Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis

Summary Nadolol, a non-cardioselective beta adrenoreceptor blocking agent, has been reported to decrease portal pressure without affecting liver function in cirrhotic patients treated for 1 month. There were no data about the long-term effects of nadolol on liver function.In 11 patients with cirrhosis and portal hypertension galactose eliminating capacity, aminopyrine metabolic capacity, ICG clearance and IGC intrinsic hepatic clearance according to the parallel tube model were measured before and after 6 months of treatment with nadolol at a dose reducing resting heart rate by approximately 25%. No significant variation in any of these parameters was found.Thus 6 months of continuous oral administration of nadolol did not further impair liver function in cirrhotics.     

Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis

Background  Endotoxaemia is commonly seen in cirrhotic patients with ascites and this may be associated with increased portal pressure.
Aim  To investigate the effect of intestinal decontamination on liver haemodynamics in alcohol-related cirrhotic patients with ascites.
Methods  We included 30 patients. At day 0, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed. Patients received rifaximin (1200 mg/day) for 28 days. At day 29, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed again.
Results  Median (range) plasma endotoxin levels decreased significantly after rifaximin administration both in systemic [1.45(0–3.1) vs. 0.7(0–2.7), P  < 0.0001] and splanchnic circulation [1.8(0–3.4) vs. 0.8(0–2.1), P  < 0.0001]. Meanwhile, the difference seen in endotoxin levels between the splanchnic and systemic circulation at day 0 ( P  = 0.001) was not noted at day 29 ( P  = 0.137). HVPG measurement was possible in 28 patients. Median (range) HVPG values were 18 mmHg (12.7–26.3) on day 0 vs. 14.7 mmHg (7–20) on day 29 ( P  < 0.0001). HVPG decreased after rifaximin in 23, remained stable in two and increased in three patients.
Conclusion  Hepatic venous pressure gradient values decreased significantly after intestinal decontamination with rifaximin in patients with alcohol-related decompensated cirrhosis and this might have been achieved through significant reduction of plasma endotoxin levels.     

Verapamil pharmacokinetics and liver function in patients with cirrhosis

In seven patients with liver cirrhosis, verapamil plasma levels were measured in blood drawn simultaneously from the hepatic vein and from an artery during the post-distributive phase after an intravenous bolus infusion of 5 mg of verapamil. In addition the hepatic plasma flow was measured using the indocyanine-green constant infusion technique. From these data the verapamil hepatic clearance and verapamil intrinsic clearance were calculated. The verapamil hepatic clearance was 423 +/- 92 ml/m, the hepatic plasma flow was 819 +/- 318 ml/m, and the verapamil intrinsic clearance was 1431 +/- 961 ml/m. As compared to values reported in the literature, a decrease of the verapamil hepatic clearance by 50% approximately was found, while the hepatic plasma flow was in the normal range and the verapamil intrinsic clearance was reduced by 75%. These data show that in patients with cirrhosis the decrease in verapamil clearance is due to an impairment in the capacity of the liver to remove the drug, and not to a decrease in liver perfusion.     

麻醉方法对肝炎肝硬化手术患者免疫功能的影响

目的 探讨麻醉对肝炎肝硬化患者围术期免疫功能的影响.方法 择期行脾切除断流手术的肝炎肝硬化患者40例,ASA Ⅰ-Ⅱ级,Child-Pugh A-B级,随机均分为两组.均用全麻:麻醉诱导采用咪唑安定0.05 mg/kg,顺式阿曲库铵0.15 mg/kg,芬太尼2μg/kg;麻醉维持用雷米芬太尼0.1-0.3μg·kg-1·min-1和顺式阿曲库铵0.06-0.12 mg·kg-1·h-1泵注.S组麻醉诱导加用8％七氟醚吸入,麻醉维持加用2％-4％七氟醚吸入;P组麻醉诱导加用丙泊酚,其后持续输注丙泊酚3-6mg· kg-1·h-1维持麻醉.分别于麻醉前30 min(T0)、手术结束时(T1)及术后1 d(T2)采静脉血2 ml,用流式细胞术测定CD4+和CD8+,计算CD4+/CD8+比值.结果 麻醉前两组CD4+、CD8+及CD4+/CD8+比值均.无统计学差异(P＞0.05).与T0比较,T1时两组CD4+和CD4+/CD8+比值均明显下降(P＜0.05),但S组T2时已恢复至麻醉前水平.T1、T2时,S组CD4+和CD4+/CD8+比值均明显高于P组(P＜0.05).两组围术期CD8+均无明显改变(P＞0.05).结论 肝炎肝硬化患者全麻下脾切除断流手术后免疫功能明显抑制.与丙泊酚比较,以七氟醚吸入为主的全麻对T淋巴细胞抑制较轻.     

