scholarly journals Growth Differentiation Factor 15: An Emerging Diagnostic Biomarker of Liver Fibrosis in Chronic Hepatitis C Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Aziza Ahmed El Sebai ◽  
Ossama Ashraf Ahmed ◽  
Azza Abdel Rahman Saab ◽  
Heba M Adel Abou Zaghla ◽  
Gina Gamal Naguib ◽  
...  

Abstract Background Chronic liver disease and cirrhosis are a major health concern worldwide being the sixth leading cause of all-cause mortality in people aged 25–64 years. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. The gold standard method of diagnosis is liver biopsy; however, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determine the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It plays a role in cardiovascular disease, inflammation, body weight regulation and cancer. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. Aim of the Work In this study we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. Patients and Methods The study was a case- control study conducted on 55 chronic HCV patients recruited from Hepatitis C virus Clinic at Faculty of Medicine Ain Shams Research Institute (MARSI), and 30 healthy subjects age and sex matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay (ELISA). Results Results of our study revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p < 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І when compared with the controls’ group (p < 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p < 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cutoff value of 150 ng/L for discrimination between patients’ and controls’ groups. Conclusion Growth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Heba M. Adel Abou Zaghla ◽  
Aziza Ahmed El Sebai ◽  
Ossama Ashraf Ahmed ◽  
Ayat Fawzy Ahmed ◽  
Azza Abdel Rahman Saab

Abstract Background Chronic liver disease and cirrhosis are of the major health concern worldwide. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. Liver biopsy is considered as standard golden method in diagnosis of liver fibrosis. However, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determination of the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. In this study, we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. The study was a case-control study conducted on 55 chronic HCV patients recruited from hepatitis C virus clinic at Faculty of Medicine Ain Shams Research Institute (MASRI), and 30 healthy subjects age- and sex-matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay. Results Our results revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p < 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І) when compared with the controls’ group (p < 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p < 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cut-off value of 150 ng/L for discrimination between patients’ and controls’ groups. Conclusion Growth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.


2019 ◽  
Vol 49 ◽  
Author(s):  
Marija Dimzova ◽  
Mile Bosilkovski ◽  
Magdalena Gasheva ◽  
Boban Toshevski ◽  
Biljana Petreska ◽  
...  

Background: The quantification of HBsAg provides different and complementary information that helps in determination of the different phases of chronic hepatitis B viral infection, evaluation and follow-up of liver disease progression as well as in treatment individualization.Aim: To evaluate the clinical significance of quantitative HBsAg (qHBsAg) in patients with HBeAg negative chronic hepatitis (CHB) and its correlation with the serum levels of alanine aminotransferase (ALT), quantitative HBV DNA and liver fibrosis.Subjects and Methods: The study included 53 treatment naïve patients with HBeAg negative chronic hepatitis B. All patients underwent complete laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. Patients’ demographic characteristics, viral and biochemical markers were recorded at one point of time.Results: Correlation analysis between the qHBsAg and ALT showed an significant, positive correlation between the parameters for R=0.42 and p<0.05; there was statistically non-significant positive correlation for R=0.25 and p>0.05 between qHBsAg and HBV DNA. There was a positive correlation between qHBsAg and liver fibrosis for R=0.08 and p>0.05. The serum levels of HBsAg had greater impact on the serum levels of ALT compared to that of HBV DNA for R=0.15 and p>0.05.Conclusion: Patients with higher ALT values and higher liver fibrosis score have higher qHBsAg; qHBsAg can reflect the serum HBV DNA levels.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Mostafa M. Sira ◽  
Behairy E. Behairy ◽  
Azza M. Abd-Elaziz ◽  
Sameh A. Abd Elnaby ◽  
Ehab E. Eltahan

Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2±30.78 pg/mL versus 37.21±5.39 pg/mL; P=0.021). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P=0.015, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P=0.071). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.


2021 ◽  
Vol 19 (2) ◽  
pp. 60-64
Author(s):  
Zh.B. Ponezheva ◽  
◽  
I.V. Mannanova ◽  
V.V. Makashova ◽  
A.A. Erovichenkov ◽  
...  

