The Correlation of the Hepcidin Ferritin Ratio and the Severity of

Liver Cirrhosis

Imelda Rey

1,2 *

, Rustam Effendi-Ys

1,3

and Khairani Sukatendel

Division of Gastroenterohepatology, Internal Medicine Department, Universitas Sumatera Utara , Medan, Indonesia

Adam Malik General Hospital, Medan, Indonesia

Pirngadi General Hospital, Medan, Indonesia

Department of Obstetric and Gynecology, Universitas Sumatera Utara, Medan, Indonesia

Keywords: Hepcidin, Liver Cirrhosis, Severity.

Abstract: Background. Hepcidin serum level was influenced by the inflammation and iron deposit in chronic liver

disease / CLD), but the correlation between the hepcidin ferritin ratio and the severity of liver cirrhosis was

still not clear. The aim of this study was to found correlation between the hepcidin ferritin ratio and the

severity of liver cirrhosis. Methods. The study was conducted in Gastroenterohepatology Division, Internal

Medicine Department, Faculty of Medicine, University of Sumatera Utara. The study was an analytic

comparative, cross sectional study. The subject were liver cirrhosis patients that fulllfiled inclusion criteria

and informed consent. Results. From 78 liver cirrhosis patients, mean age was 51.36 ± 12.6 years old. Male

was more than female ( 44 (56%), 34 (43.6%), respectively. We found that there was no significant

difference of the hepcidin ferritin ratio among Child pugh A , Child pugh B and Child pugh C patients (0.17

; 0.11 and 0.28, respectively, with p = 0.161). Conclusion. There was no significant difference of the

hepcidin ferritin ratio among severity of liver cirrhosis.

1 INTRODUCTION

Hepcidin is the hormone of iron which produced in

the liver as a response to inflammation and iron that

triggered by cytokines during inflammation.

Hepcidine inhibits iron entry into the compartment

of plasma, as the principal regulator of systemic iron

homeostasis (Piperno, 2009). It is produced almost

exclusively by the hepatocytes as response to the

iron (Pigeon, 2001) and stimuli of inflammation

(Nicolas, 2002). When the level of iron is deficient,

hepatocytes will develop less or no hepcidin, and

allowing more iron to enter into plasma (Ramos,

2011).

Iron is an essential element and required in

metabolic processes such as, oxygen transport, DNA

synthesis and energy production. The excess of iron

can be harmful, in part through the formation of

reaxtive oxygen species (ROS), and it is potentially

lethal (Hentze, 2004). The correlation between

expression of hepcidin and iron burden or

inflamation condition has been reported. The

concentration of hepcidin is affected by

inflammation and iron stores in the condition of

chronic liver disease (CLD), but less is known about

the correlation between the ratio of hepcidin :

ferritin and the severity of liver cirrhosis.

Liver cirrhosis is a liver disease complication

which characterized by the disapperance of liver

cells and the formation of connective tissue in an

irreversible liver (Dooley, 2011).

The study was conducted to evaluated level of

hepcidin, ferritin and the hepcidin:ferritin ratio by

cross sectional study in consecutive patients with

liver chirrosis. The purpose of this study was to

determine the serum levels of hepcidin ferritin ratio

and to evaluate its correlation to the severity of liver

chirrosis.

2 METHOD

This was an analytic comparative, cross-sectional

study on liver chirrosis patients, that were admitted

to Gastroenterohepatology Division, Internal

Medicine Department, Faculty of Medicine,

University of Sumatera Utara.

Rey, I., Effendi-Ys, R. and Sukatendel, K.

The Correlation of the Hepcidin Ferritin Ratio and the Severity of Liver Cirrhosis.

DOI: 10.5220/0010070304290432

In Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches (ICOSTEERR 2018) - Research in Industry 4.0, pages

429-432

ISBN: 978-989-758-449-7

429

2.1 Patients Selection

Serum hepcidin and ferritin was measured in 78

liver cirrhosis patients that fulllfiled inclusion

criteria and informed consent. The inclusion criteria

was liver cirrhosis patients that confirmed by clinical

findings, laboratory parameters, imaging or

histopathological examination.

