Publications by authors named "Julian Schulze zur Wiesch"
Background & Aims: The role of hepatocytes in producing chemokines and triggering liver inflammation and damage in chronic hepatitis D (CHD) is not fully understood. Herein, we investigated the contribution of primary human hepatocytes (PHHs) infected with HDV in triggering inflammation by producing the chemokines CXCL9-11.
Methods: We performed quantitative PCR, RNA hybridisation, activation-induced marker (AIM) assays, and FACS analysis to investigate the CXCR3/CXCL9-11 receptor/ligand axis of T cells in peripheral blood and livers from patients with chronic hepatitis B (n = 27 and 18, respectively) and CHD (n = 20 and 18, respectively).
Background And Aims: Sarcoidosis is a granulomatous multi-systemic disorder of uncertain aetiology frequently involving the liver. This study aimed to delineate the histological characteristics, treatment effectiveness and factors predictive of liver-related complications in individuals with hepatic sarcoidosis.
Methods: This retrospective cohort study included patients diagnosed with hepatic sarcoidosis by liver biopsy, which was conducted at two tertiary care centres from January 2009 to December 2023.
Background/objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.
View Article and Find Full Text PDFBackground & Aims: Patients with vascular liver diseases (VLD) are at higher risk of both severe courses of COVID-19 disease and thromboembolic events. The impact of SARS-CoV-2 vaccination in patients with VLD has not been described and represents the aim of our study.
Methods: International, multicenter, prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation.
Background & Aims: Immune responses by CD8 T cells are essential for control of HBV replication. Although selection of escape mutations in CD8 T-cell epitopes has been previously described in HBV infection, its overall influence on HBV sequence diversity and correlation with markers of HBV replication remain unclear.
Methods: Whole-genome sequencing was applied to HBV isolates from 532 patients with chronic HBV infection and high-resolution HLA class I genotyping.
B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.
Hepatol Commun
August 2024
Article Synopsis
- Chronic HCV infection can lead to serious immune complications like B cell dyscrasias, and while antiviral therapy has reduced liver damage, its effects on these complications are still unclear.
- Researchers sequenced B cell receptors in patients with chronic HCV and those who achieved sustained virological response (SVR) after treatment, identifying patterns in neutralizing antibodies and comparing them to lymphoma data.
- Findings indicated that specific mutations in B cell receptors associated with high neutralizing activity were also found in lymphoma cases, suggesting a connection between the immune response to HCV and the persistence of potential lymphoma-like cells even after successful treatment.
Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.
Lancet HIV
June 2024
Background: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT.
Methods: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation.
Background & Aims: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
View Article and Find Full Text PDFArticle Synopsis
- Drug-based antiretroviral therapies (ART) effectively control HIV replication but can't eliminate the virus since it remains as integrated proviral reservoirs in cells.
- Genome editing tools like the HIV-1 LTR-specific designer-recombinase Brec1 show promise in removing these integrated HIV genomes, indicating potential for curative therapies.
- A comprehensive preclinical study of Brec1 demonstrated it has minimal safety risks, including no harmful immune responses, making it a suitable candidate for future clinical trials aimed at eradicating HIV-1.
Background: While the sexual transmissibility of HAV in MSM has been extensively described, the potential for sexual transmission of HEV has not been definitively established. Although HEV has been detected in the ejaculate of chronically infected men, studies among MSM PrEP users in France did not observe an elevated anti-HEV seroprevalence as an indicator of increased exposure risk by sexual intercourse.
Patients And Methods: A total of 111 unselected PrEP users and 111 age- and sex-matched blood donors were tested for anti-HEV IgG, IgM and HEV (PCR).
The rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive.
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- Periodontitis is commonly diagnosed in patients with ascitic decompensated liver cirrhosis, found in 82% of the study group compared to 59% in a control group, suggesting a strong correlation between the two conditions.
- The study utilized PCR testing on gingival samples, ascites, and stool but found no evidence of specific periodontitis pathogens in ascites, although some were present in stools and gums.
- Patients with periodontitis showed a significantly higher survival rate and transplant-free survival compared to those without, indicating a potential protective effect of periodontitis in this cohort.