Objective. To identify specific clinical and laboratory characteristics of patients with chronic hepatitis C (CHC) and severe interferon (IFN) system suppression. Patients and methods. This study was conducted at the Clinical Department of Infectious Pathology, Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing. We enrolled and examined 76 patients with confirmed CHC aged 18 to 80 years who had been followed up for at least 3 years. We analyzed the level of IFN-producing T-lymphocytes, IFN status, serum levels of IFN-α, -γ and -λ depending on viral and biochemical activity, and genotype. In addition to that, we evaluated the association between the IFN system parameters and age, duration of infection, genotype, viral load, and stage of liver fibrosis. The control group comprised 30 healthy individuals who had no complaints and no clinical or laboratory changes at the time of examination. Results. We identified 3 grades of IFN system suppression: grade 1–moderate (in 21% of patients), grade 2–mild (inadequate) (in 47% of patients), and grade 3–severe (in 32% of patients). We analyzed clinical and laboratory characteristics of patients with grade 3 IFN system suppression and evaluated the IFN system depending on age, duration of infection, genotype, viral and biochemical activity. We found that severe IFN system suppression correlated with duration of infection, stage of liver fibrosis with a tendency to increased levels of T-lymphocytes expressing receptors for IFN-α and IFN-γ (CD118+, CD119+). Key words: chronic hepatitis C, genotype, interferon status


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Amal Ahmed Mohamed ◽  
Amr Ali Hemeda ◽  
Ramy Karam Aziz ◽  
Mohamed Salaheldin Abdel-Hakeem ◽  
Marwa Ali-Tammam

Abstract Background Viral hepatitis is the seventh leading cause of mortality globally, and half of this mortality is attributed to hepatitis C virus (HCV). Egypt has the highest HCV prevalence worldwide, with an estimated 14.7% of the population being HCV-positive. HCV infection is the primary cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Liver fibrosis varies in severity during chronic HCV infection, and 10–20% of chronic hepatitis C (CHC) patients with severe fibrosis develop cirrhosis. The goal of this work was to assess the clinico-demographic predictors of severity of HCV-induced fibrosis in a cohort of Egyptian patients. Results A cohort of Egyptian patients with chronic HCV genotype 4a infection showed significant association between severe fibrosis stages and obesity, represented by a higher body mass index (BMI), low albumin level, high alpha-fetoprotein (AFP) level, low thyroid-stimulating hormone (TSH) level, and high alkaline phosphatase (ALP) level. Multivariate analysis delineated BMI, TSH, and ALP as independent significant variables that could predict the risk of fibrosis severity in HCV infections. Conclusion This study argues in favor of using the biomarker profile of CHC patients infected with HCV genotype 4a to identify patients at higher risk of developing severe fibrosis, which is a necessary first step towards precision medicine via patient stratification.


2009 ◽  
Vol 29 (2) ◽  
pp. 208-212 ◽  
Author(s):  
Isabel Zvibel ◽  
Phillipe Halfon ◽  
Sigal Fishman ◽  
Guillaume Penaranda ◽  
Moshe Leshno ◽  
...  

2018 ◽  
Vol 27 (2) ◽  
pp. 115-121
Author(s):  
Mona A. Abu El Makarem ◽  
Ghada M. El-Sagheer ◽  
Moustafa A. Abu El-Ella

Objective: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). Subjects and Methods: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-β1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. Results: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-β1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-β1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-β1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-β1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8). Conclusions: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-β1 but not through the activation of hepatic stellate cells.


Author(s):  
Veronica R. Placencio-Hickok ◽  
Arsen Osipov ◽  
Sejal Mehta ◽  
Subhash D. Katewa ◽  
Jiping Zha ◽  
...  

2016 ◽  
Vol 34 (6) ◽  
pp. 650-653 ◽  
Author(s):  
Norihisa Yada ◽  
Toshiharu Sakurai ◽  
Tomohiro Minami ◽  
Tadaaki Arizumi ◽  
Masahiro Takita ◽  
...  

Objective: We have reported about real-time tissue elastography (RTE), which displays relative strain by measuring the relative distortion of the tissue, and found this information to be useful for diagnosing liver fibrosis. However, its use in predicting hepatocellular carcinoma has not been reported as yet. Here, we investigated RTE to predict liver carcinogenesis in patients with chronic hepatitis C virus (HCV) infection. Methods: We enrolled 160 patients with chronic HCV, who were followed up for 39.9 ± 22.9 weeks (median). They underwent RTE and then ultrasounds every 3-6 months. Results: Respective cumulative liver cancer incidences for years 1, 2, 3, 4, and 5 were, for the entire cohort: 2.0, 5.6, 8.8, 13.1, and 23.9%; for those whose liver fibrosis index (LFI) was ≤2.0: 0.0, 0.0, 0.0, 0.0, and 0.0%; for those whose LFI was 2-2.8: 0.0, 7.4, 7.4, 13.2 and 19.9%; and for those whose LFI was >2.8: 12.9, 12.9, 21.7, 31.4, and 31.4% (p = 0.011; log-rank test). Conclusions: Measurements of LFI by strain imaging can effectively predict liver cancer risk in patients with chronic HCV infection.


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