Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

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Nucleos(t)ide analogues for hepatitis B virus: Strategies for long-term success

Nucleoside and nucleotide analogues are potent HBV suppressors, but these agents rarely eradicate HBV. Therefore, the durability of viral response is a problem, and long-term therapy is usually required to ensure maintained HBV suppression. Studies have shown that long-term therapy starting with lamivudine may significantly improve survival, reduce the risk of liver-related major complications, and prevent the development of cirrhosis and HCC in chronic hepatitis B patients. However, drug resistance is a critical challenge during long-term nucleos(t)ide analogue maintenance therapy. The emergence of these mutants is characterized by an increasing level of serum HBV DNA, elevation of ALT level, and even hepatitis flare or decompensation. The prevention and proper management of drug resistance are crucial to ensure long-term success. To start treatment in the right patients at the right time with the right drug is essential in minimizing the problem of drug resistance. Each of these agents has a different profile of resistant mutations. In choosing a direct antiviral agent to initiate therapy, resistance profile is a crucial factor to consider, apart from potency and cost. In the case of drug resistance emerging, timely institution of a drug without cross-resistance may rescue the adverse effects of drug resistance and ensure the long-term success of nucleos(t)ide analogue therapy. To develop strategies for enhancing the therapeutic response and shortening the duration of therapy is an ultimate goal to avoid the problems of drug resistance.⁶⁸

• nucleos(t)ide analogues for hepatitis B virus (HBV) are highly effective in suppressing HBV replication but rarely eliminate the virus

• long-term therapy is usually required

• emergence of drug-resistant HBV mutations is a critical challenge

• to treat the right patient at the right time with the drug with highest genetic barrier to drug resistance is essential to minimize the problem with drug resistance

• the strategy of on-treatment adjustment based on level of suppression of HBV DNA needs to be clarified

• studies are needed to find the optimal combination therapy for both better therapeutic efficacy and less drug resistance

• oral antiviral agents able to attack cccDNA are urgently needed

Non-apnea sleep disorder and its risk for all kinds of injuries: A 14-year follow-up for a nationwide population-based retrospective study

Non-apnea sleep disorder (NASD) increases the risk of motor vehicle accidents. However, systemic review of NASD and its risk for all causes of injury is lacking. The aim of the present study was to provide a detailed demographic data on NASD and all causes of injury in a 14-year follow up.Our study utilized outpatient and inpatient data from the Longitudinal Health Insurance Database between 2000 and 2013 in Taiwan. We enrolled 989,753 individuals aged ≥20 years who were diagnosed with NASD as outpatients ≥3 times or inpatients ≥1 time. We matched the study cohort with a comparison cohort by age, index date and comorbidities at a ratio of 1:4. We used Cox proportional hazards regression to analyze the association of NASD and the cause of injury.In this 14-year follow up study, patients with NASD had 12.96% increased risk of injury compared to that of the control cohort. Fall was the first place of the cause of injury with 670.26 per 10⁵ PYs. In the stratified age group, patients aged ≧65 years had the highest risk of injury (adjusted HR= 1.381; P < .001). Kaplan–Meier analysis showed that the incidence of injury between the with- and without-NASD cohorts started from the first year and persisted until the end of the follow-up.Our study demonstrates that NASD patients were associated with higher risk of all causes of injuries, with falling being the most prevalent diagnosis. The general public should be more aware of this neglected issue of NASD.