Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2020 Feb;83(2):125-133. doi: 10.1097/JCMA.0000000000000247.
Nucleos(t)ide analogue (NA) therapy reduces the risk of disease progression in chronic hepatitis B virus-infected patients. However, the risk of liver decompensation, hepatic failure, and mortality after discontinuation of NA therapy remains unknown.
Among 51,574 chronic hepatitis B patients who received NAs in the Taiwan National Health Insurance Research Database, we identified 8,631 patients who continued NA therapy (treatment cohort) and 8,631 propensity-score matched patients who stopped NA therapy after their initial 1.5 years treatment (off-therapy cohort) between October 1, 2003 and December 31, 2011. All study subjects were followed up from the index date, that is, the date 1.5 years after the first prescription of NA, until development of liver decompensation and hepatic failure, death or end of 18-month follow-up period.
Treatment cohort had significantly lower risks of liver decompensation (1.05%; 95% confidence interval [CI], 0.81%-1.30% vs 2.13%; 95% CI, 1.82%-2.45%; p < 0.001), hepatic failure (0.35%; 95% CI, 0.21%-0.49% vs 0.63%; 95% CI, 0.46%-0.80%; p = 0.008) and overall mortality (1.67%; 1.37%-1.98% vs 2.44%; 95% CI, 2.10%-2.77%; p < 0.001) during the 18-month follow-up period. After adjusting for potential confounders, NA continuous therapy was associated with reduced risks of liver decompensation (hazard ratio [HR]: 0.47; 95% CI, 0.36-0.62, p < 0.001), hepatic failure (HR: 0.53; 95% CI, 0.33-0.86, p = 0.01) and overall mortality (HR: 0.67; 95% CI, 0.53-0.84, p = 0.001). The number needed to reduce one less disease progression and mortality was 47. The protective effect of NA continuous therapy was found in nearly all subgroups.
NA continuous therapy is associated with reduced risks of liver decompensation, hepatic failure, and overall mortality.
核苷（酸）类似物（NA）治疗可降低慢性乙型肝炎病毒感染患者疾病进展的风险。然而，NA 治疗停药后发生肝失代偿、肝功能衰竭和死亡的风险仍不清楚。
在台湾全民健康保险研究数据库中，我们纳入了 51574 名接受 NA 治疗的慢性乙型肝炎患者，其中 8631 名患者继续接受 NA 治疗（治疗组），8631 名患者在初始 1.5 年治疗后采用倾向性评分匹配停止 NA 治疗（停药组）。所有研究对象从指数日期（即首次开具 NA 处方后 1.5 年）开始随访，直至发生肝失代偿和肝功能衰竭、死亡或 18 个月随访期结束。
治疗组肝失代偿（1.05%；95%置信区间[CI]，0.81%-1.30% vs. 2.13%；95%CI，1.82%-2.45%；p<0.001）、肝功能衰竭（0.35%；95%CI，0.21%-0.49% vs. 0.63%；95%CI，0.46%-0.80%；p=0.008）和总体死亡率（1.67%；1.37%-1.98% vs. 2.44%；95%CI，2.10%-2.77%；p<0.001）在 18 个月的随访期间均显著降低。在调整了潜在混杂因素后，NA 持续治疗与肝失代偿（风险比[HR]：0.47；95%CI，0.36-0.62，p<0.001）、肝功能衰竭（HR：0.53；95%CI，0.33-0.86，p=0.01）和总体死亡率（HR：0.67；95%CI，0.53-0.84，p=0.001）风险降低相关。减少一次疾病进展和死亡的所需人数为 47。NA 持续治疗的保护作用在几乎所有亚组中均存在。
NA 持续治疗与肝失代偿、肝功能衰竭和总体死亡率降低相关。
