Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment

A. L. Gerbes

• Verlag: S. Karger
• Jahr: 2010
• ISBN:
  9783805595926
• Thema: Medicine
• Thema: Gastroenterology & Hepatology

Ascites is the most frequent and hepatorenal syndrome the most lethal complication in liver cirrhosis. In recent years, major progress has been made regarding effective treatment of these complications, thus reducing mortality in patients.This publication highlights and critically appraises recent achievements and novel advances, and at the same time provides the background needed to grasp novel concepts. Topics treated include complications of paracentesis, the right choice of plasma expanders, and selection of patients who will experience survival benefit from transjugular intrahepatic portosystemic shunt. Hepatorenal syndrome, on the other hand, is responsible for a broad spectrum of manifestations caused by acute kidney injury, which until recently was considered a lethal condition. Drug treatments to improve renal function and prolong survival are therefore also discussed, including important issues for clinical outcome which are still under debate. Moreover, the role of combined kidney-liver transplantation versus conventional liver-only transplantation is addressed, as well as the use of vaptans in hyponatremia and their controversial role in the treatment of ascites.Renowned experts share their knowledge and expertise and provide an international perspective. Their contributions include up-to-date references and a bullet-point summary, making this publication most valuable for practitioners, clinicians and scientists in the field.

Gerbes AL (ed): Ascites, Hyponatremia and Hepatorenal Syndrome: Progress in Treatment.
Front Gastrointest Res. Basel, Karger, 2011, vol 28, pp 65-82

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Spontaneous Bacterial Peritonitis - Prophylaxis and Treatment

R. Wiest^a · G. Garcia-Tsao^b

^aKlinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Regensburg, Deutschland; ^bDigestive Diseases Section, Yale University School of Medicine, New Haven, Conn., and Digestive Diseases Section, VA-CT Healthcare System, West Haven, Conn., USA

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Abstract

Cirrhosis predisposes to the development of severe bacterial infections, mainly spontaneous bacteremia and spontaneous bacterial peritonitis (SBP). These life-threatening infections occur in up to 50% of cirrhotic patients during hospitalization and are responsible for 20-40% of deaths in these patients. Therefore, prompt effective therapy and prophylaxis of these spontaneous infections are crucial in order to improve the prognosis of patients with cirrhosis and ascites. Patients with a history of SBP or those presenting with gastrointestinal hemorrhage require antibiotic prophylaxis. Despite substantial improvement in the identification of patients at high risk of developing the first episode of SBP, antibiotic prophylaxis in this setting is still controversial. This is mostly related to the emergence of bacterial resistance to antibiotics induced by widespread and long-term antibiotic treatment. In fact, SBP caused by bacteria resistant to currently recommended antibiotics is increasing and associated with increased risk of treatment failure and mortality. Therefore, this chapter discusses the current guidelines and available data on the prophylaxis and therapy of SBP as well as the potential drawbacks and limitations necessitating further well-designed clinical trials.

Copyright © 2011 S. Karger AG, Basel

Definition and Clinical Importance

Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication in cirrhotic patients with ascites. The diagnosis is based on the absence of any evident intra-abdominal source of infection (e.g. pancreatitis, perforation, tuberculosis) and the presence of an inflammatory reaction to the peritoneal infection [1, 2] evidenced by a polymorphonuclear leukocyte count (PMN) in ascitic fluid greater than 250/mm³ (0.25 × 10⁹/1), a cutoff that has been shown to result in the highest sensitivity. Despite improvements in culture techniques ascites culture is negative in more than 40% of patients fulfilling these criteria. However, treatment cannot be delayed until microbiological results are available and, hence, positive culture result is not an essential criterion for the definition of SBP.

The prevalence of SBP in cirrhotic outpatients is usually very low at about 5% whereas SBP develops in about 10-12% of patients admitted to the hospital. Moreover, SBP will develop in up to 30% of patients already hospitalized, making it the most frequent type of bacterial infection in cirrhosis. SBP-related mortality exceeded 90% when it was first described but has been reduced to about 20% due to early diagnosis and treatment [3].

SBP may present with local symptoms of peritonitis, systemic signs of infection, deterioration of liver or renal function, hepatic encephalopathy, shock or gastrointestinal bleeding. However, it is important to point out that up to 30% of patients with SBP are asymptomatic [4]. Therefore, it is recommended to perform a diagnostic paracentesis in all patients with cirrhosis and ascites at admission to rule out SBP. Moreover, a diagnostic paracentesis should be performed in patients with fever or other signs of infection, gastrointestinal symptoms as well as worsening liver and/or renal function, gastrointestinal bleeding and hepatic encephalopathy [1].

