Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion.

INTRODUCTION: Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson's disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors. METHODS: We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan-Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson's correlation was used to analyze predictors of WL. RESULTS: The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain-Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008). CONCLUSIONS: LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

Impact of SARS-CoV-2 Pandemic on the Management of Patients with Hepatocellular Carcinoma.

Worldwide, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly increases mortality and morbidity. The Coronavirus Disease 2019 (COVID-19) outbreak has had a considerable impact on healthcare systems all around the world, having a significant effect on planned patient activity and established care pathways, in order to meet the difficult task of the global pandemic. Patients with hepatocellular carcinoma (HCC) are considered a particularly susceptible population and conceivably at increased risk for severe COVID-19 because of two combined risk factors: chronic advanced liver disease and HCC itself. In these challenging times, it is mandatory to reshape clinical practice in a prompt way to preserve the highest standards of patient care and safety. However, due to the stay-at-home measures instituted to stop the spread of COVID-19, HCC surveillance has incurred a dramatic drop, and care for HCC patients has been rearranged by refining the algorithm for HCC treatment to the COVID-19 pandemic, permitting these patients to be safely managed by identifying those most at risk of neoplastic disease progression.

Differences in Humoral and Cellular Vaccine Responses to SARS-CoV-2 in Kidney and Liver Transplant Recipients.

The antibody and T cell responses after SARS-CoV-2 vaccination have not been formally compared between kidney and liver transplant recipients. Using a multiplex assay, we measured IgG levels against 4 epitopes of SARS-CoV-2 spike protein and nucleocapsid (NC) antigen, SARS-CoV-2 variants, and common coronaviruses in serial blood samples from 52 kidney and 50 liver transplant recipients undergoing mRNA SARS-CoV-2 vaccination. We quantified IFN-γ/IL-2 T cells reactive against SARS-CoV-2 spike protein by FluoroSpot. We used multivariable generalized linear models to adjust for the differences in immunosuppression between groups. In liver transplant recipients, IgG levels against every SARS-CoV-2 spike epitope increased significantly more than in kidney transplant recipients (MFI: 19,617 vs 6,056; P<0.001), a difference that remained significant after adjustments. Vaccine did not affect IgG levels against NC nor common coronaviruses. Elicited antibodies recognized all variants tested but at significantly lower strength than the original Wuhan strain. Anti-spike IFN-γ-producing T cells increased significantly more in liver than in kidney transplant recipients (IFN-γ-producing T cells 28 vs 11 spots/5x105 cells), but this difference lost statistical significance after adjustments. SARS-CoV-2 vaccine elicits a stronger antibody response in liver than in kidney transplant recipients, a phenomenon that is not entirely explained by the different immunosuppression.

Global impact of the first wave of COVID-19 on liver transplant centers: A multi-society survey (EASL-ESOT/ELITA-ILTS).

BACKGROUND AND AIMS: The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices. METHOD: A prospective web-based survey (available online from 7th September 2020 to 31st December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised 4 parts concerning transplant processes, therapy, living donors, and organ procurement. RESULTS: Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first 6 months of the pandemic in 2020 with those a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), WL mortality, and the number of LTs performed. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p <0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LTs (p = 0.002) during the pandemic. Interestingly, WL mortality was still higher in the "non-hit" countries in 2020 compared to 2019 (p = 0.022). CONCLUSION: The first wave of the pandemic differentially impacted LT practices across the world, especially with detrimental effects on the "hit" countries. Modifications to the policies of recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level. LAY SUMMARY: The health emergency caused by the coronavirus pandemic has dramatically changed clinical practice during the pandemic. The first wave of the pandemic impacted liver transplantation differently across the world, with particularly detrimental effects on the countries badly hit by the virus. The resilience of the entire transplant network has enabled continued organ donation and transplantation, ultimately improving the lives of patients with end-stage liver disease.

Italian association for the study of the liver position statement on SARS-CoV2 vaccination.

The vaccination campaign against Sars-CoV-2 commenced in Italy at the end of December 2020. The first ones to receive the immunization against the virus were the health workers and the residents of nursing homes, following which the vaccine would be available for the entire population, beginning with the most vulnerable individuals. SARS-CoV2 vaccines have been demonstrated to be safe for the general population, although no data for patients with liver diseases or those having undergone liver transplantation are available so far. The present position statement AISF is an attempt to suggest, based on the published data on the impact of Sars-Cov-2 infection in patients with chronic liver disease, a possible priority for vaccination for this category of patients.

Liver histopathology in COVID-19 patients: A mono-Institutional series of liver biopsies and autopsy specimens.

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.

Assessing the impact of COVID-19 on the management of patients with liver diseases: A national survey by the Italian association for the study of the Liver.

BACKGROUND: The COVID-19 pandemic had a huge impact on national and regional health systems. The impact of SARS-CoV-2 on the quality of care for patients with liver disease is still unknown. AIMS: The Italian Association for the Study of the Liver (AISF) conducted a survey to assess the impact of SARS-CoV-2 on hepatology units activities in Italy. METHODS: A prospective web-based survey was proposed to all AISF active members. The survey was available online from April 8 2020, to May 3 2020, (lockdown phase in Italy). RESULTS: 194 AISF members answered the questionnaire, most of whom were specialists in Gastroenterology (41%) or Internal Medicine (28%), and worked in Northern Italy (51%). 26% of hepatology wards had been converted into COVID-19 wards, and 33% had bed reductions. All hepatological activities, including the management of patients with decompensated liver disease, liver transplant and HCC had been significantly reduced/stopped. The number of physicians answering that their practices had not been modified ranged between 0.6% (for chronic hepatitis) to 47% (for the execution of paracentesis). The recorded answers were consistent among different regions, and did not show any north-south gradient CONCLUSION: COVID-19 outbreak significantly impacted on hepatological clinical activity. This survey can serve as a basis to compare the impact of future measures aimed at delivering an acceptable level of liver care during a national pandemic or crisis.