Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 721-726

Study of serum hepcidin in patients with chronic hepatitis C


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Tropical Medicine, Tanta Fever Hospital, Tanta, Egypt

Date of Submission15-Jun-2016
Date of Acceptance03-Jul-2016
Date of Web Publication15-Nov-2017

Correspondence Address:
Rania R Hamza
Kobry Kohafa, Tanta, Gharbia, 31741
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.218262

Rights and Permissions
  Abstract 

Objective
The aim of the present work was to study serum hepcidin in patients with chronic hepatitis C (CHC) as an iron homoeostasis-regulating hormone.
Background
Persistent infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Many experimental and clinical studies suggest that excessive iron in CHC is a cofactor promoting the progression of liver damage and increasing the risk for fibrosis.
Patients and methods
In all, 40 patients with CHC (group 1) and 20 healthy individuals (group 2) who served as a control group were included in this study. All patients were subjected to the following: full and detailed history taking, complete clinical examinations, routine laboratory investigations such as complete blood count, liver function tests, prothrombin time, serum creatinine, antinuclear antibody, thyroid-stimulating hormone, α-fetoprotein, viral markers, PCR for hepatitis C, serum hepcidin (ng/ml), serum iron (μg/dl), serum ferritin (ng/ml) and serum total iron-binding capacity (TIBC) (μg/dl), abdominal ultrasound and liver biopsy for CHC patients only for histopathological examination according Metavir scoring.
Results
Serum hepcidin (ng/ml) was highly significantly lower in CHC patients than in controls (7.95 ± 1.72 and 17.09 ± 1.19, respectively; P < 0.001). Serum iron (μg/dl) was highly significantly lower in CHC patients than in controls (68.34 ± 8.24 and 120.56 ± 10.03, respectively; P < 0.001). Serum ferritin (ng/ml) was significantly higher in CHC patients than in controls (246.28 ± 15.12 and 101.21 ± 11.66, respectively; P < 0.001), and serum TIBC (μg/dl) was significantly higher in CHC patients than in controls (376.75 ± 10.46 and 295.6 ± 7.10, respectively; P < 0.001).
Conclusion
Hepcidin levels (ng/ml) in patients with CHC were significantly lower than that in HCV-negative individuals. It is an important factor in iron abnormalities and is detected in such cases in which serum iron (μg/dl) levels are significantly low. However, serum ferritin (ng/ml) and serum TIBC (μg/dl) were significantly high in CHC patients compared with HCV-negative individuals.

Keywords: chronic hepatitis C, serum ferritin, serum hepcidin, serum iron, serum total iron.binding capacity


How to cite this article:
El Lehleh AM, El Shazly RA, Hamza RR. Study of serum hepcidin in patients with chronic hepatitis C. Menoufia Med J 2017;30:721-6

How to cite this URL:
El Lehleh AM, El Shazly RA, Hamza RR. Study of serum hepcidin in patients with chronic hepatitis C. Menoufia Med J [serial online] 2017 [cited 2019 Nov 18];30:721-6. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/721/218262


  Introduction Top


An estimated 180 million people worldwide are infected with hepatitis C [1]. It is well established that about 20% of patients with chronic hepatitis C (CHC) will progress to cirrhosis within 20 years from infection, further resulting into an estimated annual risk of 3–7% of hepatocellular carcinoma (HCC) [2]. CHC patients frequently develop mild-to-moderate iron overload [3]. Many experimental and clinical studies suggest that excessive iron in CHC is a cofactor promoting the progression of liver damage and increasing the risk for fibrosis, cirrhosis and HCC [4]. Hepatic iron concentration has been inversely associated with the response to antiviral therapy [5]. Iron removal by means of phlebotomy improves liver function tests and histology [6], increases the probability of sustained hepatitis C virus (HCV) eradication with antiviral therapy [7], and decreases HCC development in CHC patients [8]. Elucidating the mechanism(s) of iron accumulation in CHC may thus provide new tools for the management of CHC or for the prevention of its complications, or both [9].

