Small for size syndrome (s)

Small for size (SFS) syndrome is a condition which causes considerable confusion partly because the term has been extended beyond its original meaning. It was initially used to describe the situation in liver transplantation where a patient develops liver dysfunction and ascites because the donated organ is too small for the recipient. It is now used variably to describe any circumstance where there is post operative liver failure or dysfunction in a patient who has had liver resection or partial or small graft liver transplantation.

I think the key to simplifying SFS syndrome is to think of the cause of the liver dysfunction and the circulation of the patient.

High flow small volume SFS syndrome. 

This is the archetypal small for size syndrome. This occurs in the setting of liver transplantation with partial liver transplants or small grafts transplanted into a recipient. The key contributing factors are that the recipient has a high portal vein blood flow commensurate with cirrhosis and a hyperdynamic visceral circulation and the graft recipient weight ratio is small. It is thought that small for size syndrome in this context is driven by endothelial activation and shear stress causing release of RAGE and other molecules.  SFS in this setting does not present immediately but may take several days to develop.

Clinical symptoms include the development of large volume ascites and deterioration in liver function tests with or without encephalopathy. Treatment focuses on attempts to reduce portal vein flow. Medical management with terlipressin, beta blockers or somatostatin analogues has been attempted (these drugs are used to reduce portal hypertension). Splenic artery embolization has also been used and can produce a rapid resolution in SFS syndrome. Surgical modification of portal inflow has also been used either by splenic artery ligation or portocaval venous diversion to reduce liver inflow. The latter procedure is easier to draw than to do!

Reduction of portal flow can reverse SFS but in resistant cases liver failure may ensue requiring urgent retransplantation.

(Hepatic vein outflow can also produce high volume ascites and deterioration of liver function and although this usually presents later it is an important differential diagnosis to exclude).

Poor function small volume small for size syndrome

When a patient is left with a small functional liver volume after resection they may also develop liver dysfunction or failure. This too has been termed small for size syndrome although it used to be termed simple post operative liver failure. The important difference here is that portal hypertension is not an issue and the patient does not have a hyperdynamic cirulation. The problem is that the residual functional liver volume is too small for the patient in terms of its metabolic and detoxifying functions.

Factors predisposing to this kind of liver dysfunction include, preoperative chemotherapy associated changes such as sinusoidal obstruction syndrome, steatosis or steatohepatitis. Previous studies including our own have shown that in healthy liver a cut off future  liver remnant  volume of approximately 25% is necessary to avoid the risks of postoperative liver failure and infection. This minimum volume may need to be increased where there is underlying liver disease secondary to chemotherapy, obesity or chronic inflammation.

livervolume copy

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2 Responses to Small for size syndrome (s)

  1. Nicola Cinardi MD says:

    Dear Prof Wigmore,
    I would like to ask you a comment and thought on a “new” model of SFS syndrome: the high portal vein blood flow with enough FLR SFS syndrome in the setting of the ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) procedure. There are some unpublished experiences, and maybe underreported from the strong proponents of this challenging but rescue procedure, based on the observation that in the setting of a sufficient FLR achieved after 6 – 12 days of an ALPPS procedure and completion hepatectomy a not yet well-defined amount of patients will experience the stigmata of hepatic failure, that said SFS syndrome, for a certain amount of time. In some instances, this “new” model of SFS syndrome will conduct the patients to death. The exact pathophysiology of this entity is to be still clarified but one of the driving mechanism could be an high portal vein flow in the liver that is to be left in situ, without a corresponding outflow from hepatic veins that are somewhat flattened from the sorrounding swelled hepatocytes. The latter might be just swelled hepatocytes and just few new ones are responsible for the tremendous increase in size of the liver with the ALPPS procedure. The cytokinic milieu of the cut liver is still to be fully discovered but an huge amount of growth factots are certainly released, as you pointed out in the setting of high PV blood flow SFS syndrome. It seems easy to think that the Future Liver Volume does not necessarily means a Functional Liver Volume.

    Sent from my Iphone, pardon for my english and the typo.

    Nicola Cinardi MD, nicocinardi@hotmail.com

    • Thanks Nicola, a very good question. The situation where ALPSS is used often follows chemotherapy and I think that, although a proportion of these patients who go on to develop liver dysfunction/failure appear to have a sufficient liver volume the functional quality of the liver is actually impaired and so they fall into the “insufficient function small volume” group. The other complicating factor in ALPSS is that many patients get into trouble because in addition to a second hit surgical procedure and major liver resection they are also exposed to sepsis because the high rate of biliary leak and collections associated with this procedure. I personally think that ALPSS is often either unnecessary because proper planning and volume enhancement has not been done or is difficult to justify in an era where chemotherapy, biologics and SIRT offer so much with a much higher margin of safety. The average mortality of ALPSS studies presented at the E-A HPBA in Belgrade earlier this year was 20%!!

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