Mechanisms of hyponatremia in patients with decompensated liver cirrhosis treated with terlipressin and related treatment principles

You Jia; Jiang JiaJi

doi:10.3969/j.issn.1001-5256.2016.11.043

Issue 11

Nov. 2016

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Article Navigation > Journal of Clinical Hepatology > 2016 > 32(11): 2191-2194

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Mechanisms of hyponatremia in patients with decompensated liver cirrhosis treated with terlipressin and related treatment principles

DOI: 10.3969/j.issn.1001-5256.2016.11.043

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Published Date: 2016-11-20

Abstract

Abstract

Esophagogastric variceal bleeding and hepatorenal syndrome are common complications in patients with decompensated liver cirrhosis and portal hypertension. Terlipressin can lead to the constriction of visceral vessels,reduce portal venous pressure,and increase renal perfusion and is the first- line drug. In recent years,it has been reported that some patients experienced hyponatremia during the treatment with terlipressin. Since patients with liver cirrhosis tend to develop hyponatremia,the application of terlipressin may have an adverse effect on the management of serum sodium level in such patients. This article summarizes the incidence rate of hyponatremia during terlipressin treatment and related risk factors and introduces the pathogenesis of hyponatremia during terlipressin treatment in patients with decompensated liver cirrhosis and the treatment principles for hyponatremia. If the occurrence of hyponatremia can be controlled,terlipressin may be an effective drug for the treatment of portal hypertension.
- liver cirrhosis,
- hyponatremia,
- lysine vasopressin,
- review

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肝细胞癌(简称肝癌)术后复发是导致患者死亡的主要原因^[1]。对于复发性肝癌，临床上常用的治疗方法包括再次肝切除术、射频消融(radiofrequency ablation，RFA)、肝移植、介入、靶向药物治疗等^[2]。然而，目前国内外肝癌诊疗指南均未对复发性肝癌提供具体的诊疗推荐。再次肝切除术和RFA属于根治性治疗方法，临床应用广泛，文献报道较多。但单个研究样本量小，且研究间的结论不统一，临床上对复发性肝癌的根治性治疗方案尚存争议。本文使用Meta分析的方法，客观分析两种治疗措施对复发性肝癌的疗效与安全性。

1. 资料与方法

1.1 文献检索

系统检索PubMed、中国知网和万方数据库，检索日期自建库至2020年6月15日。英文检索词包括：recurrent、recurrence、hepatocellular carcinoma、liver cancer、hepatic resection、hepatectomy、resection、radiofrequency ablation等，中文检索词包括：复发、肝癌、肝细胞癌、手术、再次肝切除术、射频消融等。

1.2 纳入标准

(1) 研究：比较再次肝切除术与RFA治疗复发性肝癌的随机对照试验或队列研究，英文或中文发表。(2)患者：罹患原发性肝癌，接受首次肝切除术治疗后，肝癌复发，复发肿瘤符合米兰标准，且无大血管侵犯及肝外转移。(3)干预措施：肝癌复发后，接受再次肝切除术或RFA治疗。(4)结局指标：报道了总生存期(overall survival，OS)、无瘤生存期(recurrence-free survival，RFS)、围手术期并发症和围手术期病死率中的任何一项。

1.3 排除标准

(1) 肝切除和RFA治疗原发性肝癌、胆管细胞癌或转移性肝癌的研究；(2)单组样本量过小(＜10例)或单臂研究；(3)未提供病例具体纳入时间段的研究；(4)肝癌复发后，接受再次肝切除术或RFA治疗前，接受其他的治疗方案(如介入、靶向药物等)。再次肝切除术或RFA治疗后，序贯介入或其他治疗措施，不在排除标准范围之内。对于重复性发表的研究，仅纳入样本量最大的一项。

