A combination therapy of vitamin K1 and bile acid on hemorrhagic diathesis in patients with decompensated liver cirrhosis

This paper presents a study of treatment involving vitamin K₁ (VK₁) accompanied by bile acids for hemorrhagic diathesis that was applied 42 times in 35 patients with decompensated liver cirrhosis. The hepaplastin test (HPT) value showed no change during the administration of VK₁ alone. The HPT value elevated significantly, however, after the administration of VK₁ with bile acid, expecially when using ursodeoxycholic acid (UDCA). The HPT value in patients treated with VK₁ in addition to UDCA before treatment with 53.2% ± 10.2% (mean ± SD) and after that for 2.1 ± 1.1 months (mean ± SD) with 74.7 ± 16.8% showed a significant difference (p< 0.001). On the other hand, no significant difference was noted between the HPT value of 57.2 ± 13.6% before and that of 62.9 ± 13.9% after the treatment in patients treated using VK₁ in conjunction with chenodeoxycholic acid (CDCA). These results indicate that the therapy incorporating VK₁ and bile acid, especially UDCA, is useful for reducing the hemorrhagic tendency in patients with decompensated liver cirrhosis who show no improvement using VK₁ alone.     

Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis: A prospective study

AIM To assess the vitamin D(VD) deficiency as a prognostic factor and effect of replenishment of VD on mortality in decompensated cirrhosis. METHODS Patients with decompensated liver cirrhosis were screened for serum VD levels. A total of 101 VD deficient patients( 20 ng/mL) were randomly enrolled in two groups: Treatment group(n = 51) and control group(n = 50). Treatment group received VD treatment in the form of intramuscular cholecalciferol 300000 IU as loading dose and 800 IU/d oral as maintenance dose along with 1000 mg oral calcium supplementation. The VD level, clinical parameters and survival of both the groups were compared for 6-mo.RESULTS Prevalence of vitamin D deficiency(VDD) in decompensated CLD was 84.31%. The mean(SD) age of the patients in the treatment group(M:F: 40:11) and control group(M:F: 37:13) were 46.2(± 14.93) years and 43.28(± 12.53) years, respectively. Baseline mean(CI) VD(ng/mL) in control group and treatment group were 9.15(8.35-9.94) and 9.65(8.63-10.7), respectively. Mean(CI) serum VD level(ng/mL) at 6-mo in control group and treatment group were 9.02(6.88-11.17) and 29(23-35), respectively. Over the period of time the VD, calcium and phosphorus level was improved in treatment group compared to control group. There was nonsignificant trend seen in greater survival(69% vs 64%; P 0.05) and longer survival(155 d vs 141 d; P 0.05) in treatment group compared to control group. VD level had no significant association with mortality(P 0.05). In multivariate analysis, treatment with VD supplement was found significantly(P 0.05; adjusted hazard ratio: 0.48) associated with survival of the patients over 6-mo. CONCLUSION VD deficiency is very common in patients of decompensated CLD. Replenishment of VD may improve survival in patients with decompensated liver cirrhosis.     

恩替卡韦治疗失代偿期乙型肝炎肝硬化

目的探讨恩替卡韦治疗失代偿期乙型肝炎（乙肝）肝硬化临床疗效。方法选取失代偿期乙肝肝硬化患者共44例。随机分为治疗组22例,对照组22例。2组均给予还原型谷胱甘肽、促肝细胞生长素、甘草酸二铵等综合性保肝、护肝治疗。对照组加拉米夫定100mg,口服,1／d;治疗组加恩替卡韦O．5mg,口服,1／d。疗程均为52周。结果2组患者在HBVDNA水平下降,改善肝功能、血清肝纤维化指标、凝血酶原活动度及Child-Pu-sh积分等方面与治疗前比较,有统计学意义;2组治疗后比较,无统计学意义。结论恩替卡韦治疗失代偿期乙肝肝硬化患者,疗效明确,安全洼好。     

