Non-organ-specific autoantibodies with unspecific patterns are a frequent para-infectious feature of chronic hepatitis D.

Infections with hepatotropic viruses are associated with various immune phenomena. Hepatitis D virus (HDV) causes the most severe form of viral hepatitis. However, few recent data are available on non-disease-specific and non-organ-specific antibody (NOSA) titers and immunoglobulin G (IgG) levels in chronic hepatitis D (CHD) patients. Here, we examined the NOSA titers and IgG levels of 40 patients with CHD and different disease courses and compared them to 70 patients with chronic hepatitis B (CHB) infection. 43% of CHD patients had previously undergone treatment with pegylated interferon-α (IFN-α). The antibody display of 46 untreated patients diagnosed with autoimmune hepatitis (AIH) was used as a reference. The frequency of elevated NOSA titers (CHD 69% vs. CHB 43%, p < 0.01), and the median IgG levels (CHD 16.9 g/L vs. CHB 12.7 g/L, p < 0.01) were significantly higher in CHD patients than in patients with CHB, and highest in patients with AIH (96%, 19.5 g/L). Also, the antinuclear antibody pattern was homogeneous in many patients with AIH and unspecific in patients with viral hepatitis. Additionally, f-actin autoantibodies were only detectable in patients with AIH (39% of SMA). In CHD patients, IgG levels correlated with higher HDV viral loads, transaminases, and liver stiffness values. IgG levels and NOSA were similar in CHD patients irrespective of a previous IFN-α treatment. In summary, autoantibodies with an unspecific pattern are frequently detected in CHD patients with unclear clinical relevance.

Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100.

OBJECTIVES: Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4+ T cells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown. METHODS: We 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. RESULTS: 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. CONCLUSION: 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.

Evolution of liver stiffness and post-treatment surveillance by liver elastography for HCV patients in the DAA era.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Seroprevalence of SARS-CoV-2 antibodies among hospital workers in a German tertiary care center: A sequential follow-up study.

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.

Update of the simplified criteria for autoimmune hepatitis: Evaluation of the methodology for immunoserological testing.

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.