1.4 数据提取

两位评价者独立检索并提取纳入文献的数据，数据提取过程中若有分歧则通过双方讨论或询问第3位评价者解决。提取的数据包括人口统计学资料及临床基线数据、OS、RFS、围手术期并发症发生率及病死率。若原始文献未详细描述生存数据，则从其Kaplan-Meier生存曲线图估算。

1.5 统计学方法

统计分析采用RevMan 5.4.1软件(Cochrane协作组，牛津，英国)。采用从纳入文献提取的风险比(HR)进行OS和RFS的Meta分析。统计学异质性的评估采用I²检验。I²≥50%时采用随机效应模型，I²＜50%时采用固定效应模型。P＜0.05为差异有统计学意义。采用漏斗图估计发表偏倚。由于纳入文献提供的数据存在一定的局限性，无法根据患者性别、肿瘤大小、肿瘤个数、肿瘤位置等进行亚组分析。

2. 结果

2.1 基线特点

根据纳入和排除标准，18篇回顾性队列研究^[3-20]和2篇随机对照试验^[21-22]比较了再次肝切除术和RFA治疗复发性肝癌的临床疗效与安全性，共2903例患者(图 1)。全部纳入患者均来自亚洲国家，基线数据详见表 1。

图 1 文献检索流程图

下载: 全尺寸图片幻灯片

表 1 纳入研究的基线特点

第一作者和年份	国家/地区	纳入时间(年)	组别	样本量	男/女(例)	年龄(岁)	单个/多个肿瘤(例)	复发肿瘤直径(cm)	肝硬化[例(%)]	CTP分级(A/B/C，例)	随访(月)
Wang 2015^[3]	中国	2004—2010	肝切除	128	113/15	50.2±10.1	89/39	2.4±0.9	66(51.6)	-	-
			RFA	162	148/14	52.7±10.9	107/55	2.3±0.7	-	-	-
Sun 2017^[4]	中国台湾	2002—2014	肝切除	43	34/9	60(35~76)	-	1.9(0.8~3.0)	36(83.7)	42/1	53
			RFA	57	38/19	63(27~81)	-	1.8(1.0~3.0)	50(87.7)	57/0	54
Umeda 2011^[5]	日本	1998—2007	肝切除	29	-	-	-	3.20±0.57	-	29/0	48
			RFA	58	-	-	-	2.1±0.3	-	51/7	48
Song 2015^[6]	韩国	1994—2012	肝切除	39	31/8	52.5±9.8	32/7	2.2±1.1	23(59)	39/0	36.3(0.8~126.6)
			RFA	178	145/33	55.4±10.6	156/22	1.7±0.6	130(73.0)	172/6	44.7(5.6~139.8)
Liang 2008^[7]	中国	1999—2007	肝切除	44	39/5	48.8±12.0	34/10	≤3 (26)	-	44/0	33.5±24.1
			RFA	66	54/12	54.6±10.8	48/18	≤3 (44)	-	64/2	21.1±19.1
Ho 2012^[8]	中国台湾	2001—2007	肝切除	54	40/14	56.3±12.3	-	2.9±1.8	26(48.1)	51/2/1	32(0~79)
			RFA	50	39/11	61.0±11.1	-	2.3±1.9	28(56.0)	50/0	27(0~96)
Chan 2012^[9]	中国香港	2001—2008	肝切除	29	-	52(38~79)	21/8	2.1(0.8~5.5)	25(86.2)	29/0	44.9
			RFA	45	-	59(36~80)	29/16	2.2(0.8~6.0)	40(88.9)	40/5	44.9
Chen 2018^[10]	中国	2009—2015	肝切除	48	41/7	73.5±3.5	28/20	2.6±1.1	41(85.4)	39/9	36.9(2~78)
			RFA	57	51/6	73.7±2.9	30/27	2.5±1.2	49(86.0)	45/12	37.3(2~78)
岑峰2016^[11]	中国	2011—2015	肝切除	28	22/6	53.6	12/16	-	23(82.1)	18/10	-
			RFA	24	19/5	55.7	10/14	-	19(79.2)	-	-
