Literature Service

We are pleased to present our LiMAx literature service. Each quarter, we select one or more publications from international journals, which may be of interest to you regarding our unique LiMAx method.


E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy

Primavesi et al., 2023, BJS, 110, 1331-1347. doi: 10.1093/bjs/znad233 – Although hepatic surgeries became safer over the last decades, posthepatectomy liver failures (PHLF) are still one of the most frequent reasons for morbidity after hepatic surgeries. Especially as the treatment options of PHLF are very limited, preoperative liver function assessments are crucial to identify patients with increased risk for PHLF. As to date, no consensus recommendations related to the optimal tool for preoperative PHLF risks assessment exist, the aim of this work was to develop an European guideline for preoperative patient assessment for different clinical settings.  

The guideline was developed for four main topics (a: indication and timing of assessments; b: static blood markers; c: functional and morphological imaging; d: functional and morphological non-imaging) by means of systematic reviews and expert opinions.   

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Functional hepatic deterioration determined by 13C-methacetin breath test is associated with impaired hemodynamics and late Fontan failure in adults

Schleiger et al., 2022. Front. Cardiovasc. Med. 9:952080. doi: 10.3389/fcvm.2022.952080 – Fontan-associated liver disease is the most frequent end-organ dysfunction, and its treatment is characterized by abnormal hemodynamics. Although a significant increase in adult Fontan patients experiencing hemodynamic compromise and cardiac arrest can be expected in the next decade, the indications and optimal timing of cardiac transplantation in Fontan patients are still under debate. In addition, although liver-associated morbidity and mortality impact survival after cardiac transplantation in the Fontan population, the potential impact of late Fontan failure and hemodynamics on metabolic liver function is still unknown. Hence, the aim of this cross-sectional study was to analyze the associations between the maximum liver capacity and the Fontan hemodynamics and failure.  

The Liver Maximum Capacity Test (LiMAx) Is Associated with Short-Term Survival in Patients with Early Stage HCC Undergoing Transarterial Treatment

Fischer et al., 2022. Cancers (Basel), 14 (21):5323, DOI: 10.3390/cancers14215323 – Hepatocellular cancer (HCC) is the sixth most frequent cancer and the third leading cause of cancer-related deaths worldwide. Although treatment strategies such as transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) can help control tumor growth and bridge the time to liver transplantation, individual treatment response largely depends on individual factors like liver function. Subsequently, as outcome prediction is a large medical need in the context of personalized medicine, several algorithms considering parameters such as serum bilirubin levels, Child-Turcotte-Pugh (CTP) stages, model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) have been developed in the past. Nevertheless, as these algorithms depend on laboratory parameters and the subjective estimation of clinical symptoms, the aim of this study was to determine the correlation of a direct liver function measurement (LiMAx test) with short-term survival in patients with early and intermediate stage HCC after TACE and TARE.  

Liver Function – How to Screen and Diagnose: Insights from Personal Experiences, Controlled Clinical Studies and Future Perspectives

M. Buechter and G. Gerken, J. Pers. Med. 2022, Oct 5; 12(10):1657, doi: 10.3390/jpm12101657 – Acute and chronic liver diseases are major causes of morbidity and mortality worldwide. Hence, it is clear why the screening, prognosis and treatment of liver diseases was steadily enhanced during the last decades. While the screening of liver diseases was very rudimentary in the past, nowadays a variety of methods enables a better differentiation of the specific stages of a disease,  increased treatment outcome prediction as well as a personalized decision-making process (i.e. individualized instead of generalized medicine).  

¹³C-methacetin breath test predicts survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Gairing et al., 2022. Clin Transl Gastroenterol. 2022, Sep 22. doi: 10.14309/ctg.0000000000000529 – Hepatocellular cancer (HCC) – a tumor ranked third in regards of mortality among all malignant tumors worldwide - is the most common primary cancer. As the global incidence of HCC is expected to rise due to the global increase of nonalcoholic fatty liver disease (NAFD), HCC treatments receive enhanced clinical interest. Currently, the transarterial chemoembolization (TACE) is the standard-of-care treatment of intermediate-stage HCC. Unfortunately, although this procedure was designed to minimize the  harm for healthy liver tissue, TACE can reduce residual liver function in patients with HCC.