失代偿期乙型肝炎肝硬化患者营养状况分析

目的 了解和评估失代偿期乙型肝炎肝硬化患者的营养状况。方法 选取本院2015年9月～2016年8月住院的失代偿期乙型肝炎肝硬化患者32例和慢性乙型肝炎患者40例,入院后测量患者身高、体质量,并计算体质指数（BMI）。住院24小时内空腹采静脉血检测血清白蛋白（Alb）和视黄醇结合蛋白（RBP）等指标,并以BMI、Alb评估患者营养不良状况。采用营养风险筛查2002（NRS2002）评估患者营养风险。结果 失代偿期乙型肝炎肝硬化组BMI为（22.21±2.79） kg/m2,与慢性乙型肝炎组（21.70±2.74） kg/m2比,无统计学差异（P>0.05）;失代偿期乙型肝炎肝硬化组血清Alb和RBP分别为（28.05±4.71）g/L和（10.88±9.36）mg/L,均显著低于慢性乙型肝炎组【分别为（41.57±3.47） g/L和（23.67±10.48） mg/L,P<0.000］;以BMI或Alb评估失偿期乙型肝炎肝硬化患者营养不良发生率分别为81.3%和93.8%,显著高于慢性乙型肝炎组（分别为0.0%和2.5%,P<0.000）;以NRS2002评估失代偿期乙型肝炎肝硬化患者存在营养风险百分比为59.4%,显著高于慢性乙型肝炎组的2.5%（P<0.000）。结论 失代偿期乙型肝炎肝硬化患者存在高比例的营养不良及营养风险,应注意干预。     

失代偿期肝硬化患者的MELD评分与预后

目的评价MELD评分系统在晚期肝病中的应用。方法对87例住院失代偿期乙肝肝硬化患者进行MELD评分，同时进行C-T-P评分。随访3、12、24月的生存率，并分组比较。结果随访3月病死率31．0％；12月病死率40．2％；24月病死率为75．9％。以MELD系统R为18分组比较，显示〉18分组3月、12月的病死率明显高于≤18分组（P=0．001及0．006），24月无明显差异；以R≤9分、10—19分、20-29分、30-39分、≥40分组比较，显示≤9分组3月、12月病死率为0，≥40分组3月病死率为100％。10分以上者在24月均有较高的病死率。C-T-P评分有相类似的结果。结论MELD对失代偿肝病1年内的短期预后判定较为准确。C-T-P系统也是良好的肝功能评价方法之一。     

抗内毒素治疗对肝硬化患者血管活性物质的影响

目的 探讨安全有效的抗内毒素疗法对肝炎后肝硬化失代偿期血浆一氧化氮（Ｒｉｔｒｉｃ ｏｘｉｄｅ,ＮＯ）、前列环素（６－Ｋｅｔｏ－ＰＧＦ１α）,ＴＮＦ－α的影响。方法 观察了３０例肝硬化病人口服思密达脑阿尊西林抗内毒素治疗二周前后血浆内毒素,ＮＯ、６－Ｋｅｔｏ－ＰＧＦ１,ＴＮＦ－α水平变化情况及抗体功能状态与上述血管活性物质的关系。结果 肝硬化患者上述四种指标平均水平治疗前明显高于正常对照组,治疗二周     

血清钠对肝硬化失代偿期患者并发症的影响

目的研究血清钠浓度对肝硬化失代偿期患者并发症的影响。方法对212例肝硬化失代偿期的患者进行回顾性分析,根据患者入院时的血清钠浓度分为正常组和低钠血症组,而低钠血症组又分为轻度、中度、重度组。研究不同浓度的血清钠对肝硬化失代偿期患者并发症的影响。结果血清钠的浓度越低,发生并发症如:腹水、自发性腹膜炎、肝性脑病的概率越大(消化道出血除外),病死率也越高。正常组、轻度、中度、重度低钠血症组的腹水发生率为33.0%、73.8%、91.4%、100.0%,自发性腹膜炎的发生率为3.5%、14.3%、28.6%、55.0%,肝性脑病的发生率为7.0%、11.9%、28.6%、60.0%,病死率分别为6.1%、11.9%、31.4%、60.0%,正常组的并发症的发生率及病死率明显低于中度、重度组,轻度、中度低钠血症组(P0.05)。结论血清钠可作为一个监测指标判定肝硬化失代偿期患者的预后。     

