Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome ...coronavirus 2 (SARS‐CoV‐2) infection. Our aim was to describe the clinical course of patients with immunosuppressed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID‐19) infection in Italy. Our study is a case series of patients with AIH treated with immunosuppression, who tested positive for SARS‐CoV‐2 in March 2020 during the outbreak of COVID‐19. Ten patients from seven different hospitals in Italy were diagnosed with COVID‐19 during the outbreak of SARS‐CoV‐2 in March 2020. Seven subjects were female (70%), and age ranged from 27 to 73 years. Before the onset of SARS‐CoV‐2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and consequently started high‐dose steroids, as per induction protocol. All patients had a respiratory syndrome and a positive nasal swab for SARS‐CoV‐2. Five patients developed a computed tomography–confirmed COVID‐19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients, the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS‐CoV‐2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high‐dose steroids. The clinical outcome was comparable to the reported cases occurring in non‐immunosuppressed subjects. Conclusion: Patients under immunosuppressive therapy for AIH developing COVID‐19 show a disease course presumptively similar to that reported in the non‐immunosuppressed population. These data might aid in medical decisions when dealing with SARS‐CoV‐2 infection in immunocompromised patients.
We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 ...male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p < 0.0001). Bilirubin value (OR: 0.69, CI95%: 0.54-0.87, p = 0.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09-24.40; p < 0.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in "difficult to treat" HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results.
The coronavirus disease 2019 (COVID-19) pandemic and the necessary spreading control measures implemented by the governments have induced drastic changes in daily life. The reduction in mobility and ...strict social contact limitations are posing a great challenge, particularly for the adolescents. The purpose of this study is to investigate the psychological and emotional impact of lockdown and their relationship with resilience, on adolescents and young adults listed for liver transplant or liver trans-plant recipient. Social and demographic variables of subjects (n=66) were collected and the analyses were based on the Depression Anxiety and Stress Scales (DASS-21), and Connor-Davidson Resilience Scale (CD-RISC 25), exploring the following areas: emotional states of depression, anxiety and stress; and resilience factors. A correlation between the measured degrees of depression/anxiety and resilience was evaluated by Pearson’s correlation coefficient and linear regression models. The results showed a significant correlation between subscales: DASS depression/anxiety (r2=0.62) depression/stress (r2=0.65) CD-RISC commitment/optimism (r2=0.71). The total score of DAAS depression/anxiety/stress scales significantly diminished at the increasing of CD-RISC total score. The inverse correlation between CD-RISC and DAAS seems to refer to the subscale of the relationship between DAAS depression and CDRISC (β= –0.33, P=0.006). Our findings suggest that resilience can be a protective factor for adolescent liver transplant recipients and liver transplant candidates in mitigating the onset of negative psychological symptoms correlated with the pandemic.
BACKGROUND: Access to Directly Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment in Italy was initially restricted to severe patients. In 2017, AIFA expanded access to all patients, to ...achieve elimination by 2030. AIM: To investigate the impact of different hospitals’ organizational models on elimination timing, treatment capacity and direct costs. METHODS: Most Regional healthcare systems in Italy deploy a Center of Excellence (CoE) organizational model, where patients are referred to a single major hospital in the area, which is the only one that can prescribe and deliver DAAs. The study was conducted at Bergamo’s (Lombardy, Italy) Papa Giovanni XXIII hospital (PG-23), which deploys a Hub&Spoke model: the Hub (PG-23) prescribes and delivers DAAs while Spokes (four smaller hospitals) can only prescribe them. The study compares the two models (CoE vs. H&S). Patient journey and workloads were mapped and quantified through interviews with hospital stakeholders. Cost data were collected through the hospital’s IT system; the sample comprised 2,277 HCV patients, over one year. RESULTS: The study calculated the average cost to treat HCV patients (~ € 1,470 per patient). Key cost drivers are lab tests (60%) and specialist visits (30%). Over one year, H&S can treat 68% more patients than CoE. As deferred patients absorb up to 40% of total costs, the “Optimized” model was designed by streamlining specialists’ visits and involving general practitioners during follow-up. “Optimized” model increases treatment capacity and reduces costs of deferred patients by 72% vs CoE. CONCLUSION: The study demonstrates the importance of organizational models in efficiently achieving 2030 elimination.
BACKGROUNDLivers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) ...plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT.METHODSProspectively collected data on 24 cDCD LT, with aNRP alone, were analyzed.RESULTSThe median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds.CONCLUSIONSThis pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.
Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study ...was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection.
We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected.
57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer.
In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.
Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to ...assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe.
This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019.
A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27–41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9–15%); and the United Kingdom and Spain had low rates (3–5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74–87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio HR 3.14; 95% CI 1.37–7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63–8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37–5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3.
The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF.
Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes.
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•The percentage of LTs performed in patients with ACLF grade 2-3 differed significantly between European countries.•Waiting list priority should account for the 25% mortality risk in patients with ACLF-2-3.•One-year post-LT survival of patients with ACLF was in excess of 80%, independently of ACLF grade.•Factors independently associated with post-LT mortality included lactate levels >4 mmol/L need for RRT at LT, and infections with MDROs while on the waiting list.•Infections with MDROs, either precipitating ACLF or complicating its clinical course, were relevant predictors of poor outcome.
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•Glecaprevir/pibrentasvir combination has demonstrated excellent SVR rates (99.2%) in this real-world study in Italy.•Male gender (0.022) and HCV genotype3 (0.046) were associated ...with the lowest rates of SVR after 8-week G/P treatment.•8.3% of the patients reported mild adverse events and 0.7% of them prematurely withdrew antiviral treatment.
The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting.
All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment.
A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes.
In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks.
A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.
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