妊娠期HBV相关慢加急性肝衰竭的临床特征和转归
DOI: 10.3969/j.issn.1001-5256.2022.04.010
Clinical features and prognosis of HBV-related acute-on-chronic liver failure in pregnancy
-
摘要:
目的 探讨妊娠期HBV相关慢加急性肝衰竭(HBV-ACLF)患者的临床特征和转归。 方法 回顾性分析上海市公共卫生临床中心2008年6月—2020年7月收治的26例妊娠期HBV-ACLF患者的临床资料,包括年龄、发病孕周、产次、首发症状、入院时并发症、实验室指标(WBC、Hb、PLT、ALT、TBil、Alb、SCr、MELD评分、HBsAg、HBV DNA等)、腹部超声、分娩方式、胎儿情况、治疗措施、预后转归等。正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料2组间比较采用Wilcoxon秩和检验;计数资料2组间比较采用χ2检验或Fisher精确检验。 结果 26例患者中8例均在发病后28 d内死亡,病死率达30.8%。经产妇22例,占84.6%,ACLF往往发生在妊娠晚期(20/26,76.9%),平均发病孕周为(30.9±5.8)周。HBV-ACLF临床表现不典型,首发症状常为乏力、纳差(21/26,80.8%)和尿黄(19/26,73.1%)等。死亡组的TBil(Z=-2.056,P=0.041)、凝血酶原时间(Z=-2.362,P=0.016)、国际标准化比值(Z=-2.528,P=0.009)、MELD评分(Z=-2.223,P=0.026)、首发症状至诊断时间(t=-2.468,P=0.021)、HBV DNA水平(χ2=7.571,P=0.021)、肝性脑病严重程度(χ2=24.775,P<0.001)、并发症发生率(χ2=5.951,P=0.042)显著高于存活组,而纤维蛋白原(Z=-2.667,P=0.006)、凝血酶原活动度(Z=-2.365,P=0.016)水平明显低于存活组。 结论 HBV-ACLF是妊娠晚期严重并发症,经产妇多见,短期病死率极高。其早期临床表现隐匿,高MELD评分、高病毒载量和并发症的出现往往提示预后不良。 Abstract:Objective To investigate the clinical features and prognosis of pregnant women with HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A retrospective analysis was performed for the clinical data of 26 pregnant women with HBV-ACLF who were admitted to Shanghai Public Health Clinical Center from June 2008 to July 2020, including age, gestational weeks at disease onset, parity, initial symptoms, complications on admission, laboratory markers [white blood cell count, hemoglobin, platelet count, alanine aminotransferase, total bilirubin (TBil), albumin, serum creatinine, Model for End-Stage Liver Disease (MELD) score, HBsAg, and HBV DNA], abdominal ultrasound, mode of delivery, fetus conditions, treatment measures, and prognosis. The t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Results Among the 26 patients, 8 died within 28 days after disease onset, and the mortality rate reached 30.8%. There were 22 multiparous patients, accounting for 84.6%, and HBV-ACLF often occurred in the third trimester of pregnancy (20/26, 76.9%), with a mean gestational age of 30.9±5.8 weeks. HBV-ACLF often had atypical clinical manifestations, and initial symptoms included weakness, poor appetite (21/26, 80.8%), and yellow urine (19/26, 73.1%). Compared with the survival group, the death group had significantly higher levels of TBil (Z=-2.056, P=0.041), prothrombin time (Z=-2.362, P=0.016), international normalized ratio (Z=-2.528, P=0.009), and MELD score (Z=-2.223, P=0.026), a significantly longer time from initial symptom to diagnosis (Z=-2.468, P=0.021), significantly higher HBV DNA level (χ2=7.571, P=0.021), degree of hepatic encephalopathy (χ2=24.775, P < 0.001), and incidence rate of complications (χ2=5.951, P=0.042), and significantly lower levels of fibrinogen (Z=-2.667, P=0.006) and prothrombin time activity (Z=-2.365, P=0.016). Conclusion HBV-ACLF is a serious complication in the third trimester of pregnancy and is often observed in multiparous patients, with an extremely high short-term mortality. It often has atypical clinical manifestations in the early stage, and high MELD score, high viral load, and complications often indicate a poor prognosis. -
妊娠合并肝衰竭是临床常见的危重症之一,其发生的病因较多,在我国HBV感染是最重要的原因之一[1-2]。慢加急性肝衰竭(ACLF)是最常见的肝衰竭类型,是在慢性肝病的基础上,短时间内发生急剧肝功能失代偿的一组临床症候群,常合并多器官衰竭,严重威胁患者的生命安全[3-4]。目前,国内外对于妊娠期发生HBV-ACLF的研究报道较少,使得临床上缺失该疾病的具体诊疗意见。本研究拟对妊娠期HBV-ACLF患者的临床资料进行回顾性分析,描述在孕产妇这一特殊人群中HBV-ACLF的临床特征和预后,以供临床参考。
1. 资料与方法
1.1 研究对象
对2008年6月—2020年7月于本院住院的26例妊娠期HBV-ACLF患者资料进行回顾性队列分析。所有患者通过妇科超声证实均为单胎妊娠。诊断标准:(1)HBsAg和/或HBV DNA阳性超过6个月;(2)符合《肝衰竭诊治指南(2018年版)》[5]。排除标准:(1)合并HIV、HCV等其他噬肝病毒感染者;(2)其他原因引起的肝衰竭(药物性、酒精性、遗传性、代谢性、自身免疫性等);(3)合并恶性肿瘤及其他严重系统性疾病的患者。预后判断标准:对所有患者自出院起随访至少90 d,存活组标准:乏力、消化道症状及肝性脑病等明显改善或消失,肝功能指标明显好转或恢复正常[TBil降至正常值上限的5倍以下,凝血酶原活动度(PTA)>40%或国际标准化比值(INR)<1.5];死亡组标准:患者在住院期间经抢救无效死亡,或自动出院后电话随访确定死亡。急性肾损伤[6]:48 h内血清肌酐(SCr)较基础值升高≥50%或绝对值升高≥26.5 μmol/L。产后出血[7]:产后24 h内阴道分娩出血超过500 mL,剖宫产出血超过1000 mL,或血细胞比积下降10%。
1.2 数据采集
回顾性收集的资料包括年龄、发病孕周、产次、首发症状、入院时并发症、实验室指标、胸部CT、腹部超声、分娩方式、胎儿情况、治疗措施、预后转归等;实验室指标包括WBC、Hb、PLT、ALT、TBil、Alb、SCr、凝血酶原时间(PT)、PTA、INR、纤维蛋白原(FIB)、MELD评分、HBsAg、HBV DNA等指标。本研究使用MELD评分系统来评估患者病情的严重程度,其计算公式见参考文献[8]。
1.3 统计学方法
采用SPSS 25.0软件进行统计学分析。正态分布的计量资料以x±s表示,2组间比较采用t检验;非正态分布的计量资料以M(P25~P75)表示,2组间比较采用Wilcoxon秩和检验;计数资料2组间比较采用χ2检验或Fisher精确检验。P<0.05为差异有统计学意义。
2. 结果
2.1 基线资料
26例HBV-ACLF患者中初产妇4例,经产妇22例,年龄20~37岁,平均(28±4)岁。孕中期发病6例,孕晚期发病多见,有20例(20/26, 76.9%),平均发病孕周为(30.9±5.8)周。以乏力、纳差(21/26,80.8%)和尿黄(19/26,73.1%)为主要初始表现,部分患者也可以恶心、呕吐(4例),皮肤黄染、瘙痒(1例),腹胀(1例)及腹泻起病,其中2例患者无明显不适,因产检时发现转氨酶异常就诊。
2.2 临床特征比较
26例HBV-ACLF患者中死亡8例,存活18例。与存活组相比,死亡组的TBil、PT、INR和MELD评分显著升高,而PTA、FIB的水平明显下降,组间差异有统计学意义(P值均<0.05)。首发症状到明确诊断的时间在两组间比较差异有统计学意义(P=0.021)(表 1)。
