many alternatives have been tested , also including vasoconstrictors . However , in support of current recommendations , a meta-analysis of randomized trials has confirmed that albumin not only reduces the occurrence of PICD more efficiently than any other plasma expander or vasoconstrictor but is also able to lower the incidence of hyponatremia and improve survival . 22
Controversial indications ( not approved by the FDA ) for the use of albumin in cirrhosis Bacterial infections other than SBP Data on the effect of albumin administration to patients with non SBP-related infections are few . In a randomized trial of albumin ( 1.5g / kg at diagnosis and 1g / kg at day 3 ) in combination with antibiotics for infections other than SBP , threemonth survival was similar between the two groups , although adding albumin to an antibiotic resulted in improvement in circulatory and renal functions compared with antibiotic use alone . 23 Furthermore , in subsequent randomized trials , 24 – 26 the use of albumin delayed the onset of renal failure but did not improve renal function or patient survival . Therefore , future studies should focus on identifying those patients who are most at risk of developing infection-induced complications and in-hospital mortality in an effort to clarify any benefits from albumin therapy .
Hypervolemic hyponatremia Hypervolemic ( dilutional ) hyponatremia ( serum sodium < 135mmol / l ) is frequently seen in patients with cirrhosis and ascites and associated with a poor outcome . 27 Although , hyponatremia can occur spontaneously , it is often induced by diuretic administration , LVP without albumin infusion , bacterial infections and renal failure . Hypervolemic hyponatremia arises because of hypovolemia secondary to splanchnic arterial vasodilatation , which , in turn , impairs renal free water generation and evokes the non-osmotic secretion of vasopressin . Thus , in addition to withdrawal of diuretics and and water restriction , volume expansion with albumin has been proposed and many physicians commonly prescribe albumin in cirrhotic patients with hyponatremia . 27 In a retrospective analysis of 2435 prospectively enrolled hospitalized cirrhosis patients in the North American Consortium for End-Stage Liver Disease ( NACSELD ) consortium , 1126 with hyponatremia ( serum sodium < 130mmol / l ) were analysed . 28 Of this cohort , 777 patients receiving IV albumin infusion vs . 349 not receiving albumin had higher resolution of hyponatremia ( 85.4 % vs . 44.8 %, p = 0.0057 ), with 1.5-fold benefit of albumin [ OR ( 95 % CI ) 1.50 ( 1.13 – 2.00 )]. Clearly , RCTs are needed to examine the role of albumin administration in the management of hyponatremia in cirrhosis before recommending this approach in clinical practice . 11
Hepatic encephalopathy Hepatic encephalopathy ( HE ) is a neuropsychiatric syndrome complicating acute and chronic liver failure . HE is classically attributed to the accumulation of several substances ( mostly ammonia ) produced in the gut and normally metabolised by the liver . However , a growing body of evidence highlights an important pathophysiological role for factors such as inflammation , bacterial translocation and oxidative stress . 29 Thus , due to its antioxidant capacity , albumin might be able to counteract these effects . In a clinical study comparing the effect of volume expansion with
4.5 % albumin or colloid ( Gelofusine ) in patients with diuretic-induced HE , there was a statistically significant reduction in plasma ammonia levels in both groups , possibly due to an increase in urinary excretion . However , an improvement in mental state was only observed in those patients treated with albumin , in whom there was a concomitant reduction in oxidative stress . 30 A subsequent randomized trial in patients with HE demonstrated that the combination of lactulose and albumin was more effective than lactulose alone in the treatment of overt HE and led to a reduced mortality ( 18.3 % vs 31.6 %, p < 0.05 ). 31 Interestingly , a greater reduction in plasma levels of arterial ammonia , proinflammatory cytokines and endotoxins occurred in patients who received albumin , suggesting a potentially useful role for the protein in the treatment of this condition . 31
Perspectives on long-term albumin administration in decompensated cirrhosis The efficacy of long-term albumin administration to patients with cirrhosis and ascites has long been debated despite a paucity of studies examining its role . In 1999 , a prospective clinical trial randomized 126 hospitalised patients with ascites to receive diuretics or diuretics and albumin ( 12.5g / day ). All patients were subsequently followed-up as outpatients and given a higher dose of albumin ( 25g / week of albumin ) for 3 years . 32 The addition of albumin improved the response to ascites from diuretics and reduced the duration of hospital stay . In addition , 36 months after discharge patients receiving albumin had a lower probability of developing ascites ( 69 % vs 82 %, albumin vs no albumin ) and a lower probability of readmission to hospital ( 69 % vs 79 %, albumin vs no albumin ), however , rates of survival were similar . Further analysis of the study data showed that the beneficial effects of albumin were only seen in patients receiving an intermediate dose of diuretics and the cost / benefit ratio was only favorable to albumin in the first in-hospital part of the study . 32 A subsequent trial in 100 consecutive cirrhotic patients admitted for first-onset ascites , randomized participants to either diuretics and albumin ( 25g / week for the first year , then 25g every two weeks ) or diuretics alone and followed them for a median time of 84 months . Albumin-treated patients had greater survival rate and a lower probability of recurrent ascites ( 51 % vs 94 %, p < 0.0001 , albumin vs no albumin ). 33 A 2021 review of the use of long-term use of albumin in decompensated cirrhosis noted that both the oncotic and non-oncotic properties of albumin may improve clinical outcomes in these patients . 34
Three studies assessing the effect of longterm albumin administration to patients with decompensated cirrhosis have been published . The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis ( ANSWER ) study was a multicenter , randomized , open-label , pragmatic clinical trial that enrolled patients with cirrhosis and persisting uncomplicated ascites . 35 Patients treated with anti-aldosteronic drugs (> 200mg / day ) and furosemide (> 25mg / day ) were randomized to receive either SMT or SMT plus human albumin ( 40g albumin twice a week for the initial two weeks and then 40g / week ) and followed for 18 months . The primary endpoint of 18-month mortality was significantly lower in the albumin group ( mortality HR = 0.62 , 95 % CI 0.40 – 0.95 ). The cumulative incidence of complications of cirrhosis , including SBP , non-SBP bacterial infections , episodes of renal dysfunction , hyponatremia , hyperkalemia , HRS
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