Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California.
JAMA Intern Med. 2023 Feb 1;183(2):97-105. doi: 10.1001/jamainternmed.2022.5699.
Chronic hepatitis C (CHC) and its complications are associated with high rates of morbidity and mortality. However, large-scale data analysis of the long-term liver and nonliver effects of direct-acting antiviral (DAA) treatment has been limited.
To assess the association of hepatitis C virus elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up among a large nationwide cohort of insured patients with CHC in the US.
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of 245 596 adult patients with CHC using data from the Optum Clinformatics Data Mart database, 2010 to 2021. Of the total cohort, 40 654 patients had received 1 or more prescriptions for DAA medication (without interferon), and 204 942 patients were untreated.
Treatment with a DAA.
Incidence of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease, cardiovascular disease), and overall mortality.
The DAA-treated cohort (vs untreated) were older (mean [SD] age, 59.9 [10.8] vs 58.5 [13.0] years; P < .001); more likely to be male (25 060 [62%] vs 119 727 [58%] men; P < .001) and White (23 937 [59%] vs 115 973 [57%]; P < .001) individuals; and more likely to have diabetes (10 680 [26%] vs 52 091 [25%]; P < .001) or cirrhosis (17 971 [44%] vs 60 094 [29%]; P < .001). Comparing DAA-treated with untreated patients, the incidence (per 1000 person-years) of liver outcomes (eg, decompensation, 28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P < .001, and HCC in compensated cirrhosis, 20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P < .001) and nonliver outcomes (eg, diabetes, 30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P < .001; and chronic kidney disease, 31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P < .001) were significantly lower in treated patients. The all-cause mortality rates per 1000 person-years were also significantly lower in DAA-treated compared with untreated patients (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P < .001). In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted hazard ratio [aHR] for HCC, 0.73; decompensation, 0.36), nonliver (aHR for diabetes, 0.74; chronic kidney disease, 0.81; cardiovascular disease, 0.90; nonliver cancer, 0.89), and mortality outcomes (aHR, 0.43).
The findings of this retrospective cohort study indicate that DAA treatment for insured patients with CHC was associated with improved liver- and nonliver outcomes, and ultimately, with long-term overall survival.
慢性丙型肝炎（CHC）及其并发症与高发病率和死亡率相关。然而，对直接作用抗病毒（DAA）治疗的长期肝脏和非肝脏影响的大规模数据分析受到限制。
评估丙型肝炎病毒（HCV）通过 DAA 治疗消除与美国大规模全国性 CHC 参保患者长期随访期间肝脏和非肝脏发病率和死亡率风险之间的关联。
设计、地点和参与者：这是一项回顾性队列研究，使用 Optum Clinformatics Data Mart 数据库中的数据，纳入了 2010 年至 2021 年间 245596 名患有 CHC 的成年患者。在总队列中，40654 名患者接受了 1 种或多种 DAA 药物（不含干扰素）治疗，204942 名患者未接受治疗。
DAA 治疗。
肝细胞癌（HCC）、肝功能失代偿、相关非肝脏事件（非肝癌、糖尿病、慢性肾脏病、心血管疾病）和总死亡率的发生率。
与未治疗患者相比，DAA 治疗队列（vs 未治疗）的年龄更大（平均[标准差]年龄，59.9[10.8]岁 vs 58.5[13.0]岁；P<0.001）；更可能为男性（25060[62%]名 vs 119727[58%]名男性；P<0.001）和白人（23937[59%]名 vs 115973[57%]名；P<0.001）个体；并且更可能患有糖尿病（10680[26%]名 vs 52091[25%]名；P<0.001）或肝硬化（17971[44%]名 vs 60094[29%]名；P<0.001）。与未治疗患者相比，DAA 治疗患者的肝脏结局（如肝功能失代偿，28.2[95%CI，27.0-29.4] vs 40.8[95%CI，40.1-41.5]；P<0.001）和非肝脏结局（如糖尿病，30.2[95%CI，35.4-37.7] vs 37.2[95%CI，36.6-37.9]；P<0.001）和非肝脏结局（如糖尿病，30.2[95%CI，35.4-37.7] vs 37.2[95%CI，36.6-37.9]；P<0.001）的发生率（每 1000 人年）显著较低，慢性肾脏病，31.1[95%CI，29.9-32.2] vs 34.1[95%CI，33.5-34.7]；P<0.001）。与未治疗患者相比，DAA 治疗患者的全因死亡率（每 1000 人年）也显著降低（死亡率，36.5[95%CI，35.4-37.7] vs 64.7[95%CI，63.9-65.4]；P<0.001）。在多变量回归分析中，DAA 治疗与肝脏（HCC 的调整后危险比[aHR]，0.73；肝功能失代偿，0.36）、非肝脏（糖尿病的 aHR，0.74；慢性肾脏病，0.81；心血管疾病，0.90；非肝癌，0.89）和死亡率结局（aHR，0.43）风险显著降低独立相关。
这项回顾性队列研究的结果表明，DAA 治疗 CHC 参保患者与改善肝脏和非肝脏结局相关，并最终与长期总体生存率相关。