Performance of the LiMAx test, fibrinogen, and transient elastography inpatients with acute liver injury

Kreimeyer et al., 2022. Dig Dis. 2022 Feb 22. doi: 10.1159/000523696 – Acute liver failure (ALF) is a rare, sudden and extensive loss of liver function in individuals without prior liver injuries. Although specific therapies can result in full recovery of liver function in many patients, in some advanced cases of ALF a liver transplantation is required. Unfortunately, while some prognostic tools had been developed and used in clinical practice, their predicting accuracy on the benefit of liver transplantation after an ALF is very low. Hence, the aim of this study was to determine the prognostic potential of the LiMAx test, as well as its associations with transient elastography results and serum concentrations of specific coagulation factors in patients with non-acetaminophen-induced ALF and individuals with acute hepatitis without ALF.


Liver function, quantified by the LiMAx test, as a predictor for the clinical outcome of critically ill patients treated with linezolid

Alraish et al., 2022. Technology and Health Care 30 (2022) 309–321. DOI: 10.3233/THC-191847 – As bacterial infections can lead to severe health problems and high mortality rates, especially in intensive care units, it is
necessity to find the optimal antimicrobial therapies with an appropriate dosage regime. One common solution for
bacterial infections are oxazolidinone antibiotics such as linezolid. Although the clinical success of linezolid has been
shown in less severely ill patients, there is a high percentage of treatment failure in ICU patients for this treatment option. 

Prediction of Transarterial Chemoembolization (TACE) - Outcome by pre- and postinterventional 13C-Methacetin breath test

Senk et al., 2021. Clinical Hemorheology and Microcirculation, 79 (2021):73-80, DOI:10.3233/CH·219118 – Hepatocellular cancer (HCC) is the most common primary cancer and the most common cause of cancer-related mortality worldwide. Although the transarterial chemoembolization (TACE) is seen as first-line therapy in patients with intermediate-state HCC, the treatment of HCC heavily depends on tumor stage, general patient status and liver function. 

Enzymatic liver function measured by LiMAx is superior to current standard methods in predicting transplant-free survival after TIPS implantation

Rashidi-Alavijeh et al., 2021. Scientific Reports, 11(1):13824, DOI: 10.1038/s41598-021-93392-5 – Among patients with liver cirrhosis, portal hypertension (PH) is one of the main reasons for morbidity and mortality. In addition, with the occurrence of ascites and/or variceal bleeding (decompensated portal hypertension - DPH), mortality is rising.

Comparison of Liver Recovery After Sleeve Gastrectomy and Roux-en-Y-Gastric Bypass

Schmitz et al., 2021. Obesity Surgery, 31:3218–3226, DOI: 10.1007/s11695-021-05390-1 – Nonalcoholic fatty liver disease (NAFLD) – a progressive condition with an estimated prevalence of 25% worldwide – is closely linked to obesity and the likelihood of NAFLD progression to nonalcoholic steatohepatitis (NASH) and cirrhosis can be reduced by body weight loss.

Volume–Function Analysis (LiMAx Test) in Patients with HCC and Cirrhosis Undergoing TACE – A Feasibility Study

Reichert et al., 2020. Digestive Diseases and Sciences, DOI: 10.1007/s10620-020-06535-5 – Hepatocellular carcinoma (HCC) - the third most common cause for cancer-dependent death - ranges among the most frequent tumors worldwide. Its incidence differs between geographical regions and significantly increased within the last decade.

Evaluation of NAFLD and fibrosis in obese patients – a comparison of histological and clinical scoring systems

Schmitz et al., 2020. BMC Gastroenterology 20:254 –Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) are frequent in obese patients and are the most common cause of chronic liver diseases in certain countries (e.g. United States of America). They can lead to cirrhosis and hepatocellular carcinoma and a high amount of people undergoing bariatric surgery suffer from these diseases.

Validation of a new prognostic model to predict short and medium-term survival in patients with liver cirrhosis

Dziozio et al., 2020. BMC Gastroenterology 20:265 – Mathematical models or scores for classification of diseases, as well as disease or patient prognosis, are common in clinical environments. In patients with liver cirrhosis, Child-Pugh-Scores (CPS) as well as the model for end-stage liver disease (MELD) score are used to objectify and grade the risk of liver-related deaths.