陈康2019^[12]	中国	2005—2014	肝切除	77	65/12	-	-	-	57(74)	76/1	57(2~168)
			RFA	82	72/10	-	-	-	50(61)	77/5	51(4~111)
黄新辉2013^[13]	中国	2007—2011	肝切除	66	51/15	50.5±10.1	66/0	2.9±1.1	57(86.3)	66/0	-
			RFA	46	36/10	54.1±12.1	46/0	2.6±0.9	39(84.8)	46/0	-
梁惠宏2011^[14]	中国	1999—2009	肝切除	72	65/7	49±12	72/0	2.1±0.1	-	70/2	36±25
			RFA	79	69/10	55±11	79/0	2.5±0.1	-	73/6	32±21
任正刚2008^[15]	中国	2000—2005	肝切除	145	127/18	51	127/18	2.0	-	145/0	23(3~88)
			RFA	68	64/4	52	52/16	2.0	-	68/0	23(3~88)
田正灵2016^[16]	中国	2012—2015	肝切除	30	28/2	48.8±9.6	24/6	-	24(80)	-	17(6.0~42.5)
			RFA	27	26/1	50.9±10.1	19/8	-	23(85.2)	-	17(6.0~42.5)
张辉2013^[17]	中国	2003—2011	肝切除	69	-	-	-	3.5	61(88.4)	54/15	-
			RFA	99	-		-	2.1	76(76.8)	71/28	-
张婷婷2014^[18]	中国	1998—2010	肝切除	27	25/2	47±13	25/2	3.2±1.1	-	27/0	32(9~118)
			RFA	39	37/2	52±13	37/2	2.7±1.1	-	37/2	28(2~79)
Peng 2018^[19]	中国	2006—2015	肝切除	79	67/2	55	59/20	≤3(48)	-	-	53.2(4~96)
			RFA	107	95/12	57	75/32	≤3(73)	-	-	52.3(3~96)
Lu 2020^[20]	中国	2004—2015	肝切除	138	124/16	50.1±10.9	112/26	2.8±1.9	96(70)	138/0	37.6
			RFA	194	172/22	52.9±11.8	162/32	1.9±0.9	134(69)	194/0	41.6
Xia 2019^[21]	中国	2010—2013	肝切除	120	107/13	52.4(25.7~60.5)	96/24	2.9(1.0~5.0)	50(41.7)	120/0	44.3(4.3~90.6)
			RFA	120	109/11	53.5(28.0~59.9)	94/26	2.7(1.0~4.8)	55(45.8)	120/0	44.3(4.3~90.6)
刘嘉龙2019^[22]	中国	2016—2017	肝切除	39	38/1	50.0±10.0	37/2	2.1±0.7	37(94.9)	38/1	24
			RFA	41	37/4	48.9±11.3	39/2	1.8±0.8	39(95.1)	39/2	24
注：-，未报道。

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2.2 围术期并发症及病死率

15篇文献^{[4, 6-7, 9-17, 19, 21-22]}报道了再次肝切除术围手术期并发症发生率为5.5%~68.2%，中位值为22.4%，常见并发症包括肝功能不全、胸腔积液、腹水、胆瘘等。14篇文献^{[4, 6-7, 9-10, 12-17, 19, 21-22]}报道了RFA的围手术期并发症发生率为0~13%，中位值为3.3%，常见并发症包括胆漏、腹腔出血等。16篇文献^{[4, 6-7, 9-19, 21-22]}报道了再次肝切除术和RFA围手术期病死率，其中6篇文献^{[4, 6, 10, 12, 17, 19]}报道再次肝切除术组围手术期病死率为1.3%~2.6%，中位值为2%，其余文献报道发生率为0；仅1篇文献^[9]报道RFA围手术期病死率为2.2%，其余文献报道发生率为0(表 2)。

