Contributed equally
The aim of the present study was to investigate the usefulness of combined detection of liver stiffness (LS) and serum C-reactive protein (CRP) level in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). A total of 156 cases of previously untreated patients with HBV-related LC were classified into the LC group [LC without hepatocellular carcinoma (HCC)] and the HCC group (LC with HCC). Comparative analyses of LS and serum CRP level were conducted between these two groups. LS values and serum CRP levels were found to be significantly higher in the HCC group compared with those in the LC group (P<0.01). The LS values and serum CRP levels were not significantly different between α-fetoprotein (AFP)-positive and -negative patients. A high LS value was a high-risk factor for HCC in patients with chronic hepatitis B. The CRP-positive rate was significantly higher in the HCC group compared with that in LC group in a subset of patients with high LS values (P<0.01). In conclusion, the combined detection of LS and serum CRP may complement the measurement of AFP in the diagnosis of HBV-related HCC, improve the identification of patients with AFP-negative HCC and help distinguish HCC from LC.
Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver (
Liver stiffness measurement (LSM) using transient elastography (TE FibroScan®; Echosens, Paris, France) has been shown to be correlated with liver fibrosis in various chronic liver diseases (
C-reactive protein (CRP) is an acute-phase protein synthesized by the liver. Rapid, marked increases in CRP levels occur with inflammation, infection, trauma and tissue necrosis (
A total of 156 patients with HBV-related LC in our hospital were included in this study. The patients were divided into the LC group (LC without HCC) and the HCC group (LC with HCC). These cases were confirmed by clinical presentation, diagnostic ultrasound imaging and laboratory diagnosis. LC was diagnosed according to the guideline of prevention and treatment for chronic hepatitis B, 2010 version (
Scanning was performed using transient elastography FibroScan® (Echosens) according to the method described in the manufacturer's instructions. The LS grading criteria were as follows: >17.5 kPa cirrhosis; patients were subgrouped with a 5-kPa interval into 17.5–22.5, 22.6–27.5 and >27.6 kPa groups.
Measurement was performed using the latex enhanced turbidimetric method with the reagent purchased from Roche Diagnostics GmbH (Mannheim, Germany) using the Roche Modular P800 analyzer. The serum CRP normal reference range was 0–2.87 mg/l, with serum hs-CRP >2.87 mg/l considered as positive.
AFP. The plasma levels of AFP were measured using a commercial ELISA kit (Abbott Laboratories Company, Chicago, IL, USA) in accordance with the manufacturer's instructions. The HCC group was divided into AFP-positive (>20 ng/ml) and -negative (≤20 ng/ml).
The statistical analysis was performed using the SPSS v.17.0 software package (SPSS Inc., Chicago, IL, USA). Quantitative data were analyzed using the independent-samples t-test and expressed as mean ± standard deviation. The count data were analyzed using the χ2 test. P<0.05 was considered to indicate a statistically significant difference. Correlation analyses were conducted using the Pearson's and Spearman's correlation tests.
A total of 156 cases of previously untreated patients with LC were included, 125 of whom were men and 31 were women (mean age, 38±17.1 years). The patients were divided into the LC group (LC without HCC, n=89) and the HCC group (LC with HCC, n=67). Of the 50 healthy controls, 41 were men and 9 were women (mean age, 38±9.4 years). The LSM values and serum CRP levels were found to be significantly higher in the HCC group compared with those in the LC group (P<0.05 and P<0.01, respectively;
The HCC group was subdivided into the AFP-positive (AFP >20 ng/ml) and AFP-negative (AFP ≤20 ng/ml) groups. The LSM values and serum CRP levels were not significantly different between AFP-positive and -negative patients (P>0.05,
The proportional analysis of HCC and CRP positivity rate among 3 stratifications of LSM revealed that a high LSM value was a high-risk factor for HCC. In a subset of patients with LSM values >27.6 kPa, the CRP positivity rate was significantly higher in the HCC group (64.15%) compared with that in the LC group (37.97%) (P<0.01,
The diagnosis of HCC at an early stage is a prerequisite for improved prognosis. LSM using FibroScan transient elastography has been shown to be correlated with liver fibrosis in various chronic liver diseases. The LSM cut-off value of 17.5 kPa is considered optimal for diagnosing LC (
The majority of the cases of HCC are associated with cirrhosis related to chronic hepatitis (
In conclusion, the combined detection of LS and serum CRP may complement the measurement of AFP level in the diagnosis of HBV-related HCC, facilitate the identification of patients with AFP-negative HCC, and help distinguish HCC from LC.
This study was supported by grants from the National Natural Science Foundation of China (grant no. 81460301), the Natural Science Foundation of Ningxia (grant nos. NZ09115 and NZ11199), and the Scientific and Technological Foundation of Ningxia and Chinese Foundation for Hepatitis Wang Bao-En Liver Fibrosis Fund (grant no. xjs).
hepatocellular carcinoma
hepatitis B virus
C-reactive protein
liver stiffness measure
chronic hepatitis B
LSM values and serum hs-CRP levels (mean ± SD).
Groups | No. | hs-CRP (mg/l) | LSM values (kPa) |
---|---|---|---|
Healthy | 50 | 0.78±1.07 | 4.25±0.74 |
LC | 89 | 9.47±19.56 | 27.81±18.46 |
HCC | 67 | 30.78±15.17 | 39.72±29.05 |
t-test | −0.964 | −1.735 | |
P-value | 0.0337 | 0.0093 |
LSM, liver stiffness measurement; LC, liver cirrhosis; hs-CRP, high-sensitivity C-reactive protein; HCC, hepatocellular carcinoma.
LSM values and serum hs-CRP levels in AFP-positive and -negative patients (mean ± SD).
AFP status | No. | hs-CRP (mg/ml) | LSM values (kPa) |
---|---|---|---|
Positive | 35 | 13.58±27.16 | 48.95±28.59 |
Negative | 32 | 8.66±17.72 | 28.64±26.83 |
t-test | 0.815 | 1.706 | |
P-value | 0.419 | 1.104 |
LSM, liver stiffness measurement; AFP, α-fetoprotein; hs-CRP, high-sensitivity C-reactive protein.
Proportion analysis of HCC, LSM grade and serum hs-CRP positivity rate.
LC group | HCC group | ||||||
---|---|---|---|---|---|---|---|
LSM grade (kPa) | Case (no.) | CRP+, no. (%) | CRP−, no. (%) | CRP+, no. (%) | CRP−, no. (%) | ||
17.5–22.5 | 0 | 0/0 (0.0) | 0/0 (0.0) | 0/0 (0.0) | 0/0 (0.0) | ||
22.6–27.5 | 24 | 0/10 (0.0) | 10/10 (100.0) | 0/14 (0.0) | 14/14 (100.0) | ||
>27.6 | 132 | 30/79 (37.97) | 49/79 (62.03) | 34/53 (64.15) | 19/53 (35.85) | ||
χ2 test | 8.847 | 24.89 | |||||
P-value | 0.003 | 0.000 |
LSM, liver stiffness measurement; hs-CRP, high-sensitivity C-reactive protein; HCC, hepatocellular carcinoma.