肝硬化患者并发感染相关性胆汁淤积症54例临床特点及转归

目的加强对肝硬化患者并发感染相关性胆汁淤积症的认识,分析肝硬化患者并发感染相关性胆汁淤积症的临床特点、危险因素及转归。方法回顾性分析肝硬化患者并发感染相关性胆汁淤积症的临床资料,分析其临床特征及其预后,比较54例肝硬化患者并发感染相关性胆汁淤积症与同期住院的发生感染但未出现胆汁淤积症（对照组）126例肝硬化患者在年龄、性别、Child-Pugh分级、早期及时经验性抗菌药物应用的差异。结果 54例肝硬化患者并发感染相关性胆汁淤积症的感染部位：腹腔感染（自发性细菌性腹膜炎,SBP）20例、尿路感染18例、胆道感染6例、肠道感染4例、肺部感染4例、部位不明确2例,根据Child-Pugh分级约有55.56%的患者为Child C级。两组比较,年龄、Child-Pugh分级、早期及时经验性应用抗菌药物等,差异均有统计学意义（P〈0.05）;观察组中病死率15.00%,高于对照组的4.36%,差异有统计学意义（P〈0.05）。结论肝硬化患者并发感染相关性胆汁淤积症对预后有不良影响,尤其合并有肝肾综合征者病死率较高,应高度重视临床及实验诊断,针对其临床特征实施相应措施。     

肝硬化细菌移位及其后果

随着人们对细菌移位（bacterial translocation，BT）后果研究的不断深入，BT的概念已从传统的有活性的肠道菌群通过肠道屏障到达肠系膜淋巴结和肠腔外其他器官或部位，延伸到细菌释放产物（如内毒素和细菌DNA）的移位。现就细菌移位过程中的多种机制，特别是肠内菌群和黏膜屏障功能的改变及免疫防御机制综述如下。     

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.     

Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review

Spontaneous bacterial(SBP) and spontaneous fungal peritonitis(SFP) can be a life-threatening infection in patients with liver cirrhosis(LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant(MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.     

肝硬化患者医院内感染风险预测列线图模型的构建

目的 本研究旨在建立准确、可操作的医院内感染(NI)风险预测列线图模型,将感染风险量化,从而能直观地提示肝硬化患者发生NI的风险。方法 2016年1月～2020年12月我院就诊的肝硬化住院患者,依据多元Logistic回归分析筛选出的NI发生危险因素建立风险预测列线图。采用Bootstrap进行内部验证,应用受试者工作特征曲线(ROC)、校准图、 Hosmer-Lemeshow 检验和决策曲线分析法评估列线图模型的预测效能和临床获益。结果 本研究纳入503例肝硬化患者,其中131例(26.0%)发生NI;多因素Logstic回归模型分析显示存在腹水、侵入性操作、高血小板/淋巴细胞比值 (PLR)和高MELD 评分为肝硬化患者发生NI的独立危险因素;基于上述4个变量建立列线图模型并进行验证,结果ROC曲线下面积(AUC)为0.845,模型诊断效能良好;Hosmer-Lemeshow 检验显示,模型校正曲线与理想曲线拟合良好(P=0.999,P=0.688),该模型具有良好的校准和判别能力,决策曲线分析表明在较大的阈值内具有较高的临床获益。结论 我们建立的列线图可以较准确地预测肝硬化患者发生NI的风险,有助于临床医生及早识别高危患者,为临床干预和优化决策提供依据。     

乙型肝炎肝硬化的细菌感染

我们回顾性地研究了1119例乙肝肝硬化患者(其中包括400例乙肝肝硬化肝癌患者)的各种细菌感染的发生率。探讨乙肝肝硬化细菌感染的流行病学。结果显示肝硬化病人的细菌感染率为15.4%,与肝硬化肝癌病人的细菌感染率15.3%相近,当肝硬化程度按 Child-Pugh 分级时,肝硬化病人 A 级感染率为2.3%,B 级为8.0%,C级为26.4%;肝硬化肝癌病人 A 级感染率为3.3%,B 级为11.1%,C 级为31.2%。随着肝硬化程度的增加,细菌感染率越高,严重的细菌感染发生在 B 级和 C 级患者。说明乙肝肝硬化病人的细菌感染率主要与肝硬化有关,与肝癌关系不大。     

Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study

BACKGROUND: Bacterial infections have been postulated as a trigger for variceal bleeding in cirrhotic patients, and impair coagulation evaluated by thrombelastography (TEG). Endogenous heparinoids have been detected after variceal bleeding and during liver transplantation in some cirrhotics using heparinase-modified-TEG. AIM: To assess if bacterial infection is associated with endogenous heparinoids in cirrhotics, thus impairing coagulation. METHODS: Native and heparinase-modified-TEG (cleavage of heparin and heparan-sulphate) was performed in 60 cirrhotics (Grade A, 2; B, 30; C, 28): 30 infected [septicaemia, 6 (culture positive); 6 (culture negative); spontaneous bacterial peritonitis, 10; chest infection, 4; others, 4], 30 not infected, and five infected patients without liver diseases, comparing TEG parameters r, alpha, and ma. Eight cirrhotics were studied before and after infection. The diagnosis of presence and type of infection was based on international standard criteria. RESULTS: A significant heparin effect was found only in infected cirrhotics (28 of 30) with significant changes in r (P=0.0003), alpha (P<0.0001), and ma (P<0.0001), but in none of those not infected. This effect completely reversed in the eight evaluated after resolution of infection. There was no heparin effect in infected non-cirrhotics. CONCLUSIONS: A heparin effect was only found in cirrhotic patients with infection, further confirming that infection significantly modifies coagulation in cirrhotic patients.     

Intestinal permeability and complications in liver cirrhosis: A prospective cohort study

Aim: Increased intestinal permeability (IP) has been implicated as an important factor for bacterial translocation (BT), leading to bacteremia and endotoxemia, resulting in various septic complications, variceal bleeding (VB), hepatic encephalopathy (HE), hepatorenal syndrome (HRS) and death in patients with liver cirrhosis (LC). This study was planned to assess IP in patients with LC and follow them for the occurrence of complications. Methods: Patients with Child B and C cirrhosis without a history of disease‐related complications were followed up for 6 months. IP was measured by lactulose and mannitol excretion ratio (LMR) in patients and 50 healthy controls (HC). Serum endotoxin levels were also assessed in 48 patients and 20 HC. Results: Eighty patients (74 male), 41 (51.3%) Child B and 56 (70%) Child C, with a mean age of 40.7 ± 9.8 years were enrolled. IP was increased in 28 (35%) patients. LMR of patients was higher than HC (patients vs HC = 0.0238 [0.0010–1.557] vs 0.0166 [0.0018–0.720]; P = 0.007]. No significant difference was seen in the LMR of patients among various Child classes and etiologies. Serum endotoxin levels (GMU/mL) were higher in patients than HC (patients vs HC = 1.42 [0.68–2.13] vs 0.994 [0.067–1.382]; P = 0.001), but comparable between patients with abnormal and normal IP. At follow up, there was no significant difference in the incidence of complications like spontaneous bacterial peritonitis, HRS, VB, HE and death between patients with abnormal and normal IP. Conclusion: IP was increased in 35% of patients with LC; however, it was not associated with a higher incidence of disease‐related complications.     

Elective endoscopic variceal ligation is not a risk factor for bacterial infection in patients with liver cirrhosis

BackgroundPatients with cirrhosis are at high risk of bacterial infections. Invasive procedures are generally believed to increase this susceptibility.AimsWe investigated the incidence of bacterial infections in cirrhotic patients undergoing elective endoscopic variceal ligation (EVL).MethodsWe enrolled 60 consecutive cirrhotic patients who underwent a total number of 112 elective EVL procedures. One to seven bands were applied at each session until variceal eradication. Markers of inflammation/infection and blood cultures were obtained before and 24 h after EVL.ResultsAetiology of liver disease was metabolic in 27 (45%), viral in 21 (35%), alcoholic in 12 (20%) patients. Child–Pugh class A/B/C distribution was 29/26/5, respectively, 23 (38%) patients had ascites and 15 (25%) had hepatocellular carcinoma. Blood cultures were negative in all samples before EVL, whereas 3/112 (2.7%) cultures tested positive after endoscopy. Streptococcus mitis and Staphylococcus epidermidis were isolated in 1 and 2 cases, respectively. None of these three patients developed any features of clinically relevant infection, suggesting that the positive cultures were an expression of a transient bacteraemia with no clinical sequelae.ConclusionsBacterial infection is an uncommon occurrence after elective EVL in cirrhotic patients, and antibiotic prophylaxis is not necessary in this clinical setting.     

Acute‐phase proteins as indicators of bacterial infection in patients with cirrhosis

Background: Cirrhosis is associated with elevated levels of acute‐phase proteins (APP), irrespective of the presence of infection. This condition limits the clinical application of APP determination in cirrhotic patients with bacterial infections. Aims: To weigh the diagnostic value of several APP in cirrhotics with or without bacterial infection, and to correlate them with the clinical outcome. Methods: We investigated 88 consecutive cirrhotic patients (67 males, 21 females; range 28–85 years) with mean age (SD) 58.9 (13.8) on admission, according to a standard protocol for infection. We measured the following APP: C‐reactive protein (CRP), fibrinogen (FIB), haptoglobin (Hpt), ferritin (Fer), β2‐microglobulin (β2‐mg), C3, C4 and C1 inhibitor. Results: From the 88 patients, 19 (21.6%) had documented infection at the entry based on clinical, radiological and microbiological data. This group of patients did not differ in basic demographics from those without infection. CRP [17.5 (20.7) vs 77.1 (43.9), P<0.001], β2‐mg [4.4 (4.1) vs 5.6 (2.2), P<0.001] and ferritin [461.2 (776.4) vs 825.8 (870), P=0.03] were significantly higher in infection, whereas C3 was significantly lower. No significant differences were noted in the remaining APP levels between the two groups. After receiver operating characteristic curves were fitted, CRP was the best diagnostic test for infection (area under the curve 0.91), followed by β2‐mg, ferritin, FIB, C1 inhibitor, C4, Hpt and C3. Conclusions: Serum CRP is the best test, among the examined APP, to discriminate bacterial infection in cirrhotics. A cut‐off value of >55.8 mg/L has high sensitivity (79%) and specificity (96%), with the best diagnostic accuracy (92%).     

晚期肝炎后肝硬变并自发细菌性胸膜炎

目的 研究晚期肝炎后肝硬变(LC)患者并发自发性细菌性胸膜炎(SBPL)的临床特征、诊断和治疗。 方法 分析6例LC患者8次并发SBPL的临床表现和治疗结果。 结果 LC并SBPL的主要临床特征为:①有肝性胸水(83.3％为中量以上)。②突然或迅速加重的胸或胸腹痛、胸闷气短、胸水量迅速增加伴少尿或无尿、发热、黄疸或黄疸加深。③胸水为渗出液,胸膜呈化脓性炎症改变、胸水细菌培养可阳性(4例次,均为肠杆菌科)。 结论 当LC患者出现SBPL表现时,应及早诊断。及早应用抗G~-菌等抗生素治疗,预后良好。     

Small bowel bacterial overgrowth in patients with alcoholic cirrhosis

A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid.This study was supported in part by a grant (No. 91/0675) from Fondo de Investigaciones Sanitarias (FIS), Madrid, Spain.This article originally appeared inDigestive Diseases and Sciences, Volume 40, Number 6, June 1995, pp. 1252–1256.     

Acute exacerbation in patients with liver cirrhosis: a clinicopathological study

ABSTRACT— The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non-A, non-B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow-up study is required to evaluate the long-term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.