Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Saudi J Gastroenterol. 2019 Sep-Oct;25(5):319-326. doi: 10.4103/sjg.SJG_537_18.
BACKGROUND/AIM: Acute-on-chronic liver failure (ACLF-B) in spontaneous reactivation of chronic hepatitis B (SR-CHB) has high mortality. Tenofovir disoproxil fumarate (TDF) improves survival by ~40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine (LDT) with TDF may negate this risk and could boost rapid viral clearance and improve clinical outcomes.
Seventy consecutive patients with SR-CHB were randomized to TDF (300 mg/day, n = 35) or TDF plus LDT (600 mg/day; n = 35). In all, 25 had ACLF-B and none had option for liver transplantation. Primary endpoint was survival at 3 months. Secondary endpoints were survival at 3 months in ACLF-B, serial reduction in hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) loss and liver-related complications.
Overall baseline clinical and laboratory parameters in the two groups were comparable. Reduction in HBV DNA at weeks 2, 4 and 12 was independent of treatment groups and presence of ACLF-B (P < 0.01). All six patients with HBsAg loss at 12 weeks had lower HBV DNA at baseline and none had ACLF-B. Patients with no ACLF-B had more rapid decline in bilirubin and alanine aminotraminase at week 2 compared with ACLF-B. Patients on TDF plus LDT showed significant improvement in AKI on follow-up (five of six patients) compared with TDF monotherapy (none of six patients) and had less reduction in estimated glomerular filtration rate at week 12. Eight of 10 patients with liver-related deaths received TDF monotherapy (P = 0.02). New-onset septic shock, TDF monotherapy, e-antibody positivity, and higher baseline model for end-stage liver disease score were predictors of mortality in ACLF-B. None had treatment-related severe adverse effects.
Addition of LDT to tenofovir is safe and may be renoprotective in spontaneous reactivation of hepatitis B. Combination therapy improves survival in ACLF-B despite comparable HBV DNA suppression to tenofovir monotherapy.
背景/目的：慢性乙型肝炎（CHB）自发性再激活（SR-CHB）导致的慢加急性肝衰竭（ACLF-B）患者死亡率较高。替诺福韦酯（TDF）可将 ACLF-B 患者的生存率提高约 40%，但有潜在的肾毒性。替比夫定（LDT）联合 TDF 可能会消除这种风险，并能加快病毒清除速度，改善临床结局。
连续纳入 70 例 SR-CHB 患者，随机分为 TDF（300 mg/天，n=35）或 TDF 加 LDT（600 mg/天；n=35）组。所有患者均无肝移植适应证，其中 25 例为 ACLF-B。主要终点为 3 个月时的生存率。次要终点为 ACLF-B 患者 3 个月时的生存率、乙型肝炎病毒（HBV）DNA 的连续下降、乙型肝炎表面抗原（HBsAg）丢失和肝脏相关并发症。
两组患者的基线临床和实验室参数总体相似。第 2、4 和 12 周时 HBV DNA 的降低与治疗组和 ACLF-B 无关（P＜0.01）。所有 12 周时 HBsAg 丢失的 6 例患者基线 HBV DNA 水平较低，且均无 ACLF-B。无 ACLF-B 的患者在第 2 周时胆红素和丙氨酸氨基转移酶的下降速度快于 ACLF-B 患者。与 TDF 单药治疗相比（6 例患者均无），TDF 加 LDT 组患者在随访时 AKI 显著改善（6 例中有 5 例），且第 12 周时估算肾小球滤过率的下降幅度较小。10 例与肝脏相关的死亡患者中有 8 例接受了 TDF 单药治疗（P=0.02）。新发感染性休克、TDF 单药治疗、e 抗体阳性和较高的基线终末期肝病模型评分是 ACLF-B 患者死亡的预测因素。两组均无治疗相关的严重不良事件。
替比夫定联合替诺福韦酯安全，在乙型肝炎自发性再激活时可能具有肾脏保护作用。尽管与替诺福韦酯单药治疗相比，HBV DNA 抑制情况相似，但联合治疗可改善 ACLF-B 患者的生存率。
