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Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4We identified ApoB100-specific T cells in blood from healthy controls, nonalcoholic fatty liver disease (NAFLD) patients, and CVD patients by activation-induced marker expression and analyzed their differentiation pattern in correlation to the lipid profile and liver damage parameters in a cross-sectional study. To assess the induction of extrahepatic ApoB100-specific T cells upon transient liver damage in vivo, we performed hydrodynamic tail vein injections with diphtheria toxin A (DTA)-encoding plasmid in human ApoB100-transgenic mice.Utilizing immunodominant ApoB100-derived peptides, we found increased ApoB100-specific T-cell populations in NAFLD and CVD patients compared to healthy controls. In a peptide-specific manner, ApoB100 reactivity in healthy controls was accompanied by expression of the regulatory T (Treg)-cell transcription factor FOXP3. In contrast, FOXP3 expression decreased, whereas expression of pro-inflammatory cytokine interleukin (IL)-17A increased in ApoB100-specific T cells from NAFLD and CVD patients. Dyslipidemia and liver damage parameters in blood correlated with reduced FOXP3 expression and elevated IL-17A production in ApoB100-specific T-cell populations, respectively. Moreover, DTA-mediated transient liver damage in human ApoB100-transgenic mice accumulated IL-17a-expressing ApoB100-specific T cells in the periphery.Our results show that liver damage promotes pro-inflammatory ApoB100-specific T-cell populations, thereby providing a cellular mechanism for the increased CVD risk in liver disease patients.

Background & Aims The simplified criteria for the diagnosis of autoimmune hepatitis (AIH) include immunofluorescence testing (IFT) of antinuclear and smooth muscle autoantibodies (ANA and SMA) on rodent tissue sections. We aimed to establish scoring criteria for the implementation of ANA IFT on human epithelioma-2 (HEp-2) cells and ELISA-based testing. Methods ANA and SMA reactivity of 61 AIH sera and 72 non-alcoholic fatty liver disease controls were separately assessed on tissue sections and HEp-2 cells to compare the diagnostic value at increasing titers. A total of 113 patients with AIH at diagnosis and 202 controls from 3 European centers were assessed by IFT as well as 3 different commercially available ANA ELISA and 1 anti-F-actin ELISA. Results ANA assessment by IFT on liver sections had 83.6% sensitivity and 69.4% specificity for AIH at a titer of 1:40. On HEp-2 cells, sensitivity and specificity were 75.4% and 73.6%, respectively, at an adjusted titer of 1:160. Area under the curve (AUC) values of ANA ELISA ranged from 0.70–0.87, with ELISA coated with HEp-2 extracts in addition to selected antigens performing significantly better. SMA assessment by IFT had the highest specificity for the SMA-VG/T pattern and anti-microfilament reactivity on HEp-2 cells. ELISA-based anti-F-actin evaluation was a strong predictor of AIH (AUC 0.88) and performed better than SMA assessment by IFT (AUC 0.77–0.87). Conclusion At adjusted cut-offs, both ANA IFT using HEp-2 cells and ELISA-based autoantibody evaluation for ANA and SMA are potential alternatives to tissue-based IFT for the diagnosis of AIH. Lay summary Autoantibodies are a hallmark of autoimmune hepatitis and are traditionally tested for by immunofluorescence assays on rodent tissue sections. Herein, we demonstrate that human epithelioma cells can be used as a reliable substrate for immunofluorescence testing. ELISA-based testing is also a potentially reliable alternative for autoantibody assessment in autoimmune hepatitis. We propose the implementation of these testing methods into the simplified criteria for the diagnosis of autoimmune hepatitis.

We sequentially assessed the presence of SARS-CoV-2 IgG antibodies in 1253 hospital workers including 1026 HCWs at the University Medical Center Hamburg-Eppendorf at three time points during the early phase of the epidemic. By the end of the study in July 2020, the overall seroprevalence was 1.8% (n = 22), indicating the overall effectiveness of infection control interventions in mitigating coronavirus disease 2019 (COVID-19) in hospital workers.