The 1 -year survival rate after the first episode of SBP ranges between 7 and 69% underscoring the negative prognostic character of this event in the individual course of disease [4-8]. Different independent predictive factors for a poor prognosis among SBP patients have been reported including age [8, 9], Child-Pugh score [8, 10, 11], intensive care [9, 11], nosocomial genesis [11], hepatic encephalopathy [12, 13], creatinine and bilirubin [14], treatment failure and positive culture result per se [15, 16] as well as the development of bacteremia [17]. In a systematic review of the literature, the most robust independent predictors of death in SBP are the presence of acute kidney injury, the MELD score and lack of SBP resolution [Tandon and Garcia-Tsao, unpubl. obs.].

Pathogenesis and Risk Factors

Two facts point to the gut as the main source of bacteria in the development of community-acquired SBP. First, more than 70% of cases of SBP are caused by aerobic Gram-negative bacilli [18], and, second, selective gut decontamination with oral antibiotics is able to prevent most of these infections [19-21]. Intestinal bacteria reach the bloodstream and ascites through a process denominated bacterial translocation which is defined as the passage of viable bacteria from the gut to mesenteric lymph nodes and/or other extraintestinal sites [22]. Three factors have been implicated in the development of BT in liver cirrhosis: intestinal bacterial overgrowth (IBO), increased intestinal permeability and impaired immunity. It is important to stress that, although studied separately, these factors most likely act jointly, e.g. community-acquired SBP is the result of failure of the gut to contain bacteria and failure of the immune system to kill bacteria once they have escaped the gut.

IBO, predominantly with aerobic Gram-negative bacteria, has been demonstrated both in cirrhotic rats and in patients with cirrhosis, especially in severe liver disease [23-25]. An imbalance of the intestinal microflora is crucial for the process of microbial translocation since anaerobic bacteria, which represent approximately 99% of the gut flora, do not translocate readily, while aerobic Gram-negative bacilli translocate easily, even across a histologically intact intestinal epithelium [26, 27]. The majority of bacteria translocating in cirrhosis are exactly these Gram-negative bacteria, especially Enterobacteriaceae (mainly E. coli) [25, 28-32]. In addition, mucosal intestinal barrier dysfunction has been demonstrated in experimental and human advanced cirrhosis [33, 34] and is thought to be mediated at least in part by ultrastructural changes [35], oxidative stress [36] as well as alterations in the secretory barrier component, e.g. immunoglobulin A or bile acids [37]. Host defense mechanisms are defective in advanced cirrhosis including impaired innate immune response as well as changes in adaptive immunity. For instance, dysfunction of the reticuloendothelial and mononuclear system due to lack of opsonization and migratory capabilities results in reduced phagocytic and killing capacity [38, 39]. This impairment in host immune response acts synergistically with bacterial overgrowth to promote bacterial translocation and may play a crucial role in the spreading of translocated pathogenic bacteria [40]. In hospital-acquired SBP these defects in the host defense predispose to the acquisition of bacterial infections, e.g. during invasive procedures. Therefore, organisms responsible for nosocomial SBP are not exclusively enteric Gram-negative flora but predominantly nonenteric Gram-positive infections [41].

All cirrhotic patients with ascites are at risk of SBP; however, there is a wide range in incidence, depending on the presence of additional risk factors. Patients presenting with any of the following are prone to the development of SBP: (a) gastrointestinal bleeding, (b) low-protein ascitic fluid (<1.5 g/dl) or (c) a previous history of SBP. Gastrointestinal hemorrhage can trigger spontaneous bacterial infections via multiple mechanisms including increased intestinal permeability, enhanced bacterial translocation and reduced RES function [42]. Ascites protein levels correlate with local concentrations of complement factors and opsonic activity [43] and, thus, a low protein level indicates a lack of local ascites defenses. In patients with ascites protein levels >1.5 g/dl, the incidence of SBP is as low as 0-3% as compared to 14-23% in patients with an ascites protein <1.5 g/dl [5, 44]. Additional factors shown to be predictive of SBP include serum bilirubin >3.2 mg/dl and platelet count <98,000/mm [45]. Also, the risk of SBP is associated with the use of proton pump inhibitors [46] as well as increasing MELD-score [47]. Interestingly, SBP has also been shown to be increased in carriers of NOD2/ CARD 15 variants known to be linked with impaired intestinal mucosal barrier function [48]. In patients who have recovered from SBP, the recurrence rate is very high, ranging between 30 and 68% [6, 19] reflecting the persistence of risk factors that led to the first episode.

Prophylaxis

Since 30-50% of deaths in patients with cirrhosis are attributable to infections, prophylaxis is of crucial relevan...