抗病毒治疗对失代偿期乙肝肝硬化患者预后的影响

目的观察抗病毒治疗对失代偿肝硬化患者生存时间及肝癌发生的影响。方法回顾性分析1998年1月~2009年12月,于北京地坛医院住院至少3次或3次以上的HBV感染相关的失代偿肝硬化患者,抗病毒治疗对其预后的影响。所有分析对象是在最后1次住院期间死亡的患者。其中男168例,女69例。237例患者中70例患者接受了连续6个月以上的抗病毒治疗。耐药检测采用PCR法扩增病毒聚合酶相应的基因片段,并进行测序分析。结果接受核苷类似物抗病毒治疗的70例患者生存时间（34.44±28.39）个月,显著长于未接受治疗的患者（27.12±24.29）个月。167例未接受抗病毒治疗的失代偿肝硬化患者中,最终60例死亡前被确诊为肝癌,发生率为35.93%（60/167）;而接受抗病毒治疗的70例患者中,20例死亡前被确诊为肝癌,肝癌发生率为28.57%（20/70）。两组比较无显著性差异（P=0.37）。治疗期间6例患者出现耐药,但未出现病情加重。结论核苷类似物对HBV感染失代偿肝硬化患者的治疗有助于延长患者的生存期,但不能降低肝癌的发生。     

Impact of long-term gastric acid suppression on spontaneous bacterial peritonitis in patients with advanced decompensated liver cirrhosis

ObjectiveRecent studies have presented conflicting results on the association between gastric acid suppression and spontaneous bacterial peritonitis (SBP). The long-term effects of gastric acid suppression on SBP in cirrhotic patients remain unclear. This study evaluated the risk of SBP in advanced decompensated cirrhotic patients with long-term gastric acid suppression.MethodsUsing the Taiwan National Health Insurance Research Database, we identified 4788 patients with decompensated cirrhosis from 1998 to 2011. The SBP incidence rate was compared among proton pump inhibitor (PPI), H2-receptor antagonist (H2RA), and control cohorts. Multivariate Cox proportional hazards regressions analysis was conducted to confirm the association between gastric acid suppression and SBP.ResultsTotally, 4788 patients were analyzed: 1870 in the PPI cohort, 1728 in the H2RA cohort, and 1190 in the control cohort. The overall incidences of SBP were 16.8, 11.9, and 9.80 per 1000 person-years in the PPI, H2RA, and control cohorts, respectively. The adjusted hazard ratio (aHR) of SBP during the follow-up period was 1.16- (95% confidence interval [CI], 0.72–1.86) and 1.00-fold (95% CI, 0.63–1.57) higher in the PPI and H2RA cohorts, respectively, than in the control cohort; the result was non-significant. Compared with the control cohort, patients with > 180 days of PPI therapy had significantly higher risks of SBP, with an aHR of 2.28 (95% CI, 1.37–3.78).ConclusionsLong-term PPI use is associated with a high risk of SBP in advanced decompensated cirrhotic patients. Well-designed prospective studies are necessary to evaluate the safety of long-term PPI use in such patients.     

Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis.

Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver.     

恩替卡韦治疗46例失代偿期乙型肝炎肝硬化患者临床效果观察

目的分析失代偿期乙型肝炎肝硬化患者应用恩替卡韦治疗的效果。方法选取我院2012年5月~2014年6月期间收治的92例失代偿期乙型肝炎肝硬化患者作为临床研究对象,随机均分为恩替卡韦治疗组和阿德福韦治疗组,每组46例。采用荧光定量聚合酶链反应法检测HBV DNA 定量。结果在治疗48 w末,恩替卡韦治疗组患者血清HBV DNA转阴率达到82.61%,显著高于阿德福韦治疗组的63.05%（P<0.01）;恩替卡韦治疗组患者Child- Pugh评分为（6.1±1.4）分,相比阿德福韦治疗组Child- Pugh评分（7.4±1.5）分,明显降低（P<0.05）。结论应用恩替卡韦治疗失代偿期乙型肝炎肝硬化患者,临床效果较好。     

内毒素血症与肝肾综合征的关系研究

目的分析肝硬化伴I型肝肾综合征患者内毒素血症与肝肾综合征发生的关系.方法纳入肝硬化伴1型肝肾综合征患者38例和肝硬化肾功能正常患者50例,分析肝硬化病因、降钙素原、Child-Pugh分级、终末期肝功能评分、全身炎症反应评分和平均动脉压及血生化指标.结果肝肾综合征患者降钙素原水平为6.98±12.38ng/L,高于对照组（0.12±0.10ng/L,P〈0.05）;肝肾综合征患者终末期肝功能评分为36.9±9.0,高于对照组（9.9±7.7,P〈0.05）;肝肾综合征患者血清总胆红素、尿素、肌酐、半胱氨酸蛋白酶抑制剂及血钾水平分别为296.4±233.8μmol/L、29.9±11.1mmol/L、417.1±97.4μmol/L、3.5±1.2mg/L 和4.78±0.89mmol/L,高于对照组（57.5±44.1μmol/L、4.6±1.0 mmol/L、69.2±10.3μmol/L、1.2±0.5mg/L和3.68±0.41mmol/L,P均〈0.05）,而血钠、血氯水平为127.9±6.5mmol/L和91.8±6.7mmol/L,明显低于对照组（138.26±3.94mmol/L、103.23±5.06mmol/L,P均〈0.05）.结论内毒素血症可能是肝肾综合征发生的关键因素.     