表 1 妊娠期HBV-ACLF存活组和死亡组患者的临床特征比较Table 1. Comparison of clinical characteristics between HBV-ACLF survival group and death group during pregnancy临床指标 存活组(n=18) 死亡组(n=8) 统计值 P值 年龄(岁) 28.0±4.0 29.0±3.5 t=-0.886 0.385 发病孕周(周) 30.2±6.2 32.5±5.0 t=-0.897 0.379 TBil(μmol/L) 216.1(181.4~262.7) 311.9(221.4~372.4) Z=-2.056 0.041 Alb(g/L) 28.3±2.6 26.5±3.0 t=1.608 0.121 SCr(μmol/L) 51.6(37.1~56.8) 49.0(43.0~54.7) Z=-0.222 0.849 PT(s) 24.3(21.6~30.4) 43.5(25.9~46.9) Z=-2.362 0.016 PTA(%) 33.5(24.8~40.8) 17.0(15.3~33.0) Z=-2.365 0.016 INR 2.2(1.9~3.0) 4.6(2.4~5.2) Z=-2.528 0.009 FIB(g/L) 1.7(1.5~2.1) 0.9(0.6~1.5) Z=-2.667 0.006 血糖(mmol/L) 4.6±1.4 4.2±1.7 t=0.672 0.508 WBC(×109/L) 13.8±6.7 16.9±7.9 t=-1.034 0.312 Hb(g/L) 116.3±20.8 116.4±21.5 t=-0.008 0.993 PLT(×109/L) 162.3±67.8 164.6±68.5 t=-0.081 0.936 MELD评分 18.8(15.7~25.5) 28.7(20.6~32.5) Z=-2.223 0.026 首发症状至诊断时间(d) 6.5±3.5 10.0±3.0 t=-2.468 0.021 首发症状至抗病毒时间(d) 9.5±4.5 11.5±3.0 t=-0.845 0.408 2.3 并发症
所纳入患者入院腹部超声均证实无肝硬化表现,均未进行肝脏穿刺活检。住院期间常见的并发症为:感染16例、肝性脑病15例、腹水9例、急性肾损伤6例以及产后出血5例,感染以肺部感染和腹腔感染多见。死亡组肝性脑病Ⅲ~Ⅳ期的比例显著升高,合并Ⅲ、Ⅳ期肝性脑病的患者病死率高达100%,并发症≥3种的患者病死率达为60%(6/10)(表 2)。
表 2 妊娠期HBV-ACLF并发症分析Table 2. Analysis of HBV-ACLF complications during pregnancy并发症 存活组(n=18) 死亡组(n=8) χ2值 P值 感染[例(%)] 10(55.6) 6(75.0) 0.066 腹水[例(%)] 5(27.8) 4(50.0) 0.382 急性肾损伤[例(%)] 3(16.7) 3(37.5) 0.330 产后出血[例(%)] 3(16.7) 2(25.0) 0.628 肝性脑病[例(%)] 24.775 <0.001 无 11(61.1) 0 Ⅰ~Ⅱ期 7(38.9) 0 Ⅲ~Ⅳ期 0 8(100.0) 并发症数目[例(%)] 5.951 0.042 无 4(22.2) 0 1~2种并发症 10(55.6) 2(25.0) ≥3种并发症 4(22.2) 6(75.0) 2.4 治疗和结局
所有入组患者在多学科协作诊疗及内科对症支持治疗基础上,均接受了核苷(酸)类似物单药治疗,经治疗好转18例,其余8例均在发病后28 d内病死,死亡患者抗病毒疗程均未超过2周。纳入患者HBV DNA复制活跃,其中20例(76.9%)孕妇的HBV DNA≥105 IU/mL,存活组和死亡组HBV DNA水平差异有统计学意义(P<0.05)。共孕育胎儿26例,其中足月儿8例,均存活;早产儿15例,死亡2例;胎死宫内3例,1例孕妇因胎停经阴道诱导娩出一死婴,2例孕妇病情进展迅速,均在入院后2周内死亡(未生产)(表 3)。
表 3 妊娠期HBV-ACLF患者的母婴结局Table 3. Maternal and infant outcomes of HBV-ACLF patients during pregnancy母婴结局 存活(n=18) 死亡(n=8) χ2值 P值 孕妇 HBV DNA[例(%)] 7.571 0.021 <105 IU/mL 5(27.8) 1(12.5) 105~106 IU/mL 10(55.5) 1(12.5) >106 IU/mL 3(16.7) 6(75.0) HBeAg[例(%)] 0.216 阳性 10(55.6) 2(25.0) 阴性 8(44.4) 6(75.0) 生产方式[例(%)] 0.108 剖宫产 12(66.7) 5(62.5) 阴道分娩 6(33.3) 1(12.5) 未生产 0 2(25.0) 胎儿[例(%)] 21(80.8) 5(19.2) 10.301 0.002 足月儿(37~42周) 8(38.1) 0 早产儿(<37周) 13(61.9) 2(40.0) 胎死宫内 0 3(60.0) 3. 讨论
本研究发现HBV-ACLF是妊娠晚期严重并发症,经产妇多见,母婴病死率及胎儿早产率高。患者发病早期病情较隐匿,常以乏力、纳差或尿黄起病,不易引起重视,导致早期诊断困难。病程中可发生一系列并发症,而并发症的出现往往提示预后不良[9]。既往Cordoba等[10]研究表明肝性脑病是肝衰竭预后的独立危险因素和直接死亡原因之一。Banait等[11]也发现妊娠期肝衰竭的高病死率与肝性脑病的发生及分期存在相关性。本研究中死亡组患者肝性脑病严重程度、并发症≥3种的发生率显著高于存活组,Ⅲ、Ⅳ期肝性脑病患者病死率高达100%,这些结果提示妊娠期HBV-ACLF患者肝性脑病的出现,尤其是Ⅲ~Ⅳ期肝性脑病往往提示预后不良,可考虑终止妊娠,积极行肝移植挽救生命。
