Role of early transjugular intrahepatic portosystemic stent-shunt in acute variceal bleeding: An update of the evidence and future directions

Table 1 Early transjugular intrahepatic portosystemic stent-shunt in acute variceal bleeding: Key studies

Ref.	Main inclusion criteria	Primary and secondary outcomes	Results	Comments
Randomised controlled trials
Monescillo et al[12], 2004 (Italy)	HVPG > 20 mmHg within 24 h of admission.	(1) Primary: Sensitivity and specificity of HVPG cut-off value (20 mmHg) in predicting transplant-free survival (TFS), and assessment of TFS as well as short- and long-term survival; and (2) Secondary: Transfusional needs, ICU stay, complications during the first week of treatment, and causes of death.	6-wk mortality = 17% in e-TIPSS vs 38% in control (P ≤ 0.05). 1-yr mortality = 31% in e-TIPSS vs 65% in control (P ≤ 0.05). Treatment failure = 12% in e-TIPSS vs 50% in control (P = 0.001).	46% of study population had Child C and 40% had Child B cirrhosis. mean Child score = 9.2. SOC does not reflect current management and only bare metal stents were used.
García-Pagán et al[39], 2010 (Europe)	Child- B with active bleeding or Child C < 14 points.	(1) Composite Primary: Failure to control bleeding and failure to prevent clinically significant VB within 1 yr; and (2) Secondary: Mortality at 6 wk and at 1 yr, failure to control acute bleeding, early rebleeding, rate of rebleeding between 6 wk and 1 yr, other complications of PHTN, number of days in ICU, days spent in the hospital, use of alternative treatments.	6-wk survival = 97% in e-TIPSS vs 67% in control (NNT = 3.3). 1-yr survival = 86% in e-TIPSS vs 61% in control (P < 0.001). 1-yr re-bleeding = 3% in e-TIPSS vs 50% in control (P < 0.001, NNT = 2.1).	mean Child score = 9.4. mean MELD score = 16.2. About 50% of study participants had Child C cirrhosis. Majority had ALD. NSBB (propranolol or nadolol) was administered with EBL in 25 patients.
Lv et al[44], 2019 (China)	Child B and C < 14 points, regardless of active bleeding.	(1) Primary: Transplant-free survival; and (2) Secondary: Failure to control bleeding or rebleeding, new or worsening ascites, overt HE, and other complications of portal hypertension and adverse events.	6-wk TFS = 99% in e-TIPSS vs 84% in SOC (P = 0.02). 1-yr TFS = 86% in e-TIPSS vs 73% in SOC (P = 0.046; NNT = 8). 1-yr re-bleeding/uncontrolled bleeding = 11% in e-TIPSS vs 34% in SOC (P < 0.0001).	mean Child Score = 8.0. mean MELD score = 13.8. More than 55% patients had Child-Pugh B without active bleeding. 75% of patients had Hepatitis B and had Child B cirrhosis. No significant difference in the incidence of HE was observed between two groups.
Dunne et al[46], 2020 (United Kingdom)	Child B and C, 8-13 points (regardless of active bleeding at the endoscopy).	(1) Primary: 1-yr survival; and (2) Secondary: Survival at 6 wk, early rebleeding (within 6 wk) and late rebleeding (between 6 wk and 1 yr), and the development of HE.	1-yr survival = 79.3% in e-TIPSS vs 75.9% in SOC (P = 0.79). e-TIPSS group showed a trend to reduced variceal re-bleeding (P = 0.09).	Median Child score = 9.8. Median MELD score = 17. More than 90% of participants had ALD. More than 55% had Child-C disease. 23/29 received TIPSS, 13 within 72 h. 18/29 (62%) in SOC group had carvedilol, 3 had cardio-selective beta- blocker and 2 had rescue- TIPSS for early re-bleeding. Incidence of HE was higher in e-TIPSS group (P < 0.05).
Observational studies
Garcia-Pagán et al[49], 2013 (Europe)	Child-B with active bleeding or Child-C < 14 points.	(1) Composite primary: Failure to control acute bleeding or to prevent clinically significant variceal rebleeding; and (2) Secondary: mortality, development of other complications related to portal hypertension and the percentage of follow-up days spent in hospital.	1-yr survival = 86 % in e-TIPSS vs 70% in SOC (P = 0.056); e-TIPSS had lower incidence of failure to control bleeding or rebleeding than patients receiving SOC (3 vs 15, P <0.001).	mean Child score = 10. mean MELD score= 17. No significant difference in incidence of HE. Incidence of development of new or worsening ascites was low in e-TIPSS group (P < 0.01).
