Objective To investigate the influence of different durations of plasma diafiltration ( PDF) on liver function in patients with liver failure and rebound of liver function after treatment. Methods A total of 101 patients with liver failure who were admitted to Beijing You An Hospital, Capital Medical University, from January 2015 to December 2016 were enrolled, and according to the duration of treatment, these patients were divided into 4-hour group with 77 patients and 6-hour group with 24 patients. All patients were given artificial extracorporeal liver support therapy in addition to the medical treatment. The two groups were observed in terms of the reductions in alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBil) , and direct bilirubin ( DBil) after treatment and the rebound of ALT, AST, TBil, and DBil at 24 and 72 hours after treatment. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results All patients had stable hemodynamics during treatment and no patient experienced adverse events. Some patients complained of staying in bed for a long time and feeling weak. The 6-hour group had a significantly higher intolerance rate than the 4-hour group [41. 7% ( 10/24) vs 6. 5% ( 5/77) , χ2= 17. 90, P < 0. 01].There were no significant differences in the reductions in ALT, AST, TBil, and DBil after PDF treatment between the two groups ( t = 2. 53, -4. 48, -1. 52, and-0. 47, all P > 0. 05) . There were also no significant differences between the two groups in the degrees of rebound of ALT, AST, TBil, and DBil at 24 and 72 hours after treatment ( 24 hours: t =-0. 236, -1. 251, -1. 251, and 0. 943, all P > 0. 05;72 hours: t =-0. 700, 0. 596, -1. 530, and 1. 837, all P > 0. 05) . Conclusion PDF treatment with different durations has similar effect and safety. Therefore, 4-hour PDF can be applied in clinical practice to improve patients' tolerance.
按照UDCA治疗应答情况,637例患者中436例发生完全应答,201例为应答不良。性别分布中,完全应答组与应答不良组分布无统计学意义(P值均>0.05),基线存在肝硬化的患者UDCA应答率更高(78.9% vs 71.1%,P=0.032),生化指标中,TBil、AST、ALP、TBA和TC在两组间存在统计学差异(P值均<0.001)。免疫指标中,应答不良组IgA、IgM水平及抗Gp210阳性率均较高(P值均<0.05)。预后风险评分中,应答不良组MRS、Globe评分、UK-PBC评分均高于完全应答组(P值均<0.001)(表 2)。
表
2
UDCA治疗完全应答与应答不良患者基线指标及风险评分差异
Table
2.
Differences of baseline characteristics and risk scores between PBC with complete response and poor response to UDCA treatment
根据IgM预测UDCA应答不良的最佳临界值将患者分为IgM≥1.5×ULN及IgM<1.5×ULN两组,性别分布、年龄、肝硬化占比在两组中比较差异均无统计学意义(P值均>0.05);IgM≥1.5×ULN组AST、ALP、TC显著高于IgM<1.5×ULN组(P值均<0.05);IgM≥1.5×ULN组IgG水平及抗Gp210阳性率显著高于IgM<1.5×ULN组(P值均<0.001)。IgM≥1.5×ULN组经过UDCA治疗后发生应答不良患者显著高于IgM<1.5×ULN组(38.3% vs 27.1%,P=0.003)(表 5)。
表
5
不同IgM水平PBC患者基线临床特征及UDCA疗效比较
Table
5.
Comparison of baseline characteristics and the outcome of UDCA treatment between PBC with different levels of IgM
UDCA是PBC治疗的一线药物,可显著改善部分PBC患者非肝移植存活率[11-12],但仍有30%~40%的患者对UDCA治疗无应答,本研究中显示UDCA完全应答率为68.4%,对于这部分患者需要及时联合一种或两种二线药物来改善胆汁淤积以预防疾病进展[13]。UDCA治疗可能影响IgM水平,研究[14]发现UDCA能够显著降低细菌CpG诱导的总IgM和IgM-AMA的产生,但对IgG-AMA的水平却无影响。IgM与肝硬化相关症状和肝脏相关事件的发生关系密切,在UDCA联合苯扎贝特治疗过程中,不论ALP及GGT下降与否,当IgM水平持续异常时,患者的预后均较差,其生存期显著低于IgM水平正常化的患者,治疗过程中IgM水平的逐步正常化可能提示预后较好[15]。对于UDCA不完全应答的PBC患者,在给予联合利妥昔单抗治疗后,IgM水平随着肝功能指标的好转而逐步下降[16]。IgM正常化可作为长期预后的预测指标,但初始IgM正常患者IgM水平的变化情况及预测因素尚缺乏研究。在本研究中,UDCA治疗基线IgM平均水平为2.76 g/L,IgM升高的占比为56.0%,在UDCA完全应答组与应答不良组之间,基线IgM水平存在显著性差异(P=0.034),进一步分析IgM升高与IgM正常组患者的临床特征及在UDCA治疗1年后的疗效差异,发现IgM正常组UDCA应答率高于IgM升高组(71.8% vs 65.8%),但两组差异无统计学意义(P=0.108),通过ROC曲线分析获得IgM预测UDCA治疗1年后应答不良风险的最佳临界值(1.5×ULN),按最佳临界值进行分组后,结果显示IgM<1.5×ULN组的PBC患者发生UDCA应答率显著高于IgM≥1.5×ULN组(72.9% vs 61.7%, P=0.003),IgM≥1.5×ULN组发生UDCA应答不良风险是前者的1.416倍(95%CI: 1.129~1.776),因此基线IgM水平可能有助于预测PBC治疗应答。
[1] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association;Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association.Guidelines for diagnosis and treatment liver failure[J].Chin J Clin Infect Dis, 2012, 5 (6) :321-327. (in Chinese) 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 (2012年版) [J].中华临床感染病杂志, 2012, 5 (6) :321-327.
