Clinical presentation and prevalence of spontaneous bacterial peritonitis in patients with cryptogenic cirrhosis and features of metabolic syndrome.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis. The prevalence and clinical relevance that spontaneous bacterial peritonitis may have in complicating ascites due to NASH-related cirrhosis have yet to be defined. METHODS: Among 611 cases of cirrhosis-associated ascites, 45 patients with cryptogenic cirrhosis were retrospectively identified. Of these, 36 patients and a control group of subjects with viral- associated ascites were followed up and compared in a case control study. Information on the onset of ascites, with or without spontaneous bacterial peritonitis, history of risk factors for multimetabolic syndrome, and serological and ascitic laboratory data were compared between groups. RESULTS: Spontaneous bacterial peritonitis occurred significantly more often in patients with cryptogenic cirrhosis than in equally symptomatic viral controls. The prevalence of obesity, diabetes and spontaneous bacterial peritonitis was significantly higher in patients with cryptogenic cirrhosis. Although liver function was similar in both groups, cryptogenic cirrhosis patients had lower aminotransferase levels. Multivariate analysis identified diabetes, juvenile obesity and spontaneous bacterial peritonitis as independent factors associated with ascites due to cryptogenic cirrhosis. CONCLUSIONS: Features suggestive of NASH are more frequently observed in patients with ascites and cryptogenic cirrhosis than in age- and sex-matched ascitic patients with well-defined viral etiology. Ascites may be a presenting symptom of NASH-related cirrhosis, and affected patients have a twofold greater risk of spontaneous bacterial peritonitis.     

Spontaneous bacterial peritonitis and extraperitoneal infections in patients with cirrhosis

Infections are a frequent complication and a major cause of death among patients with cirrhosis. The important impact of infections in general and especially spontaneous bacterial peritonitis on the course of disease and prognosis of patients with cirrhosis has been recognized for many years. Nevertheless, such importance has recently increased due to the comprehension of infection as one of the most prominent risk factors for patients to develop acute-on-chronic liver failure. Furthermore, the issue of infections in cirrhosis is a focus of increasing attention because of the spreading of multidrug resistant bacteria, which is an emerging concern among physicians assisting patients with cirrhosis. In the present paper, we will review the current epidemiology of infections in patients with cirrhosis and particularly that of infections caused by resistant bacteria, demonstrating the relevance of the subject. Besides, we will discuss the current recommendations on diagnosis and treatment of different kinds of infections, including spontaneous bacterial peritonitis, and we will highlight the importance of knowing local microbiological profiles and choosing empirical antibiotic therapy wisely. Finally, we will debate the existing evidences regarding the role of volume expansion with albumin in patients with cirrhosis and extraperitoneal infections, and that of antibiotic prophylaxis of spontaneous bacterial peritonitis.     

Spontaneous bacterial peritonitis in Saudi Arabian patients with non-alcoholic liver cirrhosis

BACKGROUND/AIMS: Spontaneous bacterial peritonitis is a frequent and serious complication of liver cirrhosis. Its prevalence varies from one survey to another. There are only very few reports of its occurrence among Arab patients. METHODOLOGY: We studied 115 Saudi Arabian patients with cirrhotic ascites in the Gizan region, an area of hyperendemic hepatitis B, over a 2-year period. RESULTS: Of these patients 12 (10.4%) had at least 1 episode of culture-positive spontaneous bacterial peritonitis (group A), an additional 34 (29.6%) had culture-negative neutrocytic ascites. The occurrence of spontaneous bacterial peritonitis was more frequent in males but was not influenced by the severity of liver disease or age. The overall mortality was 13.9%, however, only 1 patient died of spontaneous bacterial peritonitis-related cause. The remaining deaths were due to other complications of hepatic failure and portal hypertension. The low clinical threshold for treatment and the use of effective broad-spectrum antibiotics have reduced the mortality due to spontaneous bacterial peritonitis. There were a total of 56 recurrent episodes of infection in the patients. Of these episodes 46 occurred among 29 patients with spontaneous bacterial peritonitis and 10 among 62 patients with no infection during the index admissions. CONCLUSIONS: Prophylactic therapy against spontaneous bacterial peritonitis is a feasible strategy in reducing the frequency of recurrent peritonitis and should be recommended in these patients.     

