Mood disturbances and depressive symptoms commonly occur among COVID-19 inpatients. Our results show that COVID-19 inpatients might be at higher risk for developing depressive reactive disorders and could benefit from an early psychological evaluation and strategies improving sleep quality.

Migratory flow and hepatitis delta infection in Italy: A new challenge at the beginning of the third millennium.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P < .001). HDV-RNA was checked in 63 (80.8%) of the 78 anti-HDV+ subjects, and 49 (77.8%) tested positive. Compared to non-natives, Italians were more likely males (male/female 1.6 vs 0.6; P < .05) and older (median age 57 years vs 46 years; P < .05). Multivariate analysis showed that non-natives (OR = 6.02; CI 95% = 3.06-11.84) and cirrhosis (OR 9.6; CI 95% = 5.39-17.30) were independently associated with anti-HDV positivity. A remarkable changing pattern in some characteristics of anti-HDV-positive subjects was observed over 1987-2019: a decreasing male/female ratio, an increasing mean age and proportion of cirrhotic subjects. Anti-HDV prevalence decreased from 7.4% to 6.4% among Italians, increasing from 12.2% to 26.4% among non-natives during 2001-2019. Hence, HDV infection in Italians is further decreasing and mostly affects old people and subjects with advanced disease reflecting a survival effect. Conversely, non-natives are sixfold more likely anti-HDV-positive with an increasing trend. Migratory flow may be a new challenge for HDV infection at the beginning of the third millennium.

The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. METHODS: The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. RESULTS: Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan-Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000-1.0001, p = 0.029) in multivariate Cox regression analysis. CONCLUSIONS: The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy.

BACKGROUND: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors. METHODS: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-month period. RESULTS: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg -/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child-Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC. CONCLUSION: In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials.

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies.

Active Case Finding for Communicable Diseases in Prison Settings: Increasing Testing Coverage and Uptake Among the Prison Population in the European Union/European Economic Area.

Prison populations are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors. Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs. We investigated the available evidence on modalities and effectiveness of active case-finding interventions in prisons by searching PubMed, Embase, and the Cochrane Library for records on prison and active case finding with no language limit. Conference abstracts and unpublished research reports also were retrieved. We analyzed the findings by testing modality, outcomes, and study quality. The included 90 records-63 peer-reviewed, 26 from gray literature, and 1 systematic review-reported variously on viral hepatitis, human immunodeficiency virus, sexually transmitted infections, and tuberculosis. No records were retrieved for other communicable diseases. Provider-initiated opt-in testing was the most frequently investigated modality. Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges. However, no comparative studies were identified that reported statistically significant differences between testing modalities. Positivity rates among tested inmates ranged broadly but were generally high for all diseases. The evidence on active case finding in correctional facilities is limited, heterogeneous, and of low quality, making it challenging to draw conclusions on the effect of different testing modalities. Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and, hence, prevent additional disease transmission in both prison settings and the community at large.

A systematic review on models of care effectiveness and barriers to Hepatitis C treatment in prison settings in the EU/EEA.

Hepatitis C prevalence in prison populations is much higher than in the community. Effective hepatitis C treatment within this population does not only have a direct individual health benefit, but may lead to substantial community dividend. We reviewed available evidence on hepatitis C treatment in prison settings, with a focus on the European Union/European Economic Area. A systematic review of the literature (PubMed, EMBASE, Cochrane library) was performed and complemented with searches for conference abstracts and grey literature. Thirty-four publications were included reporting on the effectiveness, acceptability and economic aspects of hepatitis C virus treatment models of care to achieve treatment completion and sustained viral response in prison settings. Available evidence shows that hepatitis C treatment in prison settings is feasible and the introduction of direct-acting antivirals will most likely result in increased treatment completion and better clinical outcomes for the prison population, given the caveats of affordability and the need for increased funding for prison health, with the resulting benefits accruing mostly in the community.

Current and future challenges in HCV: insights from an Italian experts panel.

BACKGROUND: The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages. METHODS: A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens. RESULTS AND CONCLUSIONS: Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated due to accumulating new data. Such recommendations may not be applicable to all healthcare settings for a variety of reasons. Moreover, some gaps still remain and the spectrum of patients to be treated is also evolving.