Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time

Kim, Tae-Hoon; Jun, Hong Young; Kim, Ki-Jong; Lee, Young Hwan; Lee, Myeung Su; Choi, Keum Ha; Yun, Ki Jung; Jeong, Yong Yeon; Jun, Chung Hwan; Cho, Eun Young; Yoon, Kwon‐Ha

doi:10.1002/jmri.25673

Cited by 17 publications

(22 citation statements)

References 39 publications

(78 reference statements)

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“…Moreover, mechanisms underlying the formation of and change in cellular metabolites are impacted by aging and enzymatic activity in patients with LC, CLH, and HCC. In contrast to the short TE 1 H-MRS, 1 H-MRS with a long TE is useful in differentiating metabolites with long T2 relaxation times, such as lactate (Lac) and choline (Cho), as reported in a previous in vivo 1 H-MRS study [9]. We postulated that the use of long TE 1 H-MRS would clarify the metabolic changes caused by cirrhotic liver and HCC.…”

Section: Introductionmentioning

confidence: 91%

“…In order to detect Lac and Cho metabolites with a long T2 relaxation time, the single-voxel 1 H-MRS measurements were performed using a point-resolved spectroscopy sequence (PRESS) with the following parameters: TR/TE = 2000/288 msec; six acquisitions within a single breath hold; 2000 Hz spectral width; and 1024 data points [9]. Six saturation bands were placed around the voxel to diminish tissue contamination from the adjacent structures.…”

Section: Mr Imaging and Spectroscopymentioning

confidence: 99%

“…Although hepatocellular carcinogenesis in patients with LC largely appears to be a continuous, multistep differentiation process from a benign regenerative nodule to HCC [7], early diagnosis of HCCs is still challenging [8]. Liver biopsy is the gold standard for diagnosing chronic liver disease; however, its use is limited due to its invasiveness, as well as sampling bias and interobserver variability [9]. Several imaging techniques utilizing ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) represent noninvasive alternatives to liver biopsy and can potentially be used for the early detection and localization of HCCs as well as differential diagnosis between overt HCCs and cirrhosis-related borderline lesions [10].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

Moon

Shin

Heo

et al. 2020

JCM

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Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

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Section: Introductionmentioning

confidence: 91%

Section: Mr Imaging and Spectroscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

Moon

Shin

Heo

et al. 2020

JCM

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“…Among MR non‐elastographic techniques (Table ), the 31 P‐MRS‐derived ratio between nucleotide triphosphates (α‐peak) and triphosphates (αNTP/TP), reflecting cellular energetic failure, and the concentration of specific metabolites (eg alanine, lactate, triglycerides) assessed by 1 H‐MRS, showed AUROCs ranging from 0.71 for αNTP/TP and 1.00 for alanine, the latter evaluated in a small sample of 26 patients for NAS ≥ 5. Multiparametric MRI (mpMRI) demonstrated AUROCs of 0.69, 0.74 and 0.80, respectively, in the differentiation between NASH and SS when considering corrected T1 (cT1) as index test, in the differentiation between NAS < 5 and ≥ 5 for the same index test, and in the diagnosis of NASH using Liver Inflammation and Fibrosis (LIF) score .…”

Section: Resultsmentioning

confidence: 99%

Accuracy of imaging methods for steatohepatitis diagnosis in non‐alcoholic fatty liver disease patients: A systematic review

Besutti

Valenti

Ligabue

et al. 2019

Liver International

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Abbreviations: ARFI, acoustic radiation force impulse; AUROC, area under the receiving operating characteristic curve; MRE, magnetic resonance elastography; MRS, magnetic resonance spectroscopy; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PDFF, proton density fat fraction; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2; SPIO/USPIO, superparamagnetic iron oxide/ultrasmall superparamagnetic iron oxide; TE, transient elastography. AbstractBackground & Aims: Non-invasive tests to diagnose non-alcoholic steatohepatitis (NASH) are urgently needed. This systematic review aims to evaluate imaging accuracy in diagnosing NASH among non-alcoholic fatty liver disease (NAFLD) patients, using liver biopsy as reference.Methods: Eligible studies were systematic reviews and cross-sectional/cohort studies of NAFLD patients comparing imaging with histology, considering accuracy and/ or associations. MEDLINE, Scopus, EMBASE and Cochrane Library databases were searched up to April 2018. Studies were screened on title/abstract, then assessed for eligibility on full-text. Data were extracted using a predesigned form. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results:Of the 641 studies screened, 61 were included in scoping review, 30 of which (with accuracy results) in data synthesis. Imaging techniques included: elastography (transient elastography-TE, acoustic radiation force impulse-ARFI, magnetic resonance elastography-MRE), ultrasound (US), magnetic resonance (MR), computed tomography and scintigraphy. Histological NASH definition was heterogeneous. In 28/30 studies, no prespecified threshold was used (high risk of bias). AUROCs were up to 0.82 for TE, 0.90 for ARFI, 0.93 for MRE and 0.82 for US scores. MR techniques with higher accuracy were spectroscopy (AUROC = 1 for alanine), susceptibility-weighted imaging (AUROC = 0.91), multiparametric MR (AUROC = 0.80), optical analysis (AUROC = 0.83), gadoxetic acid-enhanced MR (AUROCs = 0.85) and superparamagnetic iron oxide-enhanced MR (AUROC = 0.87). Results derived mostly from single studies without independent prospective validation. Conclusions:There is currently insufficient evidence to support the use of imaging to diagnose NASH. More studies are needed on US and MR elastography and non-elastographic techniques, to date the most promising methods. K E Y W O R D Smagnetic resonance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, ultrasonography

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“…The value of these methods should be further evaluated. 7,111,[169][170][171][172] Even if the value of quantitative imaging in staging liver inflammation remains to be established, MRI is useful for staging NASH. Indeed, fibrosis is the most important histolo-gical lesion that is associated with long-term outcomes.…”

Section: Inflammation and Nonalcoholic Steatohepatitismentioning

confidence: 99%

Quantitative Imaging in Diffuse Liver Diseases

et al. 2017

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Cross-sectional imaging methods and more specifically ultrasonography and magnetic resonance imaging (MRI), have increasing roles in the quantitative evaluation of diffuse liver diseases. Particularly, ultrasound elastography is becoming the standard first-line examination for diagnosing severe liver fibrosis. Quantitative ultrasonography also brings information for staging portal hypertension in compensated cirrhosis and for grading liver steatosis. Quantitative MRI offers a multiparametric approach to assess the severity of liver steatosis, iron overload, fibrosis, inflammation, and portal hypertension. Regional liver transport function can be assessed with combined volumetric computed tomography and 99Tc mebrofenin single-photon emission computed tomography or with gadoxetic acid-enhanced MRI. It is concluded that multiparametric MRI complements the information brought with quantitative ultrasonography and has the potential to become a method of virtual liver biopsy that may decrease the need for invasive reference examinations in diffuse liver diseases.

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Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time

Abstract: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310.

Cited by 17 publications

References 39 publications

Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

Accuracy of imaging methods for steatohepatitis diagnosis in non‐alcoholic fatty liver disease patients: A systematic review

Quantitative Imaging in Diffuse Liver Diseases

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