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PURPOSE: The majority of cirrhotic patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) experienced the first post-TIPS hepatic encephalopathy (HE) episode within the first three months after TIPS insertion. However, so far, little is known about the exact neuro-pathophysiological mechanism of TIPS's effects on brain function. We aimed to investigate the dynamics of brain function alteration of post-TIPS patients using resting-state functional MRI (rs-fMRI). MATERIALS AND METHODS: Sixteen cirrhotic patients who were scheduled for TIPS and 16 healthy controls were included in the rs-fMRI scans. Ten patients repeated the MRI study in a median 8-day follow-up interval following TIPS and seven in a median 3-month follow-up. The amplitude of low frequency fluctuation (ALFF), an index reflecting the spontaneous brain activity, was compared between patients before TIPS and healthy controls as well as patients pre- and post-TIPS. RESULTS: Compared with healthy controls, patients showed decreased ALFF in frontal and parietal regions and increased ALFF in insula. Patients who underwent the median 8-day follow-up fMRI examinations showed decreased ALFF in posterior cingulate cortex (PCC)/precuneus and increased ALFF in anterior cingulate cortex (ACC). Of 10 patients in this group, 9 had moderate to large increase rate of ALFF value (>20%, mean 49.19%) in ACC, while only one patient with the smallest increase rate of ALFF value (<10%) in ACC, who experienced three episodes of overt HE during the 3-month follow-up. In the median 3-month follow up observation, patients displayed persistently decreased ALFF in PCC, ACC and medial prefrontal cortex (MPFC), while no increased regional ALFF was observed. CONCLUSION: TIPS insertion alters cirrhotic patients' ALFF patterns in the resting state, which may imply different short-term and moderate-term effects on cirrhotic patients, i.e., both impairment and compensatory mechanism of brain functions in peri-TIPS and continuous impairment of brain function 3 months following TIPS.