Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Clin Gastroenterol Hepatol. 2020 Aug;18(9):2064-2072.e2. doi: 10.1016/j.cgh.2020.01.018. Epub 2020 Jan 23.
BACKGROUND & AIMS: Little is known about the effects of baseline hepatitis flares (level of alanine aminotransferase ≥5-fold above the upper limit of normal) on the outcomes of patients with chronic hepatitis B virus (HBV) infection with decompensated cirrhosis treated with nucleos(t)ide analogues. We aimed to investigate these effects.
We performed a cohort study of 511 consecutive patients (78.1% men; 58.7% with flares at baseline) with chronic HBV infection and decompensated cirrhosis who were treated with nucleos(t)ide analogues as soon as decompensation was noted. Patients were enrolled from January 2002 to March 2018 at a tertiary care center in Taiwan and followed up for 16 years.
Patients with hepatitis flares had higher mean baseline levels of HBV DNA (6.44 ± 1.52 vs 6.08 ± 1.46 log IU/mL; P = .003), hepatitis B surface antigen, and total bilirubin; prolonged prothrombin time; higher platelet counts (108.0 ± 42.9 vs 83.6 ± 44.7 103/μL; P < .001); and a higher proportion were infected with HBV genotype B, compared with patients without flares. Patients with flares had lower ratios of neutrophils to lymphocytes than patients with flares (6.14 ± 9.18 vs 9.12 ± 1.36; P = .019); were less likely than patients without flares to be positive for hepatitis B e antigen, ascites, esophageal varices, or splenomegaly; and a lower proportion died or underwent liver transplantation (46.5% vs 73.2% of patients without flares; P < .001), even though the patients without flares had similar short-term (<3 mo) outcomes. Factors associated independently with baseline flares were esophageal varices (odds ratio [OR], 0.165; 95% CI, 0.067-0.406), ascites (OR, 0.415; 95% CI, 0.178-0.969), levels of total bilirubin (OR, 1.158; 95% CI, 1.041-1.269), prolonged prothrombin time (OR, 1.095; 95% CI, 1.033-1.168), and higher platelet counts (OR, 1.009; 95% CI, 1.00-1.018). After we used propensity score matching to match patients with and without baseline flares, factors associated with the cumulative incidence of death or liver transplantation were flares (hazard ratio [HR], 0.491; 95% CI, 0.317-0.76), ratio of neutrophils to lymphocytes (HR, 1.278; 95% CI, 1.027-1.591), and prolonged prothrombin time (HR, 1.223; 95% CI, 1.052-1.423).
In a 16-year study of patients with chronic HBV infection and decompensated cirrhosis treated with nucleos(t)ide analogues, a baseline flare of hepatitis was associated independently with better long-term (≥3 mo) outcomes than no flare.
对于乙型肝炎病毒（HBV）感染合并失代偿性肝硬化患者，核苷（酸）类似物治疗后基线肝炎发作（丙氨酸氨基转移酶水平高于正常值上限的 5 倍以上）对其结局的影响知之甚少。本研究旨在探讨这些影响。
我们对 2002 年 1 月至 2018 年 3 月在台湾一家三级医疗中心就诊的 511 例慢性 HBV 感染合并失代偿性肝硬化且一经发现失代偿即开始接受核苷（酸）类似物治疗的患者进行了一项队列研究。随访 16 年。
肝炎发作患者的基线 HBV DNA 水平（6.44±1.52 与 6.08±1.46 log IU/mL；P=0.003）、乙型肝炎表面抗原和总胆红素水平更高；凝血酶原时间延长；血小板计数更高（108.0±42.9 与 83.6±44.7 103/μL；P<0.001）；与无肝炎发作患者相比，乙型肝炎病毒基因型 B 感染的比例更高。肝炎发作患者的中性粒细胞与淋巴细胞比值低于无肝炎发作患者（6.14±9.18 与 9.12±1.36；P=0.019）；与无肝炎发作患者相比，乙型肝炎 e 抗原、腹水、食管胃静脉曲张或脾肿大阳性的可能性更低；肝炎发作患者的死亡率或肝移植率更低（46.5%与无肝炎发作患者的 73.2%；P<0.001），尽管无肝炎发作患者的短期（<3 个月）结局相似。与基线肝炎发作相关的独立因素为食管胃静脉曲张（比值比[OR]，0.165；95%置信区间[CI]，0.067-0.406）、腹水（OR，0.415；95%CI，0.178-0.969）、总胆红素水平（OR，1.158；95%CI，1.041-1.269）、凝血酶原时间延长（OR，1.095；95%CI，1.033-1.168）和血小板计数较高（OR，1.009；95%CI，1.00-1.018）。我们使用倾向评分匹配来匹配基线有和无肝炎发作的患者后，与死亡或肝移植累积发生率相关的因素为肝炎发作（风险比[HR]，0.491；95%CI，0.317-0.76）、中性粒细胞与淋巴细胞比值（HR，1.278；95%CI，1.027-1.591）和凝血酶原时间延长（HR，1.223；95%CI，1.052-1.423）。
在一项对接受核苷（酸）类似物治疗的慢性 HBV 感染合并失代偿性肝硬化患者进行的 16 年研究中，基线肝炎发作与无肝炎发作相比，与更好的长期（≥3 个月）结局独立相关。
