Background: Coronavirus disease 2019 (COVID-19) vaccination hesitancy is a threat as COVID-19 vaccines have reduced both viral transmission and virus-associated mortality rates, particularly in high-risk subgroups. Solid organ transplant recipients (SOTRs) are particularly vulnerable, as the underlying causes of their organ failure and the chronic immunosuppression are associated with a lower immune response to COVID-19 vaccines, and with an excessive risk of death due to SARS-CoV-2 infection. We aimed to evaluate COVID-19 vaccination hesitancy and its reasons in a population of SOTRs. Methods: All the SOTRs attending our post-transplant clinics were asked to fill in a vaccination status form with specific validated questions related to their willingness to receive a third vaccine dose. In the case of negative answers, the patients were encouraged to explain the reasons for their refusal. Among the SOTRs (1899), 1019 were investigated (53.7%). Results: Overall, 5.01% (51/1019) of the SOTRs raised concerns regarding the future third dose vaccination. In more detail, hesitancy rates were 3.3% (15/453), 4.2% (7/166), and 7.3% (29/400) among the investigated liver, lung, and kidney transplant recipients, respectively (p = 0.0018). The main reasons for hesitancy were fear of adverse events (30/51, 58.8%) and perceived lack of efficacy (21/51, 41.2%). Conclusions: Full adherence to ongoing or future vaccination campaigns is crucial to prevent, or at least reduce, COVID-19-related morbidity and mortality in fragile patients. The identification of the reasons influencing COVID-19 vaccination hesitancy in these patients is very important to establish appropriate and targeted patient–doctor communication strategies, and to further implement specific vaccination campaigns.

The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT.

Background: The COVID-19 pandemic highlighted the vulnerability of immunocompromised individuals, including liver transplant recipients (LTRs), who often exhibit reduced vaccine immunogenicity. While initial vaccine doses and subsequent boosters improved immune response, LTRs were prioritized for vaccination. Studies have shown increased antibody response after each booster dose. Vaccine hesitancy, defined as delayed or refused vaccination despite availability, poses a public health challenge, often fueled by misinformation. This study aimed to evaluate anti-spike antibody responses in vaccinated LTRs after two initial doses and at least one booster, also assessing adherence to subsequent doses. Methods: We conducted a retrospective observational study at a transplant center in Milan, Italy, between January 2021 and December 2023. LTRs who had received four or more doses of mRNA vaccines (Pfizer or Moderna) were included. Anti-spike antibody levels were measured 60–80 days after each dose. Data on vaccination status were collected in January 2024. Statistical analysis was performed to compare antibody responses and identify predictive factors. Results: LTRs showed a significant increase in anti-spike antibody responses after the first booster compared to the second dose with a trend versus a further increase following the fourth dose in a subgroup of the patients receiving two booster doses. However, adherence to booster doses decreased over time. In LTRs, predictors of a weaker response after the second dose were chronic kidney disease and metabolic etiology at transplant. Conclusions: The study highlighted that in LTRs, multiple doses of the COVID-19 vaccine led to a continuous increase in anti-spike antibody responses. The progressive decline in adherence of LTRs “to further booster doses” should be related to the fact that after the spread of vaccination programs worldwide, COVID-19 is still a current infection, but it is much less severe than before.

Background and aims: Liver transplantation is effective against hepatocellular carcinoma (HCC), but recurrence remains a challenge. Traditional criteria based on tumor size, nodule number, and AFP levels have had limited success in predicting aggressiveness. [18F]FDG PET/CT has shown promise in identifying high-risk tumor features, including microvascular invasion (MVI), which is a key predictor of recurrence. Methods: In this retrospective, single-center study, all consecutive patients who underwent LT for HCC between 2010 and 2019 were included. Prior to listing, the patients underwent [18F]FDG PET/CT, and explant pathology was analyzed for MVI and other histological features. The primary objective was to identify the predictors of early HCC recurrence (within 24 months after LT). Secondary objectives included identifying predictors of high-risk histological features of the explant, describing recurrence patterns, and assessing post-recurrence survival. Results: The study included 143 patients (median age 59 years [IQR 54–64], 85% males, median MELD 10 [IQR 8–14], median AFP value 8.5 [IQR 4–39] ng/mL) and 40 (28%) with intra-hepatic [18F]FDG PET/CT positivity. HCC recurred post-LT in 25 patients (17%) (median post-LT follow-up 49 months [IQR 28.5–77]) and within 24 months in 12 patients (48%). MVI at the explant stage was independently associated with early recurrence (HR: 7.20, 95% CI 1.82–28.45, p = 0.005), while intra-hepatic [18F]FDG PET/CT positivity before LT independently predicted MVI in explants (OR 3.90, 95% CI 1.30–11.71, p = 0.01). Conclusions: [18F]FDG PET/CT may offer a valuable tool for pre-transplant risk assessment by identifying MVI, which is an independent predictor of early cancer recurrence. Its incorporation into the selection criteria for LT may enhance patient stratification and post-transplant outcomes.

