Use of a transjugular intrahepatic portosystemic shunt combined with autologous bone marrow cell infusion in patients with decompensated liver cirrhosis: an exploratory study

Background aimsCurrently, there is no treatment for decompensated liver cirrhosis except for liver transplantation. The safety and effect on liver function of a transjugular intrahepatic portosystemic shunt (TIPS) with and without autologous bone marrow cell (BMC) infusion in patients with decompensated liver cirrhosis were determined.MethodsTen patients who were diagnosed with decompensated liver cirrhosis during the period from September 2011 to July 2012 were enrolled in this study. The patients underwent TIPS (TIPS group) or combined treatment with TIPS and BMC infusion through the hepatic artery (TIPS+BMC group). All patients were monitored for adverse events, liver function and complications caused by portal hypertension during a period of 52 weeks.ResultsThe number of infused BMCs was 2.65 ± 1.20 ×10⁹. Significant improvements in the serum levels of albumin and total bilirubin and decreased Child-Pugh scores were observed in patients treated with both TIPS and BMCs (P < 0.05), whereas no such changes were observed in the TIPS group. Endoscopic findings showed that varices in the esophagus and the gastric fundus were alleviated after either treatment. All 10 patients showed a complete or partial resolution of ascites at 4 weeks. No major adverse effects were noted during the follow-up period for patients in either group.ConclusionsTIPS combined with BMC infusion is clinically safe; the treatment improved liver function and alleviated complications caused by portal hypertension; therefore, this combination has potential for treatment of patients with decompensated liver cirrhosis.     

肝硬化患者乙肝表面抗原的定量检测及意义

目的:探讨HBsAg定量测定在乙肝相关性肝硬化病程中的变化和意义。方法:选择乙肝相关性肝硬化患者60例纳入实验对象,根据2000年9月(西安)第10次全国病毒性肝炎学术会议修订的《病毒性肝炎防治方案》中的诊断标准分为代偿期组和失代偿期组,其中代偿期组35例,失代偿期组25例。另选取20例乙型肝炎病毒携带者作为对照组。应用电化学发光免疫分析法测定患者血清中HBsAg和HBeAg滴度,免疫荧光定量PCR法检测HBVDNA载量。结果:对照组、肝硬化代偿期组和肝硬化失代偿期组HBsAg滴度分别为:2574.73±3252.27COI、5494.35±2129.84COI和6921.25±1957.60COI,三组之间差别均有统计学意义(P<0.05)。肝硬化代偿期组中,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性(P<0.05()r=-0.350;r=-0.514)。肝硬化失代偿期组中,HBsAg滴度与HBVDNA及HBeAg水平均无明显相关性(r=-0.020;r=0.154)。结论:肝硬化失代偿期HBsAg滴度明显高于肝硬化代偿期,代偿期HBsAg滴度高于HBV携带者组,即HBsAg滴度随肝脏疾病进展呈阶梯型递增。肝硬化代偿期,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性,HBsAg水平可以作为评估病毒复制的参考指标。肝硬化失代偿期,HBsAg滴度与HBVDNA和HBeAg无相关性,不能反映病毒复制水平,不能作为评估病毒复制的参考指标。     

Peripheral blood monocytes from the decompensated liver cirrhosis could migrate into nude mouse liver with human hepatocyte-markers expression

Adult stem cells provide a promising alternative for the treatment of decompensated liver cirrhosis. Our previous study showed that peripheral blood monocytes (PBMCs) from decompensated liver cirrhosis could differentiate into hepatocyte-like cells in vitro. We here aimed to investigate the differential potential of the PBMCs under liver environment. PBMCs were isolated from one cirrhotic patient, who was mobilized by the recombinant human granulocyte colony stimulating factor for consecutive 3 days, and then PBMCs were transplanted into nude mice by tail vein after labeled with PKH26-GL. The location of the transplanted PBMCs was identified by PKH26-GL staining and PRINS for human SRY gene. The expressions of human hepatocyte-markers were detected by immunohistochemistry, RT-PCR, and Western blot analysis. Our results demonstrated that PBMCs from decompensated liver cirrhosis could migrate into the liver of nude mice with human hepatocyte-markers expression, indicating that autologous PBMCs transplantation might be one alternative therapy for the decompensated liver cirrhosis.     

