Longitudinal Intrinsic Brain Activity Changes in Cirrhotic Patients before and One Month after Liver Transplantation

  • Cheng, Yue (Department of Radiology, Tianjin First Central Hospital) ;
  • Huang, Li-Xiang (Department of Radiology, Tianjin First Central Hospital) ;
  • Zhang, Li (Department of Transplantation Surgery, Tianjin First Central Hospital) ;
  • Ma, Ming (Department of Transplantation Surgery, Tianjin First Central Hospital) ;
  • Xie, Shuang-Shuang (Department of Radiology, Tianjin First Central Hospital) ;
  • Ji, Qian (Department of Radiology, Tianjin First Central Hospital) ;
  • Zhang, Xiao-Dong (Department of Radiology, Tianjin First Central Hospital) ;
  • Zhang, Gao-Yan (School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University) ;
  • Zhang, Xue-Ning (Department of Radiology, The Second Hospital of Tianjin Medical University) ;
  • Ni, Hong-Yan (Department of Radiology, Tianjin First Central Hospital) ;
  • Shen, Wen (Department of Radiology, Tianjin First Central Hospital)
  • Received : 2016.04.11
  • Accepted : 2016.10.08
  • Published : 2017.04.01


Objective: To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Materials and Methods: Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. Results: In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). Conclusion: LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.



Supported by : National Natural Science Foundation of China


  1. Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology 2009;50:2014-2021
  2. Cordoba J. New assessment of hepatic encephalopathy. J Hepatol 2011;54:1030-1040
  3. Cardenas A, Gines P. Management of patients with cirrhosis awaiting liver transplantation. Gut 2011;60:412-421
  4. Mechtcheriakov S, Graziadei IW, Mattedi M, Bodner T, Kugener A, Hinterhuber HH, et al. Incomplete improvement of visuo-motor deficits in patients with minimal hepatic encephalopathy after liver transplantation. Liver Transpl 2004;10:77-83
  5. Ortiz M, Cordoba J, Jacas C, Flavia M, Esteban R, Guardia J. Neuropsychological abnormalities in cirrhosis include learning impairment. J Hepatol 2006;44:104-110
  6. Pujol A, Graus F, Rimola A, Beltran J, Garcia-Valdecasas JC, Navasa M, et al. Predictive factors of in-hospital CNS complications following liver transplantation. Neurology 1994;44:1226-1230
  7. Guo WB, Liu F, Xue ZM, Yu Y, Ma CQ, Tan CL, et al. Abnormal neural activities in first-episode, treatment-naive, shortillness- duration, and treatment-response patients with major depressive disorder: a resting-state fMRI study. J Affect Disord 2011;135:326-331
  8. Liu F, Hu M, Wang S, Guo W, Zhao J, Li J, et al. Abnormal regional spontaneous neural activity in first-episode, treatment-naive patients with late-life depression: a restingstate fMRI study. Prog Neuropsychopharmacol Biol Psychiatry 2012;39:326-331
  9. Palacios EM, Sala-Llonch R, Junque C, Roig T, Tormos JM, Bargallo N, et al. Resting-state functional magnetic resonance imaging activity and connectivity and cognitive outcome in traumatic brain injury. JAMA Neurol 2013;70:845-851
  10. Barkhof F, Haller S, Rombouts SA. Resting-state functional MR imaging: a new window to the brain. Radiology 2014;272:29-49
  11. Ni L, Qi R, Zhang LJ, Zhong J, Zheng G, Wu X, et al. Brain regional homogeneity changes following transjugular intrahepatic portosystemic shunt in cirrhotic patients support cerebral adaptability theory--a resting-state functional MRI study. Eur J Radiol 2014;83:578-583
  12. Ni L, Qi R, Zhang LJ, Zhong J, Zheng G, Zhang Z, et al. Altered regional homogeneity in the development of minimal hepatic encephalopathy: a resting-state functional MRI study. PLoS One 2012;7:e42016
  13. Qi R, Zhang L, Wu S, Zhong J, Zhang Z, Zhong Y, et al. Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. Radiology 2012;264:187-195
  14. Zhang L, Qi R, Wu S, Zhong J, Zhong Y, Zhang Z, et al. Brain default-mode network abnormalities in hepatic encephalopathy: a resting-state functional MRI study. Hum Brain Mapp 2012;33:1384-1392
  15. Zhang LJ, Zheng G, Zhang L, Zhong J, Wu S, Qi R, et al. Altered brain functional connectivity in patients with cirrhosis and minimal hepatic encephalopathy: a functional MR imaging study. Radiology 2012;265:528-536
  16. Lin WC, Hsu TW, Chen CL, Lu CH, Chen HL, Cheng YF, et al. Reestablishing brain networks in patients without overt hepatic encephalopathy after liver transplantation. J Cereb Blood Flow Metab 2014;34:1877-1886
  17. Zhang XD, Cheng Y, Poon CS, Qi R, Xu Q, Chen HJ, et al. Longand short-range functional connectivity density alteration in non-alcoholic cirrhotic patients one month after liver transplantation: a resting-state fMRI study. Brain Res 2015;1620:177-187
  18. Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev 2007;29:83-91
  19. Weissenborn K, Ennen JC, Schomerus H, Ruckert N, Hecker H. Neuropsychological characterization of hepatic encephalopathy. J Hepatol 2001;34:768-773
  20. Zhang Z, Lu G, Zhong Y, Tan Q, Chen H, Liao W, et al. fMRI study of mesial temporal lobe epilepsy using amplitude of low-frequency fluctuation analysis. Hum Brain Mapp 2010;31:1851-1861
  21. Zang Y, Jiang T, Lu Y, He Y, Tian L. Regional homogeneity approach to fMRI data analysis. Neuroimage 2004;22:394-400
  22. Chen HJ, Zhu XQ, Jiao Y, Li PC, Wang Y, Teng GJ. Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study. J Neurol Sci 2012;318:140-145
  23. Lv XF, Ye M, Han LJ, Zhang XL, Cai PQ, Jiang GH, et al. Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI. Metab Brain Dis 2013;28:485-492
  24. Qi R, Zhang LJ, Zhong J, Wu S, Zhang Z, Zhong Y, et al. Dynamic changes of intrinsic brain activity in cirrhotic patients after transjugular intrahepatic portosystemic shunt: a resting-state fMRI study. PLoS One 2012;7:e46681
  25. Lee HW, Hong SB, Seo DW, Tae WS, Hong SC. Mapping of functional organization in human visual cortex: electrical cortical stimulation. Neurology 2000;54:849-854
  26. Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006;129(Pt 3):564-583
  27. Luo S, Qi RF, Wen JQ, Zhong JH, Kong X, Liang X, et al. Abnormal intrinsic brain activity patterns in patients with end-stage renal disease undergoing peritoneal dialysis: a resting-state functional MR imaging study. Radiology 2016;278:181-189
  28. Joebges EM, Heidemann M, Schimke N, Hecker H, Ennen JC, Weissenborn K. Bradykinesia in minimal hepatic encephalopathy is due to disturbances in movement initiation. J Hepatol 2003;38:273-280
  29. Garcia-Martinez R, Rovira A, Alonso J, Jacas C, Simon-Talero M, Chavarria L, et al. Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume. Liver Transpl 2011;17:38-46
  30. Lin WC, Chou KH, Chen CL, Chen HL, Lu CH, Li SH, et al. Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation. PLoS One 2014;9:e105887
  31. Mattarozzi K, Cretella L, Guarino M, Stracciari A. Minimal hepatic encephalopathy: follow-up 10 years after successful liver transplantation. Transplantation 2012;93:639-643