Summary Background Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF). Infections with multidrug‐resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. Aim The aim of the study was to assess the influence of non‐antibiotic medication contributing to MDRO colonisation. Methods Three hundred twenty‐four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort ( n = 129) from Barcelona was included to validate. A third multi‐centre cohort ( n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. Results A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without ( p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%‐confidence interval (CI) 1.82–4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%‐CI 2.96–30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%‐CI 1.22–23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911–6.823, p = 0.075) and associated with risk of MDRO infection during follow‐up ( p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration ( p = 0.001). Conclusions Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non‐antibiotic co‐medications had negligible influence. Future prospective trials are needed to confirm these results.

Einleitung Patienten mit Leberzirrhose haben ein hohes Risiko bakterielle Infektionen zu entwickeln – ein häufiger Trigger für eine akute Dekompensation (AD) und die Entwicklung eines akut-auf-chronischen Leberversagens (ACLF). Infektionen mit multiresistenten Erregern (MRE) führen zu einer erhöhten Mortalität und finden sich häufig bei Patienten mit MRE-Kolonisation.

BACKGROUND & AIMS:In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS:In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS:Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS:This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

Background Left ventricular global longitudinal strain (LV-GLS) has been shown to better reflect the left cardiac contractility in cirrhosis than other investigations and might bear prognostic value. The aim of this study was to investigate the evolution of myocardial contractility assessed by speckle tracking echocardiography (STE) after transjugular intrahepatic portosystemic shunt (TIPS) placement and its prognostic value in outcome. Methods In this study, 206 (126 males) patients with liver cirrhosis receiving TIPS were included. In all study patients, conventional transthoracic echocardiography (TTE) was performed before and in the first weeks after TIPS placement to assess left and right ventricular volume, planar and functional parameters. Also, LV-GLS was measured by STE to assess left ventricular contractility as surrogate for myocardial dysfunction. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up. Results As expected, most conventional parameters of TTE showed a significant change after TIPS placement. However, neither the absolute values, nor the changes of conventional cardiac parameters of TTE before and after TIPS insertion were associated with survival. By contrast, an increase in contractility of more than 20% using STE after TIPS was an independent predictor of mortality. Conclusion These results demonstrate that an increase of left ventricular contractility of more than 20% after TIPS insertion is an independent predictor of survival and this may identify patients at risk and in need of closer follow-up care.

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.

Was ist neu? Leitliniengerechte Indikationen für den Einsatz von Humanalbumin bei Leberzirrhose Aktuelle Indikationen für eine Albumintherapie bei Patienten mit Leberzirrhose sind die Prävention einer Kreislauffunktionsstörung nach Parazentese, die Prävention des hepatorenalen Syndroms (HRS) bei Patienten mit spontaner bakterieller Peritonitis (SBP) sowie das Management des HRS in Kombination mit Vasokonstriktoren. Durch eine kurzzeitige Anwendung von Albumin bei dekompensierter Leberzirrhose soll dabei eine Verbesserung des effektiven Blutvolumens erreicht werden. Albumin als Plasmaexpander, Radikalfänger, Antioxidans und Immunmodulator Neue Daten belegen, dass Albumin sowohl den Kreislauf unterstützt als auch die systemische Inflammation senkt. Neben seiner onkotischen Funktion fungiert es als Antioxidans, Radikalfänger und Immunmodulator. Diese nicht onkotischen Eigenschaften erklären, warum eine Langzeit-Albumingabe bei Patienten mit dekompensierter Leberzirrhose möglicherweise Komplikationen vorbeugen kann und auch bei Nicht-SBP-Infektionen die ACLF-Rate (ACLF = akut-auf-chronisches Leberversagen) senkt. Effekte auf die Kreislauffunktion und systemische Inflammation In einer aktuellen Studie verbesserte eine 12-wöchige Albumingabe (1,5 g/kg KG/Woche) bei dekompensierter Leberzirrhose die Marker der systemischen Inflammation. Diese Effekte könnten auf die Endothelfunktion sowie die antiinflammatorischen Eigenschaften des Proteins auf die Aufnahme von Albumin durch die Endothel- bzw. Immunzellen zurückgeführt werden. Aktuelle Studien zur Langzeit-Albumintherapie Neue Daten zeigen, dass eine Langzeit-Albumintherapie bei Patienten mit Leberzirrhose und Aszites das Überleben verbessert, Komplikationen vorbeugt, das Management von Aszites vereinfacht und die Hospitalisierungsrate senkt. Die sogenannten Disease-modifying-Effekte einer Langzeit-Albumintherapie beeinflussen möglicherweise den Krankheitsverlauf günstig. Trotzdem sind die optimale Dosierung und Verabreichungsintervalle noch nicht endgültig definiert.