Albumin in cirrhosis

Fluid needs in cirrhosis

Liver diseases, specifically cirrhosis, have been recognised as very important but underestimated health issues¹

Chronic liver disease is very common², with an estimated 1.5 billion people having this condition in 2017³. The most common causes of chronic liver disease are alcoholic and non-alcoholic fatty liver disease, chronic viral hepatitis, genetic predisposition, autoimmune disorders and some drugs. Chronic inflammation and fibrosis result in progressive deterioration of liver function and can lead to cirrhosis². In cirrhosis, regenerative hepatic nodules replace the normal liver architecture, eventually resulting in liver failure¹. Progression to cirrhosis does not occur in all patients with liver disease, but is responsible for approximately half of all deaths from liver disease globally and is the 11th most common cause of death worldwide¹.

In the following video, Alastair O’Brien, Professor of Experimental Hepatology at University College London, discusses the increasing prevalence of liver disease and highlights fluid resuscitation as the cornerstone of management. Professor O’Brien defines compensated versus decompensated cirrhosis and introduces albumin and the benefits of treatment for people with cirrhosis.

Decompensated cirrhosis

Improving the understanding of fluid resuscitation in decompensated cirrhosis is key to decreasing morbidity and mortality⁴

Cirrhosis is typically asymptomatic until portal pressure increases and liver function worsens. In the asymptomatic phase, known as ‘compensated cirrhosis’, the disease may remain undetected for years while continuing to progress, and the person may enjoy a good quality of life during this phase⁵.

Portal hypertension triggers a chain of events that lead to sodium and fluid imbalances (Figure 1), culminating in acute decompensation. This is associated with potentially life-threatening complications including ascites, gastrointestinal bleeding, infection, particularly spontaneous bacterial peritonitis (SBP), and hepatic encephalopathy^4,6-8.

Figure 1. The physiological cascade of events in cirrhosis (Adapted⁴).

Decompensated cirrhosis is systemic, characterised by an increase in circulating chemokines and pro-inflammatory cytokines, and involves multiple organs and systems⁵. In 30% of cases there is rapid progression to extra-hepatic organ failure, often involving the kidneys, and acute-on-chronic liver failure (ACLF), which is associated with systemic inflammation and a high 28-day mortality rate^6-8.

The detrimental effects of cirrhosis can also be attributed to decreased synthesis of albumin as well as alterations to the structure of albumin resulting from the pro-inflammatory and pro-oxidant states⁶.

Median survival reduces from 12 years in compensated cirrhosis to approximately 2 years in decompensated cirrhosis⁵

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Guidelines for fluid management in cirrhosis

Ideally, the aim of cirrhosis management should be to prevent disease progression with treatments that target pathological changes in the liver and suppress inflammation, to enable regression of fibrosis and normalisation of portal and arterial circulation^5,6. However, such treatments do not yet exist⁵. At present, management consists of prophylactic measures to prevent decompensated cirrhosis or treatment of complications to improve outcomes⁵.

Figure 3 illustrates the indications and dosage of albumin in the natural history of decompensated cirrhosis.

Figure 3. Traditional management of decompensated cirrhosis (Adapted⁸).

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Fluid selection in cirrhosis

In the following video, Alastair O’Brien, Professor of Experimental Hepatology at University College London, discusses factors to consider when deciding which fluid is most appropriate to treat a person with cirrhosis. These factors include benefits, costs, evidence, and the amount of fluid to administer.

When considering fluid options, it may be useful to regard each fluid option as a drug, each with indications, contraindications and possible side effects¹⁰

It may be helpful to refer to the 4 Ds of fluid therapy (drug, dose, duration and de-escalation) when considering the most appropriate fluid therapy to treat patients with cirrhosis.

Review the 4 Ds of fluid therapy

The three categories of treatment options recommended for fluid management in cirrhosis are crystalloids, colloids and blood transfusion. Table 3 summarises the recommendations for fluid management using these options, from the EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. Please note that this table contains a summary only: for full information please refer to the EASL Clinical Practice Guidelines as well as your local treatment guidelines⁵.

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References

1. Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N. Liver cirrhosis. The Lancet. 2022.
2. Sharma A, Nagalli S. Chronic Liver Disease. StatPearls [Internet]. 2021.
3. Moon AM, Singal AG, Tapper EB. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clinical Gastroenterology and Hepatology. 2020;18(12):2650-2666.
4. Maynard E. Cirrhosis and Fluid Resuscitation. Surgical Clinics of North America. 2017;97(6):1419-1424.
5. Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. Journal of Hepatology. 2018;69(2):406-460.
6. Bernardi M, Angeli P, Claria J, Moreau R, Gines P, Jalan R, et al. Albumin in decompensated cirrhosis: new concepts and perspectives. Gut. 2020;69(6):1127-1138.
7. Engelmann C, Clària J, Szabo G, Bosch J, Bernardi M. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction. J Hepatol. 2021;75 Suppl 1(Suppl 1):S49-s66.
8. Tufoni M, Zaccherini G, Caraceni P, Bernardi M. Albumin: Indications in chronic liver disease. United European Gastroenterology Journal. 2020;8(5):528-535.
9. Jagdish RK, Maras JS, Sarin SK. Albumin in Advanced Liver Diseases: The Good and Bad of a Drug! Hepatology. 2021;74(5):2848-2862.
10. Mekeirele M, Vanhonacker D, Malbrain MLNG. Fluid Management in Sepsis. Springer Nature Singapore; 2022. p. 199-212.
11. Paolo Caraceni PADPMB. AISF-SIMTI position paper on the appropriate use of albumin in patients with liver cirrhosis: a 2020. 2022.
12. Caraceni P, Riggio O, Angeli P, Alessandria C, Neri S, Foschi FG, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. The Lancet. 2018;391(10138):2417-2429.
13. Fernández J, Clària J, Amorós A, Aguilar F, Castro M, Casulleras M, et al. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis. Gastroenterology. 2019;157(1):149-162.
14. China L, Freemantle N, Forrest E, Kallis Y, Ryder SD, Wright G, et al. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. New England Journal of Medicine. 2021;384(9):808-817.
15. NCT03451292. Effects of Long-Term Administration of Human Albumin in Subjects With Decompensated Cirrhosis and Ascites (PRECIOSA). 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT03451292.
16. NICE. Patient-centred care | Intravenous fluid therapy in adults in hospital | Guidance | NICE. https://www.nice.org.uk/guidance/cg174/chapter/Patient-centred-care. Accessed 2 Jul 2022.