表 2 纳入患者的治疗结局

第一作者和年份	组别	并发症发生率(%)	围手术期病死率(%)	复发[例(%)]	RFS				OS
第一作者和年份	组别	并发症发生率(%)	围手术期病死率(%)	复发[例(%)]	1年	3年	5年	P值¹⁾	1年	3年	5年	P值¹⁾
Wang 2015^[3]	肝切除	-	-	-	-	-	-	-	97.7	84.1	64.5	＜0.001
	RFA	-	-	-	-	-	-		96.9	73.4	37.0
Sun 2017^[4]	肝切除	16	2	30(69.8)	57.0	32.1	28.6	0.89	97.6	82.7	56.4	0.69
	RFA	7	0	41(71.9)	60.8	26.6	16.6		98.2	77.2	52.6
Umeda 2011^[5]	肝切除	-	-	-	-	-	-	-	93.1	66.8	58.1	0.899
	RFA	-	-	-	-	-	-		94.7	75.1	48.3
Song 2015^[6]	肝切除	64	2.6	18(46.2)	66.1	48.5	43.1	0.834	88.8	88.8	83.9	0.686
	RFA	2.2	0	117(65.7)	70.1	40.8	30.0		98.9	82.5	71.0
Liang 2008^[7]	肝切除	68.2	0	86.4	-	-	-	-	78.6	44.5	27.6	0.79
	RFA	3.0	0	78.8	-	-	-		76.6	48.6	39.9
Ho 2012^[8]	肝切除	-	-	-	-	-	-	-	-	-	72.0	-
	RFA	-	-	-	-	-	-		-	-	83.0
Chan 2012^[9]	肝切除	24.1	0	21(72.4)	41.1	24.2	24.2	0.14	89.7	56.5	35.2	0.51
	RFA	2.2	2.2	38(84.4)	32.2	12.4	9.3		83.7	43.1	29.1
Chen 2018^[10]	肝切除	25	2.1	26(54.2)	73.1	49.7	40.7	0.465	76.3	52.5	42.6	0.413
	RFA	0	0	27(47.4)	69.5	37.8	33.1		78.2	40.8	36.7
岑峰2016^[11]	肝切除	50	0	-	46.4	0	0	-	-	-	-	-
	RFA	-	0	-	20.8	0	0		-	-	-
陈康2019^[12]	肝切除	17.1	1.3	-	-	-	-	-	88.8	68.8	51.1	0.258
	RFA	9.8	0	-	-	-	-		91.4	73.4	61.1
黄新辉2013^[13]	肝切除	18.1	0	-	43.9	14.4	8.2	0.548	89.5	54.3	28.8	0.780
	RFA	0	0	-	56.9	12.4	5.0		82.6	50.8	20.5
梁惠宏2011^[14]	肝切除	36	0	≤1年: 39＞1年: 33	-	-	-	-	95.3	65.7	54.5	＞0.05
	RFA	13	0	≤1年: 37＞1年: 42	-	-	-	－	100	79.4	62.1
任正刚2008^[15]	肝切除	5.5	0	≤2年: 71＞2年: 74	79.4	48.1	34.4	0.001	88.1	62.6	41.0	0.693
	RFA	1.5	0	≤2年: 37＞2年: 31	58.0	27.8	12.4		94.7	65.1	37.3
田正灵2016^[16]	肝切除	6.7	0	10(33.3)	73.3	64.3	-	0.002	96.7	93.3	-	0.54
	RFA	3.7	0	24(88.9)	46.7	26.7	-		96.3	84.0	-
张辉2013^[17]	肝切除	15.9	1.45	-	-	-	-	-	68.2	45.4	-	＞0.05
	RFA	0	0	-	-	-	-		73.7	53.6	-
张婷婷2014^[18]	肝切除	-	0	22(56.4)	66.7	50.7	43.4	0.323	96.2	76.9	61.2	0.471
	RFA	-	0	14(52.9)	65.8	28.0	14.0		86.2	73.3	62.2
Peng 2018^[19]	肝切除	17.7	1.3	-	64.8	41.6	38.3	0.258	84.8	60.2	51.9	0.871
	RFA	4.7	0	-	58.2	35.2	29.6		84.6	66.9	49.1
Lu 2020^[20]	肝切除	-	-	-	91.8	82.0	72.9	0.38	-	-	-	-
	RFA	-	-	-	94.4	75.4	61.7		-	-	-
Xia 2019^[21]	肝切除	22.4	0	60.8	85.0	52.4	36.2	0.09	92.5	65.8	43.6	0.17
	RFA	7.3	0	64.2	74.2	41.7	30.2		87.5	52.5	38.5
刘嘉龙2019^[22]	肝切除	35.9	0	19(48.7)	69.2	-	-	＜0.001	92.3	-	-	0.292
	RFA	4.9	0	32(78.0)	26.8	-	-		85.4	-	-
注：-，未报道；1) P值来源于原文报道。

