BACKGROUND & AIMS:Baveno VII has proposed criteria for cirrhosis recompensation, but their prognostic significance in decompensated patients cured of hepatitis C virus (HCV) deserves further investigation. Thus, we studied the incidence and impact of recompensation after HCV cure as well as its predictors. METHODS:A total of 2570 patients with advanced chronic liver disease (ACLD) from 10 European centers were retrospectively included, including 2209 and 361 patients with compensated ACLD and decompensated cirrhosis who achieved sustained virologic response to direct-acting antivirals (DAAs). The association between achieving recompensation and clinical outcomes (hepatocellular carcinoma [HCC], portal vein thrombosis [PVT], and [liver-related] death) was investigated. RESULTS:During a median follow-up of 8.4 years from treatment initiation, 132 patients (36.6%) achieved recompensation. Lower albumin levels and diabetes were negatively associated with achieving recompensation. The incidence rates of liver-related death (4.2 vs 8.8 per 100 patient-years) and PVT (2.7 vs 5.4) were substantially lower after recompensation vs in the nonrecompensated state, while HCC incidence remained high (3.9 vs 5.5). Compared with decompensated cirrhosis, achieving recompensation was independently associated with decreased risks of subsequent liver-related death (adjusted hazard ratio, 0.384; 95% confidence interval, 0.225-0.655) and of PVT (adjusted hazard ratio, 0.421; 95% confidence interval, 0.224-0.759), but both risks remained higher than in compensated ACLD. Importantly, HCC incidence was not reduced as compared with decompensated cirrhosis. CONCLUSIONS:Recompensation after HCV cure is associated with substantially decreased risks of (liver-related) mortality and PVT, but not of HCC.

Background and Aims: Compensated advanced chronic liver disease (cACLD) identifies patients at risk for clinically significant portal hypertension (CSPH), and thus, for liver-related complications. The limited availability of liver stiffness measurements (LSM) impedes the identification of patients at risk for cACLD/CSPH outside of specialized clinics. We aimed to develop a blood-based algorithm to identify cACLD by fibrosis-4 (FIB-4) and CSPH by von Willebrand factor/platelet count ratio (VITRO). Approach and Results: Patients with (suspected) compensated chronic liver disease undergoing FIB-4+LSM were included in the LSM/FIB-4 cohorts from Vienna and Salzburg. The HVPG/VITRO cohorts included patients undergoing HVPG-measurement + VITRO from Vienna and Bern. LSM/FIB-4–derivation-cohort: We included 6143 patients, of whom 211 (3.4%) developed hepatic decompensation. In all, 1724 (28.1%) had LSM ≥ 10 kPa, which corresponded to FIB-4 ≥ 1.75. Importantly, both LSM (AUROC:0.897 [95% CI:0.865–0.929]) and FIB-4 (AUROC:0.914 [95% CI:0.885–0.944]) were similarly accurate in predicting hepatic decompensation within 3 years. FIB-4 ≥ 1.75 identified patients at risk for first hepatic decompensation (5 y-cumulative incidence:7.6%), while in those <1.75, the risk was negligible (0.3%). HVPG/VITRO–derivation cohort: 247 patients of whom 202 had cACLD/FIB-4 ≥ 1.75 were included. VITRO exhibited an excellent diagnostic performance for CSPH (AUROC:0.889 [95% CI:0.844–0.934]), similar to LSM (AUROC:0.856 [95% CI:0.801–0.910], p = 0.351) and the ANTICIPATE model (AUROC:0.910 [95% CI:0.869–0.952], p = 0.498). VITRO < 1.0/ ≥ 2.5 ruled-out (sensitivity:100.0%)/ruled-in (specificity:92.4%) CSPH. The diagnostic performance was comparable to the Baveno-VII criteria. LSM/FIB-4–derivation cohort findings were externally validated in n = 1560 patients, while HVPG/VITRO–derivation-cohort findings were internally (n = 133) and externally (n = 55) validated. Conclusions: Simple, broadly available laboratory tests (FIB-4/VITRO) facilitate cACLD detection and CSPH risk stratification in patients with (suspected) liver disease. This blood-based approach is applicable outside of specialized clinics and may promote early intervention.

