Human albumin : liver disease
12 renin-angiotensin system , sympathetic nervous system , and arginine vasopressin . 6
There are two types of HRS 7 : - Type-1 , which is characterised by a rapid and progressive impairment of renal function defined by doubling of the initial creatinine concentrations to a level greater than 1.5 mg / dl in less than two weeks . It often appears after a precipitating event , particularly SBP or other infections , and has a very poor prognosis , with a median survival less than two weeks . - Type-2 HRS , which is characterised by moderate renal failure ( serum creatinine from 1.5 to 2.5 mg / dl ), with a steady or slowly progressive course . It often appears spontaneously and is typically associated with refractory ascites . Type-2 HRS also has a poor prognosis , with a median survival of about six months .
The diagnosis of HRS requires the exclusion of other forms of renal failure and , in particular , of hypovolaemia . For this reason , diagnosis is made in patients who fail to improve serum creatinine to a level ≤ 1.5 mg / dl after at least 2 days of diuretic withdrawal and volume expansion . The latter is preferentially performed with albumin administration ( recommended dose : 1g / kg of body weight per day , up to a maximum of 100g / day ) rather than saline solution , in order to achieve a greater and more sustained expansion and avoid sodium load . 5 , 7
Once diagnosis is established , the most effective treatment of HRS includes the administration of vasoconstrictors ( mostly terlipressin ) in association with intravenous albumin ( 1g / kg at diagnosis , followed by 40g / day up to 2 weeks ). 5 This treatment improves renal function in about 40 % of cases and leads to the resolution of HRS in about one-third of cases . Survival is only improved in the short term , but this result should not be surprising , as patients with HRS usually have a very advanced cirrhosis . Interestingly , the association of terlipressin plus albumin is more effective than terlipressin alone . 8
These favourable effects are amenable to an improvement of effective volaemia , which not only results from plasma volume expansion , but is also due to improvements in stroke work and peripheral vascular resistance , as shown by comparing the effect of albumin and hydroxyethyl starch . These results suggest an effect of albumin on endothelial function , as plasma Von Willebrand-related antigen only decreased in patients treated with albumin and serum
Table 1 : Indications to albumin administration in patients with liver cirrhosis
Complications of cirrhosis
Albumin use
SBP 1.5g / kg on day 1 and 1g / kg on day 3 ( in association with anibiotics )
HRS
nitrates and nitrites only increased in patients treated with hydroxyethyl starch . 9 Furthermore , in an experimental model of cirrhosis , albumin infusion was also able to restore an impaired cardiac contractility . 10
Prevention of post-paracentesis circulatory dysfunction Large volume paracentesis ( LVP ) is the current treatment of choice for patients with tense and refractory ascites . 5 The removal of large volumes of ascitic fluid can be followed by post-paracentesis circulatory dysfunction ( PPCD ), defined as a significant increase (> 50 %) in plasma renin activity six days after LVP . PPCD is a circulatory dysfunction characterised by an exacerbation of arteriolar vasodilation , reduction of effective blood volume , rapid re-accumulation of ascites , increased risk of HRS , water retention with dilution hyponatraemia and shortened survival . In several randomised trials , albumin was able to lower the incidence rate of PPCD and showed its superiority when compared with other plasma expanders . On the basis of such evidences , both American and European guidelines recommend the administration of 8g of albumin / L of tapped ascites , when more than 5 litres of ascites are removed . 5 , 11 Due to high cost and potential low availability of albumin , many alternatives have been tested , also including vasoconstrictors . However , in support of current recommendations , a recent meta-analysis of randomised trials has confirmed that albumin not only reduces the occurrence of PPCD more efficiently than any other plasma expander or vasoconstrictor , but is also able to lower the incidence of hyponatraemia and improve survival . 12
1g / kg on day 1 and 40g / day from day 2 to resolution ( in association with terlipressin )
PPCD 8g / l of ascites removed ( above 51 )
Non SBP infections 1.5g / kg on day 1 and 1g / kg on day 3 ( not yet enough evidence , further studies required )
Ascites
Hyponatemia
Hepatic encephalopathy
Not yet enough evidence for the utility of chronic use ( ANSWER Study currently undergoing )
Volume expansion with albumin has been proposed ( lack of randomised controlled trials )
Detoxification properties may have a role in HE therapy
According to guidelines
Controversial or experimental use
SBP , spontaneous bacterial peritonitis ; HRS , hepatorenal syndrome ; PPCD , post-paracentesis circulatory dysfunction
Controversial indications of albumin in cirrhosis Bacterial infections other than SBP Bacterial infections are very common complications of liver cirrhosis and represent a major cause of hospitalisation and death in patients with advanced disease . As reported above , it has long been recognised that renal failure develops in about one-third of patients with SBP . It has become clear that even non SBP-related infections can be followed by renal failure ( about 25 % of cases ), which is also a major predictor of mortality in this setting . 2
Data on the effect of albumin administration to patients with non SBP-related infections are few . A recent randomised study showed that the administration of albumin ( 1.5 g / kg at diagnosis and 1 g / kg at day 3 ) in association with antibiotics was able to improve circulatory and renal functions with respect to the administration of antibiotics alone . However , no significant effects on the incidence of renal failure were seen and the cumulative 3-month survival did not differ between the two groups , even though an advantage in the albumin group was found after adjusting according to variables with independent predictive value . 13 Thus , further studies are needed to clarify the role of albumin administration in this setting , mainly aimed at identifying those patients who are most at risk of developing infectioninduced complications and mortality .
Prolonged use of albumin for the treatment of ascites Ascites is a common complication of liver cirrhosis and its occurrence is associated with a worsening of prognosis . The www . hospitalpharmacyeurope . com