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perforation , intestinal abscess ) and results from invasion of pathogenic microorganisms into the abdominal cavity . Its prevalence and mortality are high . The incidence is 40 %– 70 % in patients with terminal liver diseases such as liver cirrhosis , and mortality after treatment is 20 %– 60 %. The mortality rate is 50 %– 60 % in untreated SBP patients or patients with hospital-acquired SBP . SBP can swiftly deteriorate to hepatic and renal failure and is the leading cause of death in patients with cirrhosis and terminal liver diseases . Once infection in liver cirrhosis is suspected , empirical anti-infective treatment should be commenced immediately . Antimicrobial agents for SBP should be broadspectrum , low in hepatic and renal toxicity , and administered at sufficient doses . Once the pathogen ( s ) are identified , targeted antimicrobial agents should be selected based on susceptibility testing . Antimicrobial therapy combined with albumin can improve prognosis . Antibiotics in combination with albumin are more effective in reducing renal injury and mortality of SBP patients than antimicrobial agents alone and is widely recommended in treatment guidelines . 1 5
Furthermore , albumin level has an impact on the binding and distribution of antimicrobial agents . Low serum albumin levels will inevitably affect the efficacy of antibiotics . For example , commonly used antibiotics such as cefoperazone and ceftriaxone have a high albumin-binding rate ( albumin binding rate > 70 %). Levofloxacin , moxifloxacin , cefotaxime and piperacillin have moderate albumin-binding rates ( 30 %– 70 %). As albumin levels decrease , the concentration of free drug increases , thereby making it more likely to distribute in the tissue space so blood concentration cannot be maintained , influencing the antimicrobial effect . Albumin supplementation improves the efficacy of antimicrobial agents , not only increasing survival time of SBP patients , but also reducing mortality risk , 11 and risk of renal failure in patients with non-SBP infections . 12
Albumin in treating HRS HRS is a functional renal failure in patients with terminal liver disease . The pathogenesis of HRS is unclear . Approximately 30 % of cases of SBP treated with antimicrobial agents alone progress to HRS . The median survival time of HRS is only 3 months and the prognosis is very poor . Goals of treatment are to recover renal function and prolong survival time for potential subsequent liver transplant . As recommended in the 2017 Chinese Guideline for Diagnosis and Treatment of Ascites and Relevant
Complications of Liver Cirrhosis , patients with type 1 or 2 HRS can receive terlipressin ( 1mg / 4 – 6h ) combined with human albumin ( 20 – 40g / d ) for 3 days . If the decrease in sCr is < 25 %, the dose can be gradually increased to 2mg / 4h . Human albumin combined with terlipressin significantly reduces renal injury , improves survival rate and achieves a higher reversal rate of HRS . 13
Long-term albumin therapy in patients with liver cirrhosis and ascites Long-term use of albumin was explored in two prospective RCT studies conducted by an Italian group 14 , 15 A total of 81 patients with liver cirrhosis and ascites were included and given diuretics alone or diuretics combined with albumin ( 25g / week in the first year , 25g / 2 weeks thereafter ), followed up for 20 and 84 months , respectively . Long-term albumin therapy reduced the incidence of ascites and readmission , significantly improved transplantfree survival rate and survival time and reduced the recurrence rate of ascites . The two studies demonstrated that long-term albumin therapy can better control ascites and improve the survival rate in these patients . An RCT published in The Lancet ( ANSWER study ) included 431 decompensated cirrhosis patients with simple ascites . 9 The trial group was given diuretics plus albumin ( 40g / week ) for 18 months , while the control group was given diuretics alone . Risk of mortality decreased by 38 % in the trial group . 9 Moreover , the incidence of SBP , non-SBP bacterial infection , renal insufficiency and HRS decreased significantly , providing robust evidence for further exploration of long-term albumin application .
Studies have demonstrated that long-term albumin therapy increases the survival rate of patients with liver cirrhosis and ascites , 16 , 17 and reduces the incidence of complications , providing a new overall treatment option in cirrhosis . The potential mechanism might be associated with its effects of improving circulatory dysfunction and reducing systemic inflammation .
