Multiple Low-Level Viraemia Suggest Hindered Liver Fibrosis Regression in Chronic Hepatitis B Patients During Antiviral Therapy.

Low-level viraemia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aimed to investigate the impact of different LLV types on fibrosis regression. The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P-I-R system. Patients were grouped as the SVR (HBV DNA < 20 IU/mL persistently) or LLV (HBV DNA between 20 and 2000 IU/mL), which were further grouped as very low-level viraemia (VLLV, HBV DNA < 50 IU/mL), occasionally LLV (OLLV, HBV DNA ≥ 50 IU/mL only once) and multiple LLV (MLLV, HBV DNA ≥ 50 IU/mL more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). The analysis included 111 CHB patients. In the SVR group (n = 54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p = 0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients) and MLLV (10 patients) were 70.0%, 52.9% and 30.0%, respectively. Compared with SVR, VLLV (aOR = 0.78; 95% CI: 0.28-2.21; p = 0.644) was not associated with fibrosis regression, but patients with non-VLLV (aOR = 0.27; 95% CI: 0.09-0.85; p = 0.025), especially with MLLV (aOR = 0.19; 95% CI: 0.04-0.97; p = 0.046) is significantly associated with hindered fibrosis regression. Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once. Trial Registration: ClinicalTrials.gov identifiers NCT01938781 and NCT01938820.

Insulin resistance estimated by estimated glucose disposal rate predicts outcomes in acute ischemic stroke patients.

BACKGROUND: Estimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS). METHODS: We included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤ 6 mg/kg/min) and higher eGDR group (eGDR > 6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes. RESULTS: A total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0 mg/kg/min (interquartile range, 4.2-5.6) and 7.6 mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P < 0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P < 0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P < 0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P = 0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P = 0.41). CONCLUSION: eGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.

What predicts large vessel occlusion in mild stroke patients?

BACKGROUND AND PURPOSE: Mild acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) may benefit from thrombolysis or thrombectomy therapy. However, the predictors for LVO in mild AIS patients have not been extensively explored. We aimed to investigate the predictors for LVO in mild AIS patients. METHODS: We collected the data of consecutive AIS patients with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 from The Third China National Stroke Registry - a prospective nationwide registry of AIS or transient ischemic attack (TIA) patients in China from August 2015 to March 2018. Patients were divided into LVO and non-LVO group based on the vascular imaging during the hospitalization. Multivariable regression analyses involving clinical characteristics and NIHSS subitems was performed to detect the predictors for LVO. RESULT: A total of 7653 mild AIS patients from The Third China National Stroke Registry were included in this study. Among them, 620 patients (8.1%) had LVO. The level of consciousness (adjusted odds ratio, 1.87; 95% confidence interval, 1.08 to 3.23), visual field (adjusted odds ratio, 2.10; 95% confidence interval, 1.43 to 3.06) and sensory (adjusted odds ratio, 0.75; 95% confidence interval, 0.60 to 0.94) were predictors for mild AIS patients with LVO. CONCLUSIONS: Impaired LOC, visual field and sensory were independently predictors for LVO in mild stroke patients. Further studies are warranted to test these predictors in prehospital setting and in other population.

Histological assessment based on liver biopsy: the value and challenges in NASH drug development.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.