Background and Aims: Tenofovir alafenamide (TAF) has demonstrated comparable efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety, in Chinese participants with chronic hepatitis B enrolled in two Phase 3 trials. This study aimed to evaluate the long-term virologic efficacy, serological and biochemical responses, resistance, and renal and bone safety of TAF over eight years in this population. Methods: Participants completing the threeyear double-blind phase were eligible to receive open-label TAF 25 mg/day for up to an additional five years (totaling eight years). Analyses of viral suppression (HBV DNA < 29 IU/mL), alanine aminotransferase normalization, serological responses, resistance surveillance, and safety outcomes were conducted. Results: Among 334 enrolled participants, 212 of 227 participants randomized to TAF continued open-label TAF (TAF-TAF), and 99 of 107 participants on TDF switched to open-label TAF (TDF-TAF). At Year 8, 79.3% (180/227) and 78.5% (84/107) of participants in the TAF-TAF and TDF-TAF groups, respectively, achieved viral suppression (missing = failure); rates increased to 95.2% (180/189) and 95.5% (84/88) when excluding missing data. Alanine aminotransferase normalization rates remained high and comparable between groups. Serologic response rates continued to increase over time, with higher rates observed in the TAF-TAF group. Estimated glomerular filtration rate (by Cockcroft-Gault) and hip/spine bone mineral density remained stable in the TAF-TAF group through eight years; the small declines in these renal and bone parameters observed during doubleblind TDF treatment improved after switching to open-label TAF. No resistance to TAF was detected. Conclusions: Longterm TAF treatment demonstrated durable virologic efficacy, sustained biochemical and serological responses, and favorable renal and bone safety over eight years in Chinese participants with chronic hepatitis B.

BACKGROUND & AIMS:GOLDEN model is designed to predict hepatitis B surface antigen (HBsAg) loss based on patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues therapy. We aimed to validate GOLDEN model's effectiveness in predicting HBsAg loss or decline in interferon-α-treated patients with CHB. METHODS:Interferon-α-treated patients were enrolled from EXCEL study, a randomized controlled trial that included hepatitis B e antigen-positive, noncirrhotic, treatment-naive patients with CHB, and Search-B cohort, a prospective real-world observational cohort of CHB. Using multiple quantitative HBsAg (qHBsAg) measurements, GOLDEN model was used to calculate a patient's probability of achieving HBsAg loss or decline. RESULTS:Among 200 patients in the EXCEL study and 1041 patients from the Search-B cohort, the corresponding cumulative incidence of qHBsAg <100 IU/mL or HBsAg loss was 20.0% and 6.7%, after the median follow-up of 18.0 (interquartile range, 18.0-30.0) and 66.7 (interquartile range, 48.8-84.7) months, respectively. The GOLDEN model achieved an area under the curve of 0.820 (95% confidence interval, 0.737-0.902) for predicting qHBsAg <100 IU/mL in the EXCEL study and 0.964 (95% confidence interval, 0.953-0.974) for predicting HBsAg loss in the Search-B cohort, maintaining robust performance across subgroups. The favorable group showed higher cumulative incidences of qHBsAg <100 IU/mL (42.5% vs 4.6%; P < .001) or HBsAg loss (37.2% vs 0%; P < .001) than the unfavorable group, along with significantly lower qHBsAg levels and faster qHBsAg decline rates. Moreover, the favorable group defined by GOLDEN model and qHBsAg levels at enrollment were confirmed as independent predictors for HBsAg loss or decline. CONCLUSIONS:GOLDEN model is a robust tool for predicting HBsAg loss or decline in interferon-α-treated patients with CHB, offering valuable support for clinicians in developing personalized, effective management strategies for patients with CHB.