The exclusion criteria were hepatoma, sepsis and

chronic kidney disease and refused to participated in

the study.

2.2 Hepcidin: Ferritin Ratio

2.2.1 Hepcidin

The blood samples were collected from cubital vein

samples in the morning after 12 hours of fasting.The

determination of hepcidin hormone concentration

in the serum was used ELISA method . It is under

the following reference ranges: women - from 57.5

to 123 ng / ml; males - 88.7 to 135 ng / ml.

2.2.2 Ferritin

The blood samples were obtained by vein puncture.

The measurement of ferritin used Roche Elecsys-

170 method which a sandwich principle with a total

duration time of 18 minutes. The concentration of

iron serum (women: 10.5 to 23 mmol / L ; men: 12.5

to 26 mmol / L;), total iron-binding capacity (JAC,

44 to 66 mmol / L), and serum ferritin (females: 10

to 140 mg / L men: 20 to 280 mg / L ). It was

determinated and the saturation of transferrin (with

reference range 20-40%).

2.3 Statistical Method

The data was analyzed by univariate analysis using

the SPSS 22

version

3 RESULTS

The study was investigated 78 patients that classified

in inclusion criteria. There were 78 patients with

liver chirrosis, male patients (56,4%) were dominant

than female patients (43,6%). The average age of the

patient was 52

years. Liver chirrosis patients with

ascites are 63 persons (80,8%). The severity of liver

cirrhosis is divided accroding to the Child Pugh

category. The number of patient that included in the

Child Pugh A was 15 persons (19,2%), Child Pugh

B was 17 persons (21,8%) and Child Pugh C was 46

persons (59%). The severity of liver cirrhosis based

on the Child Pugh category will be compared to its

hepcidin ferritin ratio. Characteristic of research

subjects can be seen in Table 1.

Table 1 : Characteristic of Patients

Variable n = 78

Gender

Male

Female

44 (56,4%)

34 (43,6%)

Age 51,36+ 12,6

Ascites

Yes

63 (80,8%)

15 (19,2%)

Hepatic Encephalopathy

Yes

9 (12,5%)

69 (87,5%)

Child Pugh

15 (19,2%)

17 (21,8%)

46 (59%)

HFR Category

≥ 0,1

< 0,1

34 (43,6%)

44 (56,4%)

Categorical data : n(%)

Numeric data, normal distribution : mean + SD

From laboratory data, the average of the serum

iron was 36 mmol/L, the average of the ferritin was

237 mg/L and the average of hepcidin was 17,74

ng/mL. The laboratory characteristic of research

subjects can be seen in Table 2.

Table 2 : Laboratory characteristics of research subjects

Baseline

characteristics

Value

Hemoglobin (gr/dL) 10,15 ± 2,53

Platelet count

(thousand/mm

)

144.500 (12.000-

654.000)

Albumin (g/dL) 2,3 (0,9-3,7)

INR 1,28(0,89-3,71)

Total Bilirubin (mg/dL) 2,4 (0,2-21,9)

AST (U/L) 52 (15-377)

ALT (U/L) 43 (8-246)

ALP (U/L) 120,75 + 53,41

SI (ug/dL) 36 (10-345)

TIBC (ug/dL) 165,5 (59-520)

Ferritin (ug/dL) 237 (4,16-6078)

Reticulocyte 1,9 (0,9-7,87)

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

430

CRP (mg/dL) 2,6 (0,1-14)

Hepcidin 17,74 (1,15-275,22)

IL-6 8,22 (0,62-2107,9)

Numerical data, normal distribution : mean + SD

Numerical data, abnormal distribution : median

(minimum-maximum)

A comparison of laboratory findings between

liver cirrhosis with Child Pugh A, B and C group

can be seen in Tabel 3. There was no significant

difference between the hepcidin : ferritin ratio

among Child pugh A , Child pugh B and Child pugh

C of patients (0.17 ; 0.11 and 0.28, respectively,

with p = 0.161).