With the discovery of hepcidin, the liver has emerged as the central organ in the regulation of systemic iron homoeostasis [10]. Hepcidin is a 25-amino-acid peptide hormone primarily synthesized by hepatocytes, and it negatively controls two critical steps of iron homoeostasis: duodenal absorption and release from macrophages recycling iron through erythrophagocytosis [11]. At the molecular level, hepcidin binds to ferroportin, the membrane iron exporter highly expressed by enterocytes and macrophages [12]. This results in ferroportin internalization and degradation and hence the reduction in iron entry in the plasma compartment [13]. Hepcidin expression is modulated by iron stores, and hence it decreases in iron deficiency to facilitate iron absorption, whereas it increases in iron repletion to prevent pathological overload. Hepcidin expression is also induced by inflammation and suppressed by hypoxia and anaemia [10].


  Patients and Methods Top


This study was conducted on 60 individuals, 40 with CHC (group 1) selected from patients admitted in the Tropical Medicine Department, Menoufia University Hospital, and Kafer-Elsheikh Liver Research Centre from November 2014 to November 2015. In total 26 (65.0%) of them were male and 14 (35.0%) were female, and their ages ranged from 19 to 57 years with a mean age of 40.77 ± 10.91 years. Twenty healthy individuals of matched age and sex were also included in the study as a control group (group 2). There were 11 (55.0%) male and nine (45.0%) female controls, and their ages ranged from 18 to 57 years, with a mean age of 36.20 ± 11.68 years. Informed consent was obtained before enrolment in the study. Approval from the local research ethical committee was obtained. Exclusion criteria were as follows: associated hepatitis B virus infection, α1 antitrypsin deficiency, Wilson's disease, haemochromatosis, alcoholic liver disease, autoimmune hepatitis, associated HCC, acute inflammatory disorder, phlebotomy and iron supplementation in the year preceding the liver biopsy, previously treated with antiviral agents, associated HIV infection and renal failure.

All patients were subjected to the following: full and detailed history taking, complete clinical examinations, laboratory investigations including complete blood count, liver function tests (alanine aminotransferase, aspartate aminotransferase, prothrombin concentration, serum albumin, total bilirubin and direct bilirubin), serum creatinine, antinuclear antibody, thyroid-stimulating hormone, α-fetoprotein, viral markers and PCR for hepatitis C. Serum hepcidin (ng/ml) was evaluated using ELAab human hepcidin prohormone ELISA kit [14]. Serum iron (μg/dl) was evaluated using Iron FerroZine Colorimetric ( Atlas More Details Medical, Waltham, MA) (quantitative determination of iron) [15]. Serum ferritin (ng/ml) was evaluated using Abcam's ferritin competitive human in-vitro ELISA kit [16]. Serum total iron-binding capacity (TIBC) (μg/dl) was evaluated using Randox TIBC colorimetric method [17], and abdominal ultrasound and liver biopsy for histopathological evaluation of CHC group patients according to Metavir score. The results were collected, tabulated, and statistically analysed using SPSS (version 20; IBM, Armonk, New York, USA).


  Results Top


In this study, PCR levels of HCV RNA of CHC patients revealed that 12.5% of patients had low viraemia (HCV RNA level: <100 000 IU/ml), 37.5% of patients had moderate viraemia (HCV RNA level: 100 000–1 000 000 IU/ml) and 50.0% of patients had high viraemia (HCV RNA level: >1 000 000 IU/ml), as shown in [Figure 1].
Figure 1: PCR levels of hepatitis C virus RNA in group 1.

Click here to view


Histopathological evaluation of chronic HCV patients according to Metavir score revealed that the degree of fibrosis in 55% of patients was F1, in 42.5% it was F2 and in 2.5% it was F3. As regards the activity of the disease, 55% of patients had A1 grade and 45% had A2 grade, as shown in [Figure 2].
Figure 2: Histopathological evaluation of chronic hepatitis C patients (group 1) according to Metavir score.