Effects of nadolol and propranolol on renal function in hypertensive patients with moderately impaired renal function.

Effects of oral administration of equipotent antihypertensive doses of propranolol and nadolol on renal function were examined in 20 hypertensive patients with moderately impaired renal function. Creatinine clearance increased, and serum beta 2-microglobulin concentrations decreased, when patients were switched from propranolol to nadolol therapy (creatinine clearance = 46.7 +/- 4.9 ml min-1 on propranolol and 52.7 +/- 5.9 on nadolol; beta 2-microglobulin = 6.14 +/- 0.66 mg l-1 on propranolol and 5.62 +/- 0.62 on nadolol). When patients were put back on propranolol, their creatinine clearances (45.9 +/- 5.0 ml min-1) and serum beta 2-microglobulin concentrations (6.51 +/- 0.67 mg l-1) returned to values comparable to those obtained before the change to nadolol was made. Serum beta 2-microglobulin concentrations correlated significantly with creatinine clearance (r = -0.819, P less than 0.001).     

胎盘多肽注射液联合阿德福韦酯片对乙型肝炎肝硬化失代偿期患者肝及免疫功能的影响

目的 探讨胎盘多肽注射液联合阿德福韦酯片对乙型肝炎肝硬化失代偿期患者肝及免疫功能的影响.方法 选取2013年4月至2014年12月本院收治的乙型肝炎肝硬化失代偿期患者82例为研究对象,随机分为观察组和对照组,各41例.对照组口服阿德福韦酯片并进行保肝、休息和营养支持治疗,观察组在此基础上注射胎盘多肽注射液,均治疗3个月后比较两组肝及免疫功能,同时记录毒副作用发生率.结果 观察组治疗后ALT[(48.88±2.21) U/L]、TBil[(14.86±0.93)μmol/L]水平明显低于对照组[(52.37±2.73) U/L、(17.21±1.05)μmol/L],观察组PT[(12.11±0.98)s]较对照组[(13.46±1.24)s]短(P＜0.05);观察组外周血淋巴细胞CD3+[(69.83±3.02)％]、CD4+[(42.96±3.65)％]、NK[(22.87±1.94)％]活性显著高于对照组(P＜0.05);两组毒副反应发生率差异无统计学意义(26.8％vs.19.5％,P＞0.05).结论 胎盘多肽注射液联合阿德福韦酯片对乙型肝炎肝硬化失代偿期患者肝、免疫功能有明显改善作用,治疗安全性较好,值得临床推广.     

Renal effects of nadolol in cirrhosis

Summary The effects of nadolol on renal haemodynamics and function, and on the renin-angiotensinaldosterone system and on renal prostaglandin production were studied in eighteen cirrhotics.After 1 month of treatment, nadolol had significantly decreased cardiac output by 25% without affecting arterial pressure, renal plasma flow or renal vascular resistance. Glomerular filtration rate, filtration fraction and the proportion of the cardiac output delivered to the kidneys were significantly increased. The renin-angiotensin-aldosterone system was suppressed and urinary PGE₂ excretion was slightly increased.The latter effects were not correlated with those on renal haemodynamics and function.     