Table 3 : Comparison of Laboratory Parameters Between

Hepatic Cirrhosis of Child Pugh A, B, and C

Laborator

Child

Pugh

A (n

=15)

Child

Pugh

B (n =

17)

Child

Pugh C

(n= 46)

Total

Bilirubin

(mg/dL)

0,8

(0,3 –

4,3)

1,8

(0,2 –

21,9)

3,15

(0,2 –

13,6)

0,007

INR

1,06

(0,89 –

2,1)

1,18

(0,89

–

2,26)

1,39

(0,89 –

3,71)

0,008

Albumin

(g/dL)

3,2

(1,7 –

3,7)

2,3

(0,9 –

3,5

2,3 (1 –

3,6)

0,001

Hemoglobi

n (g/dL)

11,43

+ 2,5

10,13

+ 2,69

9,69+

2,33

Leukocytes

(cell/mm

)

8.620

(3.300

–

22.930

)

5.850

(2.100

–

29.000

)

6.625

(1.830

–

35.190)

0,140

Platelet

count

(thousand/

)

268.00

(12.00

0 –

420.00

164.00

(22.00

0 –

509.00

127.00

(15.000

–

654.00

0,010

Reticulocyt

1,3

(0,9 –

6,6)

1,9 (1

–

4,03)

2,05

(0,9 –

7,87)

0,057

(ug/dL)

36 (11

– 100)

37 (12

– 160)

31,5

(10 –

345)

0,862

TIBC

(ug/dL)

146

(59 –

452)

195

(65 –

490)

170,5

(100 –

520)

0,356

Hepcidin

34,08

(1,75 –

30,19

(1,26

9,97

(1,15 –

0,019

275,22

)

–

178,6)

109,24)

Ferritin

(ug/dL)

121

(4,16 –

896)

546,55

(5,08

–

1249,5

)

237 (8

– 6070)

0,310

Hepcidin:F

erritin

0,17

(0,0-

8,19)

0,11

(0,0-

1,65)

0,28

(0,0-

13,62)

0,161

*p<0.05

The result in this group significantly different with the

Child Pugh A group (p<0,05)

The result in this group significantly different with the

Child Pugh B group (p<0,05)

Numerical data, normal distribution : mean + SD

Numerical data, abnormal distribution : median (min-

max)

Figure 1 : Comparison of serum hepcidin ferritin ratio and

the severity of liver chirrosis

4 DISCUSSION

The concentration of hepcidin serum has been

evaluated in inflammatory diseases and iron-related

disorders (Van Der, 2010; Oustamanolakis, 2011).

There is lack of data regarding to hepcidin

concentrations in the liver chirrosis. Although some

study showed that hepcidin concentration could be

utilized as a cirrhosis diagnostic tool, but it is

remains unclear (Tsochatzis, 2010). The elevated of

iron stores and inflammation may increases serum

hepcidin and ferritin levels. However, hepcidin

levels of liver disease patients were reduced in

correlated to ferritin, resulting a decreased

hepcidin:ferritin ratio (Terrence, 2012). This was

confirm in our study, we found that there was

significantly difference of hepcidin serum level in

The Correlation of the Hepcidin Ferritin Ratio and the Severity of Liver Cirrhosis

431

Child pugh A, B and C group with p<0.05, but we

also found that there was no significant difference of

the hepcidin:ferritin ratio among Child pugh A,

Child pugh B and Child pugh C patients (0.17 ; 0.11

and 0.28, respectively, with p = 0.161).

The data showed that there was a progressive fall

in the hepcidin serum level in patient with liver

cirrhosis, indicating a correlation between the

presence and severity of liver cirrhosis and hepcidin

concentration. The increased accumulation of iron in

the body also directly related to ferritin serum level.

The study concluded that increasing hepatic

fibrosis in CLD is not associated with decreased

hepcidin, relative to ferritin. Further study are

needed for the ratio of hepcidin:ferritin as a potential

biomarker to determine the severity of liver

cirrhosis.

5 CONCLUSIONS

There was no significant difference of the hepcidin

ferritin ratio among severity of liver cirrhosis.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge that the present

research is supported by Ministry of Research and

Technology and Higher Education Republic of

Indonesia. The support is under the research grant

DRPM, PDUPT scheme 2018, Contract Number

66/UN5.2.3.1/PPM/KP-DRPM/2018.

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