News 2019 - Workgroup For The Liver

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2019/12/07

!!!CONGRATULATIONS!!! Elisabeth Blüther and Erika Valle successfully defended her doctoral theses.
We thank both medical doctors for their contribution to better unserstand the clinical importance of dynamic liver function assessment by the LiMAx test in liver transplant patients and patients with short bowel syndrome.

MANUSCRIPT ACCEPTED: The article entitled "Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis" by Tilo Wuensch et al. will be published in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

The dynamic Liver MAximum capacity (LiMAx) test reflects the overall functional capacity of the liver. The test measures the CYP1A2-dependent metabolism of an i.v. injected 13C-Methacetin bolus, which is reflected by an altered 13CO2/12CO2 ratio in the exhaled breath. The test had been shown to be highly reliable for preoperative risk assessment in liver surgery. In patients with a critical low liver function, a preoperative volume-function analysis is indicated, by projecting functional properties on a 3D liver volume reconstruction to obtain the most precise future liver remnant function. To date, it is assumed that any hepatocellular tumor lesion contains zero CYP1A2 activity and does thus not contribute to the LiMAx test outcome. In this publication, we investigated for the first time, to which extend tumor lesions harbor functional CYP1A2. We followed a translational approach of in vitro analysis of human tissue samples and the translation of the results to the clinical application by an improved volume-function analysis algorithm.
As one of the main findings, we describe for the first time that hepatocellular adenomas contain remaining CYP1A2 activities, while hepatocellular carcinomas or colorectal liver metatstasis contain infinitely small quantities of remaining CYP1A2 activity. The CYP1A2 activity levels were also reflected on protein abundance, as indicated by immunofluorescence stainings (see Figure below).

Figure. Decreased CYP1A2 immunofluorescence signal in diseased liver tissues.

Figure 2. Decreased CYP1A2 immunofluorescence signal in diseased liver tissues. Representative CYP1A2 (red) and GLUL (green) IF and H&E stainings in control (left panel), hepatocellular adenoma (HCA, middle panel) and hepatocellular carcinoma (HCC, right panel) tissues. While CYP1A2 imunoreactivity was found pericentrally, as indicated by the GLUL co-staining, in control and HCA tissues, GLUL or CYP1A2 signals were absent in HCC tissues. DAPI (blue) was used as nuclear counterstain. Scale bar = 500 µm.

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MANUSCRIPT ACCEPTED: The article entitled "Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long-Term Parenteral Nutrition Using the SF-36 Questionnaire: A German Single-Center Prospective Observational Study" by Elisabeth Blüthner et al. will be published in the Journal of Parenteral and Enteral Nutrition.
The study deals with "Parenteral nutrition (PN) as a life-sustaining therapy for patients with chronic intestinal failure (IF) [...] and "its impact on on patients' quality of life (QoL)". QoL was found to be associated with "oral intake, presence of ostomy, and citrulline levels". It is concluded that "clinical care should focus on addressing the social and emotional value of oral intake, educational interventions, early stoma closure, and application of new targeted therapies".

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Figure. Representative H&E staining, LiMAx and the corresponding THE for a representative case of liver cirrhosis. The LiMAx breath test curves show the 13C-delta-over-baseline (DOB) values (up right). Lower panel: THE with B-Mode image (left) and corresponding elastogram (right) with a threshold of 1.3 m/s and the region of interest (ROI) surrounded by a white circle.

MANUSCRIPT ACCEPTED: The article entitled "Non-invasive structure-function assessment of the liver by 2D time-harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test." by Niklas Heucke, Tilo Wuensch et al. will be published in the Journal of Gastroenterology and Hepatology.
The aim of this study was to delineate the structure‐function relationship in the progression of chronic liver disease by combined assessment of liver function by the Liver MAximum capacity (LiMAx) test and tissue‐structure related stiffness by 2D time‐harmonic elastography (THE). LiMAx values correlated negatively with liver stiffness (r = ‐0.747), while liver stiddness increases progressively with the stage of liver fibrosis. Our findings show that structural changes in the liver, reflected by increased tissue stiffness correlates with a decreased metabolic capacity of the liver.

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MANUSCRIPT ACCEPTED: The article entitled "Identification of serological markers for pre- and postoperative fasting periods." by Tilo Wuensch et al. will be published in Clinical Nutrition ESPEN.
In this pilot study, we identified pre- and postoperative metabolic markers of patients undergoing elective surgery of the upper or lower gastrointestinal tract. Our data provide the first description of reliable fasting biomarkers, suitable to identify patients in prolonged fasting conditions - and thus catabolic states. Applying our findings in clinical practice will be beneficial for targeted nutrition support to alleviate catabolic states, especially as the recommendations on pre- and postoperative fasting periods are often not achieved in clinical practice. This is of particular importance for an optimzed postoperative recovery. It could further be applied to patients of other disciplines in order identify prolonged fasting periods and to counteract mal- and undernutrition.
Preoperative fasting times were positively correlated with plasma levels of valine, leucine, serine, α-amino butyric acid, free fatty acids, 3-hydroxy butyric acid and significantly negative correlated with chloride and glutamic acid. Postoperative fasting times were correlated with erythrocytes, leukocytes and plasma levels of albumin, CRP, HDL, asparagine and 3-methylhistidine. The multivariate regression analysis revealed glutamic acid and valine as significant independent predictors of preoperative fasting periods. The regression model showed best performance (sensitivity of 90.91% and specificity of 92.31%) to detect patients fasted for ≥20h.

Figure 2. Correlations between preoperative fasting time and plasma levels of glutamic acid and valine. (A) Glutamic acid (filled circles) correlated negatively (r=-0.45, p=0.031) and valine positively (r=0.463, p=0.023) with fasting time. (B) The final regression model for predictive calculation of fasting times, including plasma levels of glutamic acid and valine (concentration in µmol/L).