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

Buechter, Matthias; Thimm, Jonas; Baba, Hideo A.; Bertram, Stefanie; Willuweit, Katharina; Gerken, Guido; Kahraman, Alişan

doi:10.1159/000493573

Cited by 22 publications

(26 citation statements)

References 35 publications

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“…However, both methods were limited in separating patients with no fibrosis from those with moderate fibrosis unlike reported for a cohort of obese adolescents with pediatric nonalcoholic fatty liver disease. 24 The ability of the LiMAx test to accurately diagnose different stages of liver fibrosis has recently been presented by Buechter et al 26 In their retrospective analysis of 102 patients with CLD, similar to our findings, clear decreasing tendencies of LiMAx values with increasing histological degrees of fibrosis, according to the Desmet & Scheuer scoring system, were observed. Furthermore, their AUROC analysis revealed that the LiMAx discriminated best between mild to moderate fibrosis (Desmet F0-3) and cirrhosis (Desmet F4) but less accurate between no and moderate fibrosis stages.…”

Section: Discussionsupporting

confidence: 90%

Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test

Heucke

Wuensch

Mohr

et al. 2019

J of Gastro and Hepatol

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Background and Aim Accurate assessment of structural and functional characteristics of the liver could improve the diagnosis and the clinical management of patients with chronic liver diseases. However, the structure–function relationship in the progression of chronic liver disease remains elusive. The aim of this study is the combined measurement of liver function by the 13C‐methacetin Liver MAximum capacity (LiMAx) test and tissue‐structure related stiffness by 2D time‐harmonic elastography for the assessment of liver disease progression. Methods LiMAx test and time‐harmonic elastography were applied, and the serological scores fibrosis 4 index and aspartate aminotransferase to platelet ratio index were calculated in patients with chronic liver diseases (n = 75) and healthy control subjects (n = 22). In 47 patients who underwent surgery, fibrosis was graded by histological examination of the resected liver tissue. Results LiMAx values correlated negatively with liver stiffness (r = −0.747), aminotransferase to platelet ratio index (r = −0.604), and fibrosis 4 (r = −0.573). Median (interquartile range) LiMAx values decreased with fibrosis progression from 395 μg/kg/h (371–460 μg/kg/h) in participants with no fibrosis to 173 μg/kg/h (126–309 μg/kg/h) in patients with severe fibrosis. Median liver stiffness increased progressively with the stage of fibrosis from no fibrosis (1.56 m/s [1.52–1.63 m/s]) to moderate fibrosis (1.60 m/s [1.54–1.67 m/s]) to severe fibrosis (1.85 m/s [1.76–1.92 m/s]). Conclusion Our findings show that structural changes in the liver due to progressing liver diseases and reflected by increased tissue stiffness correlate with a functional decline of the organ as reflected by a decreased metabolic capacity of the liver.

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Section: Discussionsupporting

confidence: 90%

Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test

Heucke

Wuensch

Mohr

et al. 2019

J of Gastro and Hepatol

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“…The superiority of LiMAx, however, is not essentially surprising: the applied substrate ( 13 C-methacetin) is metabolized by the cytochrome P450 1A2 enzyme - which is expressed in hepatocytes exclusively. In a recently published work of our group, we could demonstrate that structural changes in the course of CLD (reflected by different fibrosis-stages) were closely associated with changes of enzymatic liver function measured by LiMAx (Spearman’s r −0.68) 13 . In contrast, routine laboratory parameters - used for the calculation of above-mentioned serum indices - are not liver-specific and released in various organs of the human body.…”

