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Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen-negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age Ͻ 60 years (odds ratio ϭ 4.45, 95% confidence interval ϭ 1.39-14.19, P ϭ 0.01), viral genotype other than 1 (odds ratio ϭ 4.97, 95% confidence interval ϭ 1.59-15.48, P ϭ 0.006), and the use of CyA during treatment (odds ratio ϭ 6.85, 95% confidence interval ϭ 2.15-21.73, P ϭ 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P ϭ 0.02 and P ϭ 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P ϭ 0.03, P Ͻ 0.001, and P ϭ 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P ϭ 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT. Hepatitis C virus (HCV)-related cirrhosis is the leading indication for liver transplantation (LT) in both theUnited States and Europe.1,2 Hepatitis C recurrence is almost universal, leading to severe liver damage in 30% of patients within 5 years of transplant. 3,4 In patients with posttransplant HCV recurrence, antiviral treatment (AVT) with interferon (IFN) and ribavirin is the only way to prevent severe reinfection of the graft, even though sustained virological response (SVR) is achieved in a minority of cases. 5Although predictors of severe HCV recurrence have been identified in recent years, 5-11 factors associated with the probability of SVR are much less clear. In fact, the effectiveness of AVT may be partly influenced by the same factors determining the natural course of HCV recurrence-donor age, quality of the graft, HCV-RNA level, viral genotype, type of immunosuppression, occurrence of rejection, and occurrence of cytomegalovirus (CMV) infection-and partly linked to other variables, such as the type of AVT, patient conditions, and grading and staging of reinfection at the time of initiation of antiviral drugs. 5,12Primary immunosuppression and particularly the use of cyclosporine (CyA) or tacrolimus (TAC) have been

AIMTo investigate changes in spleen stiffness measurements (SSMs) and other non-invasive tests (NITs) after treatment with direct-acting antivirals (DAAs) and identify predictors of SSM change after sustained virological response (SVR).METHODSWe retrospectively analysed 146 advanced-chronic liver disease (ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness (LSM), spleen diameter (SD), platelet count (PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 kPa was used as a cut-off to rule-in clinically significant portal hypertension (CSPH). SSM reduction > 20% from baseline was defined as significant.RESULTSSSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence.CONCLUSIONSSM and other NITs significantly decrease after SVR, although differently according to the patient’s clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.

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Background SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI.

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Background Bacterial and fungal infections (BFI) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods We performed a two centers prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1-year. Results Among the 516 patients enrolled, 108 (21%) were infected at admission, while additional 61 (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%, p=0.553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%, p=0.011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from MELD-Na, comorbidity and basal CRP level. Finally, multivariable logistic regression showed that higher MELD score (p<0.001), QuickSOFA score ≥2 points (p=0.007), secondary bloodstream (p=0.022) and multidrug resistant pathogen isolation (p=0.030) were independently associated to ACLF in patients with BFI. Conclusions This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF.