Combination Therapy Reduces Risk for Variceal Rebleeding, Recurrence in Cirrhosis

Compared with endoscopic therapy alone, combined treatment with endoscopic therapy plus partial splenic embolization is optimal for reducing rebleeding in patients with cirrhosis with acute variceal bleeding (AVB) and hypersplenism, according to a study published in the Journal of Gastroenterology.

One of the most feared complications in patients with cirrhosis is AVB, which carries a mortality rate of approximately 20%. Treatment consists of endoscopic variceal ligation (EVL), which effectively prevents rebleeding. Hypersplenism is also a common complication, with current research suggesting partial splenic embolization (PSE) over splenectomy, as it leads to fewer postoperative complications. Study authors aimed to investigate the safety and efficacy of EVL and PSE treatment in those with cirrhosis complicated by hypersplenism, compared with endoscopic treatment alone.

Researchers conducted a prospective, randomized controlled trial (ClinicalTrials.gov Identifier: NCT02778425) on patients with AVP who were treated at any 1 of 3 hospitals. Patients aged 18 to 75 years with a diagnosis of liver cirrhosis with concomitant splenomegaly who had endoscopic therapy due to AVB within 24 hours of admission were included in the study. Individuals with prior treatment for AVB, history of isolated variceal bleeding, malignancy, or a Child-Pugh score above 13 were excluded.

Eligible patients were randomly assigned 1:1 to either the EP group (PSE and endoscopic therapy; n=57) or the E group (endoscopic therapy only; n=57).

The primary outcome of the study was rebleeding of varices at follow-up; secondary outcomes included variceal recurrence, adverse events, and death.

Of 114 patients included in the study, 34 patients experienced bleeding during the 5-year follow up, 11 from the EP group and 23 from the E group. Rebleeding rates were significantly higher in the E group than in the EP group at 6 months (17.5% vs 1.8%, P =.005), 1-year (22.8% vs 8.8%, P =.037), 2 years (33.3% vs 14.0%, P =.015), and 5 years (40.4% vs 19.3%, P =.013).

A total of 10 patients died, with 1 in the EP group due to rebleeding a week after EVL. The other 9 died after completion of the trial (4 in the EP group, 5 in the E group). Overall mortality was not found to be significantly different between the 2 groups (P =.835).

Notably, white blood cell (WBC) counts, platelet counts, and albumin concentrations were significantly higher in the EP group than in the E group during 2-year follow up (P <.05). Although the E group did not show any significant improvement in WBC counts, a considerable improvement occurred in red blood cell (RBC) counts and hemoglobin (HGB) levels (P <.05). Prothrombin time was also significantly shorter in the EP group at 1-year (P <.001), and 2 years (P =.026), and after the end of treatment. 

Patients with postembolization syndrome, characterized by fever, abdominal pain and distension found complete resolution with symptomatic treatment. Patients with postendoscopic symptoms (throat discomfort, retrosternal pain, fever) found resolution without any intervention.

Study limitations include not including treatment outcomes of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with AVP and hypersplenism. Additionally, the findings may not be applicable to patients in Child-Pugh class C, since a small number of patients with a Child-Pugh class C (score of 10-15 points) were included in the study.

“Compared to endoscopic treatment alone, EP treatment efficaciously reduced the risk of variceal rebleeding and recurrence in Child–Pugh class A or B patients with AVB

while improving the peripheral blood count, liver function, coagulation, and Child–Pugh scores,” the study authors noted.