Because of the high prevalence of NAFLD and the mentioned drawbacks of liver biopsy, much eﬀort is being expended on developing noninvasive diagnostic tools. NAFLD can be detected by magnetic resonance imaging and magnetic resonance spectroscopy . However, the availability is limited, expertise in protocol prescription is needed, and presence of metal implants or claustrophobia has to be considered . Transient elastography or other ultrasound-based tests are more accessible and cheaper, but application can be limited in extremely obese patients . Conventional biochemical parameters are easily obtained, but their sensitivity and speciﬁcity to detect NAFLD are low . In the present study, almost all patients had AST and ALT values within the normal range. Several other biochemical markers, such as IL-6, CRP, ferritin, and cyto- keratin-18, have been proposed as useful predictors of NAFLD/NASH in the past, but none of them have shown suﬃcient sensitivity and speciﬁcity in clinical routine . Campos et al. developed a clinical scoring system for predict- ing NASH in morbidly obese patients . In our cohort, liverfunction capacity is correlated to the NASH clinical scoring system. We decided to use this scoring system as it is based on data from obese patients who underwent bariatric surgery. Furthermore, the parameters for the NASH clinical scoring system can easily be obtained in standard evaluation of obese patients in a bariatric center. However, this clinical scoring system is not established in clinical routine, and ethnicity plays a minor role in a regular German bariatric surgery cohort.
non-obese patients. Weight (r = 0.40), body surface area (r = 0.32), estimated body-fat% (r = 0.43) and body mass index
(r = 0.47) showed a weak but signi ﬁcant negative (all P < 0.05) correlation with liverfunction. Moreover, body-fat% was iden-
ti ﬁed as an independent factor negatively affecting the liverfunction.
Conclusion Sarcopenia and sarcopenic obesity did not seem to in ﬂuence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liverfunction and volume in these patients. Keywords Sarcopenia; Obesity; L3 skeletal muscle index; Body fat percentage; Liverfunction; LiMAx; Volumetry
With respect to the results of this investigation, it may be argued that clinical studies have already demonstrated a good correlation between the PDR ICG and ICG clearance [ 8 – 10 ]. However, it needs to be acknowledged that in all of these studies, a great variety of underlying critical conditions was included, and the number of patients with septic shock is unknown. Furthermore, although a general correlation was acceptable, the individual values of PDR ICG showed a broad range of corresponding ICG blood clearances [ 3 ]. This indicates that the measurement of the liverfunction by means of the PDR ICG may not always accurately reflect the underlying ICG blood clearances. Regarding the data presented here, this may be especially true for hyperdynamic conditions. Thus, the determination of the liverfunction in septic shock needs to be reviewed cautiously.
Die Leber ist ein unpaares Organ, das neben der Synthese von Proteinen und Gerinnungsfaktoren maßgeblich an der Entgiftung beziehungsweise der Umsetzung und Exkretion von Metaboliten im Körper beteiligt ist . Die Leber zählt zu den wichtigsten Stoffwechselorganen des Körpers. Ihre vielseitigen Aufgaben machen es schwierig, eine Aussage über ihre globale Funktion zu treffen . Gleichzeitig bietet diese Vielseitigkeit aber auch verschiedene Ansätze, die man sich zu Nutze machen kann, um ihre Funktion zu untersuchen. In neuerer Zeit wird zwischen statischen und dynamischen Leberfunktionstests unterschieden . Mit statischen Parametern (Biomarkern im Blut) können Parenchymschäden (Alanin Aminotransferase, ALT und Aspartat Aminotransferase, AST), die exkretorische Funktion (Gesamt-Bilirubin) und die Syntheseleistung (International Normalised Ratio, INR) untersucht werden . Dynamische Parameter wie die Maximal LiverFunction Capacity (LiMAx Test) und die Indocyaningrün-Plasma-Verschwinde-Rate (ICG-PDR) geben Auskunft über die metabolische Kapazität (LiMAx) und über den Transport und die Exkretionskapazität (ICG-PDR) der Leber [2, 4].
