Successful transjugular intrahepatic portal-systemic shunt in an ineligible liver transplant patient with primary biliary cirrhosis with refractory ascites and aplastic anemia

doi:10.4236/ojgas.2013.31001

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Open Journal of Gastroenterology, 2013, 3, 1-4 OJGas

http://dx.doi.org/10.4236/ojgas.2013.31001 Published Online February 2013 (http://www.scirp.org/journal/ojgas/)

Successful transjugular intrahepatic portal-systemic shunt

in an ineligible liver transplant patient with primary

biliary cirrhosis with refractory ascites and aplastic anemia

Christopher M. Moore1, George Behrens2, Hector Ferral2, David H. Van Thiel1

1Section of Hepatology, Department of Medicine, Rush University Medical Center, Chicago, USA

2Section of Interventional Radiology, Department of Radiology, Rush University Medical Center, Chicago, USA

Email: [email protected]

Received 24 October 2012; revised 24 November 2012; accepted 1 December 2012

ABSTRACT

A transjugular intrahepatic portal-systemic shunt

(TIPS) is a standard way to decompress the portal

system in cirrhotic patients as a bridge to orthotopic

liver transplantation (OLT). Traditionally, TIPS has

been indicated for certain portal hypertensive seque-

lae such as refractory ascites, varices treatment and

even hepato-hydrothorax. Herein is a case report on

the efficacy of TIPS in an OLT ineligible patient with

primary biliary cirrhosis and aplastic anemia who

had developed refractive ascites requiring serial

paracentesis and esophageal varices. He survived 2.5

years post-TIPS placement and died from complica-

tions related to severe leucopenia and the develop-

ment of sepsis.

Keywords: Aplastic Anemia; Ascites; Liver

Transplantation; Paracentesis; TIPS

1. INTRODUCTION

The Transjugular intrahepatic portal-systemic shunt ( TIP S)

is a standard interventional radiological technique that is

utilized in cirrhotic patients to treat major complications

of portal hypertension such as refractory ascites and

hepato-hydrothorax, secondary prevention of esophageal

varices, and primary prevention of gastric varices [1-4].

TIPS is not a cure for decompensated liver disease, but

rather conceived of as a bridge to orthotopic liver trans-

plantation (OLT) [3-5].

OLT is a complex stand ard-of-care surgery for eligible

chronic decompensated liver disease and fulminant liver

failure patients [4]. The success of this technology has

rested upon improvements in immunosuppressive thera-

pies, surgical technique and appropriate patient selection.

The MELD score [1-3], albeit imperfect, has been in-

strumental in risk stratifying patients by overall 90 day

mortality. The score is the product of a mathematical

equation comprising serum bilirubin, creatinine and INR

that is updated periodically on transplant eligible pa-

tients.

In brief, the TIPS procedure bypasses the hepatic pa-

renchyma by means of a metallic stent directly linking a

branch of the portal vein to a hepatic vein with resultant

decompres sion of the portal system and high blood flow

into the cardiopulmonary system [3,4]. Given the tech-

nical challenges of TIPS, and the expected physiologic

changes induced, eligible patients must fulfill a number

of criteria including absence of sepsis, absence of severe

cardiopulmonary disease, and few prior episodes of he-

patic encephalopathy (HE). More comprehensively, it

has been determined that the best candidates for TIPS are

usually those patients with a Ch ilds-Turcotte-Pugh (CTP)

class of A, or a model for end-stage liver disease (MELD)

score of <14 [1-3]. TIPS has known side-effects includ-

ing bleeding, infection, stent malposition/thrombosis, HE,

abdominal pain and hepatic injury/necrosis.

Herein is a report of a case for the successful utiliza-

tion of a TIPS procedure in a patient with decompensated

primary biliary cirrhosis (PBC), deemed ineligible for

OLT given the high morbidity and mortality of his aplas-

tic anemia.

2. CASE REPORT

A 62-year-old white ma le with underlyin g aplastic ane mia

and PBC developed portal hypertensive sequelae includ-

ing diuretic-resistant refractory ascites and esophageal

varices. His diagnosis of aplastic anemia was made in

2007. He had been treated previously for the aplastic

anemia with sequential therapies consisting of steroids,

rituximab, and cyclosporine. He was receiving intrave-

nous immunoglobulin therapy at the time of his referral.

His diagnosis of PBC was based upon a combination of

data, including: an elevated serum alkaline phosphatase,

anti-mitochondrial antibody positivity, increased total

serum cholesterol and IgM levels, and a computed to-

OPEN ACCESS

C. M. Moore et al. / Open Journal of Gastroenterology 3 (2013) 1-4

mography (CT) scan documented hepatosplenomegaly

with increased hepatic heterogenicity.

Approximately 1 year prior to our initial evaluation, he

developed portal hypertensive ascites which was initially

responsive to sodium diet restriction and diuretic therapy,

consisting of a combination of furosemide and spiro-

nolactone at 120 mg and 300 mg per day, respectively.

However, his blood urea nitrogen (BUN) and serum

creatinine levels increased over time, reflecting worsen-

ing kidney injury, such that he became diuretic-resistant.