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2.3 RFA与肝切除术OS的比较

共有18篇研究^{[3-10, 12-18, 21-22]}报道了OS(表 2)。两组患者术后1、3、5年中位OS分别为92.3%、66.3%、51.1%与91.4%、69.2%、39.9%。共有14篇研究^{[3-10, 12, 15, 18-19, 21-22]}可提取数据统计HR，各组间不存在异质性(I²=0，P=0.77)，采用固定效应模型进行分析。结果显示，两组患者的OS差异无统计学意义(HR= 0.89，95%CI：0.77~1.02，P=0.10)(图 2)。

图 2 再次肝切除术和RFA治疗复发性肝癌患者OS的比较

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2.4 RFA与肝切除术RFS的比较

共有13篇研究^{[4, 6, 9-11, 13, 15-16, 18-19, 20-22]}报道了RFS(表 2)。两组患者术后1、3、5年中位RFS分别为67.9%、48.3%、34.4%和57.5%、27.9%、14.0%。共有10篇研究^{[4, 6, 9-10, 15, 18-22]}可提取数据统计HR，各组间不存在异质性(I²=0，P=0.53)，采用固定效应模型进行分析。结果显示，再次肝切除术组患者的RFS显著高于RFA组(HR=0.79，95%CI：0.72~0.87，P＜0.001)(图 3)。

图 3 再次肝切除术和RFA治疗复发性肝癌患者RFS的比较

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2.5 发表偏倚

基于OS和RFS HR的漏斗图提示，发表偏倚不明显(图 4)。

图 4 再次肝切除术和RFA治疗复发性肝癌患者OS及RFS HR的发表偏倚分析

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3. 讨论

肝癌术后复发是影响患者术后长期生存的主要危险因素。对于复发性肝癌，目前临床上以多学科综合治疗为主。肝移植能显著提高复发性肝癌患者的RFS和远期生存率^[23]，但肝移植适应证严格、肝源匮乏和费用昂贵等问题仍限制其广泛的临床应用。此外，既往研究^[24-25]表明再次肝切除术和RFA对复发性肝癌的疗效均优于介入。因此，针对肝内复发性肝癌患者，再次肝切除术和RFA是目前较为理想的治疗方案。有研究^[3]认为再次肝切除术是治疗复发性肝癌的首选治疗方案，即使患者的原发癌更具侵袭性，肝功能水平更差，肝癌复发后行再次肝切除术仍可以获得与RFA相似的疗效。梁惠宏等^[14]的研究则发现，RFA治疗复发性小肝癌的长期疗效优于再次肝切除术。因此，关于再次肝切除术和RFA治疗复发性肝癌的选择仍存在较大争议。本研究通过Meta分析的方法，综合评估再次肝切除术和RFA治疗复发性肝癌的疗效和安全性。