Click here to view


Serum hepcidin (ng/ml) was detected in both groups. There was a highly significant decrease in CHC patients when compared with healthy controls, with a mean ± SD of 7.95 ± 1.72 and 17.09 ± 1.19, respectively (P < 0.001). As regards serum iron (μg/dl) in both groups, there was a highly significant decrease in CHC patients when compared with healthy controls, with a mean ± SD of 68.34 ± 8.24 and 120.56 ± 10.03, respectively (P < 0.001). As regards serum ferritin (ng/ml) in both groups, there was a highly significant increase in CHC patients when compared with healthy controls, with a mean ± SD of 246.28 ± 15.12 and 101.21 ± 11.66, respectively (P < 0.001). Serum TIBC (μg/dl) was significantly higher in CHC patients than in controls, with a mean ± SD of 376.75 ± 10.46 and 295.6 ± 7.10, respectively (P < 0.001), as shown in [Table 1].
Table 1: Serum hepcidin (ng/ml), iron (μg/dl), ferritin (ng/ml) and total iron-binding capacity (μg/dl) of the studied groups

Click here to view


In this study, there was no statistically significant relation between hepcidin (ng/ml) level and degree of fibrosis, activity of the disease, HCV RNA level and sex of patients in the CHC group, as shown in [Table 2], [Table 3], [Table 4], [Table 5].
Table 2: Relation between the degree of fibrosis and serum hepcidin level (ng/ml) in chronic hepatitis C patients group

Click here to view
Table 3: Relation between the activity of the disease and serum hepcidin (ng/ml) level in chronic hepatitis C patients

Click here to view
Table 4: Relation between hepatitis C virus RNA level by polymerase chain reaction and serum hepcidin (ng/dl) of chronic hepatitis C patients

Click here to view
Table 5: Relation between sex of patients and serum hepcidin (ng/dl)

Click here to view


In this study, we found a significant positive correlation between serum hepcidin level (ng/ml) and serum iron level (μg/dl) in the CHC patient group, but a significant negative correlation between serum hepcidin level (ng/ml) and both serum TIBC level (μg/dl) and serum ferritin level (ng/ml), as shown in [Table 6].
Table 6: Spearman's correlation between serum hepcidin (ng/dl), serum iron (μg/dl), serum ferritin (ng/ml) and serum total iron-binding capacity (μg/dl) of the diseased group

Click here to view


There was a nonsignificant correlation between serum hepcidin level (ng/ml) and serum HCV RNA level, as shown in [Figure 3].
Figure 3: Correlation between serum hepcidin level and hepatitis C virus (HCV) RNA level.

Click here to view


In this study, we found a nonsignificant correlation between serum hepcidin level (ng/ml) and age of the patients in the CHC group, as shown in [Figure 4].
Figure 4: Correlation between serum hepcidin level and age.

Click here to view


As regards hepcidin/ferritin ratio, we found that there was a high statistically significant difference between CHC patients and healthy controls, as it was lower in the CHC group (0.033 ± 0.009 and 0.172 ± 0.031, respectively), as shown in [Table 7].
Table 7: Hepcidin/ferritin ratio of the studied groups

Click here to view



  Discussion Top


Egypt has the highest prevalence of adult HCV infection in the world (15–25%) and the main type of HCV genotype (90%) is type 4 [18]. Importantly, CHC often appears to be associated with disturbances in iron homoeostasis, with serum ferritin and hepatic iron stores being elevated in ~50% of patients [19]. Many hypotheses have been advanced to explain the accumulation of iron in CHC, including local release of iron from necrotic hepatocytes, incidental carriage of haemochromatosis mutations and HCV-induced perturbation of liver iron homoeostasis either directly or indirectly through immunologic and host response [9]. With the discovery of hepcidin, the liver has emerged as the central organ in the regulation of systemic iron homoeostasis [10].