七氟醚静吸复合麻醉对肝炎肝硬化手术患者肝肾功能及细胞免疫功能的影响

目的 探讨七氟醚静吸复合麻醉对肝炎肝硬化手术患者肝功能、肾功能及细胞免疫功能的影响.方法 选择2014年3月至2015年3月医院择期行手术治疗的肝炎肝硬化患者62例随机分为观察组31例和对照组31例.2组患者术前24 h停用各类药物,入室后开放外周静脉,常规检测血氧饱和度、血压、脑电图、心电图,麻醉前肌注苯巴比妥钠、阿托品.观察组采用静吸复合麻醉,麻醉诱导:静脉注射芬太尼3μg,依托咪酯注射液0.2 mg/kg,咪达唑仑注射液0.05 mg/kg,注射用顺苯磺阿曲库铵0.2mg/kg;麻醉维持:吸入3％七氟醚,持续泵入注射用顺苯磺阿曲库铵0.2 mg/(kg·h),注射用盐酸瑞芬太尼0.2μg/(kg·h).对照组采用全凭静脉麻醉,麻醉诱导时丙泊酚注射液2 mg/kg代替依托咪酯注射液,麻醉维持持续泵入丙泊酚注射液5 mg/(kg·h)代替七氟醚,其他麻醉药物同观察组.比较2组患者麻醉前(t1)、诱导后2h(t2)、术后1d (t3)时段肝肾功能、细胞免疫功能情况,并记录术后24h不良反应发生情况.结果 2组患者t2时ALT、Scr、BUN显著高于t1时,ALB、CD4+、CD4+/CD8+、NK明显低于t1时(P＜0.05),但观察组变化幅度明显小于对照组(P＜0.05);2组患者术后24 h内发生呼吸抑制、头晕头痛、恶心呕吐、咽喉疼痛、肌颤、嗜睡、咳嗽无力不良反应发生情况比较,差异无统计学意义(P＞0.05).结论 七氟醚静吸复合麻醉对肝炎肝硬化患者手术肝肾功能、细胞免疫功能影响较小,有利于免疫功能恢复,安全可靠,值得临床推广应用.     

Pharmacokinetics of metoclopramide in patients with liver cirrhosis.

The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis.     

The pharmacokinetics of perindopril in patients with liver cirrhosis.

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.     

肝硬化患者肠黏膜通透性改变与肝功能分级的关系研究

目的探讨肝硬化患者肠黏膜通透性改变与肝功能分级的关系。方法以2020年11月至2022年4月经郑州市第六人民医院医学检验科收治肝硬化患者96例为观察组, 按Child-Pugh肝功能分级分为A组(35例)、B组(43例)、C组(18例)3个亚组;同期选择无肝硬化的健康体检者40例为对照组。A组男25例、女10例, 年龄(55.01±8.71)岁;B组男30例、女13例, 年龄(55.19±8.76)岁;C组男14例、女4例, 年龄(55.34±8.81)岁;对照组男27例、女13例, 年龄(54.52±8.56)岁。收集粪便标本, 通过细菌培养测定肠道主要菌群变化, 测定肠黏膜通透性指标[D-乳酸(D-LAC)、内毒素(ETX)及二胺氧化酶(DAO)]。Pearson相关性分析分析肠黏膜通透性指标之间的相关性, Spearman相关性分析分析肠黏膜通透性指标与Child-Pugh肝功能分级的相关性, 并使用受试者工作特征曲线(ROC)分析肠黏膜通透性指标的预测价值。计量资料采用F检验、独立样本t检验, 计数资料采用χ2检验。结果 A、B、C组肠杆菌[(8.61±0.42)lgCFU/g...     

Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis

A method for rapid assessment of hepatic function in cirrhotics based on the formation of the lidocaine metabolite, monoethylglycinexylidide (MEGX), was evaluated. The formation kinetics and urinary excretion patterns of MEGX clearly distinguished cirrhotics (n = 12) from healthy volunteers (n = 16). In a prospective study, we compared the prognostic value of the MEGX test with that of traditional parameters in transplant candidates. Patients who underwent transplantation during follow-up were excluded. The study included 58 adult patients with biopsy-proven posthepatitic or biliary cirrhosis. During the follow-up period of 120 days, 10 of 58 patients died of their liver disease. At the time of inclusion, we recorded MEGX formation, indocyanine green (ICG) half-life, caffeine clearance, and the Child-Pugh score. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model). The results of the MEGX and the ICG test were significantly related to the 120-day survival. In the stepwise analysis, none of the parameters evaluated contributed to a further significant improvement of our predictive ability when added to the values of ICG (improvement: p less than 0.0005) and MEGX (improvement: p less than 0.0005). These findings suggest that the ICG and MEGX tests were the best short-term prognostic indicators. The easy handling favors the MEGX test over the ICG test as a tool for assessment of hepatic function and short-term prognosis in transplant candidates with cirrhosis.     

