Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.600
Peer-review started: July 17, 2018
First decision: August 25, 2018
Revised: September 16, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 6, 2018
Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and can lead to chronic liver diseases including chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). In managing chronic HBV infection, the objective is to detect liver injury early and then stop the progression of liver disease through effective treatment. To achieve this goal, a clear understanding of various factors involved in HBV pathogenesis is required. The relationship between HBV-related chronic liver diseases and levels of serum markers of iron metabolism and their impact on liver disease severity have not been well investigated. The aim of this study was to characterize changes in serum iron markers in patients with HBV-related diseases and to assess correlations between changes in iron metabolism and HBV-related liver injury.
In managing chronic HBV infection, the objective is to detect liver injury early and then stop the progression of liver disease through effective treatment. To achieve this goal, a clear understanding of various factors involved in HBV pathogenesis is required.
The aim of this study was to characterize changes in serum iron markers in patients with HBV-related diseases and assess correlations between changes in iron metabolism and HBV-related liver injury.
This was a case-control study, which included 78 healthy controls, 78 CHB patients including 25 diagnosed by biopsy, 85 patients with HBV-related liver cirrhosis including 5 diagnosed by biopsy, and 77 with HBV-related HCC. Blood samples were collected from all patients after overnight fasting. Serum iron metabolism markers, HBV serological markers and HBV-DNA, and biochemical markers were determined with autoanalyzers. Liver biopsy was performed with a 16 G Tru-Cut needle guided by color Doppler ultrasound. A biopsy that was 1.5 cm or longer or a liver section that contained at least five portal tracts was considered eligible for diagnosis. The liver sections from each biopsy were stained with hematoxylin and eosin and Perls, respectively. Liver fibrosis was staged using the METAVIR scoring system. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.
The serum ferritin levels were significantly higher in CHB, liver cirrhosis, and HCC groups compared with the control group. The median TIBC level was significantly lower in the CHB group, liver cirrhosis, and HBV-HCC patients than in healthy controls, as was the mean transferrin level in CHB, liver cirrhosis, and HCC patients relative to the values in controls. Among the three liver disease groups, serum iron, total iron binding capacity, and serum transferrin levels were significantly lower, and the hepcidin level was significantly higher in the patients with cirrhosis or HCC (P < 0.05) than in the patients with CHB. Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. There was a clear trend of an increase in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 and 4 (Figure 4A-F; P < 0.05). The iron level was barely detectable at stage 0 (Figure 4A), while prominent iron retention in hepatocytes was detected at S3 and S4 (Figure 4D and E). Iron deposition in liver cells was observed in 10%–50% of CHB patients. The mean iron level was significantly higher in severe fibrosis and cirrhosis compared with that in tissues with no or mild fibrosis. We also analyzed the relationships between serum hepcidin levels and demographic factors. Age, international normalized ratio, and HBV-DNA were independent factors associated with higher serum hepcidin. The cross-sectional study design limited the ability of this study to clarify causality between HBV-DNA load and altered hepcidin levels.
Iron metabolism disorders occur in patients with HBV-related liver disease. The iron metabolism disorders vary in different stages of HBV-related liver diseases.
The mechanism of iron metabolism disorders present in patients of HBV-related liver disease should be further studied in the future.