肝硬化失代偿期患者行宫腔镜手术的安全性

目的探讨肝硬化失代偿期患者行宫腔镜手术的安全性与临床效果。方法回顾性分析2012年10月至2018年12月北京佑安医院妇科宫腔镜手术治疗的肝硬化失代偿期患者45例。记录手术时间、术中出血量、术后住院时间、并发症等围手术期指标,监测围手术期的血常规、肝功能及凝血功能等指标,综合评价肝硬化失代偿期患者临床治疗效果。结果45例手术均顺利完成,手术时间为10~205 min,平均(48.82±38.40)min,术中出血量2~100 mL,平均(13.18±35.04)mL、术后住院时间为1~13 d,平均(3.78±3.16)d,术后并发症发生率为13.33%(6/45)。将术前、术后的血常规、凝血功能、肝功能等指标进行比较,其中白蛋白术前为23.8~43.5 g/L,平均(33.95±4.61)g/L,术后为22.9~42.6 g/L,平均(32.04±4.24)g/L;血小板术前30~278×10^9/L,平均(71.84±44.45)×10^9/L,术后21~266×10^9/L,平均(67.58±44.59)×10^9/L,术后均较术前显著下降,差异有统计学意义(P<0.05)。结论在严格把握手术指征、正确充分的围手术处理,熟练掌握宫腔镜手术技巧,注重止血,预防感染的前提下,肝硬化失代偿期患者行宫腔镜手术是安全可行的。     

Health-related quality of life in patients with compensated and decompensated liver cirrhosis

BackgroundCompensated (Child-Pugh [CP] A) and decompensated (CP B/C) liver cirrhosis significantly differs in terms of impairment of health-related quality of life (HRQoL). However, sufficient data on potentially treatable factors associated with HRQoL in both stages of the disease are still lacking. Consequently, aims of this study were to determine differences in HRQoL between patients with compensated and decompensated liver cirrhosis and to identify potentially treatable factors associated with HRQoL.Methods218 patients with liver cirrhosis were enrolled into this study. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL. Covert hepatic encephalopathy (CHE) was diagnosed according to a combination of Psychometric Hepatic Encephalopathy Score and Critical Flicker Frequency. Frailty was assessed by Clinical Frailty Scale (CFS).ResultsHRQoL differed between patients with CP A (n = 133) and CP B/C (n = 85) liver cirrhosis (CLDQ total score: 5.6 vs. 4.8, p < 0.001). Multivariate analysis identified a history of falls in the recent year, presence of CHE, female gender, active smoking, higher CFS, and higher serum levels of CRP as independent predictors of impaired HRQoL (all p < 0.05) in patients with CP A liver cirrhosis. In patients with CP B/C liver cirrhosis, female gender, a history of overt hepatic encephalopathy, and lower hemoglobin were independently associated with impaired HRQoL (all p < 0.05).ConclusionsPredictors of impaired HRQoL differ in patients with CP A or CP B/C liver cirrhosis. Focusing on treatable factors in routine clinical practice may improve HRQoL in all stages of liver cirrhosis.     