谷氨酰胺对肝硬化患者Treg细胞的影响及其临床意义研究

目的观察谷氨酰胺对肝硬化患者调节性T细胞(Treg)的影响及其肠黏膜保护功能,并探讨其相关的临床意义。方法收集2013年1月至2014年2月我院收治的肝硬化患者62例,随机分为常规治疗组(对照组)和谷氨酰胺治疗组(观察组),另取我院健康体检者30例作为正常对照组。流式细胞仪检测Treg细胞,ELISA法检测白介素-10(IL-10)、二胺氧化酶(DAO)、D-乳酸的表达。结果治疗前,两个治疗组Treg细胞比例和IL-10表达比较差异无统计学意义(P>0.05),但均低于正常对照组(P<0.01);治疗后,两组Treg细胞比例和IL-10表达均升高(P<0.05),且观察组升高幅度高于对照组(P<0.05)。治疗前,两个治疗组的DAO和D-乳酸表达水平比较差异无统计学意义(P>0.05),但均高于正常对照组(P<0.01);治疗后,两组DAO、D-乳酸表达均降低(P<0.05,P<0.01),且观察组降低的幅度高于对照组(P<0.05,P<0.01)。治疗前,两个治疗组ALT和AST表达比较差异无统计学意义(P>0.05),治疗后,两组ALT和AST表达均降低(P<0.05,P<0.01),且观察组降低的幅度高于对照组(P<0.05,P<0.01)。结论谷氨酰胺可以提高肝硬化患者的Treg细胞比例和IL-10表达,调节机体免疫紊乱状态,有利于肠黏膜损伤的修复和肝功能的恢复,值得临床借鉴采用。     

预防性应用抗生素对肝硬化上消化道出血患者感染的影响

目的研究肝硬化上消化道出血患者预防性应用抗生素治疗的效果及对感染的影响。方法86例肝硬化上消化道出血患者,遵照双盲法分为对照组和观察组,各43例。对照组实施常规治疗方式,观察组在常规治疗的基础上预防性使用抗生素。比较两组临床指标、病死率与再出血率、感染情况。结果观察组止血时间(2.42±0.23)d、功能恢复时间(3.32±0.54)d、治疗时间(7.46±1.43)d,均短于对照组的(4.51±0.93)、(5.76±1.18)、(11.56±2.15)d,差异有统计学意义(P<0.05)。观察组病死率为0,再出血率为9.30%,均低于对照组的9.30%、25.58%,差异有统计学意义(P<0.05)。观察组总感染率为27.91%,低于对照组的48.84%,差异有统计学意义(P<0.05)。结论预防性应用抗生素在肝硬化上消化道出血患者中比常规治疗的作用更佳,对于抑制感染情况,预防患者消化道再次出血等有十分重要的意义。     

复方鳖甲软肝片对乙肝肝硬化患者代偿期肝纤维化及炎性因子的影响

目的探讨复方鳖甲软肝片对乙肝肝硬化患者代偿期肝纤维化及炎性因子的影响。方法将76例乙肝肝硬化代偿期患者随机分为观察组和对照组,观察组采用复方鳖甲软肝片联合谷胱甘肽治疗,对照组仅给予谷胱甘肽治疗;对比分析两组治疗前后肝功指标、肝纤维化指标、炎性因子变化情况。结果肝功能指标:治疗后,两组患者的天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、丙氨酸氨基转移酶(ALT)降低,凝血酶原活动度(PTA)升高,差异有统计学意义(P<0.01);观察组患者的AST、TBil、ALT、PTA改善程度优于对照组,差异有统计学意义(P<0.01)。肝纤维化指标:治疗后,两组患者的层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)降低,差异有统计学意义(P<0.01);观察组患者的LN、PCⅢ、HA、Ⅳ-C低于对照组,差异有统计学意义(P<0.01)。炎性因子:治疗后,两组患者的白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)、内毒素(ET)降低,差异有统计学意义(P<0.01);观察组患者的IL-6、TNF-α、ET低于对照组,差异有统计学意义(P<0.01)。结论复方鳖甲软肝片治疗乙肝肝硬化患者代偿期,可进一步减轻肝细胞炎症反应,缓解肝损伤,延缓肝纤维化进程,提高肝功能。     