众所周知,INR、PT、PTA、FIB的水平异常反映机体凝血功能障碍,既往大量研究证实凝血功能[12-13]及胆红素水平[14-15]是肝衰竭诊断与临床分期的重要指标,对判断疾病进展及预后有重要价值。本研究也发现类似结果,与存活组相比,死亡组的TBil、PT、INR水平显著升高,而PTA、FIB水平明显下降。此外,Solanke等[16]曾提出MELD评分可以很好地预测妊娠期肝衰竭患者的预后。本研究中死亡组MELD评分显著升高,结果提示高MELD评分可能与患者的90 d不良预后相关。尽管样本量小,无法精准验证其预测效能,但仍有一定参考价值。
本研究中,与存活组相比,死亡组的患者HBV DNA水平较高,病毒复制活跃,这一结果提示高病毒载量的孕产妇一旦发生HBV-ACLF,往往预后不良。同时死亡组患者均在发病后28 d内死亡,抗病毒疗程均不满2周,从发病到确诊时间以及启动抗病毒时间较晚,这一结果为妊娠期HBV-ACLF应尽早进行抗病毒治疗提供了一定的循证学依据。早在2011年,Garg等学者[17]曾提出富马酸替诺福韦酯(TDF)能够显著提高HBV-ACLF患者90 d存活率,提示快速强效的病毒抑制是减少疾病死亡风险的关键。同时还有研究[18-19]表明HBV激活引起的肝脏炎症坏死是ACLF的始动因素,提出抗病毒治疗的临床获益随着启动时间的推迟以及肝损伤的严重程度而逐渐递减。因此,针对慢性HBV感染的孕妇这一特殊人群,建议临床密切监测其病毒学和肝功能指标变化,对于ALT异常或HBV DNA水平急剧上升的患者有必要进行全面检查,一旦诊断慢性乙型肝炎,可使用TDF抗病毒治疗[20]。即使患者已经出现肝衰竭,立即使用强效抗病毒治疗对于减少不良孕产结局的发生仍有一定的积极作用。
本研究尚存在一定的局限性,仅为单中心的回顾性分析,病例数相对较少,深入研究该病尚需要未来进行多中心大样本的临床研究和基础研究。
综上,妊娠期HBV-ACLF是妊娠晚期严重并发症,经产妇多见,短期病死率极高。该疾病临床表现缺乏特异性,早期诊断困难,高MELD评分、高病毒载量和并发症的出现往往提示预后不良。建议临床密切监测HBV感染孕妇的肝功能、HBV DNA水平、血清标志物、肝脏超声等相关指标,一旦诊断慢性乙型肝炎,尽早进行有效的抗病毒治疗有可能降低妊娠期HBV-ACLF的发生率。
-
表 1 妊娠期HBV-ACLF存活组和死亡组患者的临床特征比较
Table 1. Comparison of clinical characteristics between HBV-ACLF survival group and death group during pregnancy
临床指标 存活组(n=18) 死亡组(n=8) 统计值 P值 年龄(岁) 28.0±4.0 29.0±3.5 t=-0.886 0.385 发病孕周(周) 30.2±6.2 32.5±5.0 t=-0.897 0.379 TBil(μmol/L) 216.1(181.4~262.7) 311.9(221.4~372.4) Z=-2.056 0.041 Alb(g/L) 28.3±2.6 26.5±3.0 t=1.608 0.121 SCr(μmol/L) 51.6(37.1~56.8) 49.0(43.0~54.7) Z=-0.222 0.849 PT(s) 24.3(21.6~30.4) 43.5(25.9~46.9) Z=-2.362 0.016 PTA(%) 33.5(24.8~40.8) 17.0(15.3~33.0) Z=-2.365 0.016 INR 2.2(1.9~3.0) 4.6(2.4~5.2) Z=-2.528 0.009 FIB(g/L) 1.7(1.5~2.1) 0.9(0.6~1.5) Z=-2.667 0.006 血糖(mmol/L) 4.6±1.4 4.2±1.7 t=0.672 0.508 WBC(×109/L) 13.8±6.7 16.9±7.9 t=-1.034 0.312 Hb(g/L) 116.3±20.8 116.4±21.5 t=-0.008 0.993 PLT(×109/L) 162.3±67.8 164.6±68.5 t=-0.081 0.936 MELD评分 18.8(15.7~25.5) 28.7(20.6~32.5) Z=-2.223 0.026 首发症状至诊断时间(d) 6.5±3.5 10.0±3.0 t=-2.468 0.021 首发症状至抗病毒时间(d) 9.5±4.5 11.5±3.0 t=-0.845 0.408 表 2 妊娠期HBV-ACLF并发症分析
Table 2. Analysis of HBV-ACLF complications during pregnancy
并发症 存活组(n=18) 死亡组(n=8) χ2值 P值 感染[例(%)] 10(55.6) 6(75.0) 0.066 腹水[例(%)] 5(27.8) 4(50.0) 0.382 急性肾损伤[例(%)] 3(16.7) 3(37.5) 0.330 产后出血[例(%)] 3(16.7) 2(25.0) 0.628 肝性脑病[例(%)] 24.775 <0.001 无 11(61.1) 0 Ⅰ~Ⅱ期 7(38.9) 0 Ⅲ~Ⅳ期 0 8(100.0) 并发症数目[例(%)] 5.951 0.042 无 4(22.2) 0 1~2种并发症 10(55.6) 2(25.0) ≥3种并发症 4(22.2) 6(75.0) 表 3 妊娠期HBV-ACLF患者的母婴结局