[2]YOSHIBA M, SEKIYAMA K, IWAMURA Y, et al.Development of reliable artificial liver support (ALS) ——plasma exchange in combination with hemodiafiltration using high-performance membranes[J].Dig Dis Sci, 1993, 38 (3) :469-476.
[3]CHEN Y, DUAN ZP.The application of artificial liver support system in the treatment of severe hepatitis and liver failure[J].J Clin Intern Med, 2008, 25 (11) :299-301. (in Chinese) 陈煜, 段钟平.人工肝支持系统在重症肝炎和肝衰竭治疗中的应用[J].临床内科杂志, 2008, 25 (11) :299-301.
[4]YANG JL, HUANG JR.Application of artificial liver support system in treatment of liver failure[J].J Clin Hepatol, 2015, 31 (9) :1405-1410. (in Chinese) 杨建乐, 黄建荣.人工肝支持系统在肝衰竭治疗中的应用[J].临床肝胆病杂志, 2015, 31 (9) :1405-1410.
[5]YU YW, LI MX, DONG Z.Clinical application of plasma exchange combined with hemodiafiltration in patients with liver failure[J].Chin J Blood Purificat, 2009, 8 (5) :267-269. (in Chinese) 余永武, 李明旭, 董珍.血浆置换联合血液透析滤过治疗肝衰竭的临床应用[J].中国血液净化, 2009, 8 (5) :267-269.
[6]YU GQ, ZENG JH, XUAN JH, et al.Plasma exchange and hemodialysis filtration intreatment of patients with fulminan the patitis[J].J Pract Hepatol, 2010, 13 (5) :352-353. (in Chinese) 郁国强, 曾军红, 禤江华, 等.血浆置换联合血液透析滤过治疗重型肝炎的临床观察[J].实用肝脏病杂志, 2010, 13 (5) :352-353.
[7]LIN JH, GUO YX, ZHOU XH, et al.Change of blood parameters in liver failure patients with severe hepatitis after combine therapy[J].Chin Critical Care Med, 2003, 15 (2) :103-105. (in Chinese) 林加豪, 郭艳雪, 周秀华, 等.血浆置换联合高通量血液透析滤过治疗重症肝炎肝脏衰竭临床研究[J].中国危重病急救医学, 2003, 15 (2) :103-105.
[8]SUN XZ, CHEN JG.Clinical application of plasma exchange combined with hemodiafiltration in severe hepatitis patients with hepatorenal syndrome[J/CD].Chin J Clinicians:Electronic Edition, 2011, 5 (15) :4545-4546. (in Chinese) 孙西照, 陈进国.血浆置换联合血液透析滤过治疗重型肝炎肝肾综合征临床观察[J/CD].中华临床医师杂志:电子版, 2011, 5 (15) :4545-4546.
[9]CHEN N, WANG JF, QIAN ZP, et al.Continuity of plasma dialysis filter in the treatment of acute liver failure clinical curative effect evaluation[J].Chin Hepatol, 2015, 20 (1) :54-56. (in Chinese) 陈楠, 王介非, 钱志平, 等.连续性血浆透析滤过在急性肝衰竭治疗中的临床疗效评价[J].肝脏, 2015, 20 (1) :54-56.
[10]XING HQ, LIU JW, WANG KL, et al.Analysis of clinical effect of comtinuous plasma diafiltration for the therapy of liver failure[J].BMA&Clin Med, 2013, 17 (2) :152-155. (in Chinese) 邢汉前, 刘俊微, 王开利, 等.持续缓慢血浆透析滤过治疗肝功能衰竭的临床疗效分析[J].生物医学工程与临床, 2013, 17 (2) :152-155.
[11]LI S, CHEN Y.Coping with shortage of plasma-The new therapeutic pattern of non-bioartificial liver[J].J Clin Hepatol, 2017, 33 (9) :1687-1692. (in Chinese) 李爽, 陈煜.血浆紧缺情况下非生物型人工肝治疗新模式的探讨[J].临床肝胆病杂志, 2017, 33 (9) :1687-1692.
[13]CLEMMESEN JO, KONDRUP J, NIELSEN LB, et al.Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liverfailure[J].Am J Gastroenterol, 2001, 96 (4) :1217-1223.
[14]GONG DH, JI DX, XU B, et al.The application of sodium citrate anticoagulant in the continuous blood purification treatment of critically ill patient[J].Chin J Intern Med, 2003, 42 (1) :121-122. (in Chinese) 龚德华, 季大玺, 徐斌, 等.枸橼酸钠抗凝在重危患者连续性血液净化治疗中的应用[J].中华内科杂志, 2003, 42 (1) :121-122.
HAN L, LIANG QS, XIE H, et al. Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis[J]. J Clin Hepatol, 2022, 38(4): 815-820. DOI: 10.3969/j.issn.1001-5256.2022.04.015.
HAN L, LIANG QS, XIE H, et al. Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis[J]. J Clin Hepatol, 2022, 38(4): 815-820. DOI: 10.3969/j.issn.1001-5256.2022.04.015.