Hepatitis E virus infection in immunosuppressed patients and its clinical manifestations.

BACKGROUND & AIMS: Hepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections. METHODS: In this retrospective study at two large hospitals, 512 patients with borderline and positive anti-HEV-IgM and 94 patients with positive HEV-PCR between January 1999 and May 2023 were included. RESULTS: Detection by anti-HEV-IgM-ELISA led to a positive HEV-PCR in only 17.9 %. Amongst patients with positive HEV-PCR, 61 had underlying immunosuppression and 23 were patients after solid organ transplantation (SOT). All 13 patients with chronic HEV infections were immunosuppressed. Generally, immunosuppression led to higher HEV-RNA concentrations and a higher probability of receiving immediate treatment. However, all fulminant courses with liver failure happened in patients without immunosuppression. Immunocompetent patients showed symptoms more frequently and primarily had higher bilirubin levels indicating more severe liver damage. A risk factor for delayed or failed viral clearance after SOT was the administration of mTOR inhibitors. CONCLUSIONS: Fulminant HEV infections happen primarily in immunocompetent patients. Nevertheless, immunosuppressed patients bear the risk of undetected, prolonged HEV infections, reflected by the rare occurrence of symptoms.

Quantified coronary total plaque volume from computed tomography angiography provides superior 10-year risk stratification.

AIMS: Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atherosclerosis burden. The aim of this analysis was to investigate the long-term predictive value of TPV. METHODS AND RESULTS: TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0-11.4) of follow-up. The study endpoint comprised cardiac death and acute coronary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P = 0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13-0.68, P < 0.001) and resulted in reclassification of 800 (51%) patients compared with the Morise Score alone. The 10-year risk for the study endpoint was 0.6% (95% CI 0-1.3) for patients classified as low risk (n = 807), 4.8% (95% CI 2.4-7.2) for patients at intermediate risk (n = 400), and 10.3% (95% CI 6.6-13.9) for patients at high risk (n = 370) using the combined reclassification approach. CONCLUSION: Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification.

Impact of diabetes on coronary artery plaque volume by coronary CT angiography and subsequent adverse cardiac events.

BACKGROUND: To investigate the impact of diabetes on coronary artery total plaque volume (TPV) and adverse events in long-term follow-up. METHODS: One-hundred-and-eight diabetic patients were matched to 324 non-diabetic patients, with respect to age, sex, body-mass index, hypertension, smoking habits, LDL and HDL cholesterol, family history for CAD as well as aspirin and statin medication. In all patients, TPV was quantified from coronary CT angiographies (CTA) using dedicated software. All-cause mortality, acute coronary syndrome and late revascularisation (>90 days) served as combined endpoint. RESULTS: Patients were followed for 5.6 years. The endpoint occurred in 18 (16.7%) diabetic and 26 (8.0%) non-diabetic patients (odds ratio 2.3, p = 0.03). Diabetic patients had significantly higher TPV than non-diabetic patients (55.1 mm³ [IQR: 6.2 and 220.4 mm³] vs. 24.9 mm³ [IQR: 0 and 166.7 mm³], p = 0.02). A TPV threshold of 110.5 mm³ provided good separation of diabetic and non-diabetic patients at higher and lower risk for adverse events. Noteworthy, diabetic and non-diabetic patients with a TPV<110.5 mm³ had comparable outcome (hazard ratio: 1.3, p = 0.59), while diabetic patients with TPV>110.5 mm³ had significantly higher incidence of adverse events (hazard ratio 2.3, p = 0.03) compared to non-diabetic patients with TPV>110.5 mm³. There was incremental prognostic value in diabetic and non-diabetic patients over the Framingham Risk Score (Integrated Discrimination Improvement: 0.052 and 0.012, p for both <0.05). CONCLUSION: Diabetes is associated with significantly higher TPV, which is independent of other CAD risk factors. Quantification of TPV improves the identification of diabetic patients at higher risk for future adverse events.