Table 3. Maternal and infant outcomes of HBV-ACLF patients during pregnancy
母婴结局 存活(n=18) 死亡(n=8) χ2值 P值 孕妇 HBV DNA[例(%)] 7.571 0.021 <105 IU/mL 5(27.8) 1(12.5) 105~106 IU/mL 10(55.5) 1(12.5) >106 IU/mL 3(16.7) 6(75.0) HBeAg[例(%)] 0.216 阳性 10(55.6) 2(25.0) 阴性 8(44.4) 6(75.0) 生产方式[例(%)] 0.108 剖宫产 12(66.7) 5(62.5) 阴道分娩 6(33.3) 1(12.5) 未生产 0 2(25.0) 胎儿[例(%)] 21(80.8) 5(19.2) 10.301 0.002 足月儿(37~42周) 8(38.1) 0 早产儿(<37周) 13(61.9) 2(40.0) 胎死宫内 0 3(60.0) -
[1] TRAN TT, AHN J, REAU NS. ACG clinical guideline: Liver disease and pregnancy[J]. Am J Gastroenterol, 2016, 111(2): 176-194; quiz 196. DOI: 10.1038/ajg.2015.430. [2] LOBSTEIN S, FABER R, TILLMANN HL. Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany[J]. Digestion, 2011, 83(1-2): 76-82. DOI: 10.1159/000320455. [3] WANG ZL, GAO S, LI L, et al. Demethylation of tumor necrosis factor-α converting enzyme predicts poor prognosis in acute-on-chronic hepatitis B liver failure[J]. Clin Res Hepatol Gastroenterol, 2016, 40(4): 457-464. DOI: 10.1016/j.clinre.2015.12.004. [4] KATOONIZADEH A, LALEMAN W, VERSLYPE C, et al. Early features of acute-on-chronic alcoholic liver failure: A prospective cohort study[J]. Gut, 2010, 59(11): 1561-1569. DOI: 10.1136/gut.2009.189639. [5] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. [6] ANGELI P, GINÈS P, WONG F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: Revised consensus recommendations of the International Club of Ascites[J]. J Hepatol, 2015, 62(4): 968-974. DOI: 10.1016/j.jhep.2014.12.029. [7] Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guidelines for prevention and treatment of postpartum hemorrhage[J]. Chin J Obstet Gynecol, 2014, 49(9): 641-646. DOI: 10.3760/cma.j.issn.0529-567x.2016.06.001.中华医学会妇产科学分会产科学组. 产后出血预防与处理指南[J]. 中华妇产科杂志, 2014, 49(9): 641-646. DOI: 10.3760/cma.j.issn.0529-567x.2016.06.001. [8] KAMATH PS, WIESNER RH, MALINCHOC M, et al. A model to predict survival in patients with end-stage liver disease[J]. Hepatology, 2001, 33(2): 464-470. DOI: 10.1053/jhep.2001.22172. [9] LYU SC, ZHANG BZ. Etiology, clinical manifestations, and prognosis of liver failure in pregnancy[J]. J Clin Hepatol, 2020, 36(12): 2756-2760. DOI: 10.3969/j.issn.1001-5256.2020.12.023.吕苏聪, 张宝忠. 妊娠期肝衰竭的病因、临床表现及预后分析[J]. 