ARCH GASTROENTEROHEPATOL 2000; 19 ( No 3 - 4 ):
Serumski kortizol u pacijenata sa hronicnim hepatitisom B
( revised manuscript accepted November 13¸ 2000 )
Cortisolemia in chronic HBV hepatitis
1Emel Turk Aribas, 2Mustafa Altinidis
1Department of Clinical Bacteriology and Infective Diseases, Selcuk
University Medical Faculty, Konya, 2Department of Microbiology
and Clinical Microbiology, Kotacepe University Medical Faculty, Afyon,
Address correspondence to: Mustafa Altinidis, MD,PhD.
Karagozoglu sok Alimoglu apt 25
03200 – Afyon, Turkey
E-mail: [email protected]
Abbreviations used in this article: chronic active hepatitis, CAH;
chronic persistent hepatitis, CPH; hepatitis B virus, HBV; hepatitis
D virus, HDV ; hepatitis C virus, HCV.
We prospectively investigated serum cortisol level in patients with chronic hepatitis B virus infection. Forty-six patients, 36 with chronic active hepatitis and 10 with chronic persistent hepatitis enrolled this study. Sixteen cases were HBe positive, 32 HBe negative. In the patients group serum cortisol level was 17.8+6.7 ug/dl. In the control group 12.3+7.9 ug/dl what was significantly lower ( p<0.05 ). In patiens with chronic active hepatitis serum cortisol was 18.3+7.7 ug/dl, in chronic persistent hepatitis 18.8+32. ug/dl what was not of statistical significance. However, serum cortisol level in patients with chronic active hepatitis was significantly higher than in controls ( p<0.05 ). Serum cortisol level in HBe positive patients was 19.6+7.0 ug/dl, and in HBe negative 17+6.9 ug/dl what was not of statistical significance. On the contrary serum cortisol level in HBe positive group was significantly higher than in controls ( p<0.05 ).
Key words: HBV, chronic hepatitis, serum cortisol.
U ovoj studiji je sprovedeno ispitivanje nivoa kortizola u krvi u bolesnika sa hronicnom hepatitis B virusnom infekcijom. Ispitano je 46 pacijenata, 36 sa hronicnim aktivnim i 10 sa hronicnim perzistetnim hepatitisom. Sesnaestoro je bilo HBe pozitivno, 32 HBe negativno. U grupi pacijenata nivo kortizola u krvi je bio 17.8+6.7 ug/dl, a u kontrolnoj grupi 12.3+ 7.9 ug/dl sto je statisticki znacajna razlika ( p<0.05 ). U osoba sa hronicnim aktivnim hepatitisom kortizolemija je bila 18.3+7.7 ug/dl, a u onih sa hronicnim perzistentim hepatitisom 15.8+3.2 ug/dl sto nije statisticki znacajna razlika. Medjutim, u osoba sa hronicnim aktivnim hepatitisom kortizol u krvi je bio statisticki znacajnije veci nego u zdravih osoba kontrolne grupe ( p<0.05 ). Kortizolemija u HBe pozitivnih osoba je bila 19.6+7 ug/dl, a u HBe negativnih 17+6.9 ug/dl sto nije statisticki znacajno. Nasuprot tome serumski kortizol je u HBe pozitivnih bolesnika znacajno visi nego u kontrolnoj grupi ( p<0.05 ).
Kljucne reci: hepatitis B virus, hronicni hepatitis, serumski kortizol.
The exact mechanism of chronicity of hepatitis B virus ( HBV ) infection is not fully elucidated. Viral escape from T-cell recognition due to its weak peptide recognition and antigenic transformation and/or viral hiding at places isolated from components of immune system is one possible explanation ( 1 ). Insufficient cellular immune reponse, which permits viral replication and lead to chronicity, is another possible mechanism. It is well known that glucocorticoids accelerate viral replication in infected persons ( 2 ). By analogy one may presume that higher cortisolemia may play some role in chronicity of HBV infection. We therefore explored the prognostic value of serum cortisol level in chronic HBV infection.
Forty-six patients with chronic HBV infection diagnosed between December 1996 and June 1999 at Selcuk University Medical Faculty, Infectious Diseases Department enrolled this study. Parallel HDV and HCV infections were excluded. Diagnosis of chronic hepatitis was based on liver histology when HBs antigen positivity was six months or longer. In addition, HBV markers such as HBe antigen, anti-HBe, anti-HBc IgM and anti-HBc IgG antibodies were examined in all cases. Thirty-five ( 76.1% ) patients were male, 11 ( 23.9% ) females, mean age 32+12.6 years ( age range: 13 to 70 ). Thirty-eight healthy persons from the group applied for HBV immunisation served as controls. Their sex distribution was 23 ( 60.5% ) males and 15 ( 39.5% ) females, mean age 31.1+10.5 years ( age range: 17 to 63 ). All controls had normal serum transminases and negative HBV markers. HBV markers were detected by ELISA test. Cortisol level was determined by solid phase chemiluminescent immunoassay using “ Immulite cortisol “ kits. All results were evaluated by means of t test and SSPS for Windows 8.0 program.
In patients with chronic HBV infection mean serum cortisol level was 17.8+6.7 ug/dl ( range: 5.50 to 40.93 ), in controls 12.31+7.9 ug/dl ( range: 4 – 43 /28). In patient , s group cortisolemia was significantly higher than in controls ( t=3.32, p<0.05 ). Distribution of cortisol level in HBV infected patients with CAH and CPH was demonstrated on table 1. Cortisolemia in patients with CAH and CPH were 18.31+7.66 ug/dl and 15.77+3.18 ug/dl respectively. There were no differences among CAH and CPH cases. On the contrary, in patients with CAH serum cortisol was significantly higher than in controls ( t=3.33, p<0.05 ). There was no statistical difference between cortisol level between CPH and control cases. Relationship between serum cortisol concentrations and HBe positivity was shown on table 2. Cortisol level in HBe positive cases was 19.6+7 ug/dl, in HBe negative 17+6.9 ug/dl what was statistically insignificant ( t=1,18, p<0.05 ). Oppositely, cortisol level in HBe positive patients was significantly higher than in controls ( t=4.0379, p<0.01 ).
Chronic HBV infection is serious health problem which may lead to cirrhosis and liver carcinoma eventually ( 3 ). The exact mechanism(s) of its chronicity is not fully elucidated yet. Variety of viral and host immune factors are involved in this process. Deficient host immune response is particularly important in facilitating chrronicity of HBV infection, e.g. in leukemia, organ transplanted, and in persons with congenital or acquired immunodeficiency syndromes ( 1,2,3 ). CD4/CD8 lymphocytes impaired response results in incapability to restrict viral replication. Steroid treatment may aggravate HBV replication by interfering T lymphocyte functions ( 4 ).
It is reported that dexamethasone stimulates HBV DNA production, HBs, and HBe antigen expression in HBV-DNA injected hepatobalstoma cells ( 5 ). Further on, it is demonstrated that glucocorticoid receptor proteins stimulated by steroids recognizes specific HBV 30-nucleoid sequence called “ glucocorticoid response element “ ( GRE ). As consequence GRE increases HBV replication ( 6 ). There are some reports about serum cortisol level in acute and/or chronic hepatitis. Clinically and laboratory more significant acute viral hepatitis parallels higher serum cortisol level due to decreased hepatic hormone catabolism and stress reaction ( 7 ).
Several authors explored serum cortisol level in chronic hepatitis. Orbach found that this is increased in CAH and cortisol-binding globulin concentration as well ( 8 ). Kawai reported that plasma cortisol half-time is increased in chronic viral liver disease due to decreased metabolic clearance ( 9 ). Balikin and coworkers investigated serum cortisol level and imunocompetence in chronic HBV and HDV hepatitis ( 10 ). They found higher serum cortisol level in HBV and HDV CAH accompanied with secondary immunodeficiency ( 10 ).
In this study we confirmed that chronically HBV infected persons with CAH had significantly higher serum cortisol level than healthy controls ( 4,8 ). Serum cortisol level in HBV HBe positive chronic hepatitis cases was significantly higher than in healthy controls. This may lead to perpetuation of HBV replication and some degree of immunosuppresion. These data confirm the hepatic role in cortisol homeostasis, cortisol binding globulin synthesis, and their impairments in liver diseases ( 4,8,9 ). Higher serum cortisol level in our patients with HBV CAH may be partially caused by variations of cortisol-binding globulin concentration ( 8 ). In order to clarify the significance of serum cortisol level changes in chronic HBV hepatitis further studies of cortisol binding globulin concentration, corticotropin releasing hormone and ACTH levels, and parameters of immune response in chronic liver diseases are necessary
In conclusion, we demonstrate that serum cortisol level in chronic HBV infection is higher than in healthy controls. Probable positive correlation between cortisolemia, viral replication indices, and activity of liver microscopic changes warrants further studies.
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