Hintergrund: Die schwere Sepsis und der septische Schock zählen zu den häufigsten Todesursachen auf der Intensivstation mit Mortalitätsraten bis zu 54%. Bei ca. 50% dieser kritisch kranken Patienten zeigt sich eine Leberdysfunktion, die mit einer erhöhten Mortalität und Morbidität verbunden ist. Die Diagnostik der Leberdysfunktion in der Sepsis zeigt dennoch zahlreiche Lücken. Statische Leberfunktionstests können zwar eine Aussage über die Syntheseleistung, die Transportfunktion sowie die Zellschädigung der Leber treffen, jedoch kann kein bisher standardmäßig eingesetzter statischer Leberfunktionstests das gesamte Ausmaß des Leberschadens einschätzen oder gar eine valide Prognose bezüglich der Mortalität abgeben. Das Ziel dieser Arbeit war es, den Maximal LiverFunction Capacity Test (LiMAx-Test), einen neuen dynamischen Leberfunktionstest, in der Diagnostik der Leberinsuffizienz bei Sepsis zu evaluieren und im Vergleich mit der Indocyaningrün-Plasmadilutionsrate (ICG-PDR) und statischen Leberfunktionstests prospektiv zu untersuchen.
air or thrombus embolization [36–38]. This hemodynamic instability in ECMO patients may explain the pro- nounced impact of bilirubin and alkaline phosphatase on clinical outcome. Although, in agreement with the current literature , hypoxic hepatitis was found to be strongly associated with mortality in the present study population, no association of preoperative liverfunction parameters with the occurrence of hypoxic hepatitis could be shown. In addition to these param- eters, low albumin plasma levels, which indicate an impairment of synthetic liverfunction, were found to be associated with poor long-term survival. This find- ing is in line with previous data identifying albumin levels as predictive of mortality in critically ill patients . Albumin reflects the burden of noncardiac co- morbidities, as it is reduced in patients with diabetes mellitus, chronic kidney disease, and severe chronic obstructive pulmonary disease . This association may explain the association with long-term but not short-term mortality.
In this article, we will focus on hepatobiliary con- trast agents, and, in particular, gadoxetic acid (Gd-EOB- DTPA), also commercially available under the brand name Primovist® in the EU or Eovist® in the US. The multiparametric ability of gadoxetic acid-enhanced MR imaging provides morphologic and functional informa- tion about the hepatobiliary system, simultaneously. Mul- tiparametric MRI is a comprehensive MRI that includes T1-, T2-weighted, and proton density fat fraction (PDFF) images, as well as magnetic resonance cholangiopancra- ticography (MRCP), diffusion-weighted imaging (DWI), and contrast-enhanced dynamic imaging, with a 20-min hepatobiliary phase and, eventually, additional MR elas- tography (MRE) depending on the radiologic center. The compilation of all these signal characteristics enables the determination of the composition and properties of focal or diffuse liver pathologies [ 6 ]. As a gadolinium-based paramagnetic MR contrast agent with dual elimination, approximately 50% of gadoxetic acid is excreted by the kidneys through glomerular filtration, while the other 50% is taken up by functional hepatocytes and excreted into the biliary system [ 7 , 8 ]. After intravenous injection, GA is dispersed into the intra- and extravascular compartments during the arterial and portal venous phases, similar to conventional gadolinium chelates. But, subsequently, it is actively taken up by the hepatocytes during the transitional (3–5 min) and hepatobiliary phases (HBPs), 20 min after injection. Therefore, GA-enhanced MRI allows the syn- chronous evaluation of the hepatic vessels, biliary tree, and focal liver lesions [ 9 – 13 ] in addition to regional and total excretory liverfunction [ 14 ].
