Early diagnosis and accurate stage of liver fibrosis are important for conducting the clinic therapy and assessing the therapeutic outcome. Functional magnetic resonance imaging (fMRI), as a noninvasive and effective method, plays an important role in diagnosis and stage of liver fibrosis. This review focuses on the advances in fMRI evaluation of liver fibrosis.
Trying to provide ultrasonic image-aid measures for quantitative diagnosis and dynamic monitoring of liver fibrosis, we propose two scoring methods for liver fibrosis tissue in vivo, based on ultrasound radio frequency (RF) time series in this paper. Firstly, RF echo signals of human liver were recorded in this study. Then one of the recorded frame RF data was demodulated to be B model image. After that, a region of interest (ROI) in the B model image was selected. For each point in the ROI, its all frame data were acquired so that RF time series were formed. An SMR (size measure relationship) fractal dimension and six spectral features were extracted from RF time series in the ROI. With relative deviation and Fisher's discriminant ratio, seven features were weighted and summed so that the liver tissues' scores were obtained, Score-rd and Score-fisher, respectively. Area under ROC curve (AUC) and a support vector machine (SVM) were used to evaluate whether these scoring methods would be useful in distinguishing normal and cirrhosis tissues. Experimental results are shown as follows: Score-rd's AUC was 0.843, while Score-fisher was 0.816, SVM classification accuracies were both up to 87.5%. This proved that our proposed scoring methods were effective in distinguishing normal and cirrhosis tissues. Score-rd and Score-fisher have potential for clinical applications. They can also provide quantitative references for liver fibrosis diagnosis.
ObjectiveTo summarize mechanism of DNA methylation and histone methylation in liver fibrosis.MethodThe literatures on the DNA methylation and histone methylation during the liver fibrosis were reviewed and analyzed.ResultsThe DNA methylation and histone methylation were the important components of epigenetics. The up-regulation or down-regulation of genes during the liver fibrosis leaded to the activation or inactivation of the subsequent pathways. For example, the PTEN, SEPT9, Smad7, etc. were hypermethylated and the expressions were decreased in the liver fibrosis. The Spp1 was hypomethylated and the expression was increased in the liver fibrosis.ConclusionsMethylation affects expression of genes by altering epigenetics of genes. Systematic and in-depth study of role and mechanism of methylation in liver diseases provides a new direction and locations for some target treatments for liver disease.
ObjectiveTo summarize the pathogenesis, epidemiology, and risk factors of portal vein thrombosis after splenectomy, and combined with the latest advances in clinical prevention, diagnosis, and treatment of portal vein thrombosis after splenectomy, so as to provide some references for clinical prevention and treatment in the future.MethodLiteratures on portal vein thrombosis after splenectomy were collected and reviewed.ResultsThe incidence of portal vein thrombosis after splenectomy was high and its occurrence was the result of multiple factors. It was mainly related to the change of splenic venous blood flow mechanics after splenectomy. In terms of diagnosis, enhanced CT scan was the first choice. Currently, there was no consensus on treatment options, which mainly focused on individualized treatment and emphasized that preventive anticoagulant use of low-molecular-weight heparin may reduce the risk of portal vein thrombosis.ConclusionThe concept of tertiary prevention of portal vein thrombosis after splenectomy should be established, and individualized treatment should be adopted in combination with the patient’s condition.
