Discrepancies between Nonalcoholic and Metabolic-associated Fatty Liver Disease by Multiple Steatosis Assessment.

Background and Aims: The redefinition of metabolic-associated fatty liver disease (MAFLD) from nonalcoholic fatty liver disease (NAFLD) has caused a revolution in clinical practice, and the characteristics of patients with steatosis but not MAFLD remain unclear. The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steatosis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD. Methods: A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020. Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, controlled attenuation parameter (CAP), and fatty liver index (FLI). Fibrosis was assessed by the NAFLD fibrosis score, transient elastography, or shear wave elastography. Results: The study enrolled 14,985 Chinese adults. The agreement of MAFLD and NAFLD diagnoses were 83% for FLI, 95% for ultrasound, 94% for both CAP and MRI-PDFF, and 95% for liver biopsy. The body mass index, blood pressure and lipid levels among non-MAFLD-NAFLD patients were similar metabolic parameters (p>0.05 for all), but not the alanine aminotransferase and the proportion of patients with insulin resistance, which were significantly higher in non-MAFLD-NAFLD with significant fibrosis. Conclusions: The new MAFLD definition ruled out 5-17% of NAFLD cases. NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD. Non-MAFLD-NAFLD patients with significant fibrosis had more severe liver injury and increased glycemic dysregulation within the normal range. Attention should be paid to its progression.

An immediate postoperative response to therapy assessment can help avoid unnecessary RAI therapy.

Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

[Significance of Dynamic Risk Assessment in the Follow-up of Non-distant Metastatic Differentiated Thyroid Cancer Patients with Intermediate and High Risk].

Objective To tailor the subsequent treatment and follow-up strategy,this study dynamically assessed the response to initial therapy in non-distant metastatic differentiated thyroid cancer (DTC) patients with intermediate and high risk. Methods A total of 184 non-distant metastatic DTC patients (intermediate-risk 111 cases and high-risk 73 cases) were retrospectively enrolled in this study. Based on the results of initial response assessment (6-12 months after initial therapy),patients were divided into two groups:excellent response (ER) group (n=113) and non-excellent response (non-ER) group (n=71). We compared the differences in clinicopathological features between these 2 groups and evaluated the changes of dynamic response to therapy at the initial and final assessments after initial therapy in all patients. Results Compared with the ER group,the non-ER group showed a larger tumor size (U=2771.500,P=0.000),higher proportion of extrathyroidal invasion (χ 2=4.070,P=0.044),and higher preablative-stimulated thyroglobulin levels (U=1367.500,P=0.000). ER was achieved in 31% of patients in the initial non-ER group [including indeterminate response (IDR) and biochemical incomplete response (BIR)] at the final follow-up only by thyroid stimulating hormone (TSH) suppression therapy,among which 63.6% were with intermediate risk (especially the patients with IDR) and 36.4% at high risk. In addition,5.2%(6/113) of patients in the initial ER group were reassessed as IDR,BIR,or even structural incomplete response at the end of the follow-up (among which one patient developed into cervical lymph node recurrence,as confirmed by pathology);the TSH level in these patients fluctuated at 0.56-10.35 µIU/ml and was not corrected in time during the follow-up after initial therapy. Conclusions Some of non-distant metastatic DTC patients with intermediate and high risks who presented initial non-ER may achieve ER only by TSH suppression therapy over time;in contrast,the patients presented initial ER may develop into non-ER without normalized TSH suppression therapy. The dynamic risk assessment system may provide a real-time assessment of recurrence risk and tailor the subsequent treatment and follow-up strategies.

Effect of orlistat on liver fat content in patients with nonalcoholic fatty liver disease with obesity: assessment using magnetic resonance imaging-derived proton density fat fraction.

BACKGROUND: The liver effect of orlistat as a weight control treatment in patients with nonalcoholic fatty liver disease (NAFLD) with obesity remains undetermined. This study quantified liver fat improvement by orlistat in a Chinese cohort with NAFLD accompanied by obesity, diagnosed by a lower body mass index threshold than that for White patients. MATERIALS AND METHODS: We conducted a parallel-group, open-label, 24-week, randomized clinical trial registered at the Chinese Clinical Trial Registry (ChiCTR-IPR-17012258). Obese participants with NAFLD were randomized 1:1.5 to the intervention group with orlistat or conventional care. Liver fat quantification was assessed by magnetic resonance imaging-based proton density fat fraction with Dixon sequence. RESULTS: Overall, 170 (n = 68, orlistat 120 mg three times/day and n = 102, conventional therapy) and 130 patients with NAFLD (n = 56, orlistat and n = 74, conventional therapy) were included for intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. Orlistat reduced liver fat content to a greater degree than conventional care [-5.45% versus -1.96%, p < 0.001 (ITT analysis) and -6.66% versus -2.68%, p < 0.001 (PP analysis)]. The 6-month rate of decrease in steatosis grades was higher in the orlistat group [45.6% versus 22.5% (ITT analysis), 57.4% versus 30.3% (PP analysis), both p < 0.001]. Multivariate logistic regression analysis identified orlistat treatment [odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.1-5.6, p = 0.036] as an independent predictor of steatosis improvement. Among patients with orlistat therapy, weight loss (OR = 1.2, 95% CI 1.1-1.4, p = 0.040) and severe steatosis (OR = 6.7, 95% CI: 1.1-40.3, p = 0.03) remained predictive of steatosis improvement. CONCLUSIONS: Orlistat can effectively promote steatosis improvement and may serve as a treatment option for controlling NAFLD. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IPR-17012258.

PET response assessment in apatinib-treated radioactive iodine-refractory thyroid cancer.

This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from 18F-FDG PET/CT and SUV from 68Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and four of 20 had stable disease (SD) after apatinib therapy. Six progression-free survival (PFS) events occurred. A strong correlation was observed between the best change in the sum of the longest diameters of target lesions (ΔCT%) and 18F-FDG PET/CT indices after the completion of the first treatment cycle (ΔMTV% (P = 0.0019), ΔTLG% (P = 0.0021) and ΔSUVmax% (P = 0.0443)). A significant difference in PFS was observed between patients with ΔMTV% <-45% and ≥-45% (P = 0.0019) and between patients with ΔTLG% <-80% and ≥-80% (P = 0.0065). Ten of 11 patients presented a decrease in SUVmax on 68Ga-NOTA-PRGD2 PET/CT after two cycles of apatinib therapy and showed PR, whereas one patient presenting an increase in SUVmax only showed SD as the best response. When a cut-off value of the target/background ratio at -20% was used, two PFS curves showed a significant difference (P = 0.0016). Hence, early assessment by 18F-FDG and 68Ga-NOTA-PRGD2 PET/CT was effective in the prediction and evaluation of RAIR-DTC treated with apatinib.