亚胺培南与头孢哌酮舒巴坦治疗肝硬化自发性腹膜炎的疗效比较

目的比较亚胺培南与头孢哌酮舒巴坦治疗肝硬化自发性腹膜炎的临床疗效。方法 70例肝硬化自发性腹膜炎患者分成亚胺培南组(A组,35例)和头孢哌酮舒巴坦组(B组,35例),A组采用腹腔穿刺引流及亚胺培南治疗,B组采用腹腔穿刺引流及头孢哌酮舒巴坦治疗,两组疗程均为10 d。治疗结束后观察两组疗效及临床症状变化情况。结果 A组治疗总有效率(82.9%)明显优于B组(68.6%)(P<0.05);A组发热、腹胀、腹痛、腹部压痛和反跳痛等临床症状缓解时间明显早于B组(P<0.05)。结论亚胺培南治疗肝硬化自发性腹膜炎疗效显著,不良反应少,可明显缓解临床症状,值得临床推广应用。     

Bacterial infections complicating liver disease

Bacterial infection is a serious and often fatal complication of patients with liver disease and can prove fatal either directly or by precipitation of gastrointestinal bleeding, renal failure, or hepatic encephalopathy. At greatest risk are patients with alcoholic cirrhosis or decompensated chronic liver disease, or cases of acute liver disease who progress to fulminant hepatic failure or subacute hepatic necrosis. Infection appears to be unusual in patients with primary biliary cirrhosis. The site and type of infection is unrelated to the aetiology of the liver disease. Bacteraemia, pneumonia, urinary tract infection and spontaneous bacterial peritonitis are most common but infective endocarditis and meningitis, especially with pneumococci, are easily overlooked. Clinical suspicion of infection must be high as the only indication may be a general deterioration in the patients' clinical state, increasing encephalopathy or renal impairment. In the case of patients with fulminant hepatic failure, infection may precipitate the initial or recurrent encephalopathy and contributes to death in 10% of fatal cases. Spontaneous bacterial peritonitis is now recognized to occur in the absence of clinical features of peritonitis. The PMN content of the ascitic fluid may provide the only indication of infection and is the most readily available screening test. The most common types of organism responsible for all types of infection are Gram-negative enteric and streptococci, especially pneumococci, while infection with anaerobes is rare. Risk factors for infection include decompensated alcoholic liver disease, fulminant hepatic failure, gastrointestinal bleeding, invasive practical procedures and impaired host defence mechanisms against infection. Of the host defence mechanisms, impaired function of the reticuloendothelial system, complement, and PMNs represent the most common and serious defects. Defects of humoral immunity are present in ascitic fluid from patients with cirrhosis and are probably a major reason for development of spontaneous bacterial peritonitis. Diuresis improves these functions and reduces the risk of peritonitis. Treatment of infections even with the appropriate antibiotic is still associated with a high mortality but the use of adjuvant gut sterilization is promising, particularly in cases infected with Gram-negative enteric organisms. Infusions of fresh frozen plasma, blood and cryoprecipitate improve some systemic host defences and may be beneficial in the treatment and reduction of risk of infection.     

终末期肝病并发自发性腹膜炎患者血小板计数的变化及其临床意义

目的：探讨终末期肝病并发自发性腹膜炎患者血小板计数的变化及其临床意义。方法：对266例并发自发性腹膜炎的终末期肝病患者进行回顾性分析,研究对象分为失代偿期肝硬化组、慢性重型肝炎组。观察两组患者血小板计数在腹膜炎发作前、腹膜炎发生时、腹膜炎治愈后的变化,以同组中未并发自发性腹膜炎的患者为对照。结果：失代偿期肝硬化和慢性重型肝炎并发自发性腹膜炎患者血小板计数在腹膜炎发生时下降,腹膜炎治愈后回升（P均〈0.01）。结论：血小板计数变化可作为失代偿期肝硬化和慢性重型肝炎并发自发性腹膜炎诊断和治疗的一项辅助参考指标。     

