Department of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, Guangdong Province, China.
Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, Guangdong Province, China.
World J Gastroenterol. 2021 Mar 21;27(11):1101-1116. doi: 10.3748/wjg.v27.i11.1101.
China has a high prevalence of hepatitis B virus (HBV), but most chronic hepatitis B (CHB) patients do not receive standardized antiviral therapy. There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.
To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.
This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998. The median follow-up times were 10 and 7 years, respectively. A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups. The median follow-up times were 8 and 7 years, respectively. Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma (HCC), and the Cox regression model was used to analyze the risk factors for HCC.
Among the patients in the non-antiviral group, 16.9% had spontaneous decreases in HBV DNA to undetectable levels, and 32.8% showed hepatitis B e antigen (HBeAg) seroconversion. In the antiviral group, 87.2% of patients had undetectable HBV DNA, and 52% showed HBeAg seroconversion. Among CHB and hepatitis B cirrhosis patients, the cumulative incidence rates of HCC were 14.9% and 53.1%, respectively, in the non-antiviral group and were 10.7% and 31.9%, respectively, in the antiviral group. There was no difference between the two groups regarding the CHB patients ( = 0.842), but there was a difference between the groups regarding the hepatitis B cirrhosis patients ( = 0.026). The cumulative incidence rates of HCC were 1.6% and 22.3% ( = 0.022) in the groups with and without spontaneous HBeAg seroconversion, respectively. The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6% and 19.1%, respectively ( = 0.051). There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB ( = 0.119), but there was a significant difference between the two groups regarding the patients with cirrhosis ( = 0.004). The Cox regression model was used for regression of the corrected REACH-B score, which showed that alanine aminotransferase > 400 U/L, history of diabetes, and family history of liver cancer were risk factors for HCC among men aged > 40 years ( < 0.05). Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.
Antiviral therapy and non-antiviral therapy with liver protection and anti-inflammatory therapy can reduce the risk of HCC. Antiviral therapy may mask the spontaneous serological response of some patients during CHB. Therefore, the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.
中国乙型肝炎病毒（HBV）感染率高，但大多数慢性乙型肝炎（CHB）患者未接受规范的抗病毒治疗。关于大量未接受抗病毒治疗的 CHB 患者的结局，相关报道较少。
观察未接受抗病毒治疗的 CHB 患者的长期随访结局。
本研究纳入 1993 年至 1998 年期间未接受抗病毒治疗且仅接受保肝抗炎治疗的 362 例 CHB 患者和 96 例乙型肝炎肝硬化患者。中位随访时间分别为 10 年和 7 年。选择 203 例接受抗病毒治疗的 CHB 患者和 129 例乙型肝炎肝硬化患者作为对照组。中位随访时间分别为 8 年和 7 年。采用 Kaplan-Meier 曲线分析肝细胞癌（HCC）的累积发生率，采用 Cox 回归模型分析 HCC 的危险因素。
在未抗病毒组中，有 16.9%的患者 HBV DNA 自发降至不可检测水平，32.8%的患者 HBeAg 血清学转换。在抗病毒组中，87.2%的患者 HBV DNA 不可检测，52%的患者 HBeAg 血清学转换。在 CHB 和乙型肝炎肝硬化患者中，未抗病毒组 HCC 的累积发生率分别为 14.9%和 53.1%，抗病毒组分别为 10.7%和 31.9%。两组 CHB 患者 HCC 的累积发生率差异无统计学意义（=0.842），但乙型肝炎肝硬化患者差异有统计学意义（=0.026）。HBeAg 自发血清学转换组和未转换组 HCC 的累积发生率分别为 1.6%和 22.3%（=0.022）。HBV DNA 自发降至不可检测水平组和未降至不可检测水平组 HCC 的发生率分别为 1.6%和 19.1%（=0.051）。对于耐药性 CHB 患者，两组 HCC 的累积发生率差异无统计学意义（=0.119），但对于肝硬化患者，两组差异有统计学意义（=0.004）。Cox 回归模型对校正后的 REACH-B 评分进行回归分析显示，丙氨酸氨基转移酶（ALT）>400 U/L、糖尿病史和肝癌家族史是 40 岁以上男性 HCC 的危险因素（<0.05）。多因素分析显示，男性肝癌家族史是 HCC 的危险因素。
抗病毒治疗和以保肝抗炎为主的非抗病毒治疗均可降低 HCC 风险。抗病毒治疗可能掩盖了部分 CHB 患者的自发血清学应答。因此，不能高估早期抗病毒治疗降低 HCC 发生率的作用。
