Sponsored: Human albumin: Focus on liver disease | Page 5

SBP SBP is an ascitic fluid infection in patients with liver cirrhosis in the absence of exogenous sources of abdominal infection . Currently domestic and foreign guidelines or consensus on ascites management point out that the positive rate of bacterial culture of ascites is low ( 5 %– 20 %). The diagnostic criteria for SBP are ascites multinucleated cell count > 250 / μl , with or without an ascites positive culture . 9 , 10 The threshold for the multinucleated cell count in ascites in the diagnostic criteria for SBP was established based on expert consensus but there is no strong supporting evidence for the threshold . Currently , the evidence for SBP diagnostic criteria based on multinucleated cells count in ascites is lowlevel and there is no large-scale cohort supporting the data . Whether the threshold for Chinese liver cirrhosis patients with SBP related to chronic hepatitis B is suitable needs to be proved by further clinical investigations .
In clinical practice , clinicians do not comply well with the diagnostic criteria . The main reasons are :
• The percentage of inpatients with liver cirrhosis and ascites who receive diagnostic abdominal paracentesis is low , and the percentage is about 40 % in domestic teaching hospitals
• The percentage of cases of SBP diagnosed based on multinucleate cell count in ascites that is not consistent with clinical symptoms and signs is high
• The original intention is to start empirical antibiotic therapy for abdominal infection as soon as possible , which is contradictory in the context of precision medicine . The SBP diagnostic criteria are of limited significance to early and suitable antiinfective therapy
• With the development of culture technologies and pathogen testing technologies , the recognition of pathogen type and complexity of abdominal infection increases and the clinical guiding significance of the criteria decreases
• With the recognition of interaction between pathogens ( mainly bacteria ) and host immune cells , the ability of pathogenic infection to cause increased neutrophil count in ascites varies . Many cases of significant abdominal bacterial infection will be missed based on the criteria
• Critical patients usually have multiple infections . Using antibiotics impacts on the multinucleated cell count in ascites , thereby making use of the criteria to detect abdominal infection in critical patients challenging .
Bacterascites Bacterascites is another form of abdominal infection in patients with liver cirrhosis ( multinucleated cell count in ascites < 250 / μl and an ascites positive bacterial culture ). This type of abdominal infection in patients with liver cirrhosis has been rarely studied . A multicentre , retrospective study showed that bacterascites had a similar poor prognosis to SBP , including short-term mortality and acute renal injury . 11
Abdominal infection in patients with liver cirrhosis also includes spontaneous fungal peritonitis , which is relatively rare . Studies indicated that the mortality was high ( about 60 %) in patients with liver cirrhosis and fungal peritonitis . 12 , 13 Early diagnosis is very important for improving patients ’ prognoses ; however , ascites culture generally takes 3 – 5 days thereby delaying the diagnosis of abdominal infection , especially for patients with cell counts < 250 / μl . Therefore , in current clinical practice , clinicians prefer to make diagnoses of abdominal infection based on clinical manifestations of the patients , so as to administer antibiotic therapy efficiently .
Treatment of abdominal infection For treatment of SBP , European and US guidelines recommend antibiotics combined with high-dose human albumin ( 1.5g / kg on day 1 , and 1.0g / kg on day 3 ). It was reported that high-dose human albumin combined with antibiotics in treating SBP can reduce acute renal injury and 90-day mortality . 14 The Chinese Guidelines on the Management of Ascites and its Related Complications in Cirrhosis recommend treating SBP patients with 20 – 40g / d human albumin to improve the clinical prognosis . 15 However , a retrospective study in 11 Chinese grade-A tertiary hospitals showed that the prevalence of acute renal injury in Chinese SBP patients was 52.7 %, but the average daily dose of human albumin was only 0.2g / kg , much lower than the dose of human albumin recommended in domestic and foreign guidelines . It is inferred that the high prevalence of acute renal injury in SBP patients in China might be related to use of low-dose human albumin .
