Iron Metabolism Biomarkers For Assessment On Liver Inflammation In The Patients With Chronic Hepatitis B

Backgrouds Hepatitis B virus(HBV)is a double stranded DNA virus.HBV infection leads to chronic hepatitis B and gradually develop into liver cirrhosis,liver failure(LF)and hepatocellular carcinoma(HCC)if not timely and effective antiviral treatment.At present,the antiviral drugs commonly used in the treatment of chronic hepatitis B are interferon interferon-α(IFN-α)and nucleotide analogues.They play indirect or direct anti HBV activities by regulating the immune function or directly inhibiting the HBV replication.In terms of clinical indicators of IFN-and nucleotide analogues in the treatment of chronic hepatitis B,accurate assessment of hepatic inflammatory activity is one of the important steps to achieve an effective antiviral effect.The guidelines recommend that liver inflammation activity over 2 as one of the clinical antiviral pointer.Liver biopsy is a gold standard for evaluating the activity of liver inflammation.However,as a invasive invasive operation,liver puncture has inevitable limitations,which restricts its clinical application.Hence,we carried out the study of iron metabolism biomarkers on diagnosis of liver inflammation activity in patients with chronic hepatitis B.First of all,the comparative analysis of iron metabolism biomarkers in serum of patients with healthy people were performed.Secondly,we studied the relationship between serum iron metabolism biomarkers and virology and liver inflammation index in chronic hepatitis B patients,and discussed whether abnormal serum iron metabolism is closely related to HBV replication and liver inflammation.Finally,logistic regression equation and the receiver operating characteristic curve(ROC curve)were used to reveal the diagnostic value of iron metabolism biomarkers for assessment on liver inflammation in the patients with chronic hepatitis B,with the respect of providing guidance for clinical treatment of chronic hepatitis B.Objective: To investigate the clinical value of iron metabolism biomarkers in the diagnosis of liver inflammatory activity in patients with chronic hepatitis B.Methods: The 236 healthy population and 271 chronic hepatitis B patients were chosen for the study.The level of iron was measured by bipyridine colorimetric method and the level of serum ferritin,transferrin and soluble transferrin receptor were determined by immunoturbidimetry.The differences of serum iron,ferritin,transferrin and transferrin receptor level between healthy people and patients were compared by Mann-Whitney.The correlation of serum iron metabolism biomarkers with liver index and HBV replication were performed by Spearman analysis.Moreover,Kruskal-Wallis test was used to determine the differences of serum iron,ferritin,transferrin and soluble transferrin receptor level in the patients with different liver inflammation.The clinical value of ferritin in the diagnosis of liver inflammatory activity(G≥2)in patients with chronic hepatitis B were determined by logistic regression and ROC curve analysis.Results:: The levels of serum iron,ferritin,transferrin and soluble transferrin receptor in patients with chronic hepatitis B were 17.70 mol/L(13.10-23.40),148 μg/L(94.50-246.00),2 g/L(1.60-2.30)and 0.75 mg/L(0.59-0.95),respectively.Compared with healthy population,the level of ferritin in patients with chronic hepatitis B increased significantly(P =0.009),while the levels of transferrin and soluble ferritin receptor decreased significantly(P < 0.001).The level of iron in the patients was slightly higher than that of the healthy people,but there was no significant difference(P=0.085).There was a weaker positive correlation between iron with ALT and AST(r=0.161,P=0.008;r=0.147,P=0.016)and a strong positive correlation between ferritin with ALT and AST(r=0.324,P<0.001;r=0.274 P<0.001).In addition,The level of ferritin was positively correlated with HBV replication(r=0.305,P<0.001),while serum iron,transferrin and soluble transferrin receptor content were not correlated with HBV replication.The level of ferritin in the patients with different liver inflammation were 118 g/L(86.80-148.00),122 μg/L(87.60-175.00),203 μg/L(160.00-279.00)and372 μg/L(102.45-372.25).Ferritin levels and systemic inflammation index of NLR were independent risk factors of liver inflammation(G≥2)in patients with chronic hepatitis B(P=0.002,P=0.000).ROC curve analysis showed that the area under the curves of ferritin and NLR were 0.853(95% CI: 0.805-0.893)and 0.719(95% CI:0.662-0.772),respectively.When the cut-off of serum ferritin was 158 μg/L,the specificity and sensitivity were 81.72% and 75.84%,respectively.In addition,the serum ferritin also has similar diagnostic value of chronic hepatitis B patients with ALT less than 2 times the upper limit of the normal.Conclusion:(1)The disorder of iron metabolism exist in the patients with chronic hepatitis B,and ferritin was significantly increased.(2)Elevated level of serum ferritin is closely related to HBV virus replication and liver inflammation.(3)serum ferritin is an independent risk and important diagnostic biomarker of patients with liver inflammation G≥2.