He consequently required serial large-volume paracente-

sis (LVP) every two weeks for a three-month duration in

order to manage the rapidly re-accumulating ascitic fluid

in the setting of inadequate diuresis. Additionally, he

underwent standard esophagogastric-duodenoscopy (EGD )

for varices surveillance, and was found to have large

esophageal varices which were band ligated. Subsequent ly,

he was maintained on beta-blocker therapy for variceal

prophylaxis. He has never had a variceal bleeding epi-

sode. He has never had an episode of HE. Given his

known diagnosis of aplastic anemia, the referring heap-

tologists were concerned about the risks of future eso-

phageal variceal bleeding and consequence of continued

LVP upon his physiologic reserve capacity and state of

nutrition. Thus, he was referred for more definitive

treatment in the form of OLT. Additionally, it was noted

that he was quite malnourished with severe generalized

muscle wasting and a markedly protuberant abdomen

with large-volume ascites. His overall medical history

was reviewed thoroughly by the multi-disciplinary liver

transplant team, which declined him for OLT because of

his aplastic anemia and a related life expectancy of less

than 5 years even with an OLT.

Following this decision, he was evaluated for a TIPS

procedure recognizing that it would not be as a bridge

therapy to OLT, but rather, that it would simplify his

continued medical management and reduce the catabolic

state in the setting of portal hypertension and aplastic

anemia. He underwent a diagnostic and therapeutic LVP,

with removal of 2.1 L of culture negative ascitic fluid,

containing 10 white blood cells (WBC) per mm3, and an

ascitic albumin level of 2.0 g/d, which when subtracted

from his serum albumin level yielded a serum ascites-

albumin gradient (SAAG) of 1.2, consistent with his di-

agnosis of portal hypertension. A triple-phase CT scan

re-demonstrated findings consistent with advanced cir-

rhosis with arterial-venous shunts, a few hepatic cysts,

no focal lesions, and patent hepatic, portal and splenic

veins, as well as large esophageal varices.

Based upon these findings and further evaluation yi eld-

ing no significant cardiopulmonary disease, a TIPS pro-

cedure was offered to the patient, who at the time had the

following laboratory values, listed in Ta bl e 1 . The TIPS

procedure was performed in standard fashion with the

implementation of 28 cm × 10 mm Viatorr© polytetra-

fluoroethylene (PTFE)-covered stent without any com-

plications. Pre- and post-TIPS hepatic pressures as well

as the hepatic wedge pressure gradient are documented

in Table 2 and demonstrate adequate portal venous de-

compression. The patient did well post-TIPS procedure

and was discharged home the following day.

Table 1. Clinical laboratory findings in the patient†.

Pre-TIPS Day of TIPS Day after TIPS Normal value

WBC count 0.81 1.27 1.45

4 - 10 × 103/µl

Hemoglobin 7.6 9.7 10.7

13.5 - 17.5 g/dl

MCV 94.3 90.8 90.1 82 - 103 fl

Platelet count 42 35 26

150 - 399 × 103/µl

BUN 34 30 29

8 - 21 mg/dl

Creatinine 1.1 1.1 1.1 0.6 - 1.3 mg/dl

Blood glucose 94 135 93 60 - 109 mg/dl

Total protein 7.8 5.6 5.5

6.0 - 8.2 g/dl

Albumin 3.4 2.5 2.5

3.5 - 5.0 g/dl

Total bilirubin 1.3 1.3 1.4 0.2 - 1.3 mg/d

AST 20 35 36 3 - 44 U/l

ALT 13 20 24 0 - 40 U/l

Prothrombin time 13.7 X 15.7 9.5 - 14.0 s

INR 1.17 X

1.39 0.83 - 1.23 (no unit)

aPTT 34 X X 23 - 33 s

†WBC = white b l o od cells; MC V = mean corpuscular volume; BUN = blood urea nitrogen; AST = aspar t ate aminotransferase; ALT = alanine ami-

notransferase; INR= i n t ernational normalized r atio; aPTT = activated partial thromboplastin time; X = not available. Abnormal data in bold font.

C. M. Moore et al. / Open Journal of Gastroenterology 3 (2013) 1-4 3

Table 2. Calculated portal vein pressures (mmHg).

Pre-TIPS Post-TIPS Normal value

Hepatic vein 19 20 <5

Wedged portal vein 32 27 5 - 10

Gradient 13 7 0 - 5

At a follow-up outpatient visit two weeks later, an ab-

dominal ultrasound (US) with a complete duplex Dop-

pler study was performed and documented peak systolic

velocities at the portal vein end of the TIPS, mid TIPS,

and hepatic vein end of the TIPS of 57, 163 and 119

cm/sec with no high velocity jets, respectively. In the

following weeks, the patient’s ascites resolved, and his

diuretic requirements were reduced to 20 mg furosemide

and 50 mg spironolactone per day in the setting of stable

kidney disease and an adequate diuresis. In the post-TIPS

state, he no longer required paracentesis, his esophageal

varices were decompressed, his nutritional state and

overall clinical appearance improved. Most importantly,

he did not develop any complications of his TIPS proce-

dure and survived an additional 2.5 years at which time

he died as a result of severe leucopenic sepsis.