Prognosis of patients with liver cirrhosis and spontaneous bacterial peritonitis

BACKGROUND/AIMS: Patients with liver cirrhosis and ascites have a high risk of spontaneous bacterial peritonitis, but the prognostic impact of spontaneous bacterial peritonitis has not been well examined. METHODOLOGY: Patients with liver cirrhosis and ascites were included at the time of their first paracentesis during hospitalization in the Department of Hepatology, Aarhus University Hospital, Denmark, between September 1992 and September 2000. Cox regression was used to estimate the mortality of patients with spontaneous bacterial peritonitis (ascites leukocyte count > or = 250 per mm3) relative to controls without spontaneous bacterial peritonitis. Furthermore, we used Cox regression to estimate the change in mortality when controls developed spontaneous bacterial peritonitis during follow-up. RESULTS: Of 286 patients, 76 (27%) had spontaneous bacterial peritonitis at the first paracentesis. The mortality ratio of patients with spontaneous bacterial peritonitis relative to controls was 1.0 (95% confidence interval 0.7-1.5) after adjustment for age, gender, comorbidity, and alcohol abuse. Of the 210 controls, 42 (20%) were found to have spontaneous bacterial peritonitis at a later paracentesis. Their mortality rate more than doubled with the onset of spontaneous bacterial peritonitis. CONCLUSIONS: Spontaneous bacterial peritonitis at the first paracentesis did not affect the prognosis of patients with liver cirrhosis, whereas development of spontaneous bacterial peritonitis during follow-up doubled the mortality risk. This may be due to a longer diagnostic delay in those who developed spontaneous bacterial peritonitis during follow-up.     

肝硬化并发肾上腺皮质功能不全患者的临床特点分析

目的 了解肝硬化患者的血清基础皮质醇及促肾上腺皮质激素(ACTH)水平,探讨肝硬化患者并发肾上腺皮质功能不全(AI)的临床意义及特点.方法 118例肝硬化患者用化学发光方法测量血清基础皮质醇及ACTH水平,然后将其分为并发AI组和未并发AI组,前瞻性地分析两组患者的临床特点及预后.同期选取30名胃肠息肉患者为对照组.结果 本组肝硬化患者基础皮质醇水平为(329.67±136.1)nmoL/L,显著低于对照组的(460.7±165.48)nmol/L(t=-4.501,P＜0.05).肝硬化中并发AI者32例占27.1％(32/118),AI组与未并发AI的肝硬化患者比较,在并发自发性腹膜炎(SBP)、Child分级、Child评分、MELD评分及病死率方面明显增高,两组差异有统计学意义(P＜0.05)；32例并发AI的肝硬化患者白蛋白、高密度脂蛋白-胆固醇(HDL-C)水平明显减低,出现面部色素沉着及腹水的发生率较高(P＜0.05),然而其他临床特点及实验室指标,两组差异无统计学意义.结论 肝硬化患者基础皮质醇水平明显减低,并发A1的患者SBP的发生率高、肝损伤的严重、病死率增加,严重影响预后.     

Spontaneous bacterial peritonitis caused by infection with Listeria monocytogenes: a case report and review of the literature

Spontaneous bacterial peritonitis is a frequent and often serious complication of long-standing ascites in the presence of advanced liver disease. Coliform bacteria account for the infection in most cases and are thought to be related to translocation of bacteria from the bowel into the peritoneal cavity. The empiric use of cefotaxime is well established as most of the causative organisms are sensitive to this antibiotic. However, we report on a case of spontaneous bacterial peritonitis in a patient with hepatitis C related cirrhosis who was awaiting liver transplantation caused by infection with Listeria monocytogenes , in which the patient did not improve with empiric antibiotic therapy. This case adds to the 23 others reported in the literature since 1966. Our case raises some concerns about the universal empiric usage of cefotaxime for spontaneous bacterial peritonitis because it does not offer adequate coverage against organisms such as Listeria , enterococci, Pasturella , and anaerobes.     

