Short‐ and long‐term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma

Abstract

Background Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective The objective of this article is to report the secondary outcome “hepatic hemodynamics” from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days (“acute effects”), two months (“intermediate effects”) and six months (“long-term effects”) after the first TACE. Results Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9–19) mmHg). TACE had neither “acute effects” nor “intermediate effects” on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11–19) mmHg) compared with baseline (median, 10 (IQR: 5–12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

Fibroscan and Doppler Ultrasonography in the Assessment of Hepatocellular Carcinoma Interventional Therapy

“…Similar to our results an increase in PHT indices following ablation procedures was proven in previous studies [19][20][21].…”

Advances in immunotherapy for hepatocellular carcinoma

“…VEGF inhibition, therefore, reduces portal pressure in animal models 149 . However, when the hepatic venous pressure gradient was measured in 13 patients with HCC before and after chemoembolization alone or combined with bevacizumab (5 mg/kg), no changes were observed between groups of patients after acute and chronic exposure to bevacizumab 150 . This circumstantial evidence suggests that at least bevacizumab would be unlikely to aggravate portal pressure.…”

Prognostic value of splenic volume in hepatocellular carcinoma patients receiving transarterial chemoembolization

“…This is particularly true in patients who undergo TACE as most of the HCC lesions arise in the background of established cirrhosis with impaired liver compensatory capacity (1,5,16). When treating tumors, TACE simultaneously causes a series of complex and detrimental pathophysiological changes such as fibrosis, cirrhosis, PH, varices, and even liver failure, which ultimately lead to dismal prognosis (4,7,9,20). Therefore, a robust indicator for evaluating liver function reserve and patient survival is essential to accurately determine whether a patient is suitable for TACE treatment.…”

“…The mechanisms and consequences of TACEinduced liver injury are complex. In addition to the toxicity of chemotherapeutic agents, TACE also elicits a series of environmental and cytokine signals alterations such as hypoxia induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), which promote fibrosis, cirrhosis, PH, and subsequent splenomegaly (9,20,22). In the survival analysis, both pre-and post-TACE SV exhibited strong predictive power for patient survival, whereas CP score and ALBI grade failed to show prognostic value.…”

“…The damage of adjacent liver parenchyma results in inflammation, tissue hyperplasia, and fibrogenesis, leading to cirrhosis, elevated portal venous pressure (PVP), and eventually portal hypertension (PH), all of which are proven risk factors of liver dysfunction after TACE treatment (7)(8)(9). The spleen is a susceptible organ to these complex pathophysiological alterations and responds quickly and significantly in the form of splenomegaly (10,11).…”