pros and cons of tips for refractory ascites
TRANSCRIPT
Editorial
Pros and cons of TIPS for refractory ascites
A.J. Sanyal*
Department of Internal Medicine, Division of Gastroenterology, P.O. Box 980341, Richmond, VA 23298-0711, USA
0168-8278/$30.00 q 2005 Published by Elsevier B.V. o
doi:10.1016/j.jhep.2005.09.006
* Corresponding author. Tel.: C1 804 828 6314; fax: C
E-mail address: [email protected] (A.J. Sanyal).
See Article, pages 990–996
The onset of refractory ascites heralds the onset of
marked deterioration in a given patients condition and is
often the harbinger of death. The optimal treatment of
refractory ascites should ideally be universally effective in
controlling ascites, improve renal function, have no side
effects, be widely available, easy to use and affordable. Such
a treatment remains elusive and the management of cirrhotic
subjects with refractory ascites remains a complex
challenge for the practicing hepatologist.
The use of repeated large volume paracenteses has been
the mainstay for the management of refractory ascites for the
last two decades. Unfortunately, ascites recurs in the majority
of subjects and the treatment has no impact on survival [1,2].
Ascites is also associated with decreased caloric intake and a
tilt in metabolism towards catabolism. Also, the need for
repeated paracenteses is associated with protein losses. All of
these combine to worsen the nutritional status and quality of
life. Progressive ascites is often further complicated by the
development of spontaneous bacterial peritonitis and
hepatorenal syndrome. There is therefore clearly a need for
better treatment of ascites.
The development of ascites is critically linked to the
presence of underlying sinusoidal portal hypertension and
decreased effective circulating volume which triggers the
activation of Na retentive mechanisms in the kidney.
Transjugular intrahepatic portasystemic shunts (TIPS)
function as a side-to-side portacaval anastamosis which can
be created without the need for major surgery. The ability to
decompress the hypertensive portal vein, the root cause of
ascites, without general anesthesia or surgery by TIPS led to a
surge of studies in the nineties to evaluate the efficacy and
safety of TIPS for refractory ascites. Of these, five
randomized controlled trials have been reported and the
n behalf of the European
1 804828 2992.
results are summarized in the meta-analysis performed by Dr
Albillos and his colleagues in this issue of the Journal [3].
The most striking finding of analysis is that TIPS is
substantially superior to LVP for the long-term control of
ascites. While there were differences across the study
groups in terms of the amount of ascites at baseline, the use
of paracentesis prior to randomization, the criteria for
paracentesis and the use of albumin after LVP, all of the
studies reported a better control of ascites with TIPS. It has
been shown that TIPS is associated with increased venous
return to the heart, increased central volumes, left
ventricular end-diastolic pressures and cardiac output [4].
This is associated with a decrease in proximal tubular Na
reabsorption, as measured by lithium clearance, and a
natruresis which increases over a period of several weeks
after TIPS placement [5].
In contrast, the data related to mortality are somewhat
discrepant across the individual studies. The first study was
associated with a very high mortality in subjects undergoing
TIPS. This study demonstrated that subjects with advanced
liver failure do not do well with a TIPS. Subsequently, the
publication of the model for end stage liver disease
conclusively demonstrated that subjects with advanced
liver failure are not benefitted by a TIPS [6]. In two
rigorously performed large multicenter trials, the survival
outcomes of the two arms were virtually identical whereas
TIPS was somewhat better in two other studies. The latter
studies contained a substantial percent of subjects with
recidivant ascites which is associated with a better mortality
than with refractory ascites. This may explain the lower
mortality after TIPS in these studies.
As expected, TIPS increases encephalopathy. The risk of
encephalopathy is a function of the shunt fraction which
depends on the diameter of the shunt. It is also increased in
those with increasing age, prior history of encephalopathy,
azotemia and severe liver failure [7]. These findings then
Journal of Hepatology 43 (2005) 924–925
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Association for the Study of the Liver.
A.J. Sanyal / Journal of Hepatology 43 (2005) 924–925 925
begs the question: if, when and how to use a TIPS for
refractory ascites?
The ideal candidate for a TIPS is one with refractory
ascites and relatively preserved hepatic and renal function.
Unfortunately, the majority of subjects with refractory
ascites in this authors practice already have advanced liver
failure. Also, in some cases a low albumin reflects
malnutrition whereas in others it reflects severe liver failure.
There is however no controversy that an INR O2 and a
bilirubin O3 mg/dl in subjects with cirrhosis due to a non-
cholestatic liver disease indicates severe liver failure. A
high baseline bilirubin is also a risk factor for progressive
liver failure culminating in multi-organ dysfunction after
TIPS. TIPS should, therefore, not be performed in those
with severe liver failure.
The presence of a serum creatinine O2 mg/dl often
denotes the presence of type II hepatorenal syndrome in
subjects with refractory ascites. It has been reported that
TIPS can improve type II hepatorenal syndrome [8].
However, these data are contrary to other studies which
demonstrate that a high serum creatinine is a powerful
predictor of a poor outcome after TIPS [9]. It is therefore
prudent at this time to reserve TIPS for those with refractory
ascites and a serum creatinine !2 mg/dl.
The potential benefits of improved ascites control with
TIPS must be weighed against the risks of worsening
encephalopathy in each patient individually. Worsening
encephalopathy can usually be managed by lactulose or one
of several alternate strategies including the use of
metronidazole, rifaximin or neomycin. In this authors
experience, intractable encephalopathy requiring reduction
of the shunt is a rare event and in most cases the presence of
medically manageable encephalopathy is not a contra-
indication for TIPS per se.
It is worth noting that while some patients have a
remarkable improvement in nutritional status after TIPS,
others do not. As a group, there are no dramatic long-term
improvements in nutritional status after TIPS especially
when compared to long-term survivors treated with LVP.
Similarly, although the quality of life improves after TIPS,
this is not substantially better than those who survive long-
term with LVP.
It is unclear whether there is an optimal level of portal
decompression where ascites is resolved while minimizing
the risk of encephalopathy. The degree of portal
decompression or the precise hepatic venous pressure
gradient do not correlate with improvement in ascites
[10]. Also, the potential impact of underlying subclinical
cardiomyopathy on the hemodynamic response to TIPS is
not well defined. It has been suggested that such
myocardial dysfunction improves after a TIPS in subjects
with hepatorenal syndrome [11]. The occasional develop-
ment of pulmonary edema after TIPS suggests that this
may not always be so [12]. There is also some
controversy about the need for continued Na restriction
after TIPS. While the development of shunt stenosis due
to pseudointimal hyperplasia used to be a major problem
after TIPS, the use of covered stents have markedly
ameliorated this problem.
In summary, the indications for TIPS for refractory
ascites have tightened considerably. The analysis by
Albillos et al. provide evidence that although TIPS
improves ascites, it does not improve survival and is
associated with significant morbidity. In the future, the
utility of TIPS will need to be compared to newer, more
potent diuretics and aquaretics that are currently in
development. Until then, TIPS is best used as a bridge to
transplant specifically in those with relatively preserved
liver function and absence of renal failure.
References
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