Nonalcoholic fatty liver disease (NAFLD) has become one of the research hotspots in the field of liver disease. However, so far, no drugs have been approved by the U.S. Food and Drug Administration for the treatment of nonalcoholic steatohepatitis, which brings opportunities and challenges to the clinical trials on the treatment of NAFLD. Liver histology is currently considered a reliable surrogate endpoint for tracking the progression of NAFLD, but its invasiveness has limited the development of drugs for the treatment of NAFLD. In recent years, some noninvasive measurement methods have gradually been used as secondary or exploratory endpoints in existing clinical trials.

Objective To investigate the value of hydrogen proton MR spectroscopy (1H-MRS) and Dixon sequence for the quantitative diagnosis and classification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods Sixty seven patients with NAFLD confirmed by liver biopsy were prospectively collected from October 2015 to May 2017 in Hangzhou Normal University Hospital. All patients underwent 1H-MRS and Dixon sequence scan within 7 days after liver biopsy, 1H-MRS-based hydrogen proton density fraction (MRS-PDFF) and Dixon-based hydrogen proton density fraction (MRI-PDFF) were obtained. Fat grading based on the fat percentage obtained from liver biopsy. Pearson correlation analysis was performed to analyze the correlation among pathological steatosis and MRS-PDFF, MRI-PDFF. One-way ANOVA analysis was performed to compare the difference of PDFF between patients with different degrees of severity of fatty liver. And the ROC curve analysis was performed to generate the thresholds of MRS-PDFF and MRI-PDFF for determining the presence of fatty liver. Results The steatosis grade of pathological biopsy showed grade S1 in 36 cases, grade S2 in 16 cases, grade S3 in 15 cases, the MRS-PDFF values of S1, S2 and S3 patients were (8.25 ± 4.32)％, (15.67 ± 4.54)％, (23.46 ± 5.82)％and the MRI-PDFF values were (6.31 ± 2.94)％, (15.42 ± 5.07)％, (24.47 ± 6.31)％. Statistically significant differences were observed among them (P<0.01). Both MRS-PDFF and MRI-PDFF were positively correlated with histological fat percentage (r values were 0.840 and 0.892,all P<0.01), there was also a correlation between MRS-PDFF and MRI-PDFF (r=0.930, P<0.01). Area under ROC curve of MRS-PDFF and MRI-PDFF for differential diagnosis of grade S1 steatosis were 0.955 and 0.976, and area under ROC curve for differential diagnosis of grade S3 steatosis were 0.972 and 0.978. Conclusion 1H-MRS and Dixon sequces have high value in liver fat content detection and classification of patients with NAFLD, and both have similar diagnostic efficacy.

Objective: We aimed, in our prospective study, to assess the predictive value of serum non-invasive and biochemical markers for clinical diagnosis of significant fibrosis (including early stages). Methods: We measured sH2a levels in serum, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of hepatitis B patients without non-alcoholic fatty liver disease(NAFLD), which had histological grades of liver fibrosis, with NAFLD individuals and CHB with NAFLD patients. Statistical analysis was by Student′s t test, and receiver-operating characteristic (ROC) curves were drawn. Results: ROC curves showed that serum sH2a had greater diagnostic performance than routine liver function markers compared with histological grades of liver fibrosis(S0, S1-2, S3-4). ROC curves showed that using a sH2a cut-off point of 0.79 was with highest sensitivity as 63% and highest specificity as 80%. And sensitivity as 96.7% and specificity as 75.5% when using a sH2a cut-off point of 0.77. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

Objective: To investigate the value of 1H-magnetic resonance spectroscopy (¹H-MRS) in determining the content of liver triglyceride in patients with fatty liver disease (FLD), as well as its influencing factors. Methods: A total of 124 patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B (CHB), or hepatitis B complicated by FLD who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were enrolled, and the clinical data, serological markers, FibroScan results, and ¹H-MRS results were collected. A correlation analysis was performed with the results of liver biopsy as the gold standard, and the influence of factors including hepatitic B virus (HBV) infection and obesity on accuracy was analyzed. A one-way analysis of variance was used for comparison of means between the three groups, and the LSD or SNK test (for homogeneity of variance) or the Tamhane’s or Dunnett’s test (heterogeneity of variance) was used for comparison between any two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data. The MRS-PDFF receiver operating characteristic (ROC) curve was plotted, the area under the ROC curve (AUC) was calculated, the optimal cut-off points for the diagnosis of NAFLD were estimated, and sensitivity and specificity were calculated. Results: The NAFLD group (42 patients) and the CHB + NAFLD group (40 patients) had a significantly higher proton density fat fraction (PDFF, the content of triglyceride in the liver) than the CHB group (42 patients) (16.84±9.76/9.39 ± 5.50 vs 3.45 ± 1.63, P < 0.001). The results were significantly correlated with the degree of steatosis confirmed by liver biopsy (P < 0.001), but it was not significantly correlated with inflammation or fibrosis grade. The correlation analysis showed that the MRS-PDFF value measured by 1H-MRS was significantly correlated with body mass index (BMI), blood lipids, alkaline phosphatase, and blood glucose, while it was not significantly correlated with age, sex, or the presence or absence of hepatitis B. The ROC curve analysis showed that the AUCs of PDFF measured by 1H-MRS were 0.93, 0.974, and 0.976, respectively, for the diagnosis of steatosis S1(≥5%), S2(≥34%), and S3(≥66%), and the corresponding optimal thresholds were 5.14%, 11.16%, and 16.7%, respectively. Conclusion 1H-MRS has a high diagnostic value in quantitative evaluation of the degree of liver steatosis in patients with FLD and is not affected by the factors such as HBV infection, age, and sex, while it is correlated with BMI and lipid metabolism.