Early post-liver transplant use of direct-acting antivirals in naive and NS5A inhibitor-experienced HCV patients.

Direct-acting antiviral drugs (DAA) are safe and effective in the HCV population. However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma or relapse to NS5A inhibitors, response rates are lower and DAA therapy must be postponed until after liver transplant in an era of organ shortage and suboptimal donors. We aimed to assess the prevalence of patients still HCV infected at time of transplantation over the last 3 years in our Center and describe the safety and efficacy of DAA therapy started as soon as possible after surgery. We enrolled all HCV viraemic patients transplanted in our Centre from January 2019 to March 2022. The follow-up was closed in July 2022. Among 490 liver transplants, 49 (10%) patients were still HCV viraemic at operation, 43 naive to DAA and 6 were NS5A-experienced. Median donor age was 64 years; donor risk index was 1.8. In naive patients, sofosbuvir/velpatasvir was started after a median time of 1 day from surgery, while in NS5A-experienced sofosbuvir/velpatasvir/voxilaprevir after 14.5 days (p = .001). Response rate was 98%. 1 NS5A-experienced patient experienced acute cholestatic hepatitis which promptly reverted after permanent DAA discontinuation. Hence, very early post-liver transplant HCV eradication was safe and effective thanks to a close teamwork which involved anaesthesiologists, transplant surgeons and hepatologists.

Favorable experience of transplant strategy including liver grafts from COVID-19 donors: One-year follow-up results.

BACKGROUND: Since November 2020, Italy was the first country to carry out a protocol and use liver from COVID-19 donors. We aimed to evaluate the medium-term outcome of patients who underwent liver transplant (LT) with those grafts. METHODS: We consecutively enrolled 283 patients who underwent first LT from November 2020 to December 2022 in our Center (follow-up 468 days). Twenty-five of 283 (8.8%, study population) received a graft from donors with previous (4%) or active (96%) SARS-CoV-2 infection, and 258/283 (91.2%, control group) received a graft from COVID-19-negative donors. SARS-CoV-2-RNA was tested on graft tissue of COVID-19 donors and their recipients underwent weekly evaluation of SARS-CoV-2-RNA in nasal swabs for the first month after LT. RESULTS: One-year and 2-year patient survival was 88.5% and 88.5% in study group versus 94.5% and 93.5% in control group, respectively (p = .531). In study population there was no evidence of donor-recipient virus transmission, but three (12%) patients (vs. 7 [2.7%] of control group, p = .048) developed hepatic artery thrombosis (HAT): they were SARS-CoV-2-RNA negative at LT and 1/3 grafts tested SARS-CoV-2-RNA positive on liver tissue. COVID-19 donor was independently associated with HAT (odds ratio (OR) = 4.85, 95% confidence interval (CI) 1.10-19.15; p = .037). By comparing study population with control group, acute rejection and biliary complication rates were not significantly different (16% vs. 8.1%, p = .26; 16% vs. 16.3% p = .99, respectively). CONCLUSIONS: Our 1-year results of transplant strategy including liver grafts from COVID-19 donors were favorable. HAT was the only complication with significantly higher rate in patients transplanted with COVID-19 donors compared with control group.

Seroconversion After Coronavirus Disease 2019 Vaccination in Patients Awaiting Liver Transplantation: Fact or Fancy?

