The Relationship Between Serum Alpha-fetoprotein And Liver Function Index In Health Check-up Population

ObjectiveIn China, there is approximately300million people suffering from liver diseases. A series of tests were used to detect liver function, but nowsday there is not one index that can comprehensively reflect liver comprehensive function. Alpha-fetoprotein (AFP) is a major mammalian embryo-specific and tumor-associated protein, which is synthesized by the liver. The concentration of AFP is very low among healthy adults. Serum AFP level obviously rises in adults with hepatocellular carcinoma or germ cell tumors. It is also found to be increased in acute or chronic viral hepatitis and various forms of chronic hepatic disorders. However, it is unknown whether AFP can be used as a serum marker to predict liver comprehensive function. So, in the present study, we aimed to investigate the relationship of AFP in normal range with liver function indexes.MethodsSubjects who undertook a health check-up from January,2008to June,2013in one tertiary A hospital of Zhejiang province were selected in this study. The examinations included physical examinations, routine blood tests, liver function tests, tumor marker tests and chest X-ray, together with abdominal ultrasound. Tumor marker tests included AFP, CEA, CA125, CA199and so on. Liver function indexes included three aspects:(1) Indexes reflect the injury of hepatocytes (serum enzyme indexes)-alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT).(2) Indexes reflect the liver’s biosynthetic capacity-serum total protein (TP), albumin (ALB), globulin (GLOB);(3) Indexes indicate the liver’s capacity to transport organic anions and to metabolize drugs-serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL). Normal liver function was defined as all of these index including ALT, AST, ALP, GGT, TP, ALB, GLOB, TBIL, DBIL and IBIL in normal ranges, while abnormal liver function was defined as any one of these indexes beyond the reference ranges. We applied three comprehensive index to analyze the relationship between AFP and liver function indexes. An elevated liver enzyme was defined as any one of ALT, AST, ALP or GGT above the reference ranges, while a decreased liver enzyme was defined as low serum ALP levels. Those who had a high level of TP, ALB or GLOB were divided into groups with elevated serum protein, and those with a low levels of TP or ALB were in groups with decreased serum protein. Any one of the indexes including TBIL, IBIL and DBIL above reference ranges indicated an elevated serum bilirubin, while any one of these indexes below reference ranges indicated a decreased serum bilirubin. Subjects with normal range of AFP (<20ng/mL) and finished liver function tests were included in analysis, excluding those younger than18years old or with any history of malignancy. Logistic regression analysis were used to assess the relationship between AFP and liver function indexes from three aspects. We also explored the effect of liver fat accumulation on these relationships.Results1.311,691subjects were included in the final analysis, with160,585in groups of normal liver function index and151106in groups of abnormal liver function index. Compared to subjects with normal liver function index, subjects with abnormal liver function index had more males, younger, higher weight, larger waist circumference and BMI, higher blood pressure, higher fasting plasma glucose, and higher triglyceride and total cholesterol, low density lipoprotein, but lower high density lipoprotein. Mean serum AFP levels were higher in subjects with abnormal liver function indexes (3.33±1.84vs3.11±1.71ng/mL, P<0.0001). 2. For the comprehensive index, serum AFP levels was positively related to liver damage (OR=1.08,95%CI:1.08-1.09), negatively related to liver’s biosynthetic capacity (OR=0.98,95%CI:0.98-0.98) and liver’s capacity of transporting organic anions and metabolizing drugs (OR=0.97,95%CI:0.97-0.98). For a single index, serum AFP levels was positively related to ALT (OR=1.05,95%CI:1.05-1.06), AST (OR=1.08,95%CI:1.07-1.08), ALP (OR=1.03,95%CI:1.01-1.04), GGT(OR=1.09,95%CI:1.09-1.10); negatively related to TP (OR=0.98,95%CI:0.97-0.98), GLOB (OR=0.98,95%CI:0.97-0.98) and DBIL (OR=0.97,95%CI:0.97-0.98); Those who had a higher IBIL level had a higher AFP level (OR=1.01,95%CI:1.00-1.02), and those with a lower IBIL level had a lower AFP level (OR=0.97,95%CI:0.97-0.98). No relationship was found between serum AFP level and ALB, TBIL.3. Liver fat accumulation played a role in relationship between AFP and liver function index. In subjects without liver fat accumulation, serum AFP level was positively related to liver enzyme (OR=1.18,95%CP.1.16-1.20), serum protein (OR=0.94,95%CI:0.93-0.95), serum bilirubin (OR=1.03,95%CI:1.01-1.06) and negatively associated with serum bilirubin (OR=0.96,95%CI:0.94-0.97). In subjects with lipid accumulation in hepatocytes, serum AFP was only related to increased liver enzyme (OR=1.13,95%CI:1.10-1.17) and decreased serum protein (OR=0.57,95%CI:0.33-1.00). In subjects with fatty liver, serum AFP levels was related to the increased liver enzyme (OR=1.11,95%CI:1.08-1.14) and increased serum protein (OR=0.94,95%CI:0.91-0.97).Conclusion1. Serum AFP level was significantly related to liver function indexes. AFP was positively related to liver damage. It reflected the liver’s capacity to transport organic anions and to metabolize drugs. Meantime it reflected the liver’s biosynthetic capacity. AFP was a good marker for reflecting liver function.2. Liver fat accumulation modified a role in relationship between AFP and liver function indexes. AFP was a better marker for reflecting liver function in adults without liver fat accumulation.