pros and cons of tips for refractory ascites

2
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 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 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 www.elsevier.com/locate/jhep 0168-8278/$30.00 q 2005 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. doi:10.1016/j.jhep.2005.09.006 * Corresponding author. Tel.: C1 804 828 6314; fax: C1 804828 2992. E-mail address: [email protected] (A.J. Sanyal).

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Page 1: Pros and cons of TIPS for refractory ascites

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

www.elsevier.com/locate/jhep

Association for the Study of the Liver.

Page 2: Pros and cons of TIPS for refractory ascites

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

[1] Gines P, Arroyo V, Vargas V, Planas R, Casafont F, Panes J, et al.

Paracentesis with intravenous infusion of albumin as compared with

peritoneovenous shunting in cirrhosis with refractory ascites. N Engl

J Med 1991;325:829–835.

[2] Gines P, Tito L, Arroyo V, Planas R, Panes J, Viver J, et al.

Randomized comparative study of therapeutic paracentesis with and

without intravenous albumin in cirrhosis. Gastroenterology 1988;94:

1493–1502.

[3] Albillos A, Banares R, Gonzalez M, Catalina M-V, Molinero L-M. A

meta-analysis of transjugular intrahepatic portosystemic shunt versus

paracentesis for refractory ascites. J Hepatol 2005;43:990–996.

[4] Lotterer E, Wengert A, Fleig WE. Transjugular intrahepatic

portosystemic shunt: short-term and long-term effects on hepatic

and systemic hemodynamics in patients with cirrhosis. Hepatology

1999;29:632–639.

[5] Wong F, Sniderman K, Liu P, Allidina Y, Sherman M, Blendis L.

Transjugular intrahepatic portosystemic stent shunt: effects on

hemodynamics and sodium homeostasis in cirrhosis and refractory

ascites. Ann Intern Med 1995;122:816–822.

[6] Montgomery A, Ferral H, Vasan R, Postoak DW. MELD score as a

predictor of early death in patients undergoing elective transjugular

intrahepatic portosystemic shunt (TIPS) procedures. Cardiovasc

Intervent Radiol 2005;28:307–312.

[7] Sanyal AJ, Freedman AM, Shiffman ML, Purdum III PP, Luketic VA,

Cheatham AK. Portosystemic encephalopathy after transjugular

intrahepatic portosystemic shunt: results of a prospective controlled

study. Hepatology 1994;20:46–55.

[8] Spahr L, Fenyves D, N’Guyen VV, Roy L, Legault L, Dufresne MP, et al.

Improvement of hepatorenal syndrome by transjugular intrahepatic

portosystemic shunt. Am J Gastroenterol 1995;90:1169–1171.

[9] Schepke M, Roth F, Koch L, Heller J, Rabe C, Brensing KA, et al.

Prognostic impact of renal impairment and sodium imbalance in

patients undergoing transjugular intrahepatic portosystemic shunting

for the prevention of variceal rebleeding. Digestion 2003;67:146–153.

[10] Ochs A, Rossle M, Haag K, Hauenstein KH, Deibert P,

Siegerstetter V, et al. The transjugular intrahepatic portosystemic

stent-shunt procedure for refractory ascites. N Engl J Med 1995;332:

1192–1197.

[11] Brensing KA, Textor J, Perz J, Schiedermaier P, Raab P, Strunk H,

et al. Long term outcome after transjugular intrahepatic portosystemic

stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a

phase II study. Gut 2000;47:288–295.

[12] Schwartz JM, Beymer C, Althaus SJ, Larson AM, Zaman A,

Glickerman DJ, et al. Cardiopulmonary consequences of transjugular

intrahepatic portosystemic shunts: role of increased pulmonary artery

pressure. J Clin Gastroenterol 2004;38:590–594.