Downloaded from gut.bmjjournals.com on 25 September 2006 Guidelines on the management of ascites in cirrhosis K P Moore and G P Aithal Gut 2006;55;1-12 doi:10.1136/gut.2006.099580 Updated information and services can be found at: http://gut.bmjjournals.com/cgi/content/full/55/suppl_6/vi1 These include: References This article cites 148 articles, 21 of which can be accessed free at: http://gut.bmjjournals.com/cgi/content/full/55/suppl_6/vi1#BIBL Email alerting Receive free email alerts when new articles cite this article - sign up in the box at the service top right corner of the article Topic collections Articles on similar topics can be found in the following collections Liver, including hepatitis (945 articles) Notes To order reprints of this article go to: http://www.bmjjournals.com/cgi/reprintform To subscribe to Gut go to: http://www.bmjjournals.com/subscriptions/ Downloaded from gut.bmjjournals.com on 25 September 2006 vi1 GUIDELINES Guidelines on the management of ascites in cirrhosis K P Moore, G P Aithal ............................................................................................................................... Gut 2006;55(Suppl VI):vi1–vi12. doi: 10.1136/gut.2006.099580 1.0 INTRODUCTION N Grade 1 (mild). Ascites is only detectable by ultrasound examination. Ascites is a major complication of cirrhosis,1 occurring in 50% of patients over 10 years of N Grade 2 (moderate). Ascites causing moderate follow up.2 The development of ascites is an symmetrical distension of the abdomen. important landmark in the natural history of N Grade 3 (large). Ascites causing marked cirrhosis as it is associated with a 50% mortality abdominal distension. over two years,2–5 and signifies the need to consider liver transplantation as a therapeutic option.3 The majority (75%) of patients who Refractory ascites present with ascites have underlying cirrhosis, Ascites that cannot be mobilised or early with the remainder being due to malignancy recurrence of which (that is, after therapeutic (10%), heart failure (3%), tuberculosis (2%), paracentesis) cannot be satisfactorily prevented pancreatitis (1%), and other rare causes.6 The by medical therapy. This includes two different true prevalence and incidence of cirrhosis of the subgroups. liver and its complications in the UK are N Diuretic resistant ascites—ascites that is unknown. Mortality from cirrhosis has increased refractory to dietary sodium restriction and from 6 per 100 000 population in 1993 to 12.7 per intensive diuretic treatment (spironolactone 7 100 000 population in 2000. Approximately 4% 400 mg/day and frusemide 160 mg/day for at of the general population have abnormal liver least one week, and a salt restricted diet of 8 function or liver disease and approximately less than 90 mmol/day (5.2 g of salt)/day). 10–20% of those with one of the three most N Diuretic intractable ascites—ascites that is common chronic liver diseases (non-alcoholic refractory to therapy due to the development fatty liver disease, alcoholic liver disease, and of diuretic induced complications that pre- chronic hepatitis C) develop cirrhosis over a clude the use of an effective diuretic dosage. period of 10–20 years. With a rising frequency of alcoholic and non-alcoholic fatty liver disease, a huge increase in the burden of liver disease is expected over the next few years8 with an 3.0 PATHOGENESIS OF ASCITES inevitable increase in the complications of FORMATION cirrhosis. There have been several changes in A detailed description of the pathogenesis of ascites formation is beyond the scope of this the clinical management of cirrhotic ascites over 12–14 recent years, and the purpose of these guidelines article but more detailed reviews are available. is to promote a consistent clinical practice There are two key factors involved in the throughout the UK. pathogenesis of ascites formation—namely, These guidelines are based on a comprehensive sodium and water retention, and portal (sinusoi- literature search, including the results of rando- dal) hypertension. mised control trials, systematic reviews, prospec- tive retrospective studies and, in some instances, 3.1 Role of portal hypertension evidence obtained from expert committee Portal hypertension increases the hydrostatic reports. Where possible a judgement is made pressure within the hepatic sinusoids and on the quality of the information used to favours transudation of fluid into the peritoneal generate the guidelines, and the specific recom- cavity. However, patients with presinusoidal mendations have been graded according to the portal hypertension without cirrhosis rarely Oxford Centre for Evidence-based Medicine develop ascites. Thus patients do not develop Levels of Evidence (May 2001) (see appendices ascites with