Differences between the metabolic profiles of decompensated and compensated cirrhosis patients with Hepatitis B virus infections under high-performance liquid chromatography-mass spectrometry

To improve the grading and staging of liver cirrhosis among patients with HBV infection noninvasively, a high-performance liquid chromatography with mass spectrometry metabolomics method was used to investigate the potential metabolic biomarkers in the serum of patients with different degrees of hepatic cirrhosis. The results demonstrate that lysophosphatidyl choline (LPC) from positive electrospray ionization (ESI) mode, and fatty acids and bile acids from negative ESI mode play important roles in distinguishing decompensated from compensated cirrhosis. A total of 21 differential metabolites were found from the two groups of patients. LPCs, fatty acids, and taurocholic acid (TCA) 3-sulfate decreased in patients with decompensated cirrhosis, whereas other bile acids increased significantly. The levels of TCA 3-sulfate, LPC 16:0, and LPC 18:0 were significantly correlated with the stages of the decompensated cirrhosis, and they may serve as potential biomarkers for the stage assessment of liver cirrhosis in patients with HBV infections.     

肝硬化患者乙肝表面抗原的定量检测及意义

目的：探讨HBsAg定量测定在乙肝相关性肝硬化病程中的变化和意义。方法：选择乙肝相关性肝硬化患者60例纳入实验对象,根据2000年9月（西安）第10次全国病毒性肝炎学术会议修订的《病毒性肝炎防治方案》中的诊断标准分为代偿期组和失代偿期组,其中代偿期组35例,失代偿期组25例。另选取20例乙型肝炎病毒携带者作为对照组。应用电化学发光免疫分析法测定患者血清中HBsAg和HBeAg滴度,免疫荧光定量PCR法检测HBVDNA载量。结果：对照组、肝硬化代偿期组和肝硬化失代偿期组HBsAg滴度分别为：2574.73±3252.27COI、5494.35±2129.84COI和6921.25±1957.60COI,三组之间差别均有统计学意义（P〈0.05）。肝硬化代偿期组中,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性（P〈0.05（）r=-0.350;r=-0.514）。肝硬化失代偿期组中,HBsAg滴度与HBVDNA及HBeAg水平均无明显相关性（r=-0.020;r=0.154）。结论：肝硬化失代偿期HBsAg滴度明显高于肝硬化代偿期,代偿期HBsAg滴度高于HBV携带者组,即HBsAg滴度随肝脏疾病进展呈阶梯型递增。肝硬化代偿期,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性,HBsAg水平可以作为评估病毒复制的参考指标。肝硬化失代偿期,HBsAg滴度与HBVDNA和HBeAg无相关性,不能反映病毒复制水平,不能作为评估病毒复制的参考指标。     

Serum apoproteins A and B and the lecithin: cholesterol acyl transferase activities in liver cirrhosis and hepatic coma patients

Serum apoproteins A and B and LCAT activities were estimated in 80 patients, 46 with posthepatic cirrhosis and 34 with alcoholic cirrhosis. The cirrhosis patients were also divided into compensated, decompensated, and hepatic coma subgroups. Apo-A and LCAT activities were significantly decreased in both cirrhotic groups without any significant difference between posthepatitic and alcoholic cirrhotic groups, while Apo-B was decreased in hepatic coma patients only. The decompensated cirrhosis patients showed lower Apo-A levels than the compensated cirrhosis patients and hepatic coma patients showed still lower levels compared to decompensated subgroup, while no significant decrease was observed in LCAT activities between compensated and decompensated cirrhosis patients. Apo-A level was correlated more significantly with serum albumin level than the LCAT activity. The study confirms that Apo-A level is highly related to the degree of liver injury and also suggests that this decrease may be mainly due to impaired liver synthesis and that the serum levels of Apo-A and Apo-B can be utilized in the differential diagnosis of chronic liver diseases.     