拉米夫定单药及其初始联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化的疗效比较

目的 比较拉米夫定与阿德福韦酯初始联合或拉米夫定单药治疗失代偿期乙型肝炎肝硬化患者2年的疗效.方法 60例失代偿期乙型肝炎肝硬化接受初始拉米夫定(LAM)与阿德福韦酯(ADV)联合抗病毒治疗,为初始联合组;55例接受拉米夫定(LAM)单药抗病毒治疗,为LAM单药组每1～3个月检测患者肝功能、肾功能、甲胎蛋白、乙型肝炎病毒标志物、血清HBV DNA、凝血酶原时间(PT)、肝脏的超声或CT检查,分别在治疗12个月和24个月时比较疗效.组间均数比较用Mann-Whitney检验,相关性分析时采用Pearson双侧t检验.结果 初始联合组45例治疗12个月时血清HBV DNA阴转率为51.1%(23/45),而40例LAM单药组HBV DNA阴转率为47.5%(19/40);至24个月时,初始联合组HBV DNA阴转率达86.7%(39/45),LAM单药组为60.0%(24/40),两组间差异有统计学意义(P＜0.05).初始联合组治疗24个月时,HBeAg血清学转换率为43.5%(10/23),LAM单药组HBeAg血清学转换率为30.0%(6/20),两组间差异有统计学意义(P＜0.05).ALT复常率在初始联合组治疗12个月时为71.1%(32/45),LAM单药组为65.0%(26/40),至24个月时两组ALT复常率分别为88.9%(40/45)和75.0%(30/40),差异有统计学意义(P＜0.05).初始联合组在治疗12个月和24个月时,分别有4.4%(2/45)和6.7%(3/45)发生病毒学突破,但均未检测到病毒学变异,LAM单药组在12个月和24个月时分别有22.5%(9/40)和37.5%(15/40)发生病毒学突破,并分别有17.5%(7/40)和32.5%(13/40)的患者中检测到病毒学变异,均较联合治疗组高(P＜0.05).初始联合治疗更能改善肝功能,Child-Turcotte-Pugh评分和终末期肝病模型评分亦有更明显下降.随访24个月,LAM和ADV初始联合治疗组累计死亡或肝移植率为16.7%,LAM单药组累计死亡或肝移植发生率为20.0%.两组均未发现有血清肌酐超过正常值上限的病例.结论 LAM与ADV初始联合治疗失代偿期乙型肝炎肝硬化患者能更明显抑制HBV复制,改善肝功能各项指标,降低病死率,值得临床应用.

Abstract：

Objective To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years.Methods A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study,among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM.The liver and kidney functions,HBV DNA,HBV-M,AFP,Ultrasond or CT scan of liver were tested every l-3months.the treatment efficacy was evaluated by month 12 and 24.Results By month 12,the HBVDNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively,by month 24 the rates were 86.7% and 60.0% respectively.By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0%respectively,with significant difference existed between the two therapy groups (P ＜ 0.05).By month 24,the ALT normalization rates of the two groups were 88.9% and 72.5% respectively.Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group,but no viral resistance observed.Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%)by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24.Significant difference existed between the two groups (P ＜ 0.05).Improvement of liver function was more obviously in the combination group.The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group.No renal dysfunction observed in both groups.Conclusion LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.     

Effect of cholestyramine on bile acid kinetics in patients with portal cirrhosis of the liver

The kinetics of cholic acid (C) and chenodeoxycholic acid (CD) were studied in six patients with portal liver cirrhosis. The studies were conducted both before and after 5–6 weeks of treatment with cholestyramine (12 g/day). In keeping with previous observations, the pool size and formation of C showed subnormal values during the pretreatment period, while the production of CD was within normal limits. The pool sizes of C and CD did not change upon treatment with cholestyramine, but the mean total bile acid formation increased by a factor of about 2.5. The ratio between the amounts of C and CD synthesized remained essentially unchanged. Considering the therapeutic response previously observed in normal subjects and in patients with hyper-β-lipoproteinemia, the present results suggest a selective impairment of the biosynthesis of C in patients with portal liver cirrhosis. It is suggested that the primary defect may reside in the 12α-hydroxylase enzyme system.     

失代偿性乙型肝炎肝硬化抗病毒治疗的现状和思考

代偿性乙型肝炎肝硬化的抗病毒治疗指征、药物选择、疗程、治疗终点、停药指征等基本和慢性乙型肝炎患者一致,只是抗病毒治疗的指征相对更宽,疗程相对更长,停药指征相对更严.但失代偿性乙型肝炎肝硬化的抗病毒治疗原则和慢性乙型肝炎、代偿性肝硬化患者有所不同,情况更加复杂.     

丙型肝炎失代偿期肝硬化的抗病毒治疗

丙型肝炎肝硬化代偿期患者每年发展为失代偿期的比例为3.6％ ～ 6.0％,目前惟一有效的治疗方法是肝移植.由于肝移植费用高、供肝短缺以及肝移植后复发率高,因此,国内外研究者对失代偿期肝硬化患者尝试着进行抗病毒治疗.通过清除HCV可改善患者的肝功能,延缓疾病进展,减少肝脏失代偿,部分患者甚至免于肝移植,延长患者的生存期.但是抗病毒治疗的时机、剂量和疗程、疗效尚不是很明确.