本研究结果显示，两组患者的OS无显著性差异，但再次肝切除术组患者的RFS显著高于RFA组。这一结论与肝切除术和RFA治疗原发性肝癌的结果一致^[26-27]。RFA组患者RFS偏低的原因可能是：(1)再次肝切除术能将复发肿瘤以及潜在的瘤周子灶及血管癌栓同时切除，减少肿瘤再次局部复发和转移的可能性；(2)RFA后部分患者的肿瘤消融不完全而需进行二次消融或其他治疗；(3)术前影像学检查未能发现主瘤旁的微小卫星灶，导致消融不完全而引起肝癌再次复发。虽然RFA可用于治疗直径≤5 cm的肝癌，但目前认为其最佳适应证为直径≤3 cm的小肝癌^[28]。有研究^[29]发现，肝癌的直径和数目是导致RFA消融不完全的主要因素，随着肝癌直径的增加，RFA的疗效逐步下降。Livraghi等^[30]的研究也表明RFA治疗直径3~5 cm的肝癌时完全消融率显著降低，导致RFA治疗复发性肝癌后局部复发和早期复发的比例明显升高。无论是原发性还是复发性肝癌，肿瘤直径在3~5 cm时经RFA治疗后其RFS和远期生存率均低于再次肝切除术^{[21, 31]}。因此，在选择复发性肝癌治疗方案时，肿瘤直径应作为重要的参考指标。

本研究中，在围手术期并发症方面，再次肝切除术组和RFA组患者的中位发生率分别为22.4%和3.3%，与原发性肝癌接受肝切除术或RFA治疗后的并发症发生率相似^[32-33]。此外，本研究还发现RFA治疗复发性肝癌的安全性明显优于再次肝切除术。RFA组患者术后并发症发生率及严重程度更低。虽然再次肝切除术能改善患者的远期生存率及RFS，但再次肝切除术的实施仍受诸多因素的限制，例如复发肿瘤的位置、数量以及肝硬化严重程度等。手术造成较大的创伤导致患者术后更容易发生严重并发症。此外，肝癌患者常伴有不同程度的肝硬化，无疑增加了手术的风险，部分患者最终死于肝衰竭而非肝癌本身带来的肿瘤负担^[32]。相比于再次肝切除术，RFA在超声等影像学技术引导下精准地对复发肿瘤进行消融，从而最大限度地避免正常肝组织的破坏。对于手术无法切除、无法耐受手术的患者亦可选择RFA治疗。此外，RFA还可联合介入或无水酒精注射提高患者的OS和RFS^{[10, 19]}。RFA本身具有微创和可重复的优点，肝癌再次复发后相当一部分患者仍可及时接受RFA或其他治疗^[12]，从而获得与再次肝切除相似的短期OS。

值得注意的是，本研究纳入文献中多数为回顾性研究，仅有2篇随机对照试验，因此本研究结论仍需更多的随机对照试验进行验证。其次，再次肝切除术和RFA治疗复发性肝癌的适应证存在一定的区别。然而，本Meta分析纳入的多数文献均仅纳入符合米兰标准的复发性肝癌，这些患者同时符合再次肝切除术和RFA的适应证。最后，肝癌术后复发(甚至多次)比较常见，对于复发肿瘤的治疗，多采取综合治疗方案(如介入、靶向、免疫治疗等)，而非再次肝切除术或RFA等“单一”治疗模式。因此，联合治疗方案可能影响本荟萃分析对患者OS的判断。

总而言之，对于复发性肝癌的治疗，再次肝切除术能提高患者RFS，RFA则具有安全性高的优点。因此，在复发性肝癌患者的治疗中应遵循个体化和多学科治疗原则，合理选择治疗方案。

References(38)

References

[1]MOLLER S,HANSEN EF,BECKER U,et al.Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients[J].Liver,2000,20(1):51-59.