Liver resection remains the best treatment for primary and sec- ondary liver tumors, if they can be resected completely with negative margins. The major limitation for extended hepatectomy is the lack of adequate and functioning future remnant liver. Diﬀerent techniques and strategies have therefore been introduced in order to resect liver tumors despite small size of the liver remnant, e.g. portal vein ligation, portal vein embolization and ALPPS [5,11] . The amount of remnant liver after resection is known to be an important prognostic factor de- termining recovery following an extended hepatectomy. Preoperative evaluation of liverfunction is also essential, but di ﬃcult to determine accurately due to the wide variety of complex functions, including protein synthesis as well as metabolic, immune and storage functions. So far, liverfunction after portal vein embolization was assessed by conventional laboratory tests (albumin, ALT, AST, AP, bilirubin, γGT, serum glucose), Child-Pugh score, indocyanine green test (ICG)  , 99mTc-galactosyl human serum albumin scintigraphy SPECT  or Gd-EOB-MRI  . Malinowski and co-workers measured liverfunction in patients after PVE with the LiMAx test  . This liverfunction test is based on hepatic 13 C-methacetin metabolism and has already been used to determine liverfunction in liver resection  , liver transplantation  , sepsis  , liver cirrhosis  and non-alcoholic steatohepatitis  . For our patients with PHLF, mean calculated postoperative liverfunction capacity was 67 μg/kg/h, which was signiﬁcantly lower than in patients without PHLF (109 μg/kg/h). This is in line with an
The activity of the GDH enzyme was measured colorimetrically using a commercially available kit according to the manufacturer’s instructions (Abcam, Cambridge, UK). GDH catalyzes the deamination of glutamate into ammonia and alpha ketoglutarate. During this reaction NADP is converted to NADPH + leading to color development. The intensity of the color was measured using a micro plate reader at 450nm wavelength. Plasma samples were measured directly. However, liver tissue samples (20 mg) were firstly homogenized in the GDH assay buffer centrifuged at 13000 rpm for 10min at 4 °C and the clear supernatant was used for the assay. To avoid the false positive results a blank sample in which glutamate was omitted was used. Both the sample and the blank
In summary, APRI ? ALBI allows estimation of chemotherapy-associated liver damage over time. This represents a unique property because to date no noninva- sive tool exists to monitor liver damage after neoadjuvant chemotherapy. Furthermore, the findings showed that APRI ? ALBI dynamically monitors liver damage because it declined within the chemotherapy-free interval before the operation, presumably reflecting gradual liverfunction recovery. In addition, given the association with postoperative outcome, APRI ? ALBI can be used to identify patients experiencing clinically relevant
Postoperative LD was evaluated based on the previously proposed criteria by Balzan et al [ 25 ]. The so-called “50–50 criteria” identify patients with a prothrombin time (PT) < 50% and a serum bilirubin (SB) level > 50 µmol/l corresponding to an SB concentration > 2.9 mg/dl. Balzan et al. were able to demonstrate that patients with an SB value > 50 µmol/l and a PT < 50% on POD 5 had a significant increase of postoperative mortality. Furthermore, in patients with significant morbidity this “50–50 criterium” was met 3 to 8 days before clinical evidence of complications. We thus recorded the respective liverfunction parameters during the first postoperative week. As the focus of this study was to detect delayed hepatic regeneration and not only complete liver failure, an SB concentration > 2.9 mg/dl and a PT value < 50% on any day within the first postoperative week were defined as postopera- tive LD.
The socioeconomic and medical improvements of the last decades have led to a rel- evant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vascula- ture, relatively little is known about liverfunction and hepatic microcirculatory sta- tus in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcircula- tory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human liv- ers. Our results demonstrate that healthy aging is associated with hepatic and sinu- soidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typi- cal molecular changes in the cells of the hepatic sinusoid and deterioration in hepa- tocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macro- phages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study
The mildest form of ALD is hepatic steatosis (fatty liver) which may already develop after several days of alcohol use. Although this state is fully reversible with abstinence, it is a predisposition to develop ASH, fibrosis, and finally cirrhosis when continuing drinking . Similarly to NAFLD, symptoms of alcohol-induced fatty liver are very un- specific and consist of vague right upper quadrant abdominal pain, fatigue, and malaise. Frequently, clinical symptoms are not even noticed by the patient and laboratory abnor- malities are the initial finding. The diagnosis of ALD and especially the differentiation to NAFLD can only be done by combining clinical features of liver disease, a history of alcohol abuse, and corresponding laboratory findings . While in hepatic steatosis blood tests may still be normal, in ASH there characteristically is a pronounced elevation of primarily AST between twice the upper limit and 300 U/L (Figure 1.2). The aspar- tate aminotransferase/alanine aminotransferase (AST/ALT) ratio (also known as ”De Ritis ratio”) is usually greater than 2, whereas the sensitivity and specificity for diagnos- ing ASH is rather low [32, 33]. Clinically, ASH is characterized primarily by a sudden onset of jaundice. This may be accompanied by fever, ascites, proximal muscle loss, en- cephalopathy, as well as by an enlarged and tender liver. The liverfunction is typically impaired represented as reduced prothrombin time and elevated total serum bilirubin. Furthermore, peripheral white blood-cells and neutrophil count are often elevated .