Background and Aims: After 3 -years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5 -year results from 2 years into the open -label TAF treatment phase. Methods: All participants completing the 144 -week double-blind treatment were eligible to receive open -label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <2 9 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. Results: The openlabel phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open -label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open -label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. Conclusions: The 5 -year TAF treatment efficacy was high and similar to that of 3 -year TDF followed by 2 -year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Background and Aims:Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment.Results:A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

目的 探究绞股蓝皂苷改善ApoE-/-小鼠肝脏脂质沉积的可能作用机制.方法 24只健康ApoE-/-小鼠采用随机数字表法分为绞股蓝皂苷组、辛伐他汀组和模型组,每组8只;将8只C57BL/6J小鼠作为正常对照组.正常对照组给予普通饲料喂养;模型组、绞股蓝皂苷组、辛伐他汀组给予高脂饲料喂养,喂养8周.8周后,绞股蓝皂苷组给予绞股蓝皂苷灌胃,辛伐他汀组给予辛伐他汀灌胃,正常对照组和模型组使用0.2 mL/10 g生理盐水灌胃,灌胃4周.灌胃期间正常对照组继续给予正常饲料喂养,模型组、绞股蓝皂苷组、辛伐他汀组继续给予高脂饲料喂养.12周后,全自动生化分析仪检测小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、肝脏TC、TG水平;HE染色和油红O染色观察小鼠肝脏病理形态变化与脂质沉积情况;ELISA法检测肝脏组织过氧化脂质(LPO)和还原型谷胱甘肽(GSH)水平;Wes全自动蛋白质印迹定量分析系统检测GPX4、xCT和p53蛋白表达水平;RT-qPCR检测GPX4、xCT和p53 mRNA表达水平.结果 与正常对照组相比,模型组小鼠血清血脂TC、LDL-C、TG水平升高、HDL-C水平降低(P＜0.01);血清肝功能AST、ALT水平升高(P＜0.01);肝细胞体积变大,细胞内可见大量大小不等的脂肪空泡,脂质沉积明显,肝窦狭窄或消失;肝脏组织TC、TG和LPO水平显著升高,GSH水平显著下降(P＜0.01);p53蛋白和mRNA表达增高,GPX4、xCT蛋白和mRNA表达降低(P＜0.01).与模型组比较,绞股蓝皂苷组和辛伐他汀组小鼠血清血脂TG、LDL-C、TC水平降低(P＜0.01),HDL-C水平没有显著变化(P＞0.05);血清肝功能AST、ALT水平降低(P＜0.01);肝细胞体积大小有所恢复,细胞内脂肪空泡显著减少,脂质沉积情况减轻,肝窦狭窄有所缓解;肝脏组织TC、TG和LPO水平显著降低,GSH水平显著升高(P＜0.01);p53蛋白和mRNA的表达降低,GPX4、xCT蛋白和mRNA表达升高(P＜0.05或P＜0.01).结论 绞股蓝皂苷能明显改善肝脏脂质沉积和降低肝脏脂质过氧化反应,其机制可能与抑制肝细胞铁死亡有关.

代谢相关脂肪性肝病是临床常见的慢性肝脏疾病,以脂质代谢异常为主要特征.近年来有学者提出"浊毒"是代谢相关脂肪性肝病的主要病机,得到普遍认可.因此在中医"浊毒"理论指导下,探讨脂质代谢异常在代谢相关脂肪性肝病中的作用有助于开阔中西医结合防治代谢相关脂肪性肝病的新思路.

BACKGROUND AND AIMS:Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).METHODS:Chinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.RESULTS:Of the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log10 IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (-0.4 vs. -3.2 mL/min; p=0.014) and less percentage change in bone mineral density vs. TDF at hip (-0.95% vs. -1.93%) and spine (+0.35% vs. -1.40%).CONCLUSIONS:In chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.

慢性乙型肝炎是人在感染HBV病毒后产生的一种慢性传染性疾病,对人类危害极大.“治未病”是中医学传统思想,对疾病的预防和治疗起到了指导作用.茵芪三黄解毒汤是吕文良教授的经验方,前期的小样本研究已经证实了其临床疗效良好.在对茵芪三黄解毒汤进行深入研究的同时,对其疗效的理论机制进行探讨.通过控析冶未病理论对慢性乙型肝炎的指导意义,阐述菌芪三黄解毒汤的作用机制.