Section: Discussionmentioning

confidence: 78%

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

Buechter

Kersting

Gerken

et al. 2019

Sci Rep

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Chronic liver disease (CLD) is a major cause of morbidity and mortality worldwide. Non-invasive assessment of hepatic disease severity represents a relevant issue to further improve clinical management and therapeutic treatment. We retrospectively compared the diagnostic and prognostic performance of different non-invasive tools (LiMAx, transient elastography (TE), and biomarkers) in detecting different severity stages during the course of CLD. Patients were divided into four groups based on clinical parameters: (1) patients without CLD (control group), (2) patients suffering from CLD without having cirrhosis, (3) patients with CLD and compensated cirrhosis, and finally, (4) patients with CLD and decompensated cirrhosis. Patients with acute liver failure were excluded from the analysis. A total of 464 patients who underwent LiMAx measurement at the University Clinic of Essen between 10/2016 and 11/2017 were included in this study. Distribution of the different groups were n = 72 patients for group 1, n = 134 patients for group 2, n = 160 patients for group 3, and n = 98 patients for group 4, respectively. Median LiMAx values significantly declined with respect to increasing degree of CLD: (1) 510 µg/h/kg, (2) 390 µg/h/kg, (3) 264 µg/h/kg, and (4) 151 µg/h/kg (p < 0.001). When comparing the diagnostic accuracy of the LiMAx test in detecting patients with presence of cirrhosis (groups 1 and 2 vs. groups 3 and 4), an AUROC of 0.942 was found (cut-off 322 µg/h/kg, sensitivity 86.1%, specificity 91.3%, p < 0.0001). LiMAx was superior to TE and serum biomarkers in predicting patients’ outcome by 90-day mortality (AUROC 0.811, p < 0.001). Enzymatic liver function measured by LiMAx was closely associated with different severity stages of CLD and was a reliable diagnostic and prognostic tool with an accuracy comparable to current standard methods.

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“…Subsequently, our results and claims have to be interpreted with caution and warrant further validations by other groups. However, LiMAx has been shown to correlate well with histological changes in different stages of liver fibrosis and cirrhosis in chronic liver disease [45]. Despite being certainly different in pathogenesis to other more common causes of chronic liver disease, it is assumable that LiMAx might also be associated with the histological patterns of IFALD.…”

Section: Discussionmentioning

confidence: 99%

“…Data presented as mean ± standard deviation. SBS-QoL, Short Bowel Syndrome-Quality of Life.The SF-36 Physical Component Summary (PCS) showed a significant improvement in quality of life from baseline to 6 months (29(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) vs. 39(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46); 0.002), stayed constant between the 6 and 12 month time points(39 (31-46) vs. 36(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46); p = 0.069) and slightly improved between 12 and 24 months (36(30)(31)(32)(33)(34)(35)...…”

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confidence: 99%

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

et al. 2020

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Liver abnormalities in intestinal failure (IF) patients receiving parenteral nutrition (PN) can progress undetected by standard laboratory tests to intestinal failure associated liver disease (IFALD). The aim of this longitudinal study is to evaluate the ability of non-invasive liver function tests to assess liver function following the initiation of PN. Twenty adult patients with IF were prospectively included at PN initiation and received scheduled follow-up assessments after 6, 12, and 24 months between 2014 and 2019. Each visit included liver assessment (LiMAx [Liver Maximum Capacity] test, ICG [indocyanine green] test, FibroScan), laboratory tests (standard laboratory test, NAFLD [non-alcoholic fatty liver disease] score, FIB–4 [fibrosis-4] score), nutritional status (bioelectrical impedance analysis, indirect calorimetry), and quality of life assessment. The patients were categorized post-hoc based on their continuous need for PN into a reduced parenteral nutrition (RPN) group and a stable parenteral nutrition (SPN) group. While the SPN group (n = 9) had significantly shorter small bowel length and poorer nutritional status at baseline compared to the RPN group (n = 11), no difference in liver function was observed between the distinct groups. Over time, liver function determined by LiMAx did continuously decrease from baseline to 24 months in the SPN group but remained stable in the RPN group. This decrease in liver function assessed with LiMAx in the SPN group preceded deterioration of all other investigated liver function tests during the study period. Our results suggest that the liver function over time is primarily determined by the degree of intestinal failure. Furthermore, the LiMAx test appeared more sensitive in detecting early changes in liver function in comparison to other liver function tests.

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

Cited by 22 publications

References 35 publications

Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test

Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test

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

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

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