From the Guidelines
Terlipressin (1 mg/4–6 h intravenous bolus) in combination with albumin should be considered the first-line therapeutic agent for type 1 hepatorenal syndrome (HRS). The aim of therapy is to improve renal function sufficiently to decrease serum creatinine to less than 133 lmol/L (1.5 mg/dl) (complete response) 1. This approach is supported by the most recent and highest quality study, which emphasizes the importance of early recognition and prompt treatment of HRS to reduce mortality rates 1.
Key Considerations
- The dose of terlipressin should be increased in a stepwise manner up to a maximum of 2 mg/4 h if serum creatinine does not decrease at least 25% after 3 days 1.
- Treatment should be discontinued within 14 days if there is no response or only a partial response (serum creatinine does not decrease <133 lmol/L) 1.
- Patients on terlipressin need to be monitored for the development of ischemic complications such as arrhythmia, angina, and splanchnic and digital ischemia 1.
- Predictors of response to terlipressin include a baseline bilirubin of <10 mg/dL, a baseline serum creatinine of <5 mg/dL, and lower stage of acute-on-chronic liver failure 1.
Alternative Options
- If terlipressin is unavailable, norepinephrine (0.5-3 mg/hour) with albumin can be used as an alternative 1.
- Midodrine (7.5-12.5 mg orally three times daily) plus octreotide (100-200 mcg subcutaneously three times daily) with albumin is another alternative but less effective option 1.
Definitive Treatment
- Liver transplantation is the definitive treatment for eligible patients with HRS, as it addresses the underlying liver disease and can improve renal function 1.
From the Research
Definition and Pathophysiology of Hepatorenal Syndrome
- Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR 2.
- The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years 2.
Diagnosis of Hepatorenal Syndrome
- Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage 2.
- Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN 2.
- Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver-kidney transplantation 2.
Treatment of Hepatorenal Syndrome
- Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option 2.
- Terlipressin plus albumin is effective in the reversal of hepatorenal syndrome, and may improve short-term survival 2, 3.
- Midodrine and octreotide with albumin are used as an alternative treatment of hepatorenal syndrome where terlipressin is not available 3, 4.
- Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide 4.
- Liver transplantation is the only curative treatment of hepatorenal syndrome, and patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome 2, 5, 6.
Long-term Treatment and Outcomes
- Long-term terlipressin administration in selected patients with recurrent hepatorenal syndrome awaiting liver transplantation may represent an option to prevent irreversible renal failure and the need for dialysis until an organ becomes available 5.
- Patients who responded to treatment experienced improved transplant-free survival at 90 days 4.