EC Gastroenterology and Digestive System

Background and Aim: Hepatocellular carcinoma (HCC) represents most of the primary liver tumors and the process of neo angiogenesis is thought to be a significant malignant characteristic of HCC. Due to their anti-angiogenic and anti-fibrinogenic properties, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II blockers (ARBs) may play a substantial role as adjuvant therapy in prevention of HCC. The purpose of this systematic review is to better understand the therapeutic role of ACEIs and ARBs in HCC.

Methods: We conducted literature search using the most widely used internet databases (Medline, EMBASE, and Cochrane) to retrieve all the articles evaluating the use of ACEI/ARBs in the prevention or treatment of hepatocellular carcinoma, using the following keywords: “angiotensin-converting enzyme inhibitors”, "ACE inhibitors”, "ACE-I”, "angiotensin II type 1 receptor blockers", "ARBs”, "hepatocarcinoma”, and "hepatocellular carcinoma”. The following criteria were used to determine eligibility: (1) prospective or retrospective observational studies; and (2) clinical trials. We restricted our search to English-language papers and omitted animal studies, conference abstracts, review articles, case reports, case series, editorial letters, and irrelevant studies.

Results: The results of the two RCTs conducted by Yoshiji., et al. demonstrated a significant difference (p < 0.01) in recurrence rates between the control group and the group of patients who used ACEI and vitamin K2 combination therapy followed by the curative therapy, as well as a significant decline in recurrence rates i.e. p < 0.01 was observed among patients who underwent treatment with ACEIs in conjunction with branched chain amino acids (BCAA) when compared to the control group. ACEIs/ARBs treatment demonstrated a significant overall survival i.e. OS = 11.9 months vs. 6.8 months (p = 0.014) in patients diagnosed with HCC with a Child-Pugh class A in a cohort study conducted by Printer., et al. Another study conducted by Facciorusso., et al. reported a significantly improved response to Sartan therapy in terms of increased duration of recurrence (p = 0.001) and overall survival (p = 0.15). Kaibori., et al. analyzed certain metabolic factors as risk factors for the poor prognosis in patients with HCC and found that hypertension was associated with worse overall and disease-free survivals and demonstrated a significant increase in the overall and disease-free survivals in patients with HCC treated with angiotensin II blockade. However, three studies by Ho., et al, Walker., et al. and Hagberg., et al. found no protective effect of ACEIs/ARBs among patients diagnosed with HCC.

Conclusion: ACEIs/ARBs have a prognostic role in HCC, increasing survival and reduced recurrence rates and lengthening the time to recurrence; nevertheless, angiotensin II blockade for primary prevention against the development of hepatocellular carcinoma is not of considerable benefit.

 Keywords: Hepatocellular Carcinoma (HCC); Non-Alcoholic Fatty Liver Disease (NAFLD); Angiotensin-Converting Enzyme (ACE); Renin-Angiotensin System (RAS)

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