3. DISCUSSION

Cirrhosis is manifested by an extensive fibronodular re-

placement of the liver parenchyma with resultant portal

hypertension and progressive synthetic dysfunction [4].

The development of portal hypertension leads to a num-

ber of complications including HE, ascites and variceal

bleeding, which are each associated with an increased

morbidity and mortality rate [2-5]. Ascites is treated with

a combination of dietary sodium restriction and diuretics,

primarily consisting of furosemide and spironolactone. In

approximately 10% of ascites patients, a diagnosis of

refractory ascites develops wherein they no longer re-

spond to or cannot tolerate these diuretic therapies. In

such cases, LVP is instituted, and while efficacious, is

associated with complications consisting of peritoneal

bleeding, infection, and increased catabolic rate. Fur-

thermore, there are ongoing concerns of long-term cost

and quality-of-life issues [2,3,6].

It is within this setting that the theory and implementa-

tion of TIPS arose. TIPS provides a non-surgical method

of delivering blood from the portal to hepatic venous

system through the utilization of a transhepatic bypass

stent [3]. It is generally accepted that a TIPS procedure is

utilized best in patients having been classified as CTP

class A patient or with a MELD score < 14 who is await-

ing OLT, and who has experienced a number of portal

hypertensive complications consisting of refractory as-

cites or variceal bleeding. Other indications for a TIPS

include the development of a hepato-hydrothorax, al-

though experience with this problem is less-well docu-

mented [3-5]. Furthermore, given the expected physiol-

ogic effect of TIPS a number of contra-indications to its

implementation have been identified such as congestive

heart failure and severe pulmonary hypertension. While

TIPS has been successful in ameliorating the complica-

tions of portal hypertension, its long-term effectiveness,

effect on quality-of-life, and health-care cost have also

been matters of debate when compared to serial LVP [2,3,

6]. In part, some of these issues revolv e around the stud-

ies of uncovered TIPS stent compared to LVP, whereas in

the current period covered TIPS stents, which are less

likely to become occluded, are the standard-of-care [7].

In this case report, the patient had several common

portal hypertensive sequelae of his PBC, including eso-

phageal varices and refractory ascites. Furthermore, the

ascites required serial LVP, which despite being a fairly

common procedure, is nevertheless associated with com-

plications and costs that are substantial over time. Worse

still is the patient’s underlying aplastic anemia, a d isease

process itself manifested by pancytopenia including

symptomatic anemia, hemorrhage, and a risk of infection.

In addition, there is also an increased risk for the devel-

opment of hematologic cancer [8]. It was this underlying

disease process and its associated morbidity and mortal-

ity that both excluded the patient from OLT considera-

tion and made continued LVP a prohibitive option given

the well-recognized probability of complications over

time.

Given these facts, the present case report is interesting

for several reasons. Firstly, it is as best as we can deter-

mine the only case in which a TIPS procedure has been

performed in a cirrhotic individual with underlying apla s-

tic anemia. Importantly, the TIPS procedure was suc-

cessful in reducing his ascites and the need for repetitive

LVP as well as decompressing his esophageal varices.

Importantly, no complications were experienced in the

procedure or experienced in his post-procedural follow-

up. Moreover, he was able to reduce his diuretic re-

quirements and reduce his catabolic state. The benefits to

his esophageal varices were important, as any future

bleeding episodes would be complicated not only by his

baseline anemia and thrombocytopenia, but also in the

difficulty of finding an appropriate blood match given

the number of anti-platelet antibodies he had developed

over the preceding years of transfusion.

As he no longer required LVP, his nutrition status, as

assessed by physical appearance improved. LVP results

in significant ascitic fluid protein losses when compared

to diuretic therapy [9]. Additionally, in the post-TIPS

setting in the absence of ascites there is an associated

increased mobility, energy and protein intake compared

to continued LVP [10]. Post-TIPS, his quality-of-life im-

proved, a general finding well-documented in the litera-

C. M. Moore et al. / Open Journal of Gastroenterology 3 (2013) 1-4

ture [6], although this metric was not quantitatively stu-

died in the patient reported. The underlying aplastic

anemia did not precipitate any perceived complications

regarding the TIPS procedure per se or his clinical status

afterwards until his death as a result of leucopenic sepsis

2.5 years later. These outcomes support the pragmatism

of the therapeutic go als: that he was appropriately denied

an OLT given his underlying high-mortality state, but

that he could benefit clinically from a non-standard indi-

cation TIPS procedure given the severity of his portal

hypertension and aplastic anemia. Organ allocation is

especially stringent for OLT given the relative paucity of

available donors to recipients.

In summary, this case report details the non-standard

application of a TIPS procedure in a PBC OLT ineligible

patient with aplastic anemia and refractory ascites re-

quiring serial LVP. The TIPS procedure was effective in

ameliorating sequelae of his portal hypertension and was

accomplished without any complications related to his

underlying aplastic anemia. Careful application of such a

procedure, although not traditionally indicated for such a

patient as in this case report, can have reasonable bene-

fits upon quality of life, and possibly even health-care

cost.

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