目的:构建可用于预测乙型肝炎病毒相关慢加急性肝衰竭患者结局的风险模型.方法:以国家"十二五"科技重大专项课题"慢加急性肝衰竭中西医结合治疗方案优化研究"入组的乙型肝炎病毒相关慢加急性肝衰竭患者为研究对象,按照2:1分为训练集、测试集.在训练集人群中建立死亡风险模型并通过Cox回归分析,在测试集中验证模型的区分度与一致性.结果:年龄(HR=1.02,95％CI 1.01～1.04)、总胆红素(HR=1.04,95％CI 1.02～1.07)、国际标准化比值(HR=2.58,95％CI 1.98～3.37)、肝性脑病(Ⅰ/Ⅱ期:HR=2.20,95％CI 1.25～3.87;Ⅲ/Ⅳ期:HR=23.67,95％CI 7.74～72.37)、肝肾综合征(HR=3.64,95％CI 1.69～7.82)、低钠血症(HR=1.86,95％CI 1.22～2.84)、血小板计数(20～60:HR=1.42,95％CI 1.89～2.27;>60:HR=2.42,95％CI 1.94～6.20)是预后的独立影响因素;基于上述7项因素建立的列线图可以准确预测乙型肝炎病毒相关慢加急性肝衰竭人群结局;列线图在预测28、336 d结局方面优于终末期肝病模型(MELD)及MELD-Na评分(0.87 vs 0.79/0.80,0.82 vs 0.73/0.75);在预测90 d结局时优于MELD评分(0.86 vs 0.79,P=0.042),但与MELD-Na评分差异无统计学意义(0.86 vs 0.82,P=0.140).结论:以年龄、总胆红素、国际标准化比值、肝性脑病、肝肾综合征、低钠血症、血小板计数等7个关键因素构建而成的列线图,在预测乙型肝炎病毒相关慢加急性肝衰竭患者死亡风险方面具有一定的价值.

乙肝肝纤维化是由乙型病毒型肝炎导致肝内结缔组织异常增生产生的一个病理过程,进一步发展可转化成肝硬化、肝癌,因此积极治疗肝纤维化对提高患者生活质量,改善疾病预后,具有重要的价值.中医药治疗各种肝病具有较好的疗效,尤其对肝纤维化预防、治疗甚至逆转其发展等方面展现出独特的优势.茵芪三黄解毒汤是治疗乙肝肝纤维化的效方,现从中医对肝纤维化的病因病机的认识,茵芪三黄解毒汤成立的依据,茵芪三黄解毒汤的组方意义及组方中药物的现代药理研究等角度探究其疗效机理.茵芪三黄解毒汤以疏肝健脾,清热利湿法建方,切合了乙肝肝纤维化正虚邪恋,湿毒侵袭的基本病因,肝郁脾虚,湿热内结的病机.全方药物配伍严谨,共奏益气健脾、清热利湿、解毒通络、消瘀化癥之功,且其药理作用具有保护肝脏,治疗肝纤维化,使之逆转或延缓发展的作用.文章为茵芪三黄解毒汤治疗乙肝肝纤维化提供理论依据.

目的:探讨扶正通络汤治疗晚期原发性肝癌(Hepatocellular Carcinoma,HCC)的临床疗效及对免疫功能的影响.方法:采用对照研究的方法将85例HCC患者作为研究对象,按患者初次接受中医药治疗的顺序排号后,随机分为治疗组(43例)和对照组(42例).在接受常规护肝及对症治疗的前提下,对照组予槐耳颗粒口服治疗;治疗组予中药扶正通络汤进行治疗,1个月为一个疗程,共4个疗程.分别比较两组第2、4疗程的卡氏功能状态评分标准(Karnofsky Score,KPS)评分和中医证候积分,以及治疗结束后的中医临床疗效和血清免疫球蛋白(Immunoglobulins,Ig)的水平变化情况.结果:与治疗前比较,第2、4疗程的中医证候积分和KPS评分均有所改善,第2疗程后的差异具有统计学意义(P<0.05),第4疗程后的差异具有明显的统计学意义(P<0.01);疗程结束后,对照组的治疗有效率低于观察组,差异具有统计学意义(P<0.05);治疗后IgA和IgG水平较前明显降低,且治疗组优于对照组,差异具有统计学意义(P<0.05);IgM水平略有降低,但两组治疗前后组间及组内比较,差异均无统计学意义(P>0.05).结论:应用扶正通络汤加减治疗晚期HCC,临床疗效确切,能增强机体的免疫功能,值得临床推广和应用.