This study was conducted on 60 participants. These participants were classified into two groups. Group 1 included 40 patients with CHC; 65.0% of them were male and 35.0% were female. Their ages ranged from 19 to 57 years, with a mean age of 40.77 ± 10.91 years. Group 2 included 20 healthy individuals of matched age and sex who served as a control group. There were 11 (55.0%) male and nine (45.0%) female controls. Their ages ranged from 18 to 57 years, with a mean age of 36.20 ± 11.68 years. There was no significant difference between the two groups as regards age and sex, indicating no bias in this study. In the current study, there was no statistically significant difference between the studied groups as regards clinical assessment, including ascites, haematemsis, melena and encephalopathy (P > 0.05), but there was a statistically significant difference between the studied groups as regards presentation with jaundice (P < 0.05).

In the current study, there was no statistically significant difference between the studied groups as regards complete blood count, blood glucose and serum creatinine (P > 0.05). This was observed by Marzouk et al. [20] as well.

In the present work, there was a statistically significant difference between the studied groups as regards alanine aminotransferase and aspartate aminotransferase (P > 0.05), with a mean ± SD of 72.17 ± 39.37 and 67.57 ± 46.5, respectively, in the CHC group versus 30.75 ± 1.71 and 28.5 ± 1.79 in the control group. This is in agreement with the findings of Marzouk et al. [20].

In the current study, we demonstrated that CHC patients had a highly significantly lower hepcidin concentrations than those of matched controls. Hepcidin downregulation is likely to contribute to liver iron accumulation in this condition, and HCV infection may directly modulate hepcidin expression as it induces reactive oxygen species (ROS) through increased histone deacetylase activity. This is in agreement with the findings of Nagashima et al. [21], Fujita et al. [22], Nishina et al. [23] and Girelli et al. [24], who stated that serum hepcidin was significantly lower in CHC patients than in controls. They attributed this to the suppressive effect of ROS, which is induced by HCV on hepcidin production. However, our study is not in agreement with the findings of Wrighting and Andrews [25] and Trinder et al. [26], who attributed that to the upregulation of hepcidin production by proinflammatory cytokines, particularly interleukin-6 that counteracts ROS-induced hepcidin suppression. Tsochatzis et al. [27] had a midway view seeing that HCV infection downregulates serum hepcidin, whereas increasing inflammation and/or fibrosis tend to restore its levels. As a consequence, hepcidin downregulation could be indirectly documented only after normalization of ferritin values by means of the so-called hepcidin/ferritin ratio.

In the current study, we found that there was a highly statistically significant difference between the studied groups as regards serum iron (P < 0.001), as it was lower in the HCV group than in the control group, with a mean ± SD of 68.34 ± 8.24 and 120.56 ± 10.03, respectively. This is in agreement with the findings of Fujita et al. [22], who found that mild anaemia state was a complication in CHC patients, and Marzouk et al. [20], who found a highly statistically significant difference between the studied groups as regards serum iron (P < 0.001) as it was lower in the CHC group than in the control group, with a mean ± SD of 86.73 ± 15.13 and 114.22 ± 22.82, respectively. However, this is in disagreement with the findings of El Wakil et al. [28], who found no statistically significant difference between the two studied groups as regards serum iron levels (P > 0.05) that were higher in the CHC group than in the control group, with a mean ± SD of 136.1 ± 86.2 and 118.1 ± 99.9, respectively.

In the current study, serum ferritin was significantly higher in the CHC group than in control group (P < 0.001), with a mean ± SD of 246.28 ± 15.12 and 101.21 ± 11.66, respectively. This is in agreement with the findings of Fujita et al. [22], who found that serum ferritin was significantly higher in the CHC group than in the control group (P < 0.001); Sugimoto et al. [29], who found that serum ferritin was significantly higher in the CHC group than in the control group (P < 0.001) (mean ± SD: 433 ± 210 and 54 ± 30, respectively); El Wakil et al. [28], who found that serum ferritin was significantly higher in the CHC group than in the control group (P < 0.05) (mean ± SD: 165.9 ± 120.9 and 98.5 ± 77.6, respectively) and Marzouk et al. [20], who found that serum ferritin was significantly higher in the CHC group than in the control group (P < 0.001) (mean ± SD: 284.45 ± 63.19 and 93.06 ± 28.82, respectively).

