Low host immune pressure may be associated with the development of hepatocellular carcinoma: a longitudinal analysis of complete genomes of the HBV 1762T, 1764A mutant.

Background: It has been reported that hepatitis B virus (HBV) double mutations (A1762T, G1764A) are an aetiological factor of hepatocellular carcinoma (HCC). However, it is unclear who is prone to develop HCC, among those infected with the mutant. Exploring HBV quasispecies, which are strongly influenced by host immune pressure, may provide more information about the association of viral factors and HCC. Materials and methods: Nine HCC cases and 10 controls were selected from the Long An cohort. Serum samples were collected in 2004 and 2019 from subjects with HBV double mutations and the complete genome of HBV was amplified and sequenced using next-generation sequencing (NGS). Results: The Shannon entropy values increased from 2004 to 2019 in most cases and controls. There was no significant difference in mean intrahost quasispecies genetic distances between cases and controls. The change in the values of mean intrahost quasispecies genetic distances of the controls between 2004 and 2019 was significantly higher than that of the cases (P<0.05). The viral loads did not differ significantly between cases and controls in 2004(p=0.086) but differed at diagnosed in 2019 (p=0.009). Three mutations occurring with increasing frequency from 2004 to 2019 were identified in the HCC cases, including nt446 C→G, nt514 A→C and nt2857T→C. Their frequency differed significantly between the cases and controls (P<0.05). Conclusions: The change in the values of mean intrahost quasispecies genetic distances in HCC was smaller, suggesting that HBV in HCC cases may be subject to low host immune pressure. Increasing viral loads during long-term infection are associated with the development of HCC. The novel mutations may increase the risk for HCC.

Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials.

BACKGROUND: The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. AIM: To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. METHODS: We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. RESULTS: In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). CONCLUSION: There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.

Neuropsychiatric Symptoms, Parenting Stress and Social Support in Chinese Mothers of Children with Autism Spectrum Disorder.

Although little is known about the current situation regarding autism spectrum disorder (ASD) in mainland China, psychiatric disorders are common among Chinese mothers of preschool children with ASD. Previous studies showed ASD child's behavioral symptoms, maternal anxiety, and maternal depressive symptoms were associated with overall parenting stress in northern China. In the present study, we retrospectively analyzed medical records at the hospital related to neuropsychiatric symptoms, parenting stress and social support in mothers of children with ASD from southern China. A total of 80 mothers of children with ASD were screened. Among them, 34 mothers were in low-functioning ASD group (L-ASD group) and 46 mothers were in high-functioning ASD group (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. Neuropsychiatric symptoms, parenting stress and social support were measured by neuropsychiatric inventory (NPI), parenting stress index short form (PSI-SF), and multi-dimensional scale of perceived social support (MSPSS). Total mean score of the NPI in the L-ASD group was significantly higher than that in the H-ASD group (P<0.01). The subscale scores of NPI, including depression, anxiety, apathy, irritability, agitation, night time behavior disturbances and change in appetite were significantly higher in the L-ASD group than those in the H-ASD group (P<0.01 or P<0.05). Meanwhile, the total PSI-SF scores and the scores of parental distress (PD), parental-child dysfunctional interaction (PCDI) and difficult child (DC) in the L-ASD group were significantly higher than those in the H-ASD group (P<0.01 or P<0.05). The total score of MSPSS was also higher in the L-ASD group than in the H-ASD group (P<0.01). This study goes further to show the neuropsychiatric symptoms and parenting stress are significantly higher in mothers of children with ASD, and more social supports are needed for mothers of children with ASD from southern China, especially for mothers of children with low-functioning ASD.