From the Guidelines
Hepatorenal syndrome (HRS) should be treated with terlipressin (1–2 mg every 6 hours) plus albumin (20-40g/day) for up to 14 days, as this combination has been shown to improve renal function and reduce mortality rates, especially in patients with type 1 HRS 1.
Diagnosis and Treatment
Hepatorenal syndrome is a serious complication of advanced liver disease characterized by rapid kidney function deterioration without structural kidney damage. The diagnosis of HRS is based on major criteria, including advanced chronic or acute liver failure with portal hypertension, serum creatinine greater than 1.5 mg/dL or 24-hour creatinine clearance less than 40 mL per minute, and absence of shock, ongoing bacterial infection, or recent treatment with nephrotoxic drugs 1.
Treatment Options
The treatment of HRS focuses on improving circulatory function with vasoconstrictors combined with albumin. Terlipressin is the first-line therapy, and it is usually administered as intravenous bolus doses at 1–2 mg every 6 hours for up to 14 days 1. Albumin helps expand plasma volume and improve cardiac output. Patients should be monitored for fluid status, electrolytes, and kidney function. Diuretics should be discontinued, nephrotoxic medications avoided, and infections treated aggressively.
Alternative Therapies
In countries where terlipressin is unavailable, norepinephrine (0.5-3 mg/hour) with albumin or midodrine (7.5-12.5mg orally three times daily) plus octreotide (100-200mcg subcutaneously three times daily) with albumin are alternatives 1. However, the efficacy and safety of these alternative therapies are not as well established as terlipressin.
Definitive Treatment
The definitive treatment for HRS is liver transplantation, as reversing the underlying liver dysfunction addresses the root cause of the renal failure 1. Without treatment, HRS carries a poor prognosis with high mortality rates, especially for the more severe type 1 HRS.
Key Considerations
Patients on terlipressin need to be monitored for the development of ischemic complications such as arrhythmia, angina, and splanchnic and digital ischemia 1. Terlipressin should not be resumed in patients who experience cardiac or ischemic symptoms, even if the symptoms have subsided following discontinuation of treatment. 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.
From the FDA Drug Label
TERLIVAZ is a vasopressin receptor agonist indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.
The drug Terlipressin is indicated for the treatment of hepatorenal syndrome with rapid reduction in kidney function.
- The primary efficacy endpoint was the incidence of Verified HRS Reversal, defined as the percentage of patients with 2 consecutive SCr values of ≤1.5 mg/dL.
- A greater proportion of patients achieved Verified HRS Reversal in the TERLIVAZ arm compared to the placebo arm 2.
- Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit from the treatment 2.
From the Research
Definition and Characteristics of Hepatorenal Syndrome
- Hepatorenal syndrome (HRS) 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 3.
- HRS is associated with high mortality without treatment, and liver transplantation is the only curative treatment 4, 3, 5, 6.
Treatment Options for Hepatorenal Syndrome
- Terlipressin plus albumin is effective in the reversal of HRS, and terlipressin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS 4.
- Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option for HRS 3.
- The combination of octreotide, midodrine, and albumin has shown possible benefit in improving renal function and short-term survival in patients with HRS type 1 and type 2 7.
- Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant 5.
Predictors of Response to Treatment and Outcomes
- Improvement in renal function and lower baseline Model for End-Stage Liver Disease score are associated with better survival 4.
- Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin 6.
- Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival and higher transplant-free survival at Day 90 6.
- Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes 6.
Differentiation from Acute Tubular Necrosis
- Differentiating HRS from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN 3.
- HRS and ATN may be considered as a continuum rather than distinct entities, and emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation 3.