In the present work, serum TIBC was significantly higher in the CHC group than in the control group (P < 0.001), with a mean ± SD of 376 ± 75 and 295.6 ± 7.10, respectively. This is in agreement with the findings of Olmez et al. [30], who found that serum TIBC was significantly higher in group 1 than in group 2 (P < 0.05), with a mean ± SD of 427.44 ± 94.11 and 363.16 ± 49.38, respectively, and this confirmed the low serum iron level.

To evaluate the relative amounts of hepcidin in relation to iron burden, we calculated the ratio of serum hepcidin/ferritin in each participant. The hepcidin/ferritin ratio was significantly lower in the CHC group than in the control group (P < 0.001), with a mean ± SD of 0.023 ± 0.053 and 0.141 ± 0.266, respectively, indicating that hepcidin production per iron burden was relatively impaired in CHC patients. This is in agreement with the findings of Fujita et al. [22], who found that the hepcidin/ferritin ratio was significantly lower in the CHC group than in the control group (P < 0.05); Sugimoto et al. [29], who found that the hepcidin/ferritin ratio was significantly lower in the CHC group than in the control group (P < 0.05) (mean ± SD: 0.33 ± 0.41 and 0.73 ± 0.36, respectively); Tsochatzis et al. [27], who found that the hepcidin/ferritin ratio was significantly lower in the CHC group than in the control group (P < 0.05) (mean ± SD: 0.46 ± 0.82 and 15 ± 21, respectively) and Alkhateeb AA et al. [16], who found that the hepcidin/ferritin ratio was significantly lower in the CHC group than in the control group (P < 0.05) (mean ± SD: 0.21 ± 0.021 and 1.74 ± 2.75, respectively). However, it is in disagreement with the findings of El Wakil et al. [28], who found no statistically significant difference between the CHC group and the control group (P > 0.05) (mean ± SD: 0.58 ± 0.3 and 0.60 ± 0.4, respectively).

In the current study, there was a negative correlation between serum ferritin and serum hepcidin (r=−0.40). This is in agreement with the findings of Nagashima et al. [21], who found that prohepcidin had a negative correlation with serum ferritin (r=−0.182). However, it is in disagreement with the findings of Aoki et al. [31] and Fujita et al. [32], who found a positive correlation between mRNA hepcidin and ferritin (r = 0.60 and 0.823, respectively).

In the present study, there was a significant positive correlation between serum hepcidin and serum iron. Similarly, Girelli et al. [24] and El Wakil et al. [28] found a positive correlation between serum prohepcidin and serum iron (r = 0.326 and 0.216, respectively). However, it is in disagreement with the findings of Olmez et al. [30], who found no significant correlation between serum iron and serum hepcidin.

In the current study, there was no statistically significant relation between serum hepcidin and histopathological grading of CHC (P > 0.05). This is in agreement with the findings of Aoki et al. [31], who found no significant relation between serum hepcidin and histopathological grading of CHC. Fujita et al. [32] and Sugimoto et al. [29] found no statistically significant relation between serum hepcidin level and the histological inflammatory activity (P > 0.05).

According to the hypothesis of a direct suppressive effect of HCV on liver hepcidin expression, one could anticipate an inverse relationship between viral load and circulating hepcidin levels. However, in our study we found no statistically significant relation between serum hepcidin and HCV RNA level (P > 0.05). This is in agreement with the findings of Aoki et al. [31] and Marzouk et al. [20], who found no statistically significant relation between PCR level for HCV and serum hepcidin level (P > 0.05).

In the present work, we found a nonsignificant correlation between serum hepcidin and both degree of fibrosis and activity of the disease (r = −0.064 and −0.061, respectively). This is in agreement with the findings of Détivaud et al. [33] and Nagashimo et al. [21], who found a nonsignificant correlation between serum hepcidin and both degree of fibrosis and activity of the disease. However, it is different from the findings of Tsochatzis et al. [27], as they found a significant correlation between serum hepcidin and both degree of fibrosis and activity of the disease up to finding hepcidin as an independent predictor of fibrosis.

