Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin in treatment naïve patients and their correlations with interleukin-6, tumour necrosis factor-α, viral load and liver damage

Abstract

The importance of activins and follistatin in liver diseases has recently emerged. The aim of the present study was to measure the influence of chronic infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α. Sera samples collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (ten males and ten females for each genotype), and 40 gender- and age-matched healthy participants were analysed for activin-A, activin-B and follistatin using enzyme-linked immunosorbent assay and their levels were correlated with IL-6, TNF-α, viral load and AST platelet ratio index (APRI). Serum activin-A, activin-B, IL-6 and TNF-α were significantly increased, while serum follistatin was significantly decreased, in both genders of CHC patients compared with control subjects, In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-α, and negatively with albumin (P < 0.01). Activin-B showed the same correlations of activin-A only in CHC genotype 1 patients, but it was weaker than activin-A. No correlation was detected with follistatin. Serum activins, particularly activin-A, and follistatin are significantly altered by CHC genotype 1 and 4. This dysregulation of activins/follistatin axis may be associated with viral replication, host immune response and liver injury. Further studies are needed to illustrate the definite role(s) and clinical value of activins and follistatin in CHC.

Prevalence of thyroid disorders and the correlation of thyroid profile with liver enzymes, serum activin-A and follistatin during the treatment of patients with chronic hepatitis C genotype 1 and 4

“…Activin-A has been established as a main regulator of immune responses [20,21] and pathological activin-A levels have been associated several autoimmune diseases such as rheumatic diseases [40], systemic lupus erythematosus [41] and allergic airway diseases [42]. Therefore, we suggest that activin-A and/or follistatin are involved in HCV and Peg-INF-α induced autoimmune thyroiditis.…”

“…The interpretation of the APRI results was performed according to previously published studies [20,21]. All samples were collected following the calculation of their APRI and only samples with ≤ 1.2 were included into the study to avoid samples collected from patients suffering from liver cirrhosis.…”

“…Additionally, we have previously reported that CHC and Peg-INF-α based therapy modulate the serum concentrations of activin-A and follistatin [20,21]. The present study was therefore conducted to measure the frequency and types of thyroid disorders associated with CHC and/or its therapy in treatment naïve Saudi patients diagnosed with HCV genotype 1 and 4.…”

Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-αBased Therapy

“…At the present time, infection with hepatitis C virus (HCV) is a major health problem worldwide and it is the main cause of end stage liver diseases [ 1 , 2 ]. Only 20%–30% of infected persons are expected to resolve following the acute phase without any therapeutic intervention, while the remaining 70%–80% develop chronic hepatitis C (CHC) within six months of infection [ 3 ].…”

“…Activins and their binding proteins, follistatin, are secreted by the hepatocyte and regulate the immune system and their serum concentrations have been shown to increase during CHC [ 1 ]. Activins and follistatin have recently been suggested as potential sensitive and specific prognostic markers for the prediction of achieving sustained viral response at the end of Peg-INF- α based therapy [ 1 , 2 ]. The present review summarizes the roles of activins and follistatin in the regulation of immune responses and their role in liver biology and pathology with specific emphasis on CHC.…”