Background and aims: The CC5, CXC3, and CC2 chemokines (CK) are known to play a role in the pathogenesis of autoimmune hepatitis (AIH). However, no data are available on their potential utility as markers of disease progression or response to treatment. Material and methods: We analyzed their role as markers of remission in a population of patients with AIH. We retrospectively investigated the kinetics of RANTES (CCL5), IP-10 (CXCL10), and MCP-1 (CCL2) in 48 patients with AIH at the time of treatment initiation and also in 32 at biochemical, clinical and histological remission. Forty-nine healthy donors (HDs) served as controls. Results: At baseline, IP-10 and MCP-1 levels were higher in AIH patients than in HDs (261 vs. 101 pg/mL and 689 vs. 330 pg/mL, p < 0.01), and RANTES levels showed no differences. Correlations were observed between RANTES and IgG concentrations (r = 0.36 p = 0.04) and between IP-10 and Ishak’s grade (r = 0.52 p = 0.02). At remission, in 32 patients, while IP-10 and MCP-1 values showed a significant decrease from baseline reaching HD levels (261 vs. 106 pg/mL and 689 vs. 387 pg/mL, p < 0.01), RANTES did not. However, two kinetics patterns emerged, with 20 patients showing lower and 12 higher baseline RANTES values compared to HDs (29,450 pg/mL and 70,960 pg/mL vs. 52,010 pg/mL, p < 0.01). The former required longer treatment to reach remission and had higher Ishak’s grades than the latter (p < 0.01). Conclusions: RANTES, IP-10, and MCP-1 may help in predicting response to treatment and stable remission and in supporting the decision if and when to discontinue immune suppressive therapy.

Background.: Adult solid organ transplant recipients (SOTRs) have decreased responsiveness to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination and higher incidence of infection, but there are few data on the serological response in pediatric SOTR. The aim of this study was to determine serological response to SARS-CoV-2 vaccination in pediatric liver (LT) and kidney transplant (KT) recipients and compare it with adult SOTR. Methods.: A European, prospective, multicenter study was performed. Samples were taken at 7 and 32 wk following COVID-19 vaccination and serological endpoints were measured by ELISA. Results.: A total of 42 pediatric (16 post-LT and 26 post-KT) and 117 adult (all post-LT) were included. All pediatric participants and 94% adult participants received mRNA vaccines. Paediatric SOTR patients had significantly higher anti-Spike IgG levels than adult participants at week 7 (114 220.7 [59 285.92–220 058.55] versus 8756.7 [5643.69–13 586.71], P < 0.0001) and week 32 (46 113.2 [10 992.91–193 436.14] versus 8207.0 [3561.20–18 913.43], P = 0.0032). No significant difference in week 7 anti-Spike IgG response was found between pediatric LT and KT (129 434.4 [51 888.64–322 869.69] versus 105 304.5 [39 910.20–277 849.50], P = 0.9854). No differences were seen between children and adults in the rate of decline of anti-Spike IgG between weeks 7 and 32 (P = 0.8000). Male sex and hemolytic-uremic syndrome or postischemic kidney disease were associated with lower anti-Spike IgG levels at week 7 in pediatric SOTR. Conclusions.: Paediatric SOTR demonstrate greater SARS-CoV-2 vaccine responses than comparable adult SOTR patients. These data support efficacy and safety of SARS-CoV-2 vaccination in child SOTR and may alleviate vaccine hesitancy in this patient group.