Human albumin combined with third-generation cephalosporin antibiotics is currently the standard treatment regimen for SBP . An early typical randomised controlled clinical trial showed that , compared with third-generation cephalosporin antibiotics alone , human albumin at 1.5g / kg within 6 hours of antibiotic therapy and 1.0g / kg on day 3 significantly reduced the incidence of renal injury in SBP patients ( 33 % vs 10 %, p = 0.02 ), improved clinical prognosis and significantly reduced hospital mortality and 3-month mortality . 16 Additionally , the 2019 Chinese Guidelines on the Management of Liver Cirrhosis recommend that high-dose human albumin can be given to patients with sepsis and serious infection when using antibiotics , and vasoactive agents should be used in the event of hypotension .
As mentioned above , patients with bacterascites and fungal peritonitis have a similar poor prognosis to SBP , but treatment of ascites in these patients is not described in international or Chinese guidelines , particularly regarding the infusion dose and the number of courses of human albumin . Consequently , studies on the optimal dose and courses of human albumin should be conducted in SBP patients with hepatitis B-associated liver cirrhosis in China , so as to instruct clinical practice .
Conclusion Abdominal infection in patients with liver cirrhosis is an important clinical problem in end-stage disease and there are still many clinical problems to be solved . In terms of SBP diagnosis , the diagnostic criteria based on neutrophil cell count in ascites are only of limited clinical support . Ascites positive culture rate is low and empirical antibiotic therapy is therefore mainly adopted . There are no alternative diagnostic markers in clinical practice . In terms of SBP treatment , Chinese guidelines on the management of ascites in cirrhosis mainly emphasise antibiotic treatment . However , the dose of human albumin in clinical practice is lower than that recommended in the guidelines . Moreover , data on the use of intravenous human albumin is mainly derived from SBP patients with alcoholic cirrhosis in Europe and America . More studies should be conducted to explore whether it is applicable for hepatitis B-associated liver cirrhosis , and investigate the optimal dose , and course of treatment .
References 1 Wang FS et al . The global burden of liver disease : the major impact of China . Hepatology 2014 ; 60 ( 6 ): 2099 – 108 . 2 Zeng DY et al . Global burden of acute viral hepatitis and its association with socioeconomic development status , 1990 – 2019 . J Hepatol 2021 ; May 04 . 3 Fan JG , Farrell GC . Epidemiology of non-alcoholic fatty liver disease in China . J Hepatol 2009 ; 50 ( 1 ): 204 – 10 . 4 Simonetto DA et al . Management of sepsis in patients with cirrhosis : Current evidence and practical approach . Hepatology 2019 ; 70 ( 1 ): 418 – 28 . 5 Piano S et al . Infections complicating cirrhosis . Liver Int 2018 ; 38 Suppl 1:126 – 33 . 6 Runyon BA , Squier S , Borzio M . Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis . J Hepatol 1994 ; 21 ( 5 ): 792 – 6 . 7 Evans LT et al . Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites . Hepatology 2003 ; 37 ( 4 ): 897 – 901 . 8 Fernandez J et al . Multidrugresistant bacterial infections in patients with decompensated cirrhosis and with acute-onchronic liver failure in Europe . J Hepatol 2019 ; 70 ( 3 ): 398 – 411 . 9 Runyon B . Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012 . Hepatology 2013 ; 57 ( 4 ): 1651 – 3 . 10 EASL Clinical Practice Guideline : Occupational liver diseases . J Hepatol 2019 ; 71 ( 5 ): 1022 – 37 . 11 Li B et al . Clinical features and outcomes of bacterascites in cirrhotic patients : A retrospective , multicentre study . Liver Int 2020 ; 40 ( 6 ): 1447 – 56 . 12 Bucsics T et al . Prognosis of cirrhotic patients with fungiascites and spontaneous fungal peritonitis ( SFP ). J Hepatol 2016 ; 64 ( 6 ): 1452 – 4 . 13 Li B et al . Spontaneous fungal ascites infection in patients with cirrhosis : An analysis of 10 cases . Infect Dis Ther 2021 ; 10 ( 2 ): 1033 – 43 . 14 Grange JD , Amiot X . Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis . Gastroenterol Clin Biol 2000 ; 24 ( 3 ): 378 – 9 . 15 Chinese Society of Hepatology , CMA . Guidelines on the management of ascites and its related complications in cirrhosis . J Clin Hepatol 2017 ; 33 ( 10 ): 1847 – 63 . 16 Sort P et al . Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis . N Engl J Med 1999 ; 341 ( 6 ): 403 – 9 .
hospitalpharmacyeurope . com | 2021 | 5