Management of refractory ascites in cirrhosis: Are we out of date?

Table 2 Randomized control studies evaluating transhepatic portosystemic shunts vs paracentesis in patients with cirrhosis and refractory ascites

Ref.	Study design	Results	Conclusions/comments
Lebrec et al[30], 1996	Total of 25 13 TIPS 12 LVP Excluded: Age > 70 Severe diseases other than liver Pulmonary hypertension Hepatocellular carcinoma Hepatic encephalopathy Sepsis/spontaneous bacterial peritonitis Severe alcoholic hepatitis Portal/hepatic vein obstruction/thrombosis Obstruction of biliary tract or hepatic artery Plasma creatinine > 150 mmol/L	Deaths: TIPS - 9/13 LVP - 4/12 3/13 TIPS unsuccessful, of the remaining 10/13 TIPS patients: 8 required a second shunt and 2 required 3 shunts 1/12 LVP patients received liver transplant Survival at 2 yr with "intention to treat" analysis 29% ± 13% for TIPS and 60% ± 16% for LVP Survival at 2 yr with "per protocol" analysis was 38% ± 16% for TIPS and 70% ± 15% for LVP	The authors concluded that intrahepatic shunts were selectively effective in patients with Childs-Pugh class B, although they did not improve survival, and actually decreased survival in class C patients compared to LVP. They believed that the prominent factor is ascites management were dependent on both neurohormonal factors which control natriuresis and the hepatic sinusoidal pressures
Rössle et al[31], 2000	Total of 60 patients Randomized to 2 groups: TIPS 29/60 LVP 31/60 Excluded: Hepatic encephalopathy > Grade 2 Serum bilirubin > 5 mg/dL Serum creatinine > 3 mg/dL Portal-vein thrombosis Hepatic hydrothorax Advanced cancer Continual ascites after paracentesis or multiple paracentesis within 1 wk	Deaths: TIPS - 15/29 LVP - 23/31 13/29 patients had shunt insufficiency, 11/29 underwent reestablishment of the shunt after 10 ± 16 mo and 5 of these patients required a second reestablishment 1/29 TIPS patients received liver transplant 2/31 LVP patients received liver transplant These patients were alive 60 mo following transplant Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5 ± 4 mo after randomization; 4 had a response to this rescue treatment Estimated probability of survival without transplant: TIPS: 69% and 58% at 1 and 2 yr; LVP: 52% and 32% at 1 and 2 yr In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P = 0.02) At three mo, 61% of the patients in the shunt group and 18% of those in the paracentesis group had no ascites (P = 0.006) Age > 60 yr, female sex, bilirubin > 3 mg/dL, and serum sodium < 125 mmol/L significantly decreased survival in the TIPS group	In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites
Ginès et al[32], 2002	Total of 70 patients randomized into 2 groups TIPS: 35 LVP + Albumin (8 g/L ascites removed): 35 Primary endpoint: Survival without liver transplantation Secondary endpoints: Complications of cirrhosis and cost Excluded: < 18/> 75 yesrs old Serum bilirubin > 10 mg/dL Prothrombin time < 40% Platelet count < 40000/mm³ Serum creatinine > 3 mg/dL Hepatocellular carcinoma Complete portal vein thrombosis Cardiac/respiratory failure Organic renal failure Bacterial infection Hormonal measurements (plasma renin	Deaths: TIPS 20/35 LVP 18/35 Transplanted: TIPS 7/35 LVP 7/35 1 TIPS patient required repeat LVP’s 3 LVP patients required TIPS placement Ascites recurrence: TIPS - 17 patients developed 60 episodes of ascites (30 episodes attributed to 1 patient who experienced a total occlusion of their shunt), LVP - 29 patients developed 341 episodes of ascites Median time of the first recurrence of ascites: TIPS - 171 d LVP - 20 d 13 TIPS patients experienced shunt dysfunction	They concluded that TIPS lowers the rate of ascites recurrence and the risk of developing hepatorenal syndrome, but does not improve survival and has increased occurrence of encephalopathy and higher cost that LVP
	activity, aldosterone, norepinephrine, and atrial natriuretic peptide) were measured at 1 wk, 1 mo and 6 mo in 18 TIPS patients and 23 LVP patients	Total costs for TIPS patients (calculated separately in United States dollars on intention-to-treat basis from Spanish and then United States hospitals that participated in the study) demonstrated that total costs and costs per patient were greater in the TIPS group TIPS $693460, or $19813 per patient. LVP patients were $341760, or $9765 per patient
Sanyal et al[33], 2003	109 patients with refractory ascites were randomized into 2 groups 52 patients received TIPS with medical therapy (low sodium diets, diuretics, and LVP) 57 patients received medical therapy without TIPS Excluded: Similar criteria to prior studies All patients placed on low Na diets and diuretics All patients placed on low Na diets and diuretics Diuretics stopped 5 d prior to LVP Albumin infusion followed LVP at 6-8 g/L removed TIPS patients received shunts Some patients from both groups received repeat LVP’s plus Albumin for tense, symptomatic ascites with weight gain > 10 pounds	Deaths: TIPS - 21/52 LVP 21/57 Failed Treatments: TIPS 3/52 unsuccessful LVP 2/57 patients required TIPS Failed treatments in the first year after randomization requiring repeat LVP for tense ascites: TIPS - 22/52 LVP 48/57 Average rate of LVP per patient in the first year after randomization: for TIPS - 1.69 LVP - 6.11 Transplants: TIPS 16/52 LVP 17/57	Although TIPS plus medical therapy is superior to medical therapy alone for the control of ascites, it does not improve survival, affect hospitalization rates, or improve quality of life
Salerno et al[34], 2004	66 patients randomized into 2 groups TIPS group: 33 LVP + Albumin group: 33 Excluded: Similar criteria to prior studies Diuretic doses continued throughout the study and doses adjusted for each patient’s clinical needs All patients on low Na diets (80 mg/d) TIPS placed LVP patients received Albumin replacements at 8 g/L ascites removed Patients discharged and followed at 1, 3 and 6 mo, then every 3-6 mo or as clinically necessary Mean follow up time was 18.2 ± 2.3 mo	Deaths: TIPS - 13/33 LVP - 20/33 Failed treatments: TIPS - 3/33 Initial LVP - 0/33 reported Estimated probability of survival at 1 yr: TIPS - 77% LVP - 52% Estimated probability of survival at 2 yr: TIPS 59% LVP 29% Transplanted: TIPS 4/33 LVP 4/33 Cox proportional hazard model indicated that treatment assigned and MELD scores were independent predictors of mortality Failure of treatment noted in 7/33 TIPS patients: 2 patients received LeVeen Shunts and 5 LVP’s Failure of treatment noted in 19/33 LVP patients: 1 received a LeVeen Shunt, 11 received TIPS, and 7 elected to continue with LVP treatment	Treatment failure was more frequent in patients assigned to paracentesis, whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS The number and duration of re-hospitalizations were similar in the two groups Compared to large-volume paracentesis plus albumin, TIPS improves survival without liver transplantation in patients with refractory ascites

LVP: Large-volume paracentesis; TIPS: Transhepatic portosystemic shunts; MELD: Model for end-stage liver disease.