Analysis of clinical course and prognosis of culture-positive spontaneous bacterial peritonitis and neutrocytic ascites

The clinical significance and prognosis of culture-negative neutrocytic ascites in cirrhotic patients is a controversial topic. In the present study, the clinical and humoral presentation and the short-and long-term prognosis were analyzed in 36 patients with cirrhosis and culture-positive spontaneous bacterial peritonitis and in 28 patients with cirrhosis and ascitic fluid polymorphonuclear count greater than 250/mm³, a negative ascitic fluid culture, and without previous antibiotic therapy. On admission there were no significant differences between groups related to age, sex, alcoholism, fever, abdominal pain, serum albumin, serum urea, serum creatinine, Child-Pugh score, polymorphonuclear count, and total protein concentration in ascitic fluid. A greater frequency of positive blood culture was found in patients with spontaneous bacterial peritonitis (15/21 vs 2/18) (P<0.001). Mortality during the first episode was 36% in patients with spontaneous bacterial peritonitis and 46% in patients with culture-negative neutrocytic ascites (NS). Mortality during follow-up was high and survival probability at 12 months was 32% in spontaneous bacterial peritonitis and 31% in culture-negative neutrocytic ascites. The probability of recurrence at 12 months was 33% in spontaneous bacterial peritonitis and 34% in culture-negative neutrocytic ascites. Our results show that spontaneous bacterial peritonitis and culture-negative neutrocytic ascites are variants of the same disease with a high mortality and poor prognosis.     

红外热像图诊断自发性细菌性腹膜炎的应用研究

目的 利用红外热像图协助乙型肝炎肝硬化合并自发性细菌性腹膜炎的诊断。方法对43例乙型肝炎硬化腹水合并自发性细胞性腹膜炎患者和35例单纯乙型肝炎肝硬化腹水患者的腹部红外热像图进行对照研究结果实验组与对照组病人腹部红外热像图相比有特征性改变，两组间腹部红外热像图温度存在显著差异。结论 红外热像图协助诊断自发性细菌性腹膜炎具有简单易行，无创、费用低廉等特点，自临床应用价值。     

Ascites and spontaneous bacterial peritonitis in patients with liver cirrhosis

Liver cirrhosis is a frequent phenomenon in chronic liver diseases such as hepatitis B, hepatitis C, alcohol-related liver damage, autoimmune hepatitis and hemochromatosis. Ascites is the most frequent complication of cirrhosis. We discuss pathogenesis, diagnosis and state-of-the-art clinical management of ascites with emphasis on recent promising developments, such as covered transjugular intrahepatic portosystemic shunt (TIPS). Spontaneous bacterial peritonitis occurs in up to 10% of patients with ascites because of bacterial overgrowth with translocation through the increased permeable small intestinal wall and impaired defence mechanisms. The addition of albumin to standard antibiotic therapy may decrease mortality of spontaneous bacterial peritonitis by decreasing the incidence of renal insufficiency. Patients with coexistent marked hyperbilirubinaemia or pre-existent renal impairment could benefit from adjuvant albumin. Probiotics (bacterial food supplements) have been claimed to improve the state of underlying liver disease and may be useful in the primary and secondary prevention of spontaneous bacterial peritonitis.     

Spontaneous Bacterial Peritonitis Associated with Cardiac Ascites

A patient who developed fatal spontaneous bacterial peritonitis associated with cardiac ascites is reported. Spontaneous bacterial peritonitis most frequently occurs in patients with decompensated cirrhosis of alcoholic or nonalcoholic type. Although there are reports of spontaneous bacterial peritonitis occurring in patients with nephrotic syndrome, or with acute or chronic hepatitis, there appear to be no reports of spontaneous bacterial infection developing in cardiac ascites.     

失代偿期肝硬化腹水并发白发性细菌性腹膜炎52例临床分析

目的探讨失代偿肝硬化腹水并发自发性细菌性腹膜炎（SBP）的临床特点及治疗方法。方法回顾性分析52例肝硬化腹水并发SBP患者的临床资料。结果52例肝硬化腹水并发SBP患者中,腹水细菌培养阳性率为3．85％,致病菌以革兰阴性杆菌为主,多数患者缺乏典型腹膜炎的症状及体征。结论及时准确的早期诊断和有效抗菌素治疗可明显提高SBP患者的治愈率。     

Spontaneous bacterial peritonitis in cirrhotic patients: Is prophylactic propranolol therapy beneficial?