Background Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear. Methods Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed. Results HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg. Conclusion Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment. Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530 .

ObjectiveTo investigate the clinical efficacy and safety of sofosbuvir combined with ribavirin in the treatment of treatment-nave patients with genotype 2 chronic hepatitis C virus (HCV) infection. MethodsTreatment-nave patients with genotype 2 HCV infection were screened in sixteen research centers of China. All patients received sofosbuvir (400 mg/tablet, 1 tablet/d) combined with ribavirin (1000 mg/d for patients with a body weight of ＜75 kg and 1200 mg/d for those with a body weight of ≥75 kg) for 12 weeks and were followed up for 12 weeks after drug withdrawal. The primary outcome measure was sustained virologic response at week 12 of follow-up, and the secondary outcome measures included the proportion of patients with HCV RNA below the lower limit of quantitation at weeks 2, 4, 8, and 12 of treatment and after 4 weeks of drug withdrawal, virological rebound rate at weeks 4, 8, and 12 of treatment, and recurrence rate at weeks 4 and 12 of follow-up. Adverse events were observed during treatment to evaluate drug safety. ResultsA total of 136 subjects were enrolled, among whom 121 had no liver cirrhosis and 15 had compensated liver cirrhosis. The sustained virologic response (SVR) rate was 92.6% (95% confidence interval: 88.3%-97.0%) after 12 weeks of drug withdrawal. At week 8 of treatment, 1 patient experienced virological rebound; after 4 weeks of drug withdrawal, 8 patients experienced virological rebound; after 12 weeks of drug withdrawal, 10 patients experienced virological rebound. Among the 136 subjects, 128 (94.1%) reported 549 cases of treatment-emergent adverse events, among which 243 cases were associated with sofosbuvir and/or ribavirin and were reported in 99 subjects (72.8%). No adverse events leading to the adjustment or discontinuation of sofosbuvir were observed. A total of 7 serious adverse events were reported in 6 patients (4.4%), among which only one (a low echo area in the liver with unknown nature) was considered possibly associated with sofosbuvir and/or ribavirin. No adverse events leading to study discontinuation or death were observed. ConclusionSofosbuvir combined with ribavirin can achieve a high SVR rate in treatment-nave patients with genotype 2 chronic HCV infection, with mild adverse reactions and acceptable safety profile.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9–43.2%) in the experiment group and 27.21% (95% CI 22.0–32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4–12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

原发性肝癌(Primary Hepatocellular Cglcinoma,PHC)为临床中最常见的恶性肿瘤之一.PHC在我国已被列入重点筛查和预防治疗的疾病.PHC起病隐匿,临床中PHC早期多没有特征性临床表现.因此,血清学标志物的诊断价值对肝癌早期诊断尤为重要.目前,甲胎蛋白(AFP)作为诊断和监测PHC最常用的指标,具有一定的价值,但临床中小肝癌的AFP可呈阴性,同时一些慢性肝病患者的血清AFP可呈现阳性,因此,新型灵敏度及特异度高的血清肿瘤标志物,成为学者们研究的热点.现就用于原发性肝癌肿瘤标记物的研究进展做一综述.

BackgroundNucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal.Methods/designThe study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5mg per day for consolidation therapy for 96weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial.ConclusionThis study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population.Trial registrationChinese Clinical Trial Registry No. ChiCTR1900021232. Registered on February 2, 2019

随着国人生活质量的改善及饮食结构的改变,导致代谢性疾病的发病率逐年上升.其中与脂代谢和胰岛素抵抗相关的非酒精性脂肪性肝病合并Ⅱ型糖尿病进入了笔者的视野.中医药对于该病的治疗具有一定优势,诸多基础及临床研究能够提供一定的数据说明中医药对该病的治疗效果,是临床上值得推广的治疗方法.但具体的作用机制尚不明确,仍需进一步研究.

Background: In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported. Methods: A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion. Results: The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r = 0.094, P = 0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC = 0.821). Conclusions: The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.