The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan

Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010–2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066–4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702–1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.     

Proton pump inhibitors: Risks of long‐term use

Proton pump inhibitors are among the most commonly prescribed classes of drugs, and their use is increasing, in particular for long‐term treatment, often being over‐prescribed and used for inappropriate conditions. In recent years, considerable attention has been directed towards a wide range of adverse effects, and even when a potential underlying biological mechanism is plausible, the clinical evidence of the adverse effect is often weak. Several long‐term side effects have been investigated ranging from interaction with other drugs, increased risk of infection, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia. The most recent literature regarding these adverse effects and their association with long‐term proton pump inhibitor treatment is reviewed, and the mechanisms through which these possible complications might develop are discussed.     

Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study

The incidence and disease severity of Clostridium difficile infection are rising. There is increasing evidence of a potential association between proton-pump inhibitors (PPI) and C. difficile infection. We performed a case-control study to examine the relationship between PPI and polymerase chain reaction (PCR)-proven C. difficile infection in 137 hospitalised patients in a tertiary hospital in Western Australia. Only antibiotic exposure within 3 months prior to onset of diarrhoea was associated with PCR-proven C. difficile infection (odds ratio 5.97, 95% confidence interval 2.40-14.8, P= 0.001). A restricted analysis on those who had exposure to antibiotics within 3 months before the onset of diarrhoea did not change the negative association between PPI exposure and PCR-proven C. difficile infection. Long-term PPI usage and intensity of PPI exposure prior to onset of diarrhoea were not significantly associated with C. difficile infection.     

终末期肝病模型评估失代偿期肝硬化患者预后的价值

目的: 评价终末期肝病模型(model for endstage liver disease,MELD)对肝硬化患者短期预后预测的价值.方法: 对肝硬化失代偿期患者203例进行回顾性分析,随访患者在3、6及12 mo内的预后. 记录每例患者入院第1天的MELD及Child-Turcotte-Pugh(CTP)评分. 应用接受者工作特征曲线(ROC曲线)及其曲线下面积(AUC)比较MELD、CTP评估患者生存时间的准确性. 依据ROC曲线的截断值绘制Kaplan-Meier生存曲线,应用非参数秩相关即Spearman等级相关检验分析MELD与CTP评分的相关性.结果: 3、6及12 mo内分别死亡23、39、85例,MELD评分与CTP评分均显著相关( r = 0.76,0.69,0.71,均P<0.01). 3、6及12 mo内MELD与CTP对住院患者预后预测的AUC分别为0.886和0.775( P<0.01)、0.892和0.876( P>0.05)、0.873和0.866( P>0.05). 生存分析表明2评分系统均可有效预测3、6及12 mo内患者可能的生存率和死亡率( P<0.01).结论: MELD模型可预测失代偿肝硬化患者12 mo内的生存率,3 mo内MELD模型优于CTP评分,但6 mo及12 mo内MELD模型和CTP评分相比没有明显优势.     

终末期肝病模型对肝硬化患者预后评估价值的研究进展

客观、准确地判断肝硬化患者的病情及预后有助于指导临床医生选择正确的治疗方案。终末期肝病模型（MELD）是目前被广泛认可的评估终末期肝病严重程度的评分体系。近年来各种基于MELD评分发展而来的新评分系统不断涌现。加入新的变量例如血清钠可进一步提高MELD的预测能力,此文就MELD的研究现状作一综述。     

终末期肝病模型对肝硬化失代偿期患者预后的预测价值

目的评估终末期肝病模型（MELD）、终末期肝病模型联合Na评分（MELD-Na）、终末期肝病模型评分／血钠比值（MESO指数）、Child-Pugh（CTP）分值对失代偿期肝硬化患者预后的预测价值。方法对140例失代偿期肝硬化患者进行回顾性分析。分别比较3、6及12个月内死亡组和存活组之间的MELD评分、MELD-Na评分、MESO指数及CTP分值,并用受试者工作曲线（ROC）及曲线下面积（AUC）比较MELD、MELD—Na评分、MESO指数和CTP分值判断肝硬化患者预后的准确性并获取最佳临界值。结果在随访的3、6及12个月内死亡组和存活组MELD、MELD—Na、MESO及CTP评分比较有显著差异,在判断患者3、6及12个月生存率的ROC曲线Auc比较中,MELD—Na评分与MESO指数、MELD评分及CTP分值比较具有统计学意义差异（P〈O．05）。而MELD评分与Child-Pugh分值比较差异无统计学意义（P〉0．05）。结论MELD—Na评分、MESO、MELD及CTP均能较好预测肝硬化失代偿期患者预后,其中MELD—Na仍是以上预测失代偿期肝硬化预后中最具优势的评分模型。     

Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark

BACKGROUND: Patients with liver cirrhosis are at increased risk of serious bacterial infections carrying a high case fatality rate. Case reports have suggested an association between liver cirrhosis and pyogenic liver abscess. AIMS: To estimate the risk and case fatality rate of pyogenic liver abscess in Danish patients with liver cirrhosis compared with the background population. METHODS: Identification of all patients with liver cirrhosis and pyogenic liver abscess over a 17 year period in the National Registry of Patients. Information on death was obtained from the Danish Central Person Registry. RESULTS: We identified 22 764 patients with liver cirrhosis and 665 patients with pyogenic liver abscess, of whom 21 were cirrhotics and 644 were non-cirrhotics. The crude incidence rate of liver abscess in cirrhotics was 23.3 (95% CI 14.4-35.6) per 100 000 person years. The age adjusted risk of liver abscess was increased 15-fold in patients with cirrhosis compared with the background population. The 30 day case fatality rates in patients with liver abscess and cirrhosis were 38.5% (13.9-68.4) in alcoholic cirrhosis and 62.5% (24.5-91.5) in non-alcoholic cirrhosis compared with 26.9% (23.5-30.5) in liver abscess patients from the background population. After adjustment for sex, age, and comorbidity, the relative risk of death was increased more than fourfold in alcoholic cirrhosis and non-alcoholic cirrhosis compared with the background population. CONCLUSIONS: Liver cirrhosis is a strong risk factor for pyogenic liver abscess associated with a poor prognosis.     

MELD-Na模型评分对评估失代偿期肝硬化患者短期预后的临床价值

目的 评价终末期肝病模型（MELD）评分、Child-Pugh（CTP）计分及MELD-Na模型评分（MELD-Na^＋）对失代偿期肝硬化患者短期预后的预测价值。方法 分别计算116例失代偿期肝硬化患者的MELD、Child-Pugh及MELD-Na分值,运用ROC曲线及曲线下面积（AUC）比较三种评分系统判断失代偿期肝硬化患者短期预后的准确性。结果 116例患者随访3个月内有34例患者死亡,死亡组MELD-Na评分（24．1±2．5）与生存组（15．4±2．9）比较差异有统计学意义（P〈0．001）;在判断患者预后的ROC曲线AUC比较中,MELD-Na评分（0．825）〉MELD评分（0．779）〉Child-Pugh分级（0．626,P〈0．05）。结论 Child-Pugh计分、MELD计分和MELD-Na计分均可有效地预测失代偿期肝硬化患者的短期预后,而MELD-Na模型评分对短期评估效率优于其他两种方法,能更准确地反映病情的轻重,更具有临床应用价值。     

肝功能评级指标预测肝硬化患者食管静脉曲张程度价值分析

目的探讨门静脉内径(PV)、血清钠(Na+)水平、凝血酶原时间(PT)、Child-Pugh评分(CPS)、终末期肝病模型(MELD)及MELD-Na评分对预测食管静脉曲张(EV)程度的意义。方法回顾性分析96例肝硬化患者的临床资料,计算Child-Pugh分级、CPS、MELD及MELD-Na评分。根据胃镜检查结果将EV程度分为轻、中、重度三组,分析以上各指标与EV程度的关系,并运用受试者工作特征曲线下面积(AUC)评价上述无创性指标预测中重度EV的能力。结果 EV程度与Child-Pugh分级或评分、PV、MELD评分及MELD-Na评分均呈正相关(r值分别为0.281、0.371、0.302、0.500、0.537,P均<0.05);与血清钠呈负相关(r=-0.574,P<0.05)。Na+水平的AUC为0.780,当Na+水平<133.25mmol/L时预测中重度EV的敏感度为97.7%,特异度为76.9%。结论 Child-Pugh分级和评分、PV、Na+水平、MELD及MELD-Na评分均能较好地反映EV程度;Na+水平是预测中重度EV较敏感的无创性指标。     

四种评分系统对失代偿期肝硬化患者短期预后的评价

目的比较终末期肝病模型(MELD))评分系统、MELD-Na评分系统、MESO指数评分系统以及iMELD评分系统对失代偿期肝硬化患者短期(3个月)预后的预测价值。方法选择2008年10月至2011年10月云南省第三人民医院消化内科的失代偿期肝硬化患者230例,分别计算每例患者入院时的MELD、MELD-Na、MESO及iMELD分值,采用Kaplan-Meier法比较生存率,运用受试者工作特征曲线(ROC)及曲线下面积(AUC)比较四种评分系统判断失代偿期肝硬化患者短期预后的价值。结果 230例失代偿期肝硬化患者,随访3个月内死亡68例,生存组MELD、MELD-Na、MESO及iMELD评分分别为22.34±4.36、24.26±5.45、1.62±0.23和37.59±6.97,死亡组MELD、MELD-Na、MESO及iMELD评分分别为27.76±5.28、30.11±6.19、2.05±0.1 8和46.65±7.01。死亡组与生存组的MELD、MELD)-Na、MESO及iMELD评分比较,差异均有统计学意义(P=0.005,0.005,0.000,0.003)。MELD、MELDNa、MESO及iMELD评分系统在判断230例失代偿期肝硬化患者3个月生存时间的ROC曲线下面积分别为0.852、0.856、0.857和0.847,95%可信区间分别为0.759～0.897、0.754～0.893、0.760～0.898、0.781～0.906,四种评分系统比较差异无统计学意义(P>0).05)。结论 MELD、MELD-Na、MESO及iMELD评分系统对失代偿期肝硬化患者短期预后均有一定的预测价值,但四种评分系统比较差异无统计学意义,较准确的预后判断仍需要结合临床实际。     