In this study, we found a nonsignificant correlation between serum hepcidin and HCV RNA level (r = −0.206). This is in agreement with the findings of Aoki et al. [31], who found a nonsignificant correlation between serum hepcidin and HCV RNA level (r = −0.23).

In this study, we found a nonsignificant correlation between serum hepcidin and age of patients (r = −0.185). This is in agreement with the findings of Aoki et al. [31], who found a nonsignificant correlation between serum hepcidin and age of patients (r = −0.12).


  Conclusion Top


Hepcidin levels in patients with CHC were significantly lower than that in HCV-negative individuals. It is an important factor in iron abnormalities and is detected in such cases in which serum iron levels were significantly low. However, serum ferritin and serum TIBC were significantly high in CHC compared with HCV-negative individuals.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Houghton M. The long and winding road leading to the identification of the hepatitis C virus. J Hepatol 2009; 51:939–948.  Back to cited text no. 1
    
2.
Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127:S35–S50.  Back to cited text no. 2
    
3.
Bonkovsky HL, Troy N, McNeal K, Banner BF, Sharma A, Obando J, et al. Iron and HFE or Tfr1 mutations as comorbid factors and progression of chronic hepatitis C. J Hepatol 2002; 37:848–858.  Back to cited text no. 3
    
4.
Guyader D, Thirouard AS, Erdtmann L, Rakba N, Jacquelinet S, Danielou H, et al. Liver iron is a surrogate marker of severe fibrosis in chronic hepatitis C. J Hepatol. 2007; 46:587–595.  Back to cited text no. 4
    
5.
Lebray P, Zylberberg H, Hue S, Poulet B, Carnot F, Martin S, et al. Influence of HFE gene polymorphisms on the progression and treatment of chronic hepatitis C. J Viral Hepat 2004; 11:175–182.  Back to cited text no. 5
    
6.
Kageyama F, Kobayashi Y, Kawasaki T, Toyokuni S, Uchida K, Nakamura H. Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C. Am J Gastroenterol 2000; 95:1041–1050.  Back to cited text no. 6
    
7.
Fargion S, Fracanzani AL, Rossini A, Borzio M, Riggio O, Belloni G, et al. Iron reduction and sustained response to interferon-α therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study. Am J Gastroenterol 2002; 97:1204–1210.  Back to cited text no. 7
    
8.
Kato J, Kobune M, Nakamura T, Kuroiwa G, Takada K, Takimoto R, et al. Normalization of elevated hepatic 8-hydroxy-2′-deoxyguanosine level in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res 2001; 61:8697–8702.  Back to cited text no. 8
    
9.
Pietrangelo A. Hemochromatosis gene modifies course of hepatitis C viral infection. Gastroenterology. 2003; 124:1509–1523.  Back to cited text no. 9
    
10.
Pietrangelo A. Hemochromatosis: an endocrine liver disease. Hepatology. 2007; 46:1291–1301.  Back to cited text no. 10
    
11.
El-Shafie AM, El-Mashad GM, Hegran HH, El-Deeb MM. Serum hepcidin level in children with chronic renal failure either on hemodialysis or on conservative therapy. Menouf Med J 2015; 28:571–577.  Back to cited text no. 11
    
12.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004; 113:1271–1276.  Back to cited text no. 12
    
13.
Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003; 102:783–788.  Back to cited text no. 13
    
14.
Pardanani A, Finke C, Abdelrahman RA, Lasho TL, Tefferi A. Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis. Am J Hematol 2013; 88:312–316.  Back to cited text no. 14
    
15.
Budak H, Kocpinar EF, Gonul N, Ceylan H, Erol HS, Erdogan O. Stimulation of gene expression and activity of antioxidant related enzyme in Sprague Dawley rat kidney induced by long-term iron toxicity. Comp Biochem Physiol C Toxicol Pharmacol 2014; 166:44–50.  Back to cited text no. 15
    