Background & Aims The LiverRisk score has been proposed as blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM≥10kPa) and liver-related events in subjects without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care. Methods Subjects referred to two hepatology outpatient clinics (cohort-I: n=5897; cohort-II: n=1558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD compared to FIB-4/APRI. The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated. Results In cohort-I/II, mean age was 48.3/51.8years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/ metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 [5.1-10.9]/ 5.8 [4.5-8.8]kPa, and 1690 (28.7%)/ 322 (20.7%) had cACLD.Despite a moderate correlation (Pearson’s r: 0.325/0.422), the LiverRisk score systematically underestimated LSM (“bias”: 2.93/1.80points/kPa lower) and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (AUROC: 0.757/0.790) was comparable to FIB-4 (0.769/0.813) and APRI (0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9/93.4%), but low negative predictive value (76.6/84.5%, Cohen’s κ=0.260/0.327).In cohort-I, 208 (3.5%) developed hepatic decompensation (median follow-up: 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1-5 years (AUROC: 0.778-0.832). However, it was inferior to LSM (0.847-0.901, p<0.001) and FIB-4 (0.898-0.913, p<0.001). Similar to the strata of other NIT, proposed LiverRisk groups had distinct risks of hepatic decompensation. Conclusions The LiverRisk score did not improve diagnosis of cACLD or prediction of hepatic decompensation in tertiary care setting. IMPACT AND IMPLICATION The LiverRisk score has been proposed as non-invasive tool to estimate liver stiffness measurement and thus, the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question on its applicability outside of opportunistic screening in the general population arises.In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately predict liver stiffness, did not improve cACLD identification, and had a lower predictive performance for hepatic decompensation as compared to FIB-4.While being a major step forward for screening patients without known liver disease in primary care, our findings indicate that the LiverRisk score does not improve patient management outside the primary care setting, i.e., in cohorts with a higher pre-test probability of cACLD.

BACKGROUND & AIMS: Liver stiffness measurements (LSMs) provide an opportunity to monitor liver disease progression and regression noninvasively. We aimed to determine the prognostic relevance of LSM dynamics over time for liver-related events and death in patients with chronic liver disease. METHODS: Patients with chronic liver disease un-dergoing 2 or more reliable LSMs at least 180 days apart were included in this retrospective cohort study and stratified at baseline (BL) as nonadvanced chronic liver disease (non-ACLD, BL-LSM < 10 kPa), compensated ACLD (cACLD; BL-LSM > 10 kPa), and decompensated ACLD. Data on all consecutive LSMs and clinical outcomes were collected. RESULTS: There were 2508 patients with 8561 reliable LSMs (3 per patient; interquartile range, 2-4) included: 1647 (65.7%) with non-ACLD, 757 (30.2%) with cACLD, and 104 (4.1%) with decompensated ACLD. Seven non-ACLD patients (0.4%) and 83 patients with cACLD (10.9%) developed he-patic decompensation (median follow-up, 71 months). A 20% increase in LSM at any time was associated with an approx-imately 50% increased risk of hepatic decompensation (haz-ard ratio, 1.58; 95% CI, 1.41-1.79; P < .001) and liver-related death (hazard ratio, 1.45; 95% CI, 1.28-1.68; P < .001) in patients with cACLD. LSM dynamics yielded a high accuracy to predict hepatic decompensation in the following 12 months (area under the receiver operating characteristics curve 1/4 0.933). The performance of LSM dynamics was numerically better than dynamics in Fibrosis-4 score (0.873), Model for End-Stage Liver Disease (0.835), and single time-point LSM (BL-LSM: 0.846; second LSM: 0.880). Any LSM decrease to <20 kPa identified patients with cACLD with a substantially lower risk of hepatic decompensation (hazard ratio, 0.13; 95% CI, 0.07-0.24). If reliable, LSM also confers prognostic information in decompensated ACLD. CONCLUSIONS: Repeating LSM enables an individual and updated risk assessment for decompensation and liver-related mortality in ACLD.