终末期肝病模型及Child-Pugh分级对失代偿期肝硬化患者的预后分析

目的探讨MELD评分及Child-Pugh分级对失代偿期肝硬化患者预后评估的应用价值。方法回顾性分析2000-01～2004-11北京大学人民医院收治的失代偿期肝硬化患者41例死亡病例及71例好转出院病例MELD评分及Child-Pugh分级并进行比较。结果MELD分值死亡者(17.93±8.22),出院者(11.18±6.54)(t=4.781,P=0.000)。Child-Pugh分值死亡者(10.07±1.84),出院者(8.04±2.09)(t=5.179,P=0.000)。MELD≤9分者占死亡患者的14.63%,占出院患者的42.25%(χ2=9.09,P=0.003)。20～29分者占死亡患者的26.83%,占出院患者的8.45%(χ2=6.819,P=0.009)。ChildA级占死亡患者的21.95%,占出院患者的56.34%(χ2=12.488,P=0.000)。ChildC级占死亡患者的29.27%,占出院患者的5.63%(χ2=11.857,P=0.001)。结论死亡与存活患者MELD与Child-Pugh评分显著不同。低MELD评分患者预后好于高MELD评分者。ChildA级患者预后优于ChildC级者。MELD评分可对失代偿期肝硬化患者病情严重程度及预后作出判断。     

Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy

Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.

Material and methods: Out-patients (n?=?1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.

Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 µg/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032–1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338–6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162–5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085–3.448) were significantly associated with an elevated FC (>50 µg/g).

Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.     

239例肝硬化失代偿期患者的短期预后评估

目的评价终末期肝病模型（MELD）、MELD-Na、Child—Turcotte—Pugh（CTP）和包含血肌酐值的CTP（CrCTP）评分对肝硬化患者短期预后的评估意义。方法回顾性收集自2005年1月-2007年12月我院收治的239例肝硬化失代偿期患者的病例资料,分别应用CTP、CrCTP、MELD和MELD—Na模型进行评分,并了解其3个月内的病死率。以受试者工作特征曲线（ROC）下面积（AUC）衡量各评分系统预测肝硬化失代偿期患者短期预后的能力,并运用Z检验比较各系统的预测能力。结果30例患者在3个月内死亡。死亡组患者的CTP、CrCTP、MELD和MELD—Na分值（分别为11．47±2．46、12,47±2．05、19．70±6．71、27．97±10．79）与生存组（分别为8．73±2．03、8．95±2．13、10．92±4．74、14．48±6．55）相比差异有统计学意义（P〈0．001）。CTP、CrCTP、MELD和MELD-Na评分对肝硬化失代偿期患者3个月预后评估的ROC曲线下面积分别为0．799、0．822、0．873、0．870。结论CTP、CrCTP、MELD和MELD-Na模型均可有效预测我国肝硬化失代偿期患者的短期预后;MELD评分在判断肝硬化失代偿期患者的短期预后方面优于CTP;在CTP中引入血肌酐值即CrCTP评分可以提高对肝硬化失代偿患者短期预后的判断准确性;MELD-Na模型未显示比MELD更佳的预测能力。     

血清前白蛋白和MELD评分对失代偿期乙型肝炎肝硬化患者预后的预测价值*

目的 研究应用血清前白蛋白（PA）水平联合终末期肝病模型（MELD）评分预测失代偿期乙型肝炎肝硬化患者预后的临床价值。方法 2015年12月~2016年12月我院治疗的失代偿期乙型肝炎肝硬化患者231例,随访6个月。常规检测血清PA水平、计算MELD评分和Child-Pugh评分（CTP评分）,在MELD评分的基础上,加入PA项目的 评分,建立MELD联合PA评分模型。应用受试者工作特征曲线（ROC）分析各指标对患者死亡的预测效能。结果 在随访的6个月里,死亡83例;死亡组血清PA水平为（32.2±9.3）mg/L,显著低于生存组的[（47.3±26.4） mg/L,P<0.05];死亡组MELD评分为（24.1±5.6）分,明显高于生存组的[（18.0±6.7）分,P<0.05];死亡组CTP评分为（11.8±1.2）分,明显高于生存组的[（9.0±2.0）分,P<0.05];ROC曲线分析结果显示,MELD评分预测死亡的ROC下面积（AUC）为0.868（95%CI：0.823~0.912）,显著高于CTP评分的[0.753（95%CI：0.690~0.816）,P<0.05]或血清PA的[0.675（95%CI：0.606~0.743）,P<0.05];进一步采用MELD联合PA评分分析的AUC为0.896（95%CI：0.857~0.935）,显著高于MELD评分（P<0.05）。结论 应用血清PA联合MELD评分对失代偿期乙型肝炎肝硬化患者6个月内死亡的预测效能显著高于MELD评分或CTP评分,其临床应用价值还需要扩大验证。