Serum angiotensin-converting enzyme level as a marker of fibrosis in patients with chronic hepatitis B

Abstract

Background and aims: Hepatitis B virus (HBV) infection is a public health problem and affects nearly 350 million people worldwide. The present study was conducted in order to investigate the role of circulating angiotensin-converting enzyme (ACE) in the context of renin-angiotensin-aldosterone in newly diagnosed chronic hepatitis B infection. Moreover the association between liver fibrosis and serum ACE levels was also investigated. Materials and methods:The study was performed on 50 chronic hepatitis B (CHB) patients (24 males, 26 females; median age 39.4 years, range 18-63) and 20 healthy controls. The clinical features of CHB patients including demographics, laboratory and liver biopsy findings were summarized. Serum ACE levels were measured by using commercially available kits. Results: Serum median ACE levels were 48.4 (14-83) U/L and 26.2 (12-48) U/L for the CHB patients and controls, respectively. Serum ACE levels were significantly higher in patients with CHB compared with the control group (p<0.001). Twenty-two patients (44%) had advanced liver fibrosis (Ishak score >2) and 28 patients (56%) had mild liver fibrosis (Ishak score ≤ 2). Mean serum levels of ACE were significantly higher among patients with advanced fibrosis as compared with those without advanced fibrosis (60.3±14.2 U/L vs. 39.0±10.5 U/L, p<0.001). Receiver operating characteristic (ROC) curve analysis suggested that the optimum ACE level cut-off point for advanced fibrosis was 52.5 U/L (sensitivity: 81.8%, specificity: 82.1%, PPV 78.3%, NPV 85.2%, accuracy 82%, AUC: 0.890). Conclusions: Our study showed that elevated circulating ACE levels are commonly observed in CHB patients. This finding was more prominent in patients with advanced fibrosis in liver. When evaluating a patient along with other parameters, the inclusion of ACE levels in the evaluation of CHB patients may grant additional prognostic information.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Many of these articles concern hypertension, heart failure, or nephropathy (Ahmed et al, 2012;Pedrinelli et al, 2012). Other articles study hepatitis C, Alzheimer's disease, tumor growth, or even erectile dysfunction (Kehoe and Passmore, 2012;Purnak et al, 2012;Santos et al, 2012;Wang et al, 2012). Given the many in vivo roles of ACE, both classic ACE inhibitors and newer compounds inhibiting only one ACE domain may evolve into important treatments for diseases outside the cardiovascular system.…”

Angiotensin-converting enzyme gene polymorphism (insertion/deletion) and liver fibrosis in Turkish patients from the western Black Sea region, Turkey

“…Mackawy et al (2012) also reported an association between serum ACE levels and ACE gene alleles and furthermore reported serum ACE levels to be higher in HCV patients with DD alleles than in those with ID and II alleles. Purnak et al (2012) identified a relationship between serum ACE levels and liver fibrosis stage in patients with HBV infection and found serum ACE levels of patients to be significantly elevated compared with those in healthy controls. In the present study, no significant difference was observed between serum ACE levels among the fibrosis groups; however, HAI, MELD, and Child-Pugh scores differed significantly (P < 0.001) between the two groups.…”

“…Genetics and Molecular Research 14 (4): 17079-17090 (2015) Authors Study group Result and/or conclusion Powell et al (2000) 128 HCV patients No significant association between ACE gene (I/D) polymorphism and fibrosis stages Jonsson et al (2001) Rats treated with Captopril control rats ACE inhibitor, captopril can inhibit the progression of hepatic fibrosis through transforming growth factor-β Forrest et al (2005) 195 HCV patients No significant association between ACE gene (I/D) polymorphism and fibrosis stages. Necroinflammatory activity (P < 0.001) and age (P < 0.001) were associated significantly with fibrosis (2012) 90 HCV patients 30 healthy controls Serum ACE levels in patients with ACE gene DD polymorphism is more than the patients with DI and II polymorphisms (P < 0.05) Purnak et al (2012) 50 HBV patients 20 healthy controls Serum ACE levels in patients with advanced fibrosis was found to be higher than patients with mild fibrosis (P < 0.001) Shahid et al (2013) Cirrhotic rats, control rats ACE gene expression in liver tissue of cirrhotic rats were higher than the controls (P < 0.05) Yuan et al (2013) 293 HCC patients, 384 healthy controls D allele frequencies in the ACE gene of HCC patients were lower than controls (P = 0.003). Significantly decreased HCC risk was associated with the DD genotype (P < 0.001) Zha et al (2014) 210 HCC patients 206 healthy controls D allele frequencies in the ACE gene of HCC patients were higher than controls (P = 0.036) Goh et al (2015) 290 hypertensive patients with NAFLD Patients treated with RAS blockers had less advanced hepatic fibrosis than the patients treated without RAS blockers (P = 0.002) HCV = hepatitis C virus; PBC = primary biliary cirrhosis; NAFLD = non-alcoholic fatty liver disease; HBV = hepatitis B virus; HCC = hepatocellular carcinoma; RAS = renin angiotensin system.…”

Is serum angiotensin converting enzyme level a useful non-invasive marker for liver fibrosis in patients with chronic hepatitis C?

“…Up to today, the measurement of serum ACE level for liver fibrosis has only been studied in the context of hepatitis B and autoimmune hepatitis, with promising results according to the authors. 17,18 However, in these studies, the value of serum ACE could not be assessed in deepth due to the insufficient number of patients and controls, as well as a lack of studies on usability. Many patients with chronic liver disease are usually detected and treated later in life and so plenty of comorbidities that often affect the serum ACE level can exist.…”