[2]ARROYO V,GUEVARA M,GINES P.Hepatorenal syndrome in cirrhosis:pathogenesis and treatment[J].Gastroenterology,2002,122(6):1658-1676.

[3]de FRANCHIS R,BavenoⅥFaculty.Expanding consensus in portal hypertension:Report of the BavenoⅥConsensus Workshop:stratifying risk and individualizing care for portal hypertension[J].J Hepatol,2015,63(3):743-752.

[4]TRIPATHI D,STANLEY AJ,HAYES PC,et al.UK guidelines on the management of variceal haemorrhage in cirrhotic patients[J].Gut,2015,64(11):1680-1704.

[5]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Endoscopy,Chinese Medical Association.Guidelines for the diagnosis and treatment of esophageal and gastric variceal bleeding in cirrhotic portal hypertension[J].J Clin Hepatol,2016,32(2):203-219.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会内镜学分会,等.肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J].临床肝胆病杂志,2016,32(2):203-219.

[6]ANGELI P,GINS 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].Gut,2015,64(4):531-537.

[7]RUNYON BA,AASLD.Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis2012[J].Hepatology,2013,57(4):1651-1653.

[8]DING XH,GU JY.Clinical efficacy of terlipressin in treatment of typeⅡhepatorenal syndrome[J].J Clin Hepatol,2015,31(5):745-748.(in Chinese)丁晓红,顾建英.特利加压素治疗Ⅱ型肝肾综合征的临床疗效观察[J].临床肝胆病杂志,2015,31(5):745-748.

[9]JOHN S,THULUVATH PJ.Hyponatremia in cirrhosis:pathophysiology and management[J].World J Gastroenterol,2015,21(11):3197-3205.

[10]GINS P,BERL T,BERNARDI M,et al.Hyponatraemia in cirrhosis:from pathogenesis to treatment[J].Hepatology,1998,28(3):851-864.

[11]JALAN R,HAYES PC.Sodium handling in patients with well compensated cirrhosis is dependent on the severity of liver disease and portal pressure[J].Gut,2000,46(4):527-533.

[12]GEILSWIJK M,THOMSEN KL,PEDERSEN EB,et al.Urinary aquaporin-2 excretion before and after transjugular intrahepatic portosystemic shunt insertion for refractory ascites[J].Scand J Gastroenterol,2015,50(4):454-461.

[13]NAKANISHI H,KUROSAKI M,HOSOKAWA T,et al.Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites[J].J Gastroenterol,2016,51(6):620-627.

[14]CHEN C,CHEN RP,LIN HH,et al.Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites[J].World J Gastroenterol,2016,22(12):3363-3371.

[15]HUANG YY,SUN JY,WANG JY,et al.Terlipressin resolves ascites of cirrhotic rats through downregulation of aquaporin 2[J].J Int Med Res,2012,40(5):1735-1744.

[16]ESTEVA-FONT C,BACCARO ME,FERNNDEZ-LLAMA P,et al.Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis:relationship with ascites and hepatorenal syndrome[J].Hepatology,2006,44(6):1555-1563.

[17]LEE WC,LIN HC,YANG YY,et al.Hemodynamic effects of a combination of prazosin and terlipressin in patients with viral cirrhosis[J].Am J Gastroenterol,2001,96(4):1210-1216.

[18]TRIANTOA CK,SAMONAKIS D,THALHEIMER U,et al.Terlipressin therapy for renal failure in cirrhosis[J].Eur J Gastroenterol Hepatol,2010,22(4):481-486.

[19]FERNNDEZ-VARO G,ORD,CABLE E,et al.Evasopressin 1αreceptor partial agonist increases sodium excretion and reduces portal hypertension and ascites in cirrhotic rats[J].Hepatology,2016,63(1):207-216.

[20]FENTON RA,KNEPPER MA.Mouse models and the urinary concentrating mechanism in the new millennium[J].Physiol Rev,2007,87(4):1083-1112.