肝硬化患者血清胆碱酯酶和腺苷脱氨酶联合检测的临床意义

目的：探讨血清胆碱酯酶和腺苷脱氨酶联合检测在诊断肝硬化不同病程分期的临床意义。方法：选择20例失代偿期肝硬化患者分为失代偿组,随机选取20例代偿期肝硬化患者和20例健康人群分别分为代偿组和健康组,对3组人群的血清胆碱酯酶和腺苷脱氨酶活性进行检测并比较其差异。结果：代偿组和失代偿组的CHE活性均要显著低于健康组,差异有统计学意义（t=-8．34,P〈0．01、t=12．03,P〈0．01）,失代偿组要显著低于代偿组,差异有统计学意义（t=4.07,P〈0．01）;代偿组和失代偿组ADA活性均要显著高于健康组,差异有统计学意义（t=11．19,P〈0．01、t=-17．07,P〈0．01）,失代偿组要显著高于代偿组,差异有统计学意义（t=7．38,P〈0．01）。结论：血清胆碱酯酶和腺苷脱氨酶活性随着肝硬化病程发展发生显著变化,其联合检测可以为病程发展的临床诊断提供一定的依据。     

Assessment of the Fecal Lactobacilli Population in Patients with Hepatitis B Virus-Related Decompensated Cirrhosis and Hepatitis B Cirrhosis Treated with Liver Transplant

This study aims to provide an overview of the diversity of intestinal Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related decompensated cirrhosis and who received liver transplant for hepatitis B cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain reaction technology with species-specific primers was applied to investigate lactobacilli 16S rDNA in crude DNA, extracted from fecal samples. Software package Statistical Package for the Social Sciences and Palaeontological Statistics for Windows was used to analyze the data. Lactobacilli population of the two patient groups was different from the healthy control subjects, principal differences being marked decrease in the population of Lactobacillus rhamnosus (p?Lactobacillus fermentus (p?p?p?p?相似文献   

阿德福韦酯片治疗60例老年失代偿期乙肝肝硬化的疗效观察

目的:探讨阿德福韦酯片治疗老年失代偿期乙肝肝硬化的疗效.方法:收集2008年1月～2010年12月我院收治的老年失代偿期乙肝肝硬化患者106例,46例给予常规治疗(对照组),其余60例加用阿德福韦酯片(观察组).比较两组肝功能、Child-Pugh评分、HBV-DNA阴转率及不良反应.结果:观察组总有效率为96.67％(58/60),对照组为78.26％(36/46),差异有统计学意义(P＜0.05);两组治疗后ALT、ALB和TBiL水平及Child-Pugh评分均较治疗前显著改善(P＜0.05),观察组改善显著优于对照组(P＜0.05);观察组HBV-DNA阴转率为56.67％(34/60),明显高于对照组的19.56％(9/46),差异有统计学意义(P＜0.05);观察组未发现与服用阿德福韦酯片相关的不良反应,无死亡病例.结论:阿德福韦酯片治疗老年失代偿期乙肝肝硬化能显著提高疗效,改善肝功能,且安全性高,值得临床推广应用.     

Increased renin release by exogenous prostaglandin E1 in liver cirrhosis with and without ascites

To evaluate the sensitivity of the renin-angiotensin-aldosterone system in patients with liver cirrhosis, prostaglandin E1 was intravenously administered at the rate of 50 micrograms/hour for two hours to the 11 control subjects and 11 patients with liver cirrhosis (6 compensated and 5 decompensated). Basal plasma renin activity (PRA) in decompensated patients was significantly higher than those in control and compensated cirrhotics (P less than 0.01). Basal plasma aldosterone was also higher in decompensated than in control and compensated patients, but without significance. PGE1 had no virtual effect on PRA in control, but stimulated PRA in liver cirrhotics, in which statistical significance was only observed in decompensated (basal vs. one hour after PGE1: 2.4 +/- 0.9 ng/ml/min (mean +/- SE) vs. 6.9 +/- 2.1: P less than 0.025). The rate of renin release was significantly higher in compensated than in decompensated (327 +/- 50% vs. 143 +/- 26: P less than 0.05). Though PGE1 also increased plasma aldosterone in liver cirrhotics, statistical change was not seen. Fractional excretion of urinary sodium after PGE1 increased significantly in control (P less than 0.025), but not in liver cirrhotics. These results indicate that the renin-angiotensin-aldosterone system is easily activated by PGE1 in patients with liver cirrhosis and further suggest that the sensitivity of this system in compensated is more augmented than in decompensated patients.     

