Published online Feb 27, 2022. doi: 10.4254/wjh.v14.i2.429
Peer-review started: November 20, 2021
First decision: December 26, 2021
Revised: January 8, 2022
Accepted: February 15, 2022
Article in press: February 15, 2022
Published online: February 27, 2022
Processing time: 93 Days and 13.8 Hours
Variceal bleeding is a life-threatening complication of portal hypertension (PHT). Nonselective β-blockers (NSBB) are used as primary or secondary prophylaxis in patients with PHT. The use of NSBB has been associated with the development of refractory ascites and spontaneous bacterial peritonitis in a subgroup of patients. β-arrestin-2 (β-Arr-2) has been shown to predict the short-term response to NSBB in a few studies.
There is a gap of knowledge still present. The previous research about β-Arr-2 was about the acute hemodynamic response to NSBB infusion, but no data about the long-term effects. About two-thirds of patients with PHT fail to respond to NSBB, with the exposure to undesirable side effects. Identifying this subset of patients noninvasively is of clinical importance. Again, the long-term changes in β-Arr-2 expression after NSBB therapy have not yet been investigated.
We aimed to investigate the role of both serum and tissue expression of β-Arr-2 as a minimally invasive to predict the long-term clinical response of PHT to NSBB therapy, as well as to investigate the long-term changes in β-Arr-2 expression after NSBB therapy.
We prospectively enrolled 120 patients with cirrhotic PHT. Full history and clinical evaluation were done. Laboratory investigations including serum β-Arr-2 were done. Doppler ultrasound of the portal circulation to measure the portal vein congestion index (PVCI) was obtained. Esophagogastroduodenoscopy (EGD) was performed to evaluate the presence and grade of varices and to obtain mucosal biopsies to define the expression of β-Arr-2. NSBB therapy was initiated. A follow-up for 18 mo (540 d) was done. Another endoscopic biopsy was obtained at the end of the study to re-assess the tissue expression of β-Arr-2. Patients were designated as “NSBB responders” if they didn’t experience variceal bleeding until the end of follow-up; or “NSBB non-responders” if they had bled. PVCI was re-evaluated at the end of the study.
A higher serum level and antral expression of β-Arr-2 were associated with better clinical response to NSBB (longer bleeding-free intervals, and improved grade of varices). Only 17.6% of patients with low baseline β-arr-2 expression responded to NSBB, whereas, 95.1% of patients with strong β-arr-2 expression were responders (P < 0.001). A serum β-Arr-2 value ≥ 2.23 ng/mL was associated with a lower likelihood of variceal bleeding with 90% sensitivity and 71% specificity. β-arrestin-2 expression significantly decreased after nonselective β-blocker therapy. Serum β-Arr-2 level (P < 0.001), the intensity of β-Arr-2 expression in the gastric antrum (P < 0.001), and platelet count (P = 0.006), were the only independent predictors for variceal bleeding
The serum level and tissue expression of β-Arr-2 in the gastric antrum are correlated to the severity of PHT. The lower β-Arr-2 expression can predict non-response to NSBB therapy. Stronger expression is linked to a better long-term clinical response to NSBB in terms of variceal bleeding-free interval. We introduce serum β-Arr-2 level as a potential, noninvasive biomarker for selecting patients with PHT who are potentially good candidates for NSBB therapy.
Future studies are needed to validate the results of our study on a wider scale of patients. Prospective research is needed to explore the relation between the expression of β-Arr-2 and the development of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhotic PHT.