including all main tumor entities of the liver [ 31 – 34 ]. Hence, we conducted a study with the aim to elucidate the influence of IP-5HT on the oncological outcome of patients undergoing liver resection [ 35 ]. Strikingly, patients with high preoperative levels of IP-5HT were found to suffer more frequently from early tumor re- currence within 1 year postoperatively. This study put a huge caveat on platelet-based therapy. The initially considered pharmacological manipulation might in- duce adverse effects and a potential intervention has to be investigated with caution. Likewise, not only 5HT, but also other platelet-contained factors were shown to interact with malignant cells and metasta- sis [ 36 ]. Further, these data question the beneficial effect of a proliferation-based approach for improve- ment of postoperative liver regeneration, as induction of proliferation in hepatocytes most likely also induces proliferation in remaining micro-metastases and cir- culating tumor cells.
We performed a retrospective cohort analysis of all adult patients (>18 years old) who underwent primary LT for chronic liver disease between 1 January 2002 and 31 December 2016 using the European Liver Transplant Registry (ELTR) database. A study request was reviewed and approved by the ELTR data committee. The ELTR prospectively collects LT data from 174 centres in 33 countries and ensures data quality and validity by annual audit and cross checking with key European organ sharing organisations as previously described. 12–14
Important mechanisms for the reversibility of liver fibrosis are the cessation of chronic damage (allowing hepatocyte recovery and modulating the microenvironment), shifting the balance from inflammation to resolution (leading to phenotypic adjustments of the immune cells, especially induction of restorative macrophages), deactivation of myofibroblasts (by senescence, apoptosis and inactivation) and, finally, matrix degradation (reflected by an altered balance between matrix stabilizing and matrix degrading factors).
Patients with borderline resectable metastases were included into a multicenter, prospective noninterven- tional study [ 2 ]. Patients received first line chemother- apy (mostly FOLFOX or FOLFIRI) in combination with bevacizumab, a humanized monoclonal anti- body targeting VEGF. A total number of 218 patients were included with 205 evaluable for outcome anal- ysis. The primary objective was the rate of patients without detectable metastatic disease (no evidence of disease; NED) with or without secondary resec- tion. Overall, 86% of patients had liver-only disease, and 104 patients (51%) were resected after first-line chemotherapy. NED was achieved in 92 patients (48%; 88 with surgery and 4 with chemotherapy alone). Progression-free survival (PFS) was 15.7 months in patients with NED as compared to 11.5 months in patients without; OS at 36 months was 77% and 52%, respectively. Therefore, this real-life study suggests that chemotherapy plus bevacizumab is an effective and well-tolerated treatment option in patients with borderline resectable CLM.
Discussion. The introduction of a new LT program requires maximum safety measures for all of the parties involved. Both surgical
and anaesthesiological management (reperfusion) can be controlled very reliably using a VVP bypass device. Particularly when using marginal grafts, this approach helps to minimise both surgical and anaesthesiological complications in terms of less volume overload, less use of vasopressive drugs, less myocardial injury, and better peripheral blood circulation. Conclusion. Based on our experiences while establishing a new liver transplantation program, we advocate the reappraisal of the extracorporeal VVP bypass.