Prognostic impact of ICG-PDR in patients with hypoxic hepatitis

Background: Hepatic impairment is found in up to 20 % in critically ill patients. Hypoxic/ischemic hepatitis (HH) is a diffuse hepatic damage associated with high morbidity and mortality. Indocyanine green plasma disappearance rate (ICG-PDR) is an effective tool assessing liver function in acute and chronic hepatic diseases. Aim of this study was to evaluate the prognostic impact of ICG-PDR in comparison to established parameters for risk stratification. Methods: Patients with HH were included in this prospective observational study and compared to cirrhosis, acute liver failure (ALF) and patients without underlying liver disease. ICG-PDR, measured non-invasively by finger pulse densitometry, was assessed on admission and in patients with HH serially and results were compared between groups. Diagnostic test accuracy of ICG-PDR predicting 28-day mortality was analyzed by receiver operating characteristics (ROC). Results: ICG-PDR on admission was significantly lower in patients with liver diseases than in patients without hepatic impairment (median 5.7 %/min, IQR 3.8-7.9 vs. 20.7 %/min, IQR 14.1-25.4 %/min;p = 9.0 %/min 48 h after admission. Conclusions: ICG-PDR is an independent predictor of mortality in patients with liver disease. Diagnostic test accuracy of ICG-PDR was superior to standard liver function parameters and established scoring systems in patients with HH

Proof of infectivity of hepatitis E virus particles from the ejaculate of chronically infected patients

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36–67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100-fold higher compared to the serum, while in two patients, the viral load was more than 10-fold lower. However, it has remained unclear whether viral particles shed in the ejaculate were infectious, as a previous cell culture model had failed to demonstrate the infectivity. In the current study, we employed an optimized HEV cell culture system based on overconfluent PLC/PRF/5 cells to investigate the infectivity of HEV particles from ejaculate and other body fluids. With this approach, we were able to show for the first time that HEV particles in the ejaculate from several patients were infectious. HEV replicated to high viral loads of 1e9 HEV RNA copies per ml. This indicates that HEV-positive ejaculate could bear a risk of infection for sexual partners

Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation

Abstract Sarcopenia, the loss of muscle mass and quality, contributes to worse clinical outcome in patients with end-stage liver disease, but its impact on short- and long-term survival remains insufficiently understood. The aim of this study was to evaluate the development of computed tomography (CT) muscle parameters and their impact on short-term and long-term survival after liver transplantation. This retrospective study included patients with liver transplantation between 2011 and 2015 and a pre-transplant CT scan. Clinical characteristics, CT muscle mass and density were assessed pre-transplant, and in available CT scans at short-term (11 months) and long-term follow-up (56 months). Overall, 93/152 (61%) patients (109 male, 55 ± 10 years) suffered from sarcopenia pre-transplant. In short- (n = 50) and long-term follow-up (n = 52) the muscle mass (− 2.65 cm2/m2 95% CI [− 4.52, − 0.77], p = 0.007; − 2.96 cm2/m2 [− 4.7, − 1.23], p = 0.001, respectively), and muscle density (− 3 HU [− 6, − 1], p = 0.007; − 2 HU [− 4, 0], p = 0.069) decreased. Myosteatosis was associated with a higher post-transplant mortality (survival probability: 3 months 72% vs. 95%, 1 year 63% vs. 90%, 5 years 54% vs. 84%, p = 0.001), while muscle mass was not. In conclusion, muscle mass and quality did not improve after transplant. Muscle quality predicts short- and long-term survival and could help to identify a patient’s risk profile

The Clinical Perspective on Hepatitis E

Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible

Role of angiogenic factors/cell adhesion markers in serum of cirrhotic patients with hepatopulmonary syndrome

Background & Aims: Hepatopulmonary syndrome is a complication of chronic liver disease resulting in increased morbidity and mortality. It is caused by intrapulmonary vascular dilations and arteriovenous connections with devastating influence on gas exchange. The pathogenesis is not completely understood but evidence mounts for angiogenesis. Aims of this study were to identify angiogenic factors in serum of patients with hepatopulmonary syndrome and to study the possibility to predict its presence by these factors. Methods: Multiplex assays were used to measure the concentration of angiogenic factors in patients with (n=30) and without hepatopulmonary syndrome (n=30). Diagnosis was based on the presence of gas exchange abnormality and intrapulmonary vasodilations according to published guidelines. Results: Patients with and without hepatopulmonary syndrome had similar MELD scores (median: 11.2 vs. 11.6; P=0.7), Child-Pugh score (P=0.7) and PaCO2 values (median: 35 vs. 37; P=0.06). PaO2 and P(A-a) O-2 gradient were significantly different (respectively median of 80 vs. 86, P=0.02; and 24 vs. 16, P=0.004). Based on area under the curve (AUC) data and P-values, the best predictors were vascular cell adhesion molecule 1 (VCAM1) (AUC=0.932; P<0.001) and intercellular adhesion molecule 3 (ICAM3) (AUC=0.741; P=0.003). Combining these factors results in an AUC of 0.99 (after cross-validation still 0.99). Conclusions: VCAM1 and ICAM3 might be promising biomarkers for predicting hepatopulmonary syndrome. Combining these factors results in an AUC of 0.99 and a negative predictive value of 100%. Determining the concentration of these biomarkers might be a screening method to detect hepatopulmonary syndrome. The use of these biomarkers should be validated in larger groups of patients