Rudler et al[52], 2014 (France)	Child-C 10–13 cirrhosis or Child-B with active bleeding	(1) Primary: prevention of rebleeding at 1 yr; and (2) Secondary: 3 and 6-mo survival, liver transplantation, control of bleeding, rate of rebleeding at 6 wk, between 6 wk and 1 yr, and the occurrence of adverse events (HE, acute cardiac failure, sepsis).	1-yr survival = 71% in e-TIPSS vs 74% in control (P = 0.77). 1-yr free of rebleeding = 97% in e-TIPSS vs 51% in control (P < 0.001).	mean Child score = 11.2. mean MELD score = 21.5. 77% had ALD and 77% had Child-C cirrhosis. Patients with previous history of variceal bleeding or with PVT were also included.
Thabut et al[50], 2017 (France)	Child-C (< 14) or Child-B with active bleeding	Survival at 5-d, 6-wk and 1-yr.	1-yr survival = 85% in e-TIPSS vs 59% in control (P = 0.04).	67% had ALD. 52% undergoing TIPSS had Child C cirrhosis. 35% were eligible for e-TIPSS. Severity of liver disease was the only parameter that influenced survival.
Hernández-Gea et al[51], 2018 (Europe and Canada)	Child-C score (< 14 points) or Child-B plus active bleeding	(1) Primary: Survival at 6 weeks and 1 year; and (2) Secondary: (a) The composite end-point of failure to control acute bleeding (up to day 5), early rebleeding (from day 5 to day 42), and late rebleeding (from day 42); (b) onset or worsening of ascites; and (c) development of HE.	6-wk survival = 92% in p-TIPSS vs 77% in control. Overall, 1-yr survival = 78% in p-TIPPS vs 62% in control (P = 0.014). 1-yr survival in Child C patients = 78% in e-TIPSS vs 53% in control (P = 0.002). 1-yr survival in Child-B + AB = 77% in p-TIPSS vs 75% in control (P = 0.935).	Median MELD score= 15.5. Median Child Score= 10. More than 75% of patients had ALD. Development of de novo or worsening of previous ascites was significantly less in p-TIPSS group (P < 0.001). No difference in incidence of HE was observed in two groups.
Lv et al[45], 2018 (China)	Any grade of cirrhosis (with Child score < 14) and AVB.	(1) Primary: All-cause mortality; and (2) Secondary: Failure to control acute bleeding or rebleeding, new or worsening ascites and development of overt HE.	Overall 6-wk mortality = 3.6% in e-TIPSS vs 10.6 % in SOC (P = 0.002). Overall 1-yr mortality = 14.1% in e-TIPSS vs 17.3% in SOC (P = 0.218). e-TIPSS group had significantly lower mortality in MELD ≥ 19 category.	Patients with Child A cirrhosis were also included. Only small number (< 20%) had Child C cirrhosis. Survival benefit was not seen in Child B patients without active bleeding. Incidence of HE was not significantly different between two groups.
Trebicka et al[22], 2020 (Multicentre)	Child-C, Child- B with active bleeding.	(1) Primary: All-cause mortality or liver transplantation at 6 wk and 1 yr; and (2) Secondary: Rebleeding.	6-wk mortality = 13.6 % in e-TIPSS vs 51% in SOC group of patients with ACLF (P = 0.002). 1-yr mortality = 22.7% in e-TIPSS vs 56.5% in SOC group with ACLF (P = 0.002).	Patients with ACLF had a higher rate of rebleeding compared to patients without ACLF (42-d: P < 0.001; 1-yr: 22.9% vs 17.7%, P = 0.024).

e-TIPSS: Early transjugular intrahepatic portosystemic stent-shunt; RCT: Randomised controlled trial; HVPG: Hepatic venous pressure gradient; HCC: Hepatocellular carcinoma; PHTN: Portal hypertension; PVT: Portal vein thrombosis; TFS: Transplant-free survival; HIV: Human immunodeficiency virus; ICU: Intensive care unit; NSBB: Non-selective beta-blockers; EBL: Endoscopic band ligation; IGV: Isolated gastric varices; MELD: Model for end-stage liver disease; ALD: Alcohol-related liver disease; NNT: Number needed to treat; HE: Hepatic encephalopathy; SOC: Standard of care; ACLF: Acute on chronic liver failure.