A systematic PCR record-based re-call of HCV-RNA-positive people enables re-linkage to care and HCV elimination in Austria - The ELIMINATE project.

BACKGROUND AND AIMS: Identification of people living with hepatitis C virus (HCV) via readily available laboratory records could be a key strategy for macro-elimination, aligning with the WHO elimination goal. Therefore, the ELIMINATE(ELIMINation of HCV in AusTria East) project aimed to systematically re-link people with a 'last-positive' HCV-RNA PCR record to care. METHODS: In 10 major liver centres in Eastern Austria, a systematic readout of 'last-positive' HCV-RNA PCR test records obtained between 2008 and 2020 were conducted and linked to available patient contact data. Between 2020 and 2023, individuals were contacted first by phone, then by letter, to inform them about the availability of effective direct-acting antiviral (DAA) treatment and invite them for pre-treatment evaluation. RESULTS: The overall cohort of last-positive HCV+ individuals included 5695 subjects (62.5% males, mean age 57.3 ± 17.3 years); of note, 1931 (34%) of them had died and 759 (13%) individuals had no valid contact information. Of the remaining 3005 individuals, 1171 (40.0%) had already achieved sustained virological response (SVR) at the time of re-call. We successfully reached 617 (20.5%), of whom 417 (67.6%) attended their pre-treatment visit, and 397 (64.3%) commenced DAA-therapy. HCV cure has been confirmed in 326 individuals, corresponding to an SVR rate of 82.1%. CONCLUSION: The ELIMINATE project identified 5695 people living with HCV who were 'lost to care' despite documented HCV viraemia. While invalid contact data were an evident barrier to HCV elimination, premature deaths among the cohort underscored the severity of untreated HCV. The implementation of a systematic HCV-RNA PCR recorded-based re-call workflow represents an effective strategy supporting the WHO goal of HCV elimination.

The Distinct Regulation of the Vitamin D and Aryl Hydrocarbon Receptors in COVID-19.

(1) Background: SARS-CoV-2 affects several immune pathways, including the vitamin D (VDR) and the aryl hydrocarbon receptor pathways (AhR). The aim of the study was the evaluation of the VDR and AhR pathways in the blood of COVID-19 patients with regard to the severity of disease. (2) Methods: Observational, single-center, case-control design. A total of 240 samples were selected for exploration. Patients who tested negative for SARS-CoV-2 but suffered from other respiratory infections (ORIs) served as a control group. (3) Results: VDR-specific mRNA in the blood of patients with mild symptoms (131.2 ± 198.6) was significantly upregulated relative to the VDR expression of the ORI group (23.24 ± 42.60; p < 0.0001); however, VDR expression of critically ill patients showed an impaired upregulation (54.73 ± 68.34; p < 0.001). CYP27B1 expression was not significantly regulated during SARS-CoV-2 infection. There was a downregulation of VDR and CYP27B1 compared to survivors. There was no significant difference in 25(OH)-vitamin D3 levels between critically ill patients with regard to survival (24.3 ± 9.4 vs. 27.1 ± 11.3; p = 0.433). (4) Conclusion: The VDR and AhR pathways are distinctively regulated in patients suffering from COVID-19 depending on the severity of disease. A combination treatment of antiviral drugs and vitamin D substitution should be evaluated for potentially improved prognosis in COVID-19.

ELIMINATE: a PCR record-based macroelimination project for systematic recall of HCV-RNA-positive persons in Austria.

BACKGROUND AND AIMS: Micro-elimination projects targeted to specific hepatitis C virus (HCV) risk populations have been successful. Systematic identification of persons with HCV viremia, regardless of risk group, based on already available laboratory records may represent an effective macroelimination approach to achieve global HCV elimination. METHODS: Persons with a last positive HCV-RNA PCR result between 2008-2020 in the reference virology laboratories in eastern Austria were identified. First, (i) we described their demographic characteristics, (ii) we systematically recalled persons to the respective centers and (iii) started antiviral treatment if HCV-RNA viremia was confirmed, and (iv) recorded sustained virologic response (SVR). This interim report includes the preliminary results from 8 participating centers. RESULTS: During the study period 22,682 persons underwent HCV-RNA PCR testing, 11,216 (49.4%) were positive at any point in time, and 6006 (26.5%) showed detectable HCV-RNA at the last PCR test, suggesting ongoing HCV viremia. At the time of this interim report, 2546/6006 HCV-RNA PCR(+) persons were evaluated: 443/2546 (17.4%) had died, 852/2546 (33.5%) had invalid contact data, and 547/2546 (21.5%) had achieved SVR between data retrieval and recall. Contact could be established in 236/704 (33.5%) of the remaining target population with 97/236 (41.1%) presenting at the clinic for treatment evaluation. Ultimately, 71/236 (30.1%) started antiviral treatment and SVR was documented in 47/71 (66.2%). CONCLUSION: This ELIMINATE project based on systematic assessment of HCV-RNA PCR-records, identified 6006 persons with potential persisting HCV viremia. Invalid contact data and missed visits for treatment evaluation were the main barriers towards HCV elimination within this project. Importantly, many subjects with HCV viremia lost to follow-up were successfully linked to care and started antiviral treatment.

Performance study of the anterior nasal AMP SARS-CoV-2 rapid antigen test in comparison with nasopharyngeal rRT-PCR.

