Chapter 4 Hepatorenal syndrome

4.1 HAS and vasopressors

In 2021, two large multi-centre RCTs tested the role of human albumin solution and terlipressin in type I HRS.

ATTIRE (2021): - 20% HAS to target serum albumin 30 g/L vs standard care (HAS only for LVP, SBP, HRS) in decompensated cirrhosis. In the UK; predominantly EtOH. Composite endpoint of infection, AKI, death within 2 weeks. Median albumin dose 200 vs 20 g. Targeted HAS conferred no benefit and caused signifant harm (more pulmonary oedema / pneumonia).

CONFIRM (2021): - terlipressin 1mg qds vs placebo in type I HRS (SCr > 200 mcM). In the USA / Canada; predominantly EtOH. Endpoint was HRS reversal (SCr < 133 mM) and survival without RRT for 10 days. Terlipressin was effective at inducing HRS reversal (17% vs 32%) but caused more adverse events including abdominal pain, diarrhoea, respiratory failure. The rates of RRT and death by 90 days were 39 and 45% respectively in the placebo group and 29 and 51% in the terlipressin group. Respiratory failure (10 vs. 3%) and death from respiratory causes (11 vs. 2%) were both more common in the terlipressin group.

Prior to this, evidence supporting the use of human albumin solution for the prevention of hepatorenal syndrome came from small, single-centre RCTs:

Sort et al. (1999): comparing HAS vs no HAS in SBP. Reduced renal failure and death in the HAS group.

Sola-Vera et al. (2003): comparing 0.9% NaCl vs. HAS at time of large-volume paracentesis. Less circulatory dysfunction in HAS group (restricted to drain volumes $\ge$ 6L).

Ditto, the use of terlipressin to treat HRS was previously supported by small, single-centre RCTs:

Sanyal et al. (2009): - terlipressin vs. placebo in type 1 HRS. Treatment of HRS was greater in terlipressin group.

A meta-analysis of these trials included just over 1000 patients:

Wang et al. (2018): - terlipressin vs. placebo or active control in HRS. Terlipressin increases renal recovery and survival (compared to placebo, octerotide or dopamine); terlipressin and noradrenaline conferred similar benefit.

4.2 Volume status in cirrhosis

Meticulous tracer studies in the 1960s showed that patients with cirrhosis have an expanded plasma volume (i.e. the commonly-encountered discription of these patients as having “interstital space overload but vascular volume depletion” is almost always a misconception):

Lieberman & Reynolds (1967): - plasma volume determined using ¹³¹I-albumin and ⁵¹Cr-RBCs in control patients and patients with cirrhosis. Plasma volume was expanded in patients with cirrhosis and correlated with portal venous pressure.