Bursting with symptoms: A review of palliation of ascites in cirrhosis

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Abbreviations

ALFApump

automated low‐flow ascites pump

DIC

disseminated intravascular coagulation

HE

hepatic encephalopathy

LVP

large‐volume paracentesis

QOL

quality of life

RA

refractory ascites

TIPS

transjugular intrahepatic portosystemic shunt

PVS

peritoneovenous shunting

Palliative care is a medical specialty that focuses on symptom management and ensures that treatment plans are congruent with goals of care in patients with chronic diseases. Multiple studies have suggested that patients have improved quality, and possibly quantity, of life when palliative care specialists are involved in their care. Patients with cirrhosis and their caregivers bear a significant burden of symptoms ranging from emotional distress to refractory ascites (RA). Quality of life (QOL) of patients with cirrhosis increasingly suffers as patients experience clinical decompensation from liver disease. In particular, the development of either hepatic encephalopathy (HE) or ascites has been shown to be an independent predictor of severe impairment of QOL.1 Decompensating events have also been associated with a negative impact on survival. For example, the onset of ascites has been linked with a 50% 2‐year mortality rate and RA with a median survival time of 6 months2 (Fig. 1). Despite the high burden of symptoms and mortality of patients with cirrhosis, palliative care has been underutilized, leaving hepatologists and primary care physicians to not only manage symptoms but address goals of care. This was recently highlighted in a study that revealed only 11% of patients removed from the liver transplant list at one medical center were referred to palliative care.3 Given that ascites is the most common presentation of decompensated cirrhosis4 and its implication in morbidity and mortality, we will review current options for the management of ascites.

Figure 1.

Actuarial probability of survival of (A) patients with cirrhosis with ascites and (B) patients who did and did not develop complications during the follow‐up. Reproduced with permission from Clinical Gastroenterology and Hepatology.5 Copyright 2006, AGA Institute.

Most patients experience relief of ascites through conservative medical treatment, that is, combined furosemide, spironolactone, and restriction of fluid and dietary sodium intake.4 The probability of development of RA within 5 years after the initial presentation of ascites is about 17%. The initial development of ascites was also associated with increased probability of development of hyponatremia (37.1%), hepatorenal syndrome (6.7%), and mortality.The overall 1‐year survival rate after the development of RA was found to be 31.6%.5 Although liver transplant offers definitive resolution of ascites, it becomes a reality for only a small minority of patients. With these statistics in mind, ascites can be seen as a harbinger of significant morbidity and mortality. Despite large‐volume paracentesis (LVP) being associated with more complications than diagnostic paracentesis, major complications occurred in only 1.6% of procedures.6 Even though paracentesis has been shown to be safe, patient relief is often short‐lived because of reaccumulation of fluid.

In patients with RA who require frequent LVPs, either because of limited response to maximal diuretic doses or because they are intractable to diuretics due to side effects or renal failure, providers are pressed to find other treatment options.Transjugular intrahepatic portosystemic shunt (TIPS) placement has led to complete or partial response in more than half of these patients. A meta‐analysis of four large, randomized clinical trials comparing patients receiving TIPS versus paracenteses revealed only that TIPS was associated with lower recurrence of tense ascites (42% versus 89.4%) and significantly longer transplant‐free survival. Although the probability of developing a first episode of HE was not different between the groups, patients treated with TIPS not only had more total but also more severe episodes of HE.7 Furthermore, although HE limits candidacy for TIPS in many patients, advanced age and high Model for End‐Stage Liver Disease scores have also been associated with worse outcomes.7 Given these limitations, the medical community has been left searching for other management options.

Indwelling peritoneal catheters serve as another potential palliative option for RA with the benefit of fluid removal on demand from the patient's home. Unfortunately, the risk for peritonitis has limited the utilization of this practice. In one recent retrospective study of 227 patients with cirrhosis who had a peritoneal drain placed, 10% experienced development of bacterial peritonitis within 72 hours of placement. Those who developed peritonitis had a 50% mortality rate at 5 months compared with 50 months in those who did not.8 At our institution, provider fears of these complications have limited the use of these catheters to the minority of patients who are enrolled in hospice care.

Peritoneovenous shunting (PVS), for example, the LeVeen or Denver shunt, was more common before liver transplant and TIPS became more conventional. The procedure involves placement of a shunt that returns ascites fluid to the central venous circulation (Fig. 2). Unlike TIPS where age, degree of hepatic decompensation, and HE must be carefully considered, these are not an issue with PVS. However, despite its effectiveness, the utilization of PVS has been significantly limited by its complications, which include shunt occlusion, peritonitis, disseminated intravascular coagulation (DIC), and bleeding.⁹ With a decline in the numbers of these shunt procedures, the number of surgeons willing to perform them has also declined.

Figure 2.

Drawings show graphic representation of transjugular placement of Denver shunt (CareFusion). Note that valve must be placed over immobile portion of thoracic cage to allow efficient valve compression. Reproduced with permission from American Journal of Roentgenology.9 Copyright 2012, American Roentgen Ray Society.

One promising technology being studied is an automated low‐flow ascites pump (ALFApump) system, which is a subcutaneous battery‐powered pump that directs ascites to the bladder in small amounts to allow for elimination by micturition (Fig. 3). Theoretically, the low‐flow state should avoid hemodynamic complications of fluid shifts previously reported after LVPs. In a recent trial of 40 patients equipped with the ALFApump system, 40% did not require additional LVPs. Of the patients needing further intervention, 70% required less than 1 paracentesis per month compared with a median of 3.4 LVPs per month before pump placement. There were a significant amount of surgical complications, for example, dislodgement of the bladder catheter, which decreased in frequency as experience with the pumps grew and modifications of the equipment were made. Notably, urinary tract infections were rarely encountered. Further safety and efficacy data are needed, and a multicenter clinical trial comparing outcomes of patients with RA randomized to receive either LVPs or the ALFApump system is currently under way.10

Figure 3.

ALFApump system placement. Reproduced with permission from Journal of Hepatology.10 Copyright 2013, European Association for the Study of the Liver.

Caring for patients with cirrhosis is challenging because they suffer from a significant burden of symptoms and decompensating events that often indicate increased mortality. The development of ascites is the most prominent decompensating event, and despite improvements in management, there continues to be ample need for new treatment strategies. A multidisciplinary approach, including increased involvement of palliative care specialists, is likely to lead to the best care for this unique patient population.