Pharmacokinetics of tigecycline in critically ill patients with liver failure defined by maximal liver function capacity test (LiMAx)

Alraish et al., 2020. Annal. Intensive Care 10:106 – Tigecycline (TGC), often considered as last resort option for difficult-to-treat infections, is an important therapeutic option against multiresistant Gram-positive and Gram-negative bacteria. Its efficient application in critically ill patients is quite complex and challenging due to altered pathophysiology in this cohort. 

The new LiMAx® measuring device – Liver function measurements have never been so easy!

The LiMAx® test is the only known and clinically validated real-time test to determine a patient’s liver function by analysing his/her breathing air. The test has already been described in more than 70 scientific publications, some of them highly renowned, and has found its way into everyday clinical practice. 

Future liver remnant function as a predictor of postoperative morbidity following liver resection for hepatocellular carcinoma – a risk factor analysis

Bluethner at al., Surgical Oncology, June 2020 – Liver resection is the method of choice for patients with resectable, hepatocellular carcinoma (HCC). Advances in surgical techniques and perioperative patient management have led to a markedly reduced mortality and also allow patients with underlying chronic liver disease to undergo surgery.

Preoperative Liver Function Guiding HCC Resection in Normal and Cirrhotic Liver

Anger et al., Visceral Medicine, June 2020 – Liver resection is the method of choice for patients with hepatocellular carcinoma (HCC); a recent meta-analysis could even show similar 5-year survival times compared to transplantation. However, postoperative liver failure is still one of the main causes of postoperative mortality, especially in the case of accompanying liver cirrhosis.

Assessing Non-Invasive Liver Function in Patients with Intestinal Failure Receiving Total Parenteral Nutrition – Results from the Prospective PNLiver Trial

Bluethner et al., Nutrients, April 2020 – Intestinal failure is a malobsorptive disorder resulting from the physical loss of bowel mass or function. Although curative treatments like transplantation or glucagon analogues do exist, parenteral nutrition is the main therapy for the majority of patients. 

Mini Health Technology Assessment – LiMAx System for Assessing the Liver Function

Competence Center for Medical Devices GmbH, Sept. 2019 – In many countries, Health Technology Assessments are one of the requirements for reimbursement of new medical methods by insurance companies or health care payers. For the LiMAx system such an assessment did not exist so far, therefore a Mini Health Technology Assessment was conducted by the Austrian Competence Center for Medical Devices on behalf of Humedics GmbH. 

Dynamic determination of functional liver capacity with the LiMAx test in post cardiac arrest patients undergoing targeted temperature management – a prospective trial

Nee et al., Acta Anaesthesiol Scand, April 2020 – An increase in transaminases, particularly of ASAT, is frequently seen in survivors of cardiac arrest. ASAT levels higher than 10.000 U/L define a hypoxic hepatitis as a secondary form of acute liver failure associated with shock and hypoxemia.

Innovation in liver function diagnostics: Possibilities and opportunities of the LiMAx test in clinical application

Rebscher et al., WdK, Dez. 2019 – In the diagnostic of liver function the LiMAx test offers a completely new approach which can improve the treatment and care of patients. Publications in visceral surgery and hepatology show that due to the superiority of the LiMAx test conventional liver diagnostics can be dispensed with in some cases.

Dosing of Antimycotic Treatment in Sepsis-Induced Liver Dysfunction by Functional Liver Testing with LiMAx

Rebscher et al., WdK, Dez. 2019 – In the diagnostic of liver function the LiMAx test offers a completely new approach which can improve the treatment and care of patients. Publications in visceral surgery and hepatology show that due to the superiority of the LiMAx test conventional liver diagnostics can be dispensed with in some cases.

Predictive Power of Liver Maximum Function Capacity Test in Transjugular Intrahepatic Portosystemic Shunt Patients: A Pilot Study

Reichert et al, Dig Diseases, Oct. 2019 – A transjugular, intrahepatic shunt (TIPSS) is performed in patients with various advanced liver diseases, the procedure itself however often leads to complications associated with liver function, too.

Dynamic liver function is an independent predictor of recurrence-free survival after curative liver resection for HCC - A retrospective cohort study

Blüthner et al, Int J Surg, Nov 2019 – Although perioperative morbidity and mortality after liver resection are decreasing due to meticulous patient selection and improved surgical and anesthesiologic techniques, the long-term survival rate is still not satisfactory considering the high 5-year recurrence rate of 60–80 %.