ObjectiveTo investigate the utility of stretched exponential model diffusion-weighted imaging (DWI) for diagnosing of advanced liver fibrosis.MethodsThe patients with chronic liver disease complicated with vary degrees of fibrosis confirmed by pathological examination underwent DWI using different b-values (0, 50, 600 s/mm2) at the First Affiliated Hospital of Chengdu Medical College from June 2015 to February 2020 were collected. In addition, patients who underwent upper abdominal MRI examination in the same hospital at the same time and had no liver disease or disease affecting liver function were collected as a control group. The apparent diffusion coefficient (ADC) was calculated by using a mono-exponential model. The distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) were calculated by using a stretched exponential model. The fibrosis stage was evaluated by using the Metavir scoring system. The ADC, DDC, and α among different fibrosis groups were compared. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of these three quantitative parameters for advanced liver fibrosis.ResultsA total of 42 patients with chronic liver disease were collected in this study, including mild liver fibrosis (S1–S2, n=16) and advanced liver fibrosi (≥S3, n=24); 15 patients in the control group. The values of ADC, DDC, and α of the patients with mild liver fibrosis and advanced liver fibrosis were significantly lower than those of the control patients (P<0.05). The area under the ROC curve of ADC, DCC, and α in diagnosing liver fibrosis (≥S1) was 0.915, 0.974, and 0.835, respectively, which in diagnosing advanced liver fibrosis (≥S3) was 0.744, 0.869, and 0.758, respectively. However, further the area under ROC curve among these three metrics had no statistical differences (P>0.05).ConclusionDDC based on stretched exponential model is valuable for diagnosis of advanced liver fibrosis.
ObjectiveTo investigate the imaging characteristics of gallium-68 labeled fibroblast activation protein inhibitor (68Ga-FAPI)-positron emission tomography/magnetic resonance (PET/MR) imaging in patients with liver fibrosis or liver tumor. MethodsThirteen patients with suspected liver tumor who underwent 68Ga-FAPI-PET/MR examination from May 2020 to April 2021 were retrospectively analyzed. Maximum standard uptake value (SUVmax) was investigated. All patients underwent liver surgery or biopsy. Scheuer scoring system was used to evaluate the liver fibrosis. The imaging characteristics of liver fibrosis or liver tumor were analyzed. ResultsThe liver fibrosis was confirmed in 6 patients, including 1 case of S2, 2 cases of S3, and 3 cases of S4. Among them, 4 patients had increased uptake of 68Ga-FAPI, with patchy or diffuse abnormal concentration of liver, and the SUVmax was 7.9±3.1. The liver imaging of the other 2 patients with liver fibrosis showed no obvious radioactive concentration. In addition, 2 patients were diagnosed with hepatocellular carcinoma, its SUVmax was 7.2 and 6.1; 1 patient was diagnosed with hepatobiliary duct carcinoma and its SUVmax was 13.8. Moreover, increased uptake of 68Ga-FAPI was observed in 4 patients with metastatic liver cancer, with SUVmax of 6.7±2.7. ConclusionBoth liver fibrosis and liver tumor are suitable for 68Ga-FAPI-PET/MR examination, which have different imaging characteristics.
Evidence from numerous animal models and clinical studies in recent years has demonstrated that macrophages play an important role in the regulation of liver fibrosis regression. The safety and efficacy of utilizing autologous macrophages for the treatment of liver fibrosis have been demonstrated in patients and shows promising application prospects, but the therapeutic effects need to be improved. Cirrhotic liver undergoes a process of marked extracellular matrix degradation after partial hepatectomy surgery, and single-cell sequencing identified multiple restorative macrophage subsets that express different matrix metalloproteinases (MMPs) at high levels. Future efforts to further characterize this population of macrophages and improve their enrichment in the liver may allow macrophage therapy to be a highly effective strategy to reverse liver fibrosis.
ObjectiveTo summarize the role of ionized free calcium/calmodulin/calmodulin-dependent protein kinase Ⅱ (Ca2+/CaM/CaMKⅡ) signaling pathway in liver fibrosis so as to provide a theoretical basis for the treatment of liver fibrosis. MethodThe recent literature relevant research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis both domestically and internationally was reviewed. ResultsThe Ca2+/CaM/CaMKⅡ signaling pathway played a bidirectional regulatory role in the process of liver fibrosis, potentially facilitating the activation of hepatic stellate cells and triggering hepatocyte apoptosis through synergistic transforming growth factor-β1 and platelet-derived growth factor pathways. ConclusionsAt present, there is very little research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis, and there is still insufficient understanding. Future research should focus on the mechanism of this signaling pathway in liver fibrosis, especially its upstream genes or downstream target proteins, which will aid to develop targeted and effective treatment strategies, achieve the reversal of liver fibrosis and even liver cirrhosis, and provide more effective treatment options for patients with liver fibrosis.