Contents
Introduction
Hepatorenal syndrome is renal failure secondary to liver disease. It is a life-threatening acute complication of liver failure. It is most commonly seen in alcoholic hepatitis, although can occur in liver failure of any cause. It has a very high mortality of >50%. Long-term management involves liver transplantation.
Epidemiology
- Seen in approximately 40% of cases of liver failure
- Seen in 20% of cases of liver failure within 1 year of diagnosis
- Most commonly presents after an episode of acute illness or acutely worsening liver failure (e.g. often seen after Spontaneous Bacterial Peritonitis (SBP) in patients with ascites)
- Often, even when the acute episode has been treated (e.g. antibiotics for SBP) the renal failure does not resolve
- Usually seen in alcoholic hepatitis, but can be seen in any cause of liver disease, including portal vein hypeterension, or liver metastases
- High mortality: >50%
Pathology
- Not entirely known
- Thought that fulminant liver failure causing portal vein vasodilation results in the release of vasodialting agents, or has a vasodilating effect on the renal arteries, reducing blood supply to the kidneys.
- These vasodilating agents are thought to be released into the splanchnic circulation, hence their local (abdominal cavity) effects
- The main agent involved thought to be nitric oxide
- The renal failure is a result of reduced blood supply, and not as a result of some direct insult to the kidney
- The reduced blood supply reduces GFR, and also subsequently sodium excretion
Type 1 HRS
- More severe
- Rapid decline in renal function
- Often associated with other systemic signs including hypotension
- Mortality >50% within 1 month of onset
Type 2 HRS
- More insidious type onset
- Median survival 6 months without liver transplantation
- Often associated with ascites, which is resistant to diuretics. Because the ability of the kidneys to excrete sodium is so poor, diuretic therapy becomes ineffective
- Patients who develop type 2 HRS often have diuretic resistance ascites beforehand
Diagnosis
- There are many causes of renal failure in liver failure patients. HRS should be a diagnosis of exclusion, once other causes have been ruled out.
- Urine microscopy, cultures and sensitives (MC+S) should be performed, and other causes of AKI actively looked for before HRS is diagnosed. In particular, Acute Tubular Necrosis (ATN) is common in liver failure patients.
- HRS diagnosis is clinical, based on blood tests (urea and electrolytes) showing an increased serum creatinine
- Oliguria is often a feature, but may not be present initially
- Depends on the type of HRS being diagnosed
Type I
- Rise of creatinine to >220 μmol/L in less than two weeks (as long as creatinine level has doubled from baseline)
Type 2
- Serum creatinine rise to > 133 μmol/L
- Urinary sodium often low (less than 100 mmol/L)
Also be aware that urea and creatinine are often abnormally low in liver disease patients, and so when they are raised, they may appear to be within the ‘normal’ range. This can also make eGFR values appear more normal than they really are.
Treatment
- Definitive treatment involves treatment of the underlying liver disease. This is often liver transplantation.
- Terlipressin (1mg IV QDS) with albumin (usually 20% albumin continually infused at 25mls/hr) is widely used. Evidence suggests it reduces the degree of renal failure and improves outcomes, particualrly in patients with type 1 HRS. However, although trials are promising, they are not of high enough quality, or large enough sampe sizes to be sure that it is actually effective, as outlined in this cochrane review from 20091, and subsequent review articles2
- This treatment can be administered on the ward (usually specialist gastroenterology ward) or in HDU / ICU setting
- Treatment is typically given for 2 weeks
- It helps to improve blood flow to the kidneys, increase GFR and increase sodium excretion
- Noradrenlaine with albumin is also used in an intensive care setting
- Midodrine, plus octreotide and albumin are recommended if terlipressin is not available
- Portasystemic shunting (the most common type of which is Transjugular intrahepatic portosystemic shunt (TIPS)) involves shunting blood around the portal system via a stent from the portal vein to the inferior vena cava. It is not widely used, but some trials suggest it is an effective long term treatment for both portal hypertension and HRS. Complications are frequent, and often HRS patients aren’t well enough to undergo the procedure, or risk high mortality. The need to use contrast during the procedure can also worsen renal failure. Dialysis is sometimes used beforehand to minimise this risk.
References
- Terlipressin for hepatorenal syndrome. Gluud LL1, Christensen K, Christensen E, Krag A.
- Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
- Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
- Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy
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