Monitoring Liver Function of Patients Undergoing Transarterial Chemoembolization (TACE) by a 13C Breath Test (LiMAx)

Barzakova et al, Cardiovasc Intervent Radiol 2019 – Transarterial Chemoembolization (TACE) is an established procedure for patients with primary or secondary liver tumors. Because TACE is mainly applied in patients with advanced liver disease, the liver function of these patients is often already markedly reduced. 

Enzymatic liver function measured by LiMAx – a reliable diagnostic and prognostic tool in chronic liver disease

Büchter et al, Scientific Reports 2019, 9:13577. – Liver cirrhosis is the clinical endpoint of chronic liver disease (CLD), irrespective of its underlying cause. Portal hypertension following on liver cirrhosis is, in turn, a major determinant of mortality and morbidity in this patient group.

Non-invasive structure-function assessment of the liver by 2D time-harmonic elastography and the dynamic Liver Maximum capacity (LiMAX) test

Heucke et al, J Gastroenterol Hepatol, Feb 2019 – Despite the progressive severity of a liver disease, it often remains undetected because of the lack of clinical symptoms.

Gd-EOB-DTPA-enhanced MRI T1 relaxometry as an imaging-based liver function test compared with 13C-methacetin breath test

Theilig et al, Acta Radiologica, July 2017 – Gd-EOB-DTPA (Gadolinium) enhanced magnetic resonance imaging (MRI) and especially MRI T1 Relaxometry is a procedure allowing the assessment of spatial distribution of liver function without ionizing radiation and can be easily integrated into preoperative clinical routine.

The utility of the 13C-methacetin breath test in predicting the long-termsurvival of patients with decompensated cirrhosis

Moran, et al, J Breath Research 11 (2017) – During the natural course of liver cirrhosis there are 2 phases with different survival rates; the compensated phase with a hepatic venous pressure gradient less than 10mmHg and the decompensated phase with a pressure gradient higher than 10mmHg and complications like variceal bleeding, ascites, and encephalopathy.

Hepatic CYP1A2 Activity in Liver Tumors and the Implications for Preoperative Volume-Function Analysis

Wünsch T et al, Am J Physiol Gastrointest Liver Physiol, May 2019 – The human liver is the main location for drug metabolism by the Cytochrome P450 enzyme family. While some enzymes of this family are also present in the kidneys, lungs, brain or the skin, others are expressed exclusively in one organ, e.g. CYP1A2 in the liver.

Advanced Liver Function Assessment in Patients with Intestinal Failure on Long-term Parenteral Nutrition

Bluethner et al, Clinical Nutrition, April 2019 – Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of death in patients needing long term parenteral nutrition due to chronic intestinal failure. Root cause is often biochemical changes which may convert into steatosis, cirrhosis, and liver failure.

Noninvasive Evaluation of Liver Function in Morbidly Obese Patients

Alizai et al, Gastroenterology Research and Practice, Feb 2019 – The prevalence of overweight and obesity has dramatically increased over the last decades. Hepatic manifestation of morbid obesity is the non-alcoholic fatty liver disease (NAFLD) which can turn via nonalcoholic fatty liver inflammation (NASH) into Cirrhosis and Liver Cancer.

Current Status, Problems, and Perspectives of Non-alcoholic Fatty Liver Disease Research

Tanaka et al, World Journal of Gastroenterology, Jan 2019 – The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased in recent years in many countries among children and adults alike. In the USA 25% of all adults have a fatty liver, in Japan one third of the population and 20% of the Chinese in the year 2020.

Prospective Assessment of Liver Function by an Enzymatic Liver Function test to Estimate Short-Term Survival in Patients with Liver Cirrhosis

Jara et al, Digestive Diseases and Sciences, November 2018 – The MELD Score is used by all transplant societies worldwide for an objective donor liver allocation. Although this score has led to a significant reduction of waiting list mortality, some patient cohorts may not be represented sufficiently.

Liver Maximum Capacity: A Novel Test to Accurately Diagnose Different Stages of Liver Fibrosis

Buechter et al, Digestion, October 2018 – Chronic liver disease is – due to the increasing fraction of nutritional fatty liver – a major cause of mortality and morbidity worldwide and frequently lead to liver fibrosis followed by liver cirrhosis.