Background and Aim: It has been suggested that propranolol may have a protective effect on the development of spontaneous bacterial peritonitis by increasing the motility of the bowel and lowering the pressure of the portal vein. The aim of this study is to evaluate the association between the use of propranolol and development of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. Methods: We retrospectively evaluated 134 patients with cirrhosis and ascites admitted consecutively for a period of 2 years. Diagnosis of spontaneous bacterial peritonitis was based on an ascitic fluid neutrophilic count of >250/mm³ and/or a positive culture without evidence of secondary peritonitis. Results: Spontaneous bacterial peritonitis was diagnosed in 39 of 134 (29%) patients and 12 of 39 (31%) patients died in hospital compared to only 4% (four of 95) of those without spontaneous bacterial peritonitis (P < 0.001). At admission, patients with spontaneous bacterial peritonitis, as compared to those without, had significantly more encephalopathy (28 vs 11%, P = 0.02) or fever (18 vs 4%, P = 0.01) and less frequently tense ascites (33 vs 57%, P = 0.02). Spontaneous bacterial peritonitis was diagnosed in six of 33 (18%) patients who did and in 33 of 101 (33%) who did not receive propranolol therapy (OR = 0.46, 95% CI: 0.17–1.22, P = 0.17). Conclusion: Our data indicate that spontaneous bacterial peritonitis significantly increases mortality in patients with cirrhosis. Propranolol therapy was not found to be associated with a significantly lower risk for spontaneous bacterial peritonitis, but a Type II statistical error cannot be definitely excluded. The potential protective effect of propranolol on the incidence of spontaneous bacterial peritonitis might deserve evaluation in properly designed prospective studies.     

Spontaneous bacterial peritonitis in patients with hepatitis B-related cirrhosis and hepatocellular carcinoma.

To delineate the natural clinical course of spontaneous bacterial peritonitis in hepatitis B-related cirrhosis and to determine if it occurs in hepatocellular carcinoma, a prospective survey was conducted in 262 patients over 2 1/2 years. The in-hospital incidence and mortality rates of spontaneous bacterial peritonitis were 21.6% and 36.4%, respectively, in cirrhosis and 7.3% and 50% in hepatocellular carcinoma. In cirrhosis, the cumulative probability of annual recurrence of spontaneous bacterial peritonitis was 47.3%, which was significantly higher than the annual probability of occurrence of 11.3% in those with no previous attack (P less than 0.0001). The cumulative probability of annual survival was 27.6% in the spontaneous bacterial peritonitis patients, significantly lower than the probability of 64.0% in the control group (P = 0.0001). A univariate analysis, with Kaplan-Meier curves compared by the Mantel-Cox test, and subsequent multivariate analysis by stepwise Cox regression procedure were used to evaluate 37 variables recorded immediately after admission. Blood urea nitrogen concentration greater than 10.5 mmol/L urea (greater than 30 mg/dL) and ascitic fluid protein concentration less than 7.35 g/L (less than 735 mg/dL) were found to be the only significant predictors of lower annual survival; ascitic fluid protein concentration less than 7.50 g/L (less than 750 mg/dL) was the only significant predictor of higher annual recurrence. The authors conclude that spontaneous bacterial peritonitis has a high risk of recurrence in hepatitis B-related cirrhosis and that the same disease occurring in patients with hepatocellular carcinoma is related to the underlying cirrhosis rather than the hepatocellular carcinoma.     

Listeria monocytogenes Peritonitis: Case Report and Literature Review

Listeria monocytogenes is a Gram-positive bacillus that is pathogenic in both the normal and compromised host. We describe Listeria peritonitis and cerebritis in a patient with cirrhosis due to non-A, non-B hepatitis, and review the 11 other cases of Listeria peritonitis reported in the English-language literature. Listeria is a rare cause of peritonitis in debilitated, older patients, with two-thirds of the cases occurring in patients with chronic liver disease. Listeria peritonitis may also occur in patients undergoing peritoneal dialysis, or in those with malignancy. Peritonitis due to Listeria is clinically similar to spontaneous bacterial peritonitis, and is associated with fever, variable abdominal pain, and neutrocytic ascites; bacteremia commonly accompanies Listeria peritonitis. This syndrome can be successfully treated with antimicrobial drugs, although the third-generation cephalosporins commonly used in the therapy of spontaneous bacterial peritonitis are not recommended. Ampicillin may be the drug of choice, with combination therapy with an aminoglycoside reserved for cases that do not respond to ampicillin alone.     

Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis

Bacterial infections and severity of associated inflammatory reaction influence prognosis in patients with advanced cirrhosis. We compared the innate immune response to bacterial DNA (bactDNA) translocation with that caused by viable bacteria translocation in patients with spontaneous bacterial peritonitis and the relationship between the cytokine response and serum levels of bactDNA. The bactDNA translocation was investigated in 226 patients with cirrhosis and noninfected ascites, 22 patients with spontaneous bacterial peritonitis, and 10 patients with ascites receiving continuous norfloxacin. Serum and ascitic fluid tumor necrosis factor alpha, interferon-gamma, interleukin-12, and nitric oxide metabolites were measured via enzyme-linked immunosorbent assay. Bacterial genomic identifications were made via amplification and sequencing of the 16S ribosomal RNA gene and digital quantization with DNA Lab-on-chips. The bactDNA was present in 77 noninfected patients (34%) and in all cases of spontaneous bacterial peritonitis, even in those with culture-negative ascitic fluid. No patient receiving norfloxacin showed bactDNA translocation. Levels of all cytokines were similar in patients with bactDNA translocation or spontaneous bacterial peritonitis and significantly higher than in patients without bactDNA or in those receiving norfloxacin. Serum bactDNA concentration paralleled levels of all cytokines and nitric oxide in a series of patients with bactDNA translocation or spontaneous bacterial peritonitis followed during 72 hours. Antibiotic treatment in the series of patients with spontaneous bacterial peritonitis did not abrogate bactDNA translocation in the short term. CONCLUSION: bactDNA translocation-associated cytokine response is indistinguishable from that in patients with spontaneous bacterial peritonitis and is dependent on bactDNA concentration. Norfloxacin abrogates bactDNA translocation and cytokine response.     

Spontan bakterielle Peritonitis bei Leberzirrhose

Spontaneous bacterial peritonitis is the most common bacterial infection in patients with liver cirrhosis and ascites. The diagnosis is based on a cell count of more than 250 polymorphonuclear granulocytes per mm³ ascites. Spontaneous bacterial peritonitis results from bacterial translocation from the gut lumen and an altered immune response in cirrhotic patients. Clinically, spontaneous bacterial peritonitis often presents as deterioration of liver function and development of hepatic encephalopathy. In certain cases, the disease can also lead to sepsis with organ failure. Spontaneous bacterial peritonitis has a limited prognosis and antibiotic therapy is mandatory. Antibiotic treatment is usually initiated with third generation cephalosporins or chinolons. The success of antibiotic therapy should be validated by a decrease in ascitic neutrophil count after 48 hours. A secondary prophylaxis is an established treatment after survival of the first episode of spontaneous bacterial peritonitis. A primary prophylaxis of the disease is effective in patients with low ascites protein levels and reduced liver and/or kidney function. Cirrhotic patients with gastrointestinal hemorrhage also benefit from prophylactic antibiotic treatment.     

肝硬化患者稀释性低钠血症的研究现状与展望

稀释性低钠血症（DH）是肝硬化腹水患者常发生的一个并发症,并与难以控制的腹水、肝性脑病（HE）、自发性细菌性腹膜炎（SBP）及肝肾综合征（HRS）密切相关。肝硬化患者DH,轻者可表现为疲乏无力、肌张力低,重者可出现低钠性脑病,表现为认知、运动功能障碍,严重者可出现抽搐或昏迷。肝移植前存在DH的患者,其移植后的并发症和病死率明显增加。治疗上限制水摄入、输入白蛋白以纠正DH,严重低钠血症,静脉补充高张钠。几种非肽V2受体拮抗剂有望在肝硬化患者DH的治疗上发挥一定的作用。