Francesco Ideo

Background: Bergamo was the most severely affected Italian province at the onset of the 2020 COVID-19 pandemic. The liver transplant (LT) patient population should be among the more sensitized to the concept of health prevention. Long-term data on both perception and outcomes of SARS-CoV-2 vaccination in LT recipients since the COVID-19 vaccine became available in Italy are still lacking. Methods: From May to October 2023, a survey on actively followed LT recipients at our institution was carried on by the local patient’ advocacy (Associazione Amici del Trapianto di Fegato) to define the rate of vaccinated subjects, SARS-CoV-2 infections and self-reported COVID-19-related outcomes. Results: Out of the consecutive 753 adult LT recipients invited to the survey, 356 responded (47.3%) [71% male, 63 years old (20–85), LT performed a mean of 9 years (1–26) before vaccination] and were included in the analysis. All patients received the first vaccine dose between December 2020 and January 2022 (81.7% Cominarty^®, 17.7% Spikevax^®, 0.3% Vaxzevria^® and 0.3% Jcovden^®). In the following years, adherence to the vaccination policy decreased progressively over time: the second, third, fourth, and fifth vaccine doses were administered to 99%, 94%, 72%, and 22% of the LT population by October, 2023. In total, 43 (12%) and 93 (26%) patients reported a COVID-19 episode before and after [13 (7–21) months] the first vaccination, respectively; none of the LT recipients reported a second COVID-19 infection after the following vaccination cycles. Forty-six (13%) reported short-term post-vaccination mild adverse events but none developed either acute or chronic rejection episodes or hospitalization for COVID-19-related symptoms. A total of 64% of LT recipients resulted positive for anti-nucleocapsid serological test in 2023. Conclusions: COVID-19 vaccines are safe and effective in LT recipients, underlining once again the importance of vaccination in this special population at higher risk of complications from communicable infectious diseases.

Background and Objective: Drug-induced liver injury (DILI) is increasingly becoming a cause of acute hepatitis. The study evaluated the role of liver-specific microRNAs (miRNAs) and keratin-18 (K-18) markers M30 (apoptosis) and M65 (necrosis) as biomarkers of acute hepatitis. Methods: Sixty-eight patients were sub-grouped as DILI, HBV- and alcohol-related acute hepatitis. Five healthy controls were included. The expression of plasma miR-21-5p, miR-34a-5p and miR-122-5p was evaluated by RT-qPCR analysis using healthy volunteers as reference. M30 and M65 were determined with ELISA kits. Results: All markers were significantly higher in the acute liver disease patients compared to controls. In DILI, miRNA levels positively correlated with M30, M65 and ALT. miR-122-5p had the highest AUC of 0.73, sensitivity of 76.2 and specificity of 72.2 in identifying DILI from other groups. Patients with hepatocellular-pattern DILI showed higher miR-122-5p and miR-21-5p compared to patients with cholestatic or mixed pattern. A new score to discriminate DILI versus other causes of acute hepatitis was developed using the identified risk factors as follows: 0.012 × miR-34a-5p + 0.012 × miR-122-5p − 0.001 × M30 + 2.642 × 1 (if mixed pattern) + 0.014 × 1 (if hepatocellular pattern) + 1.887. The AUC of the score was 0.86, with a sensitivity and specificity of 81%, better than the values of the single markers. Conclusions: Liver-specific miRNAs and K-18 could be promising serum biomarkers of DILI, especially when used in combination.