Objective. To clarify the application value of 5-hydroxymethylcytosine (5hmC) in evaluating the progression of chronic hepatitis B (CHB) to hepatocellular carcinoma (HCC) based on difference analysis. Methods. A total of 180 patients were enrolled. Among them, 84 patients with chronic hepatitis B virus (HBV) infection while no progression to hepatocellular carcinoma (HCC) were included in the control group (CG), and 96 patients with HCC developed from HBV infection were included in the research group (RG). Two-thirds of the samples were used in the training set and 1/3 samples in the validation set to detect the level of 5hmC in both groups based on the modified nano-hmC-Seal technique. The expression levels of 5hmC-related genes TET2 and TET3 were quantified by qPCR, and the correlation between TET3 and 5hmC was analyzed by Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were drawn to evaluate the application value of the TET3-based 5hmC prediction model in the early diagnosis of HCC. Results. (i) The expression of 5hmC in RG was lower than that in CG, no matter in the training set or the validation set. (ii) 5hmC was significantly enriched in the region between the transcription initiation site and the transcription end site but was depleted in the flanking region. (iii) 5hmC-related genes TET2 and TET3 were significantly downregulated in HCC patients, whether in the training set or the validation set. (iv) In both the training and validation sets, TET3 showed a positive association with 5hmC. (v) ROC analysis results showed that the 5hmC prediction model could be used to predict the progression of CHB to HCC (training set: AUC=0.81, 0.729-0.893; validation set: AUC=0.84, 0.739-0.936). Conclusions. TET3 expression based on 5hmC sequencing is a landmark molecule for evaluating the progression of HCC in CHB patients, which is worthy of further study and promotion.
Objective Real-world efficacy and safety of switching to TAF in decompensated hepatitis B-related cirrhotic patients poor responsive or with low-level viremia(LLV)to nucleos(t)ide analogue(NA)therapy are unclear.The purpose of this study was to investigate the efficacy and safety of the sequential therapy in order to optimize antiviral treatment.Methods In this prospective cohort study 56 patients with decompensated hepatitis B cirrhosis were enrolled who had been switched to TAF monotherapy due to poor response to NA therapy or LLV for at least 6 mooths.According to the baseline HBV DNA level,they were divided into LLV group(HBVDNA＜2000 IU/mL)and poor response group(HBV-DNA≥2000 IU/mL).All patients were followed up every 12 weeks.Their virological/biochemical responses were evaluated after switchover.Results(1)Complete virological response(CVR)at 48 weeks[32.14％(18/56)]after swithing to TAF was significantly increased than that at 12 weeks[80.00％(16/20)](P＜0.05).(2)Subgroup analysis of LLV group and poor response group showed that the former achieved favours CVR at 12 weeks[61.54％(16/26)vs 6.67％(2/30)].However,there was no statistical difference between the two groups at 24 weeks,36 weeks and 48 weeks.(3)Additionally,the mean changes in HBsAg and HBV DNA levels were significant at 48 weeks(-0.44 and-3.38 logIU/mL,respectively)(P＜0.05).(4)The normalization rate of ALT at 48 week was 95.00％(19/20),which were significantly higher than that of 66.07％(37/56)at the baseline(P＜0.05).(5)The mean Child-Pugh score and the proportion of Child-pugh A at 48 weeks was 5.45±0.76 and 85％(17/20),respectively,which were significantly improved than those of 8.66±2.30 and 21.43％(12/56)at the baseline(P＜0.05).(6)During the 48-weeks'treatment period,there were no significant changes in serum creatinine,phosphorus,and eGFR(P＞0.05),However,the median urinary β2-microglobulin(β2-MG)at 24-weeks was 0.98,compared to 1.14 at the baseline,however,the difference was not statistically significant.Conclusion(1)Switching to TAF monotherapy is effective in patients with decompensated hepatitis B-related cirrhosis due to poor response to NA therapy/LLV,regarding both CVR and the liver function benefits.(2)TAF has a good renal safety in the treatment of decompensated hepatitis B-related cirrhosis.
目的 提高全科医生对丙型肝炎认知、诊断和治疗的能力.方法 组织丙型肝炎诊治专家下沉社区,在社区开展以丙型肝炎为主题的健康教育巡讲,并编制合适的问卷,内容包括受访者基本信息、对丙型肝炎的认识、丙型肝炎政策的了解和丙型肝炎预防与治疗4部分.在巡讲前后分别行上述问卷调研,对比基层巡讲对于提升社区全科医生丙型肝炎认识的意义.结果 从2021年5月至2022年4月底,在陕西省基层社区卫生中心举办了10场讲座,分别回收有效问卷112份和105份.结果 显示:巡讲前全科医师对丙型肝炎疾病认知水平、政策认知水平和预防与诊治水平的得分分别为2.89±0.76、2.37±0.75和2.63±0.76,巡讲后分别为3.82±0.83、3.55±1.14和3.75±0.85,差异有统计学意义(P<0.05).通过主题巡讲,全科医生对丙型肝炎高危人群和传播途径的认识有所提高;全科医生愿意对侵入性受试者进行丙型肝炎抗体检测率从巡讲前57.10％ 提升至巡讲后75.20％,对HCV抗体阳性患者进行HCV RNA检测从巡讲前59.80％提升至巡讲后68.6％;巡讲前有53.6％ 的全科医生愿意对患者宣教和62.5％ 的全科医生愿意将丙型肝炎患者转诊至上级医院,巡讲后分别提高至67.6％ 和74.3％.结论 通过下沉基层进行丙型肝炎主题巡讲,不仅可有效提升社区全科医务工作者丙型肝炎规范防治认知水平,而且是开展以社区为中心的丙型肝炎消除模式的重要探索,更是实现"2030年消除病毒性肝炎"战略目标的关键之举.
随着直接抗病毒时代的到来,持续的病毒应答(SVR)可以以近100％ 的速度实现,丙型病毒性肝炎的治疗已不再是关注的重点问题.然而,丙型病毒性肝炎相关病死率仍然在逐年上升,其原因之一是丙型病毒性肝炎肝外疾病同样也会影响患者疾病的进展及病死率,说明病毒清除并不能完全缓解肝外表现.所以本文旨在阐述丙肝的肝外疾病,加强对丙肝的全面认识,有助于对丙肝患者病毒清除后的进一步诊治提供参考.
肌肉减少症是机体营养不良的重要表现之一,系指进行性和全身性的肌肉质量降低以及肌肉功能的丧失,其发生与进展与多种急慢性疾病互为因果,尤其在终末期肝病患者中普通存在,并与该类患者在院时长、生活质量低下、死亡等不良事件的发生率增加密切相关.近年来已得到该领域的广泛关注,并成为终末期肝病临床研究热点之一.本文通过对肌少症与终末期肝病相关研究进行综述,旨在为终末期肝病合并肌少症的治疗提供新的方向和证据,以期缩短住院时间、节约医疗资源、提高生活质量与生存率,改善终末期肝病患者临床结局.