16.
Alkhateeb AA, Leitzel K, Ali SM, Campbell-Baird C, Evans M, Fuchs EM, et al. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy. PLoS One 2012; 7:51379.  Back to cited text no. 16
    
17.
Siek G, Lawlor J, Pelczar D, Sane M, Musto J. Direct serum total iron-binding capacity assay suitable for automated analyzers. Clin Chem 2002; 48:161–166.  Back to cited text no. 17
    
18.
Nouroz F, Shaheen S, Mujtaba G, Noreen S. An overview on hepatitis C virus genotypes and its control. Egypt J Med Hum Genet 2015; 16:291–298.  Back to cited text no. 18
    
19.
Silvia TSS, Perez RM, Oliveira PV, Cantagalo MI, Dantas E, Sisti C, et al. Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study. J Gastroenterol Hepatol 2005; 20:243–248.  Back to cited text no. 19
    
20.
Marzouk HA, Azayed N, Al-Ansary M, Abdelbary MS, Hunter SS, Safwat W, et al. Hepcidin levels in Egyptian patients with chronic hepatitis C. World Appl Sci J 2013; 22:1145.  Back to cited text no. 20
    
21.
Nagashima M, Kudo M, Chung H, Ishikawa E, Hagiwara S, Nakatani T, et al. Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 2006; 36:288–293.  Back to cited text no. 21
    
22.
Fujita N, Sugimoto R, Motonishi S, Tomosugi N, Tanaka H, Takeo M, et al. Patients with chronic hepatitis C achieving a sustained virological response to peginterferon and ribavirin therapy recover from impaired hepcidin secretion. J Hepatol 2008; 49:702–710.  Back to cited text no. 22
    
23.
Nishina S, Hino K, Korenaga M, Vecchi C, Pietrangelo A, Mizukami Y, et al. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology 2008; 134:226–238.  Back to cited text no. 23
    
24.
Girelli D, Pasino M, Julia B, Nemeth E, Guido M, Castagna A, et al. Reduced serum hepcidin levels in patients with chronic hepatitis C. J Hepatol 2009; 51:845–852.  Back to cited text no. 24
    
25.
Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006; 108:3204–3209.  Back to cited text no. 25
    
26.
Trinder D, Ayonrinde OT, Olynyk JK. HCV, iron, and oxidative stress: the new choreography of hepcidin. Gastroenterology 2008; 134:348–351.  Back to cited text no. 26
    
27.
Tsochatzis E, Papatheodoridis GV, Koliaraki V, Hadziyannis E, Kafiri G, Manesis EK, et al. Serum hepcidin levels are related to the severity of liver histological lesions in chronic hepatitis C. J Viral Hepat 2010; 17:800–806.  Back to cited text no. 27
    
28.
El Wakil R, Mokhles M, Tohamy A, Sharaf W, Rasmy H, Ibrahim A. Hepcidin and chronic hepatitis C: exploring the controversy. Aust J Basic Appl Sci2012; 6:558–565.  Back to cited text no. 28
    
29.
Sugimoto R, Fujita N, Tomosugi N, Hara N, Miyachi H, Tanaka H, et al. Impaired regulation of serum hepcidin during phlebotomy in patients with chronic hepatitis. Hepatol Res 2009; 39:619–624.  Back to cited text no. 29
    
30.
Olmez OF, Gurel S, Yilmaz Y. Plasma prohepcidin levels in patients with chronic viral hepatitis: relationship with liver fibrosis. Eur J Gastroenterol Hepatol 2010; 22:461–465.  Back to cited text no. 30
    
31.
Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL. Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 2005; 39:71–74.  Back to cited text no. 31
    
32.
Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R, Tanaka H, et al. Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C. Mol Med 2007; 1:97–104.  Back to cited text no. 32
    
33.
Détivaud L, Nemeth E, Boudjema K, Turlin B, Troadec MB, Leroyer P, et al. Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood 2005; 106:746–748.  Back to cited text no. 33
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed688    
    Printed6    
    Emailed0    
    PDF Downloaded78    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]