[21]FEU F,RUIZ del ARBOL L,BANARES R,et al.Doubleblind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage.Variceal Bleeding Study Group[J].Gastroenterology,1996,111(5):1291-1299.

[22]ESCORSELL A,ARBOL LRD,PLANAS R,et al.Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding:the TEST study[J].Hepatology,2000,32(3):471-476.

[23]SOLA E,LENS S,GUEVARA M,et al.Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension[J].Hepatology,2010,52(5):1783-1790.

[24]YIM SY,SEO YS,JUNG CH,et al.Risk factors for developing hyponatremia during terlipressin treatment:a retrospective analyses in variceal bleeding[J].J Clin Gastroenterol,2015,49(7):607-612.

[25]KANG YJ,BAE EJ,HWANG K,et al.Initial serum sodium concentration determines the decrease in sodium level after terlipressin administration in patients with liver cirrhosis[J].Springerplus,2013,2:519.

[26]ZAKI SA.Terlipressin-induced hyponatremic seizure in a child[J].Indian J Pharmacol,2013,45(4):403-404.

[27]BRUHA R,MARECEK Z,PROCHAZKA V,et al.Doubleblind randomized multicenter study comparing the efficacy and safety of 10-day to 5-day terlipressin treatment of bleeding esophageal varices[J].Hepatogastroenterology,2009,56(90):390-394.

[28]CHANG TT,LEE FY,TSAI YT,et al.A randomized control ed study of low-dose and high-dose terlipressin in the control of acute oesophageal variceal haemorrhage[J].J Gastroenterol Hepatol,1991,6(5):481-484.

[29]KRAG A,BENDTSEN F,PEDERSEN EB.Effects of terlipressin on the aquaretic system:evidence of antidiuretic effects[J].Am J Physiol Renal Physiol,2008,295(5):1295-1300.

[30]NIELSEN S,FROKIAR J,MARPLES D,et al.Aquaporins in the kidney:from molecules to medicine[J].Physiol Rev,2002,82(1):205-244.

[31]KALAMBOKIS GN,PAPPAS K,BALTAYIANNIS G.Effects of terlipressin on water excretion after oral water load test in nonazotemic cirrhotic patients with ascites without hyponatremia[J].Scand J Gastroenterol,2010,45(12):1509-1515.

[32]BANKIR L.Antidiuretic action of vasopressin:quantitative aspects and interaction between V1a and V2 receptor-mediated effects[J].Cardiovasc Res,2001,51(3):372-390.

[33]URIZ J,GINES P,CARDENAS A,et al.Terlipressin plus albumin infusion:an effective and safe therapy of hepatorenal syndrome[J].J Hepatol,2000,33(1):43-48.

[34]ORTEGA R,GINES P,URIZ J,et al.Terlipressin therapy with and without albumin for patients with hepatorenal syndrome:results of a prospective,nonrandomized study[see comment][J].Hepatology,2002,36(4 Pt 1):941-948.

[35]BOYER TD,SANYAL AJ,GARCIA-TSAO G,et al.Terlipressin Study Group.Predictors of response to terlipressin plus albumin in hepatorenal syndrome(HRS)type 1:relationship of serum creatinine to hemodynamics[J].J Hepatol,2011,55(2):315-321.

[36]SHARMA P,SINGH S,SARIN SK.Hyponatremia in patients with acute variceal bleeding treated with terlipressin[J].Hepatology,2011,53(2):714.

[37]DUNWOODIE E,JOWETT S.Terlipressin causing a hyponatraemic seizure[J].Scand J Gastroenterol,2007,42(5):665.

[38]SIMA M,POKORNY M,PAD OUR F.Terlipressin induced severe hyponatremia[J].Prague Med Rep,2016,117(1):68-72.

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Mechanisms of hyponatremia in patients with decompensated liver cirrhosis treated with terlipressin and related treatment principles

DOI: 10.3969/j.issn.1001-5256.2016.11.043