isolated chronic extrahepatic portal See end of article for 1 and 2).9 These guidelines conform to the venous occlusion or non-cirrhotic causes of authors’ affiliations portal hypertension such as congenital hepatic ....................... international guidelines recently published by the International Ascites Club10 and are intended fibrosis, except following an insult to liver Correspondence to: for use by physicians. We hope to revise these function such as gastrointestinal haemorrhage. Professor K Moore, The guidelines in three years time. Conversely, acute hepatic vein thrombosis, caus- UCL Institute of ing postsinusoidal portal hypertension, is usually Hepatology, Royal Free associated with ascites. Portal hypertension and University College 2.0 DEFINITIONS Medical School, UCL, occurs as a consequence of structural changes Rowland Hill St, London The terms used in this article have been defined within the liver in cirrhosis and increased NW3 2PF, UK; kmoore@ by the International Ascites Club.11 splanchnic blood flow. Progressive collagen medsch.ucl.ac.uk deposition and formation of nodules alter the Uncomplicated ascites Revised 28 April 2006 Accepted for publication Ascites that is not infected and which is not Abbreviations: TIPS, transjugular intrahepatic 28 April 2006 associated with the development of the hepato- portosystemic shunt; SBP, spontaneous bacterial ....................... renal syndrome. Ascites can be graded as follows: peritonitis; PMN, polymorphonuclear cell www.gutjnl.com Downloaded from gut.bmjjournals.com on 25 September 2006 vi2 Moore, Aithal normal vascular architecture of the liver and increase reflex.23 24 Similarly, in addition to systemic vasodilation, the resistance to portal flow. Sinusoids may become less severity of liver disease and portal pressure also contribute to distensible with the formation of collagen within the space the abnormalities of sodium handling in cirrhosis.25 of Disse. While this may give the impression of a static portal system, recent studies have suggested that activated hepatic 4.0 DIAGNOSIS stellate cells may dynamically regulate sinusoidal tone and 4.1 Initial investigations thus portal pressure. The underlying cause of ascites is frequently obvious from the Sinusoidal endothelial cells form an extremely porous history and physical examination. However, it is important to membrane which is almost completely permeable to macro- exclude other causes of ascites. It should not be assumed that molecules, including plasma proteins. In contrast, splanchnic the alcoholic patient has alcoholic liver disease. Therefore, capillaries have a pore size 50–100 times less than that of tests must be directed at diagnosing the cause of ascites. The hepatic sinusoids. As a consequence, the trans-sinusoidal essential investigations on admission include a diagnostic oncotic pressure gradient in the liver is virtually zero while it paracentesis with measurement of ascitic fluid albumin or is 0.8–0.9 (80%–90% of maximum) in the splanchnic protein, ascitic fluid neutrophil count and culture, and ascitic circulation.12 Oncotic pressure gradients at such extreme fluid amylase. Ascitic fluid cytology should be requested ends of the spectrum minimise any effect the changes in when there is a clinical suspicion of underlying malignancy. plasma albumin concentration may have on transmicrovas- Other investigations should include abdominal ultrasound cular fluid exchange. Therefore, the old concept that ascites is scan to evaluate the appearance of the liver, pancreas, and formed secondary to decreased oncotic pressure is false, and lymph nodes as well as the presence of splenomegaly, which plasma albumin concentrations have little influence on the may signify portal hypertension. Blood tests should be taken rate of ascites formation. Portal hypertension is critical to the for measurement of urea and electrolytes, liver function tests, development of ascites, and ascites rarely develops in patients prothrombin time, and full blood count. with a wedged hepatic venous portal gradient of ,12 mm Hg.15 Conversely, insertion of a side to side porta- 4.2 Abdominal paracentesis caval shunt to decrease portal pressure often causes resolu- The commonest site for an ascitic tap is approximately 15 cm tion of ascites. lateral to the umbilicus, with care being taken to avoid an enlarged liver or spleen, and is usually done in the left or the 12 3.2 Pathophysiology of sodium and water retention right lower abdominal quadrant. The inferior and superior The classical explanations of sodium and water retention epigastric arteries run just lateral to the umbilicus towards occurring due to ‘‘underfill’’ or ‘‘overfill’’ are oversimplified. the mid-inguinal point and should be avoided. For diagnostic