Introduction: Tumor-associated macrophages (TAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype and function of these cells. The present study aims to characterize macrophages in high-grade serous ovarian cancer (HGSOC).
Methods: Phenotype and expression of co-regulatory markers were assessed on TAMs derived from malignant ascites (MA) or peripheral blood (PB) by multiparametric flow cytometry.
Background & Aims: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes.
Methods: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries.
Comparative analysis of characteristics and outcomes in hospitalized COVID-19 patients infected with different SARS-CoV-2 variants between January 2020 and April 2022 - A retrospective single-center cohort study.
J Infect Public Health
November 2023
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the roll-out of vaccines and therapeutic agents, as well as the emergence of novel SARS-CoV-2 variants, have shown significant effects on disease severity.
Methods: Patients hospitalized at our center between January 2020 and April 2022 were attributed to subgroups depending on which SARS-CoV-2 variant was predominantly circulating in Germany: (i) Wild-type: January 1, 2020, to March 7, 2021, (ii) Alpha variant: August 3, 2021, to June 27, 2021, (iii) Delta variant: June 28, 2021, to December 26, 2021, and (iv) Omicron variant: December 27, 2021, to April 30, 2022.
Results: Between January 2020 and April 2022, 1500 patients with SARS-CoV-2 infections were admitted to the University Medical Center Hamburg-Eppendorf.
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes.
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- Hepatitis D virus (HDV) is linked to severe viral hepatitis and this study investigates antibody levels in 40 chronic hepatitis D (CHD) patients compared to 70 chronic hepatitis B (CHB) patients.
- The study found that CHD patients have significantly higher non-disease-specific antibody (NOSA) titers and immunoglobulin G (IgG) levels than CHB patients, with CHD showing 69% and 16.9 g/L respectively.
- Autoantibodies in CHD patients are common but have unclear clinical implications, and their IgG levels correlate with higher viral loads and liver damage indicators, regardless of prior treatment with pegylated interferon-α.
Background: Coinfection with hepatitis D virus (HDV) accelerates the progression of liver disease associated with chronic hepatitis B. Bulevirtide inhibits the entry of HDV into hepatocytes.
Methods: In this ongoing phase 3 trial, patients with chronic hepatitis D, with or without compensated cirrhosis, were randomly assigned, in a 1:1:1 ratio, to receive bulevirtide subcutaneously at 2 mg per day (2-mg group) or 10 mg per day (10-mg group) for 144 weeks or to receive no treatment for 48 weeks followed by bulevirtide subcutaneously at 10 mg per day for 96 weeks (control group).
Background And Aims: Chronic HEV infections remain a serious problem in immunocompromised patients, as specifically approved antiviral drugs are unavailable. In 2020, a 24-week multicenter phase II pilot trial was carried out, evaluating the nucleotide analog sofosbuvir by treating nine chronically HEV-infected patients with sofosbuvir (Trial Number NCT03282474). During the study, antiviral therapy reduced virus RNA levels initially but did not lead to a sustained virologic response.
View Article and Find Full Text PDFBackground: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus.
Methods: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms.
Article Synopsis
- The study investigates the T-cell responses specific to NSP12 protein in COVID-19 patients and compares them to those in uninfected individuals and pre-pandemic controls.
- It finds that both COVID-19 patients and seronegative controls exhibit similar breadth of T-cell responses to NSP12 peptides, but COVID-19 patients have a higher magnitude of response.
- The presence of cross-reactive T-cell responses from common cold coronaviruses suggests pre-existing immunity, while also highlighting the complex nature and incomplete understanding of T-cell responses to SARS-CoV-2.
History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.
Eur J Neurol
August 2023
Article Synopsis
- The study investigated the impact of pre-existing neurological conditions like dementia and cerebrovascular disease on severe outcomes in COVID-19 patients hospitalized in 2022.
- A total of 1,249 patients were analyzed, revealing low in-hospital mortality (3.8%) and ICU admission rates (9.9%), with no significant increase in risk due to dementia or cerebrovascular disease.
- However, patients with chronic cerebrovascular disease and a history of myocardial infarction showed a higher likelihood of developing vascular complications after SARS-CoV-2 infection.
Background: Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown.
Methods: We retrospectively analyzed data collected during a single-center observational study (March 2020-November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany.