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Correlation of growth factors and liver histological changes in patients with chronic viral hepatitis and liver cirrhosis

Yagoda A.V. Koroy P.V.
Stavropol State Medical Academy, Russia

The aim of study to assess diagnostic importance of growth factors as noninvasive markers of degree of liver inflammation and fibrosis in chronic viral liver diseases.

Materials and methods: serum levels of transforming growth factor-β1 (TGF-β1), insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) were determined by ELISA method in 43 patients with chronic viral hepatitis, in 5 patients with liver cirrhosis viral etiology and in 10 healthy subjects. “Index regeneration” (IR) as ratio of IGF-I+EGF to TGF-β1 was calculated. Histological activity score and fibrosis stage (according index Knodell and index Desmet, respectively) were estimated in liver biopsies.

Results: TGF-β1, EGF were increased in chronic viral hepatitis and liver cirrhosis, the maximal contents were observed in cases of liver cirrhosis. IGF-I was increased in patients with chronic viral hepatitis and reduced in liver cirrhosis.

TGF-β1 was elevated with increased histological activity. IGF-I and EGF were enlarged at minimal and slight histological activity and decreased at high Knodell’s index. IR was decreased with increased histological inflammatory activity. Positive correlation between TGF-β1 and histological activity were observed (r= 0,39, p<0,05). IGF-I, EGF, IR were negatively correlated with histological activity (r= -0,32, r= -0,48, r= -0,43, p<0,05, respectively).

Table
Growth factors and IR in patients with different expressiveness of liver fibrosis ()






Groups

TGF-1, ng/ml

IGF-I, ng/ml

EGF, pg/ml

IR

Control, n=10

2,09±0,3

125,01±6,02

20,59±1,41

86,02±6,53

Patients with fibrosis’s index

F0, n=6

(1)

9,87±1,62

442,80±23,27 *

45,93±2,28 *

56,96±9,13 *

F1, n=17

(2)

16,72±2,99 *

252,72±18,27 *

37,84±2,22 *

24,66±3,64 *

F2, n=15

(3)

24,33±2,38 *

228,71±16,73 *

26,73±2,00

11,62±1,05 *

F3, n=5

(4)

30,92±0,43 *

169,56±17,20

18,84±2,29

6,11±0,65 *

F4, n=5

(5)

33,87±0,88 *

64,30±5,25 *

53,29±1,75 *

3,47±0,20 *

р1-2

>0,05

<0,05

<0,05

<0,05

р1-3

<0,05

<0,05

<0,05

<0,05

р1-4

<0,05

<0,05

<0,05

<0,05

р1-5

<0,05

<0,05

>0,05

<0,05

р2-3

<0,05

>0,05

<0,05

<0,05

р2-4

<0,05

<0,05

<0,05

<0,05

р2-5

<0,05

<0,05

<0,05

<0,05

р3-4

>0,05

>0,05

>0,05

>0,05

р3-5

>0,05

<0,05

<0,05

>0,05

р4-5

>0,05

<0,05

<0,05

>0,05

* – р<0,05 in comparison to control.

TGF-β1 was elevated with increased liver fibrosis, its maximal content was at stage 4 on Desmet (tab.). IGF-I was elevated at fibrosis’s index 0, 1 and 2 and reduced in liver cirrhosis (index Desmet 4). EGF was elevated at fibrosis’s index 0, 1 and 4. IR was decreased with increased liver fibrosis. Significant positive correlation between TGF-β1 and liver fibrosis were observed (r= 0,82, p<0,05). IGF-I, EGF, IR were significant negatively correlated with liver fibrosis (r= -0,65, r= -0,73, r= -0,71, p<0.05, respectively).

Liver fibrosis stage was positively correlated with degree of inflammation (r= 0,64, p<0,05).

Conclusion: serum levels of growth factors are closely connected to expressiveness of liver inflammation and fibrosis. Measurement of serum levels of growth factors may be useful for noninvasive assessment of liver histological changes in chronic viral liver diseases.