Quantitative P‐31 MR spectroscopy of the liver in alcoholic cirrhosis

Abstract

To determine the cause of reduced urea synthesis in cirrhosis, absolute concentrations of phosphorus metabolites in the human liver have been measured in vivo with magnetic resonance (MR) spectroscopy. One-dimensional chemical shift imaging was used to obtain phosphorus-31 spectra from five healthy volunteers and five patients with alcoholic cirrhosis. A reference standard included in all studies enabled the calculation of absolute concentrations. In contrast to hepatic metabolite ratios, absolute concentrations reveal that in the cirrhotic patients, concentrations of adenosine triphosphate (ATP) were significantly reduced and concentrations of phosphomonoesters slightly reduced. Intracellular pH was unchanged. Histologic evidence suggests that the amount of ATP per cell was unchanged and could not account for the reduced urea production. Instead, urea synthesis depends on the functional liver cell mass, which was reduced by 31% in alcoholic cirrhosis. Quantitative in vivo P-31 MR spectroscopy of liver has potential clinical applications and can supplement the more generally used P-31 metabolite ratios.

Abnormal hepatic energy homeostasis in type 2 diabetes

“…[32][33][34][35][36][37] In addition to MRS-dependent differences, the great interindividual variability within and across these studies could be due to the nutritional status and variations of age and BMI. To overcome such influences, we controlled for dietary intake and matched the controls for age and BMI.…”

“…Of note, the high intraindividual and interobserver reproducibilities of ␥ATP and Pi made it possible to investigate more subtle changes in phosphorus metabolites across a range of hepatic insulin resistance and fat contents. 22 The decrease in absolute levels of ␥ATP in viral and alcoholic hepatitis 32,37 and obesity 38 has been commonly interpreted as "energy deficit" or impaired "ATP homeostasis". Decreased ␥ATP could result from hepatocellular ␥ATP depletion due to increased ATP utilization by energy-demanding processes such as Na ϩ /K ϩ adenosine triphosphatases, lipogenesis, or gluconeogenesis.…”

The relationship of in vivo31P MR spectroscopy to histology in chronic hepatitis C

“…These studies have reported good correlation with either an increased PME resonance or decreased PDE resonance in cirrhotic livers. [10][11][12][13][14][15][16][24][25][26][27][28][29] However, none has studied precirrhotic disease, apart from a relatively recent study by Kiyono et al 29 They found no correlation between the spectra obtained and histopathologic grading in a cohort of patients with either chronic viral hepatitis (hepatitis B or hepatitis C viruses) or autoimmune hepatitis. This study was flawed in that the etiology of the disease was not stratified properly and there was no clear or accepted histologic grading system used.…”

“…Even in this relatively small cohort, the sensitivity and specificity of this test for assessing disease severity approaches that reported in larger studies that used serum biochemical or extracellular matrix component markers for assessing fibrosis. 33 Previous studies have shown significant reduction in hepatic adenosine triphosphate levels with cirrhosis of differing disease etiology, 15,16 possibly related to reduced hepatic mass or differing hepatic bioenergetics in the cirrhotic liver, but subject numbers have been small. We, in contrast, did not find any significant change in MRmeasurable %adenosine triphosphate among the groups in our cohort of 48 patients with HCV-related liver disease, but most of our patients had precirrhotic disease.…”

“…[7][8][9][10][11] Several previous studies have shown abnormalities in the PME resonance or PME/NTP, PME/PDE, and PDE/NTP ratios in patients with cirrhosis. [12][13][14][15][16] However, our study compared the spectral abnormalities in a cohort of patients with precirrhotic liver disease to assess the use of MRS in grading disease severity, compared with histology from liver biopsy. Our aims were to assess whether changes in in vivo 31 P MR spectra in patients with hepatitis C virus (HCV)-related liver disease correlated with histologic scores from liver biopsy and thus could provide an alternative noninvasive test for assessment of disease severity and a possible means for measuring the response of the liver to treatment intervention.…”