Conclusion With an in-depth knowledge of the mechanisms of decompensated liver cirrhosis , it is known that albumin , with its multiple physiological functions , reduces the risk of various complications and improve patients ’ prognoses . 18 However , in addition to considering long-term albumin therapy , dose selection , frequency and course of treatment still need to be explored in further clinical studies .
References 1 Xu X et al . Guideline for diagnosis and treatment of ascites and relevant complications of liver cirrhosis . Chin J Exp Clin Infect Dis 2017 ; 11 ( 5 ): 417 – 32 . 2 Biggins SW et al ; AASLD . Diagnosis , evaluation , and management of ascites and hepatorenal syndrome . Hepatology 2021 ; doi : 10.1002 / hep . 31884 . 3 European Association for the Study of the Liver . EASL clinical practice guidelines on the management of ascites , spontaneous bacterial peritonitis , and hepatorenal syndrome in cirrhosis . J Hepatol 2010 ; 53 ( 3 ): 397 – 417 . 4 Aithal GP et al . Guidelines on the management of ascites in cirrhosis . Gut 2021 ; 70 ( 1 ): 9 – 29 .
5 Angeli P et al . Diagnosis and management of acute kidney injury in patients with cirrhosis : revised consensus recommendations of the International Club of Ascites [ published correction appears in J Hepatol . 2015 Jul ; 63 ( 1 ): 290 ]. J Hepatol 2015 ; 62 ( 4 ): 968 – 74 . 6 Arora V et al . Paracentesisinduced circulatory dysfunction with modestvolume paracentesis is partly ameliorated by albumin infusion in acute-on-chronic liver failure . Hepatology 2020 ; 72 ( 3 ): 1043 – 55 . 7 Sen Sarma M et al . Safety , complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease . J Hepatol 2015 ; 63 ( 5 ): 1126 – 32 . 8 Fernández J et al . Effects of
albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis . Gastroenterology 2019 ; 157 ( 1 ): 149 – 62 . 9 Caraceni P et al . Long-term albumin administration in decompensated cirrhosis ( ANSWER ): an open-label randomised trial [ published correction appears in Lancet . 2018 Aug 4 ; 392 ( 10145 ): 386 ]. Lancet 2018 ; 391 ( 10138 ): 2417 – 29 . 10 China L et al . A randomized trial of albumin infusions in hospitalized patients with cirrhosis . N Engl J Med 2021 ; 384 ( 9 ): 808 – 17 . 11 Salerno F , Navickis RJ , Wilkes MM . Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis : a meta-analysis of randomized
trials . Clin Gastroenterol Hepatol 2013 ; 11 ( 2 ): 123 – 30 . 12 Thévenot T et al . Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis . A randomized trial . J Hepatol 2015 ; 62 ( 4 ): 822 – 30 . 13 Wong F et al . Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome . N Engl J Med 2021 ; 384 ( 9 ): 818 – 28 . 14 Gentilini P et al . Albumin improves the response to diuretics in patients with cirrhosis and ascites : results of a randomized , controlled trial . J Hepatol 1999 ; 30 ( 4 ): 639 – 45 . 15 Romanelli RG et al . Longterm albumin infusion improves survival in patients with cirrhosis and ascites : an unblinded randomized trial . World J Gastroenterol 2006 ; 12 ( 9 ): 1403 – 7 .
16 Di Pascoli M et al . Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites . Liver Int 2019 ; 39 ( 1 ): 98 – 105 . 17 Bureau C et al . Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites [ published correction appears in Gastroenterology 2017 ; 153 ( 3 ): 870 ]. Gastroenterology 2017 ; 152 ( 1 ): 157 – 63 . 18 Bernardi M , Caraceni P . Novel perspectives in the management of decompensated cirrhosis . Nat Rev Gastroenterol Hepatol 2018 ; 15 ( 12 ): 753 – 64 .
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