The Model for End-Stage Liver Disease Score in Acute Heart Failure: Hepatorenal Dysfunction Hides Behind

This article refers to ‘Impaired hepato-renal function defined by the MELD XI score as prognosticator in acute heart failure’ by J. Biegus et al., published in this issue on pages 1518–1521. Heart failure (HF) is a complex syndrome with a huge impact on public health. In the developed world, it affects about one out of 10 persons over 65 years old, while it represents the leading cause of hospitalization in this age group.1 Each HF hospitalization highlights an increased risk of subsequent death, as it is associated with a 10% short-term (30-day) and 50% long-term (5-year) mortality. Strategies to reduce HF morbidity and mortality include a better understanding of the pathophysiology of this complex syndrome and an accurate risk stratification in order to determine the high risk group, appropriate for a more advanced and sophisticated approach. Since hospitalized patients reveal a multifaceted morbidity profile, resulting not solely from pump failure, but also from maladaptive cross-talk between the heart and peripheral organs leading to multiorgan dysfunction, multimarker scoring systems have already emerged. In this issue of the journal, Biegus et al.2 showed for the first time that a score including simple biomarkers of daily practice reflecting peripheral organ injury may determine prognosis in the acute HF setting. Although the authors investigated the prognostic value of this score in 203 acute heart failure (AHF) patients providing useful information for clinicians, larger scale registries and/or subanalyses of randomized clinical trials should evaluate its role as prognosticator in more representative (multicentre and multiregional) patient populations with AHF. The Model for End-stage Liver Disease (MELD) is a prospectively developed and validated chronic liver disease severity scoring system that was initially developed to predict mortality within 3 months of surgery in patients who had undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure.3 Subsequently, it was used to prioritize candidates for liver transplantation.4 In addition to its established role in determining the urgency for liver transplantation, the MELD scoring system has been used for outcome prediction in cirrhotic patients undergoing cardiac surgery,5 patients with advanced HF undergoing left ventricular assist device implantation,6 and patients undergoing heart transplantation.7 The MELD score includes three non-cardiac biomarkers that reflect hepatic synthetic activity [international normalized ratio (INR)], metabolism (bilirubin), and renal function (creatinine), while modified MELD scores are also available: the MELD-XI score excludes INR and can be used in patients receiving anticoagulation, and MELD-Na may also reflect volume status.8 Liver involvement in AHF has recently been recognized, and reflects the systemic haemodynamic changes that occur during an acute episode. Contrary to what was previously believed, the role of hypotension as the main cause of hypoxic hepatitis has been questioned, as hypotensive trauma patients rarely demonstrate an ischaemic liver, probably because of the dual hepatic supply (hepatic artery–portal vein). The combination of an abrupt output decrease along with high systemic venous pressures may better explain acute liver injury in decompensated HF patients. In a subanalysis of the SURVIVE trial, where acute decompensated HF (ADHF) patients were randomized to dobutamine or levosimendan, abnormal liver function tests were observed in 46% of ADHF patients, and this increase was clearly associated with a two-fold increase in short- (31 days) term mortality and a 1.5-fold increase in long- (180 days) term mortality.9 Data from the PROTECT trial and ASCEND-HF trial also verified the major role of liver injury in the prognosis of AHF patients.10, 11 The link between liver function and creatinine levels has been described as hepatorenal syndrome. A number of vasoactive substances that affect both systemic and renal circulation, such as nitric oxide, tumour necrosis factor, endothelin, endotoxin, glucagon, and intrarenal vasodilating prostaglandins,12 are involved. More recently, data from animal studies have shown that decreased intrahepatic blood flow, as caused by alpha-adrenergic-mediated portal vasoconstriction, leads to accumulation of intrahepatic adenosine, which is produced by the metabolism of hepatocytes and leaves the liver through the lymphatic and venous systems. As a result, hepatic afferent nerves stimulate renal efferent nerves and renal vasoconstriction, and water retention is promoted.13 This is called the hepatorenal reflex (Figure 1). In conclusion, the MELD score is a useful and easy to administer score in AHF patients. In patients receiving anticoagulants, MELD-XI (omitting INR) can be used instead. Bilirubin and creatinine are two biomarkers that reflect the status of the liver and kidney, but most importantly the interaction of the two. Conflict of interest: J.P. has received horonaria for lectures and advisory meetings from Novartis, Servier, Orion Pharma, and Roche Diagnostics. A.M. reports personal fees from Novartis, Orion, Roche, Servier, Cardiorentis, and Zs Pharma, grants and personal fees from Adrenomed, and grants from MyCartis and Critical diagnostics, outside the submitted work. M.N. declares no conflict of interest.