肝硬化门静脉高压患者血浆肾上腺髓质素的表达及其与血流动力学的关系研究

目的探讨肾上腺髓质素（ADM）在肝硬化门静脉高压患者血浆中的表达及其与血流动力学的关系。方法采用放射免疫法测定82例肝硬化门静脉高压患者血浆中ADM的含量,然后观察其与门静脉血流动力学之间的关系。结果 Pearson相关分析表明,肝硬化门脉高压患者血浆ADM含量与门静脉截面内径（PVD）和门静脉血流量（PVFV）之间呈正相关,与门静脉最大血流速度（PVV）之间呈负相关。结论 ADM的表达水平与肝硬化门静脉高压患者门静脉血流动力学有关,患者血浆中ADM的含量可作为肝硬化门静脉高压的诊断及预后的指标,也为其治疗提供新的靶点。     

Lidocaine elimination in patients with liver cirrhosis

The aim of the study was to evaluate lidocaine elimination in patients with liver cirrhosis. The study was carried out in 30 cirrhotic patients classified according to the Child-Pugh's score to subgroups A (n=11). B (n=12) and C (n=7), and 14 healthy volunteers. Lidocaine was administered intravenously, at a dose of I mg/kg, and blood samples for lidocaine and monoethylglycinexylidide (MEGX) assays were collected for up to 6 h. Decreased elimination half-live for lidocaine as well as reduced formation rate of MEGX was found in cirrhotic patients. Lidocaine metabolising capacity of the liver was irrespective of etiology of cirrhosis. It was also found that evaluation of elimination half-life of lidocaine is more closely related to the Child-Pugh's staging of liver dysfunction than 15-minute MEGX concentration.     

肝硬化患者的营养状况评估

目的旨在通过运用NRS2002对122名肝硬化住院患者的营养风险评估与营养参数分析,为临床医生提供依据,早期发现和早期纠正营养不良,改善患者预后。方法安徽医科大学第一附属医院2010年3月到10月诊断为肝硬化的住院病人122例,在住院第一天进行NRS2002营养风险评估、营养参数指标测量,分为营养不良风险组(NRS≥3)和无营养不良风险组(NRS3),同时分析营养不良风险组与无营养不良风险组间营养参数指标的差异。结果 122例中有93例肝硬化住院患者存在营养不良风险,营养不良发生率为76%。其中营养不良风险患者中Child-Pugh A级为10人,营养不良发生率为30%(10/30);Child-Pugh B级55人,营养不良发生率为86%(55/64);Child-Pugh C级28人,营养不良发生率100%(28/28)。营养不良发生率与疾病严重程度成正比。对有无营养不良风险的肝硬化病人进行比较,结果显示2组间肝硬化营养指标测定值均有显著差异。结论 NRS2002可用于肝硬化营养风险筛查,肝硬化患者营养不良程度评价需综合分析。旨在通过对122名肝硬化住院患者的营养参数分析,为临床医生提供依据,早期发现和早期纠正营养不良,改善患者预后。     

The pharmacokinetics of enalapril in patients with compensated liver cirrhosis.

The possibility of an impaired hepatic de-esterification of enalapril to enalaprilat due to hepatic dysfunction was assessed in seven patients with compensated liver cirrhosis and 10 normal control subjects. The peak serum concentration and time to the peak serum concentration of enalaprilat, as well as the suppression of serum angiotensin converting enzyme activity, following a single oral dose of enalapril maleate (10 mg) were not different in the two groups. The elimination half-life of enalaprilat was related to renal function. The results suggest that hepatic biotransformation of the drug may not be disturbed in a clinically significant manner in patients with moderate hepatic dysfunction due to compensated liver cirrhosis.