Chronic liver disease increased the risk of severe coronavirus disease 2019 (COVID-19). Trials to assess efficacy/safety of COVID-19 vaccines in liver disease are underway. We evaluated the humoral immune response and safety of anti-COVID-19 vaccination among patients waiting liver transplantation (LT). We enrolled all pre-LT adults who completed anti-COVID-19 vaccination between January 2021-August 2021 as study group. Patients with histories of COVID-19 received 1 vaccine dose, and all others received 2 doses. Patients were tested for COVID-19 immunoglobulin G (IgG) within 1 and 2 months after vaccination. Safety was evaluated with telephone interviews/outpatient visits. A control group of 30 healthcare workers who underwent vaccination in January 2021 and tested for IgG after 4 months was included. In the 89 pre-LT patients, at T1 (23 days after vaccination), seroconversion rate was 94.4%, and median IgG value was 1980 binding antibody units/mL (interquartile range 646-2080), and at T2 (68 days after vaccination) was 92.0%, with IgG value of 1450 (577-2080); (T1 versus T2, P = 0.38). In the 10/89 patients who received 1 vaccine dose, the median IgG value was 274 (68-548) before vaccine (T0), 2080 (1165-2080) at T1, and 2030 (964-2080) at T2 (T0 versus T1, P = 0.03; T1 versus T2, P = 0.99). All controls tested positive at 4 months after vaccination, with a median value of 847 (509-1165; P < 0.001 versus T1 and P = 0.04 versus T2 in the study group). No serious adverse event was reported in both groups. Our data from 89 pre-LT patients suggest a high rate of immunization (94.4%) after a median time of 23 days from safe COVID-19 vaccine. None of the patients developed COVID-19.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

High anti-TNF alfa drugs trough levels are not associated with the occurrence of adverse events in patients with inflammatory bowel disease.

Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.Results: During a median follow-up of 16 months (range 1-144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p = .21) in median TLs between patients who did 6.7 mcg/mL; range 0.0-36.2) or did not (7.7 mcg/mL; range 0.0-20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p = .38), as well as between elderly (i.e., >65 years) and younger patients (p = .32). Considering a TL cutoff of 7 mcg/mL for infliximab and 12 mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.

Gastroesophageal reflux disease: key messages for clinicians.

Gastroesophageal reflux disease (GERD) is a chronic common disorder for which patients often refer to specialists. In the last decades, numerous studies helped to clarify the pathophysiology and the natural history of this disease. Currently, in the clinical setting, GERD is defined by the presence of symptoms that, when endoscopic investigation is required, permit to distinguish between cases with or without associated esophageal mucosal injuries. These conditions are called erosive reflux disease and non-erosive reflux disease (NERD), respectively. The latter is the most common manifestation of GERD. Symptoms are defined typical, as heartburn and regurgitation, and atypical (also called extra-esophageal), as coughing and/or wheezing, hoarseness, sore throat, otitis media, and dental manifestations. In this context, it is crucial for clinicians to investigate the presence of features of suspected malignancy, as unexplained weight loss, anemia, dysphagia, persistent vomiting, familiar history of cancer, long history of GERD, and beginning of GERD symptoms after the age of 50 years. The presence of these risk factors should induce to perform an endoscopic examination. Particular attention should be given to functional conditions that can mimic GERD, such as functional heartburn and hypersensitive esophagus as well as, more rarely, eosinophilic esophagitis. The former ones have different pathophysiology and this explains the frequent non-response to proton pump inhibitor drugs. This narrative review provides to clinicians a useful and practical overview of the state-of-the-art on advancements in the knowledge of GERD.

Carrying on with liver transplantation during the COVID-19 emergency: Report from piedmont region.

BACKGROUND: The COVID-19 pandemic is an emergency worldwide. In Italy, liver transplant activity was carried on, but despite all efforts, a 25% reduction of procured organs has already been observed during the first 4 weeks of the outbreak. AIMS: To analyze if our strategy and organization of LT pathway during the first two months of the COVID-19 emergency succeeded in keeping a high level of LT activity, comparing the number of LT in the first two months with the same period of time in 2019. METHODS: We compared the liver transplants performed in our Center between February 24th and April 17th, 2020 with liver transplants performed in the same period in 2019. RESULTS: In 2020, 21 patients underwent liver transplantation from deceased donors, exactly as the year before, without statistically significant difference. All patients survived in both groups, and the rate of early graft dysfunction was 24% in 2020 and 33% in 2019. In 2020 Median MELD was higher (17 vs 13). We were able to perform 3 multiorgan transplants and one acute liver failure. Nobody died on waiting list. The performance of our Center, despite the maxi-emergency situation, was steady and this was the result of a tremendous team working within the hospital and in our region. CONCLUSIONS: Team working allowed our Center to maintain its activity level, taking care of patients before and after liver transplantation. Sharing our experience, we hope to be helpful to other Centers that are facing the pandemic and, if another pandemic comes, to be more prepared to deal with it.