Background: Glecaprevir/pibrentasvir (GLE/PIB) is the latest approved pan-genotypic direct-acting antiviral agent (DAA) for the treatment of chronic hepatitis C virus (HCV) infection. However, real-world data of GLE/PIB in European patient cohorts are limited. Methods: A single-center cohort of 100 unselected HCV patients seen at the Outpatient Clinic of the University Medical Center Hamburg-Eppendorf from October 2017 until September 2019 was retrospectively analyzed by chart review with a special focus on demographic clinical and virologic aspects as well as treatment compliance outcome. Results: A total of 99 patients with chronic HCV infection (genotype (GT) 1 - 6), who started antiviral treatment with GLE/PIB, were included. Treatment duration lasted from 4 to 16 weeks. The primary endpoint was a sustained virological response at week 12 (SVR12) after the end of treatment (EoT). Only three patients (3/100; 3%) were diagnosed with liver cirrhosis by non-invasive measures. Ten patients (10/100; 10%) were pre-treated with Interferon (IFN) containing regiments. Most patients received 8 weeks of treatment (96/100; 96%). One patient discontinued treatment after four weeks due to poor compliance (1/100; 1%). A high number of patients were lost to follow-up (22/100; 22%). All patients who were regularly seen to follow-up visits (76/100; 76%) achieved SVR12 (76/76; 100%). Virological relapse occurred in none of the patients. Adverse events (AEs) were rarely reported (4 patients) (4/100; 4%), and none of these patients discontinued treatment. Conclusions: This study demonstrated that initial and re-treatment with GLE/PIB were effective and safe in a German cohort with chronic HCV infection in real-life settings, regardless of GT.

Baseline liver stiffness (LS) is prognostically relevant in patients with chronic hepatitis C virus (HCV) infection but may change after successful HCV eradication. Data on post-treatment LS for a further risk stratification remain scarce. Here, we study the kinetics of LS and laboratory parameters in patients undergoing HCV treatment and analyze the association of post-treatment LS with outcome parameters. In a cohort of 1011 chronic HCV patients undergoing DAA treatment, we identified 404 patients with sequential LS and laboratory assessments with or without viral eradication. Additionally, outcome parameters were correlated with post-treatment LS after successful HCV therapy. LS significantly decreased from a median of 8.8 to 6.1 kPa in 346 patients after HCV eradication, but significantly increased from a median of 10.5 to 11.9 kPa in 58 patients without viral clearance. In 78 patients with two sequential post-treatment measurements, LS decreased from 12.6 to 8.7 kPa after a median 344 d, with a further decrease to 7.0 kPa after a median of 986 d after end of treatment (EoT). In 400 patients with a post-treatment LS assessment after viral eradication, only 9 liver-related events occurred over a median follow-up (FU) of 23 months. All events were observed in patients with a post-treatment LS >20 kPa. After successful HCV eradication, LS improves sequentially, suggesting an initial phase of necroinflammation regression followed by a second phase of true fibrosis regression. Overall, liver-related events were rarely observed and seem to be limited to patients with a post-treatment LS >20 kPa, so that these patients require a closer clinical monitoring.

ObjectiveTo assess the effectiveness of multimodal infection control interventions in the prevention of SARS-CoV-2 infections in healthcare professionalsDesignSequential follow-up studySettingLargest tertiary care centre in northern GermanyParticipants1253 employees of the University Medical Center Hamburg-Eppendorf were sequentially assessed for the presence of SARS-CoV-2 IgG antibodies at the beginning of the covid-19 epidemic (20 March – 9 April), one month (20 April – 8 May), and another two months later (22 June – 24 July). Of those, 1026 were healthcare workers (HCWs) of whom 292 were directly involved in the care of covid-19 patients. During the study period, infection control interventions were deployed, those included i) strict barrier nursing of all known covid-19 patients including FFP2 (N95) masks, goggles, gloves, hoods and protective gowns, ii) visitor restrictions with access control at all hospital entries, iii) mandatory wearing of disposable face masks in all clinical settings, and iv) universal RT-PCR admission screening of patients.Main Outcome MeasuresSARS-CoV-2 IgG seroconversion rateResultsAt the initial screening, ten participants displayed significant IgG antibody ratios. Another ten individuals showed seroconversion at the second time point one month later, only two further participants seroconverted during the subsequent two months. The overall SARS-CoV-2 seroprevalence in the study cohort at the last follow-up was 1.8%, the seroconversion rate dropped from 0.81% to 0.08% per month despite a longer observation period. Amongst HCWs seropositivity was increased in those directly involved in the care of patients with SARS-CoV-2 infections (3.8%, n=11) compared to other HCWs (1.4%, n=10, P=0.025). However, after the adoption of all multimodal infection control interventions seroconversions were observed in only two more HCWs, neither of whom were involved in inpatient care.ConclusionMultimodal infection control and prevention interventions are highly effective in mitigating SARS-CoV-2 infections of healthcare professionals.