临床肝胆病杂志, 2020, 36(12): 2756-2760. DOI: 10.3969/j.issn.1001-5256.2020.12.023. [10] CORDOBA J, VENTURA-COTS M, SIMÓN-TALERO M, et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF)[J]. J Hepatol, 2014, 60(2): 275-281. DOI: 10.1016/j.jhep.2013.10.004. [11] BANAIT VS, SANDUR V, PARIKH F, et al. Outcome of acute liver failure due to acute hepatitis E in pregnant women[J]. Indian J Gastroenterol, 2007, 26(1): 6-10. [12] SAHAI S, KIRAN R. Acute liver failure in pregnancy: Causative and prognostic factors[J]. Saudi J Gastroenterol, 2015, 21(1): 30-34. DOI: 10.4103/1319-3767.151221. [13] SHAO Z, ZHAO Y, FENG L, et al. Association between plasma fibrinogen levels and mortality in acute-on-chronic hepatitis B liver failure[J]. Dis Markers, 2015, 2015: 468596. DOI: 10.1155/2015/468596. [14] CUI YP, LIU FH, SHI QF, et al. Logistic regression analysis of prognostic factors in 106 acute-on-chronic liver failure patients with hepatic encephalopathy[J]. J Clin Hepatol, 2014, 30(10): 992-995. DOI: 10.3969/j.issn.1001-5256.2014.10.005.崔燕平, 刘凤华, 石庆凤, 等. 106例慢加急性肝衰竭合并肝性脑病患者预后影响因素的Logistic回归分析[J]. 临床肝胆病杂志, 2014, 30(10): 992-995. DOI: 10.3969/j.issn.1001-5256.2014.10.005. [15] ROUILLARD SS, BASS NM, ROBERTS JP, et al. Severe hyperbilirubinemia after creation of transjugular intrahepatic portosystemic shunts: Natural history and predictors of outcome[J]. Ann Intern Med, 1998, 128(5): 374-377. DOI: 10.7326/0003-4819-128-5-199803010-00006. [16] SOLANKE D, RATHI C, PANDEY V, et al. Etiology, clinical profile, and outcome of liver disease in pregnancy with predictors of maternal mortality: A prospective study from Western India[J]. Indian J Gastroenterol, 2016, 35(6): 450-458. DOI: 10.1007/s12664-016-0704-6. [17] GARG H, SARIN SK, KUMAR M, et al. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure[J]. Hepatology, 2011, 53(3): 774-780. DOI: 10.1002/hep.24109. [18] LIU CR, LI YP, LUO S, et al. Influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37(1): 56-62. DOI: 10.3969/j.issn.1001-5256.2021.01.012.刘晨瑞, 李亚萍, 罗森, 等. HBV相关慢加急性肝衰竭患者短期预后的影响因素分析[J]. 临床肝胆病杂志, 2021, 37(1): 56-62. DOI: 10.3969/j.issn.1001-5256.2021.01.012. [19] HSU C, HSIUNG CA, SU IJ, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: A randomized trial[J]. Hepatology, 2008, 47(3): 844-853. DOI: 10.1002/hep.22106. [20] Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 期刊类型引用(1)
1. 吴水莲. 妊娠期急性肝衰竭患者预后的影响因素分析. 中国医学创新. 2023(15): 145-149 . 百度学术
其他类型引用(0)
-