Introduction: The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is real-time reverse transcription PCR (rRT-PCR), which is expensive, has a long turnaround time and requires special equipment and trained personnel. Nasopharyngeal swabs are uncomfortable, not suitable for certain patient groups and do not allow self-testing. Convenient, well-tolerated rapid antigen tests (RATs) for SARS-CoV-2 detection are called for. Gap statement: More real-life performance data on anterior nasal RATs are required. Aim: We set out to evaluate the anterior nasal AMP RAT in comparison with rRT-PCR in a hospital cohort. Methodology: The study included 175 patients, either hospitalized in a coronavirus disease 2019 (COVID-19) ward or screened in a preadmittance outpatient clinic. Two swabs were collected per patient: an anterior nasal one for the RAT and a combined naso-/oropharyngeal one for the rRT-PCR. Sixty-five patients (37%) were rRT-PCR-positive [cycle threshold (C t) <40]. Results: The anterior nasal AMP RAT showed an overall sensitivity and specificity of 29.2 % (18.6-41.8, 95 % CI) and 100.0 % (96.7-100.0, 95 % CI) respectively. In patients with a C t value <25, <30 and <33, higher sensitivities were observed. Time since symptom onset was significantly higher in patients with a false-negative RAT (P=0.02). Conclusion: The anterior nasal AMP RAT showed low sensitivities in this cohort, especially in patients with a longer time since symptom onset. Further knowledge concerning the viral load and antigen expression over time and in different swabbing locations is needed to outline the usage time frame for SARS-CoV-2 RAT.

Immunological Aspects of AXL/GAS-6 in the Context of Human Liver Regeneration.

AXL and its corresponding ligand growth arrest-specific 6 (GAS-6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory responses might essentially involve the shift of macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory M2. We aimed to assess the relevance of the AXL/GAS-6-pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Soluble AXL (sAXL) and GAS-6 levels were analyzed at preoperative and postoperative stages in 154 patients undergoing partial hepatectomy and correlated with clinical outcome. Perioperative dynamics of interleukin (IL)-6, soluble tyrosine-protein kinase MER (sMerTK), soluble CD163 (sCD163), and cytokeratin (CK) 18 were assessed to reflect pathophysiological processes. Preoperatively elevated sAXL and GAS-6 levels predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients failed to respond with an immediate increase of sAXL and GAS-6 upon induction of liver regeneration. Abolished AXL pathway response resulted in a restricted increase of sCD163, suggesting a disrupted phenotypical switch to regeneratory M2 macrophages. No association with sMerTK was observed. Concomitantly, a distinct association of IL-6 levels with an absent increase of AXL/GAS-6 signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by CK18M65. sAXL and GAS-6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome but also AXL/GAS-6 signaling might be of critical relevance in human liver regeneration. Refractory AXL/GAS-6 signaling, due to chronic overactivation/stimulation in the context of underlying liver disease, appears to abolish their immediate release following induction of liver regeneration, causing overwhelming immune activation, presumably via intrahepatic immune regulation.

Evaluation of the AMP SARS-CoV-2 rapid antigen test in a hospital setting.

OBJECTIVES: Quick and inexpensive SARS-CoV-2 screening and frontline testing are in growing demand. Our study aimed to evaluate the performance of the immunochromatographic AMP rapid antigen test (AMP RAT) compared to the gold-standard real-time reverse transcription PCR (rRT-PCR) in a hospital cohort. METHODS: A total of 392 patients, who presented consecutively with COVID-19 symptoms in our emergency department, were included in this retrospective study. Two swabs were collected per patient: a nasopharyngeal for the RAT and a combined naso- and oropharyngeal for the rRT-PCR. A positive rRT-PCR (defined as cycle threshold (Ct) < 40) was found in 94 (24%) patients. RESULTS: In our cohort with a median patient age of 70, overall sensitivity and specificity of the AMP RAT was 69.2% (58.8-78.3, 95% CI) and 99.7% (98.1-100.0, 95% CI), respectively. In patients with a Ct value < 25 and < 30, higher sensitivities of 100.0% (89.4-100.0, 95% CI) and 91.8% (81.9-97.3%, 95% CI) were observed. CONCLUSIONS: The AMP RAT showed a high sensitivity in patients with a Ct value < 25 and < 30 and might be helpful for frontline testing whenever rRT-PCR is not readily available.

NT-pro-BNP in patients with left ventricular hypertrabeculation/non-compaction.

AIMS: Left ventricular hypertrabeculation/non-compaction (LVHT) is a cardiac abnormality of unknown pathogenesis and frequently associated with neuromuscular disorders. The N-terminal fragment of the pro brain natriuretic peptide (NT-pro-BNP) is a prognostic marker in heart failure whose relevance in LVHT patients is largely unknown. The aim of the study was to assess the role of NT-pro-BNP levels as prognostic markers in LVHT. METHODS AND RESULTS: Data of LVHT patients were collected in a database from one echocardiographic laboratory since 1996. The hospital information system was screened for measurements of NT-pro-BNP levels, and their association with clinical and echocardiographic baseline parameters was retrospectively assessed. During follow-up, the endpoints were death and heart transplantation. In 113 patients (median age 57 years, 24% women), data about NT-pro-BNP measurements were found, ranging from 8 to 121 152 (median 2029) ng/L. High NT-pro-BNP levels were associated with heart failure, valvular abnormalities, diabetes mellitus, hypertension, angina pectoris, number of LVHT-affected segments, end-diastolic diameter, and systolic dysfunction. During a follow-up of 73 (±64; 0-237) months, 35% of the patients reached an endpoint. High NT-pro-BNP levels were associated with the occurrence of an endpoint (P < 0.001). By multivariate analysis, predictors for endpoints were increased age (P = 0.0025), atrial fibrillation (P = 0.0023), natural logarithm of NT-pro-BNP levels (P = 0.0073), diabetes mellitus (P = 0.014), and thromboembolic events before diagnosis (P = 0.0347). CONCLUSIONS: Also in LVHT patients, high NT-pro-BNP levels are indicators for death and heart transplantation.