Extreme elevation of serum alpha fetoprotein in decompensated cirrhosis without HCC: an ominous sign

Three cases of extreme elevation of serum alpha fetoprotein (>10,000 ng/mL) with decompensated cirrhosis without demonstrable hepatocellular carcinoma are reported. While 2 patients died of liver failure, 1 survived after liver transplantation. Extreme elevation of alpha fetoprotein not associated with hepatocellular carcinoma in liver cirrhosis heralds an ominous prognosis necessitating urgent liver transplantation.     

扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗乙型肝炎病毒感染失代偿期肝硬化的临床研究

目的:探讨扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗乙型肝炎病毒(HBV)感染失代偿期肝硬化的临床效果。方法:选取2015年6月～2019年6月期间我院收治的HBV感染失代偿期肝硬化患者73例,根据随机数字表法分为对照组(n=36)和研究组(n=37),对照组患者予以微生态制剂和恩替卡韦治疗,研究组则在对照组的基础上联合扶正化瘀胶囊治疗,比较两组患者疗效、T淋巴细胞亚群、肝功能[天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]以及肝纤维化指标[透明质酸(HA)、层黏连蛋白(LN)],记录两组乙肝表面e抗原(HBeAg)、乙肝病毒基因(HBV-DNA)转阴情况,记录两组不良反应发生情况。结果:研究组治疗6个月后的临床总有效率为91.89%(34/37),高于对照组的72.22%(26/36)(P0.05)。两组治疗6个月后AST、TBIL、HA、LN、CD8+~均下降,且研究组低于对照组(P0.05)。两组治疗6个月后CD4+~、CD4+~/CD8+~升高,且研究组高于对照组(P0.05)。两组治疗6个月后HBeAg、HBV-DNA转阴率比较无统计学差异(P0.05)。两组不良反应发生率对比未见统计学差异(P0.05)。结论:扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗HBV感染失代偿期肝硬化疗效显著,虽在HbeAg、HBV-DNA转阴率方面未见明显改善,但可有效改善肝功能,减轻肝纤维化,提高机体免疫功能,且不增加不良反应发生率,安全性较好。     

脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响

目的:观察脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响。方法:选取30例失代偿期肝硬化患者,用负收集法分离提取脐带血干细胞,经股动脉穿刺插管,从肝固有动脉缓慢注入。同时选择20例失代偿期肝硬化患者,分别于治疗前,治疗后1周、1个月、3个月、6个月观察肝功能、凝血指标、AFP、CT肝脏容积、门静脉血流动力学等指标。结果:干细胞治疗组与对照组同期比较:白蛋白治疗后4、12、24周明显改善,PT治疗后12、24周降低;AFP治疗后4、12、24周升高;两组患者治疗前后门静脉血流动力学参数变化差异无统计学意义;肝脏体积治疗组与对照组同期比较,肝脏体积有增大趋势但差异无统计学意义;治疗组1例第10周确诊为原发性肝细胞癌,与对照组比较差异无统计学意义。结论:脐血干细胞治疗失代偿期肝硬化可以改善肝脏的合成功能,促进肝组织再生,有新生血管重建情况发生,未发现门静脉血流动力参数的改变。     

Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice

We have previously developed autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis patients. One problem associated with ABMi therapy is that general anesthesia is required to obtain 400 ml bone marrow fluid from liver cirrhosis patients. However, many patients with decompensated cirrhosis do not meet the criteria, because of decreased liver function or an increased bleeding tendency. To overcome these issues, our aim is to derive liver repair cells from small amounts of autologous bone marrow aspirates obtained under local anesthesia and to use these cells in liver cirrhosis patients. Here, we conducted, by using a mouse model, basic research aimed at achieving novel liver regeneration therapy. We cultured bone marrow cells aspirated from the femurs of C57 BL/6 Tg14 (act-EGFP) OsbY01 mice (green fluoresent protein [GFP]-transgenic mice). After 14 days of culture with serum-free medium (good manufacturing practice grade), the obtained spindle-shaped GFP-positive cells were injected (1×10⁴ cells) via the caudal vein into mice with carbon tetrachloride (CCl₄)-induced cirrhosis. Numerous cultured macrophages and some mesenchymal stem cells repopulated the cirrhotic liver. The results showed that serum albumin, liver fibrosis and liver function were significantly improved in the group treated with cultured bone marrow cells (P<0.01). Moreover, matrix metalloproteinase-9 expression was increased in the liver (P<0.01). Thus, infusion of bone-marrow-derived cultured cells improved liver function and liver fibrosis in mice with CCl₄-induced cirrhosis.     

脐血干细胞移植治疗肝硬化的临床研究

目的:观察脐血干细胞移植治疗失代偿期肝硬化的临床疗效。方法:对60例失代偿期肝硬化患者进行自身对照的临床研究。在无菌条件下取健康产妇足月生产的脐带血,分离纯化脐血干细胞,通过肝动脉途径,将纯化的脐血干细胞移植入患者肝脏内,于移植后2周、4周、8周进行肝功能、凝血指标检测,并于4周及8周行腹部B超及胃镜检查,观察患者移植后不同时间症状改善情况及术后不良反应的发生情况。结果:60例接受脐血干细胞移植的肝硬化患者术中术后无明显不良反应发生。移植后,患者临床症状改善明显,食欲不振、乏力、腹水等减轻甚至消失;血清学检测:白蛋白水平较术前明显升高,凝血酶原时间、总胆红素较术前明显下降;术后8周复查胃镜,食道静脉曲张没有明显变化。结论:脐血干细胞移植治疗失代偿期肝硬化是一种安全、有效的方法,尤其是在提高白蛋白水平及改善凝血功能方面有很好的疗效,可作为肝移植治疗的过渡或补充治疗。     

Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics

We applied our 'clinical glycomics' technology, based on DNA sequencer/fragment analyzers, to generate profiles of serum protein N-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry-based Fibrotest biomarker, compensated cirrhosis was detected with 100% specificity and 75% sensitivity. The current 'gold standard' for liver cirrhosis detection is an invasive, costly, often painful liver biopsy. Consequently, the highly specific set of biomarkers presented could obviate biopsy in many cirrhosis patients. This biomarker combination could eventually be used in follow-up examinations of chronic liver disease patients, to yield a warning that cirrhosis has developed and that the risk of complications (such as hepatocellular carcinoma) has increased considerably. Our clinical glycomics technique can easily be implemented in existing molecular diagnostics laboratories.     

Advanced oxidation protein products and inflammatory markers in liver cirrhosis: a comparison between alcohol-related and HCV-related cirrhosis

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.     

丽珠肠乐（回春生）对肝硬化的疗效观察

丽珠肠乐（回春生）为双歧杆菌活菌制剂,给７３例肝硬化失代期病人口服２２～６７天。治疗前后分别检测血内毒素含量及肝功能,观察其疗效。结果表明本制剂对肝硬化的疗效明显,总有效率为７９．４５％,其中内毒素水平治疗后明显下降,与治疗前比较,Ｐ＜０．０１,有效率为８７．６７％。肝功能各指标有不同程度的改善,有效率７８．０８％。说明回春生是当代最新的微生态调节剂。     

Serum catalase enzyme activity in liver diseases

Serum catalase activity was moderately increased in fatty liver, acute alcoholic hepatitis and in the decompensated form of cardiac circulatory failure. It showed significant increase in acute yellow atrophy and in toxic hepatitis while no changes were detected in liver cirrhosis and viral hepatitis. Serum catalase activity showed a good correlation (r = 0.820) with the serum glutamate dehydrogenase activity. In accordance with our results, the inexpensive assay of serum catalase activity is suggested for the detection of severe liver cell damage.     

Risk Factors for Invasive Cryptococcus neoformans Diseases: A Case-Control Study

Background

Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.

Methods

All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002–2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors.

Results

A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio [aOR] = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia.

Conclusions

The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.