Zhang Siyu, Zhang Xiaoxiao, Jin Huiming, Dou Yao, Li Lu, Yuan Xiwei, Dong Chen, Hou Mengmeng, Nan Yue-Min, Shang Jia
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang, Hebei, China.
Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
J Clin Transl Hepatol. 2023 Feb 28;11(1):67-75. doi: 10.14218/JCTH.2022.00066. Epub 2022 May 13.
The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation.
Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR).
We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, <0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, =0.036), grade of steatosis (G2 [HR: 0.447, =0.004]; G3 [HR: 0.085, =0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, <0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, <0.001) accelerated the CVR.
In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.
非酒精性脂肪性肝病（NAFLD）对慢性乙型肝炎（CHB）治疗结局的影响尚不明确，值得深入研究。
纳入经组织学证实接受一线抗病毒方案作为初始治疗的CHB患者，并根据是否合并NAFLD进行分组，每6个月随访一次。记录多个时间点与治疗反应相关的数据并进行比较。采用Kaplan-Meier和Cox回归分析评估NAFLD对完全病毒学应答（CVR）的影响。
我们纳入了267例患者（CHB：164例；合并NAFLD的CHB：103例），随访时间相当。他们在基线HBV DNA水平和HBeAg阳性率方面也具有可比性。合并NAFLD的患者随着时间推移，HBV DNA、定量HBsAg、pgRNA和肝酶水平下降不显著；此外，在6、12、18、24个月时，他们的CVR累积发生率显著较低，低水平病毒血症（LLV）累积发生率显著较高。合并NAFLD时CHB的首次CVR延迟（11.0对7.0个月，<0.001），且随着肝脂肪变性程度加重进一步延长（2-3级对1级：13.0对9.0个月）。多因素分析显示，HBeAg阳性（HR：0.650，P=0.036）、脂肪变性程度（G2[HR：0.447，P=0.004]；G3[HR：0.085，P=0.002]）和HBV DNA（log10 IU/mL）（HR：0.687，P<0.001）与CVR延迟显著相关，而坏死性炎症程度（HR：1.758，P<0.001）加速CVR。
在接受初始抗病毒治疗的CHB患者中，NAFLD与较高的HBV DNA、pgRNA和肝酶水平相关，且LLV发生率较高和CVR延迟。