Hintergrund Die Lebersteifigkeitsmessung (LSM) mittels transienter Elastographie wird zur Diagnose der kompensierten fortgeschrittenen Lebererkrankung (cACLD; Identifikation von Risikopatient_innen) und klinisch signifikanten portalen Hypertension (CSPH; Indikation zur Carvedilol-Therapie) empfohlen, jedoch ist die Verfügbarkeit auf spezialisierte Zentren begrenzt. Der Billroth-IV Konsensus schlägt als Alternative laborchemische Tests – FIB-4 für cACLD und von-Willebrand Faktor/Thrombozyten-Ratio (VITRO) für CSPH – vor.Ziel dieser Studie war es, einen laborbasierten und breit anwendbaren Algorithmus als Datengrundlage für die Billroth IV-Empfehlung zu etablieren.

Das Spektrum von dermatologischen Notfällen ist vielgestaltig. Häufige Gründe für die Vorstellung im dermatologischen Notdienst sind Infektionen, anaphylaktische Reaktionen und kutane Arzneimittelreaktionen. Bei Verdacht auf eine sexuell übertragbare Infektion ist es für den Arzt wichtig zu erkennen, bei welchen Krankheitsbildern eine sofortige Behandlung zur Vermeidung von Spätkomplikationen nötig ist. Dies setzt eine sichere Diagnose und Kenntnis der jeweiligen adäquaten Therapie voraus. Kutane Arzneimittelreaktionen können sich vielgestaltig darstellen. Es existiert ein Spektrum von unmittelbar nach Zuführung eines Medikaments auftretenden Reaktionen, die sich als Anaphylaxien äußern, bis hin zu solchen, die sich erst Wochen nach Therapiebeginn zeigen. Diese Reaktionen können dabei harmlos und selbstlimitierend sein, aber auch lebensbedrohlich verlaufen. Es ist daher für den klinischen Alltag essenziell, Arzneimittelunverträglichkeiten rechtzeitig zu erkennen und zu behandeln.

The spectrum of dermatological emergencies is diverse. Infections, in particular sexually transmitted infections, anaphylactic reactions, and cutaneous drug reactions are common causes for patients to present themselves to the dermatological emergency service. If a sexually transmitted infection is suspected, it is important for the physician to recognize which diseases need immediate treatment to avoid late complications. This requires a reliable diagnosis and knowledge of the appropriate therapy. Cutaneous drug reactions can take many forms. There is a spectrum of reactions that occur immediately after the administration of a medication (which manifest themselves as anaphylaxis), to those that can appear weeks after the initiation of a therapy. These reactions can be harmless and self-limiting, but also be life-threatening. It is essential for physicians in everyday clinical practice to recognize drug intolerances in time and to treat them appropriately.

Die Graft-versus-Host-Disease (GvHD) ist trotz Fortschritten in der Transplantationsmedizin weiterhin eine der Hauptursachen für Morbidität und Mortalität nach allogener Stammzelltransplantation. Wir berichten über einen Patienten mit chronischer GvHD der Haut, bei dem es nach Umstellung der Immunsuppression auf einen Mammalian-target-of-rapamycin (mTor)-Inhibitor zu ausgeprägten Ulzerationen der Haut kam.

Graft-versus-host-disease (GvHD) is despite improvement in transplantation medicine the major cause for morbidity and mortality after allogeneic stem cell transplantation. We describe a patient with chronic cutaneous GvHD who developed massive skin ulcerations after changing the immunosuppressive therapy to a mammalian target of rapamycin (mTOR)-inhibitor.