| BackgroundsPrimary liver cancer(PLC)is widely considered to be one of the most common malignant tumors in most regions and even in the whole world,ranking the third leading cause of cancer-related death,with poor prognosis and low survival rate.With the accelerating process of population aging and the change of people’s lifestyle in China,the prevalence of diabetes is gradually increasing,especially type 2 diabetes mellitus(T2DM).A number of studies at home and abroad have shown that patients with type 2 diabetes are at high risk of malignant tumors,especially those of the digestive system,with the highest incidence rate of malignant tumors.In the past three decades,the mortality of type 2 diabetic patients with primary liver cancer in about 70%of countries and regions has increased,suggesting that type 2 diabetes may be one of the risk factors for the occurrence of primary liver cancer.China is a country with a high infection rate of hepatitis B virus(HBV),which is the most common reason in China.Therefore,early screening of liver cancer is particularly important for chronic hepatitis B(CHB)patients with type 2 diabetes mellitus,tumor markers are widely used here.However,in recent years,some studies have suggested that,serum tumor marker levels of cancer patients with type 2 diabetes mellitus may show special changes compared with those without diabetes,which is likely to affect the screening and diagnosis of liver cancer,resulting in serious consequences such as misdiagnosis and even missed diagnosis.In addition,some studies have found that there are certain differences in the clinical characteristics of primary liver cancer patients with and without type 2 diabetes mellitus.Although there are studies suggesting that the incidence rate of primary liver cancer in type 2 diabetic patients has increased,the series questions about whether the occurrence of liver cancer is the same is still uncertain,whether there is a difference in the population,the choice of hypoglycemic regimens,the course of disease and the control situation.China is a country which has a large amount of people with chronic hepatitis B,the risk of primary liver cancer in chronic hepatitis B patients with type 2 diabetes is still unclear.At the same time,the serological indexes,especially the changes of tumor makers,and clinicopathological characteristics of hepatitis B related primary liver cancer patients with type 2 diabetes mellitus are unclear,and there are few studies.ObjectiveTo investigate the risk of primary liver cancer in chronic hepatitis B patients with type 2 diabetes,and analyze the changes of serum markers,especially tumor markers,and clinicopathological features in hepatitis B related liver cancer patients with type 2 diabetes mellitus.MethodsA total of 593 patients with chronic hepatitis B who were hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2020 were selected as the research subjects,including 251 patients with primary liver cancer and 83 patients with type 2 diabetes mellitus.General clinical profiles such as age,gender,type 2 diabetes mellitus and family history of liver cancer were collected after admission.Venous blood was collected the next morning after 12 hours of water fasting to detect serum indexes such as five markers of hepatitis B,liver function,coagulation function and tumor markers.We also collected imaging examination results such as color ultrasound and CT,and pathological data after liver cancer surgical resection.All the subjects were divided into type 2 diabetic group(83 cases)and non-diabetic group(510 cases).The incidence of primary liver cancer in the two groups was compared by chi-square test and the relative risk(RR)was calculated.251 patients with primary liver cancer were divided into type 2 diabetic subgroup(58 cases)and non-diabetic subgroup(193 cases),the differences of general data,serological indicators and clinicopathological characteristics between the two groups were compared by t test,chi-square test and non-parametric test.Results1.Comparison of general data of chronic hepatitis B patients with type 2 diabetes and without diabetes:Type 2 diabetic group included 83 patients,male 64 cases,female 19 cases,58 cases(69.9%)with primary liver cancer and 25 cases without liver cancer,the average age was 50.06±9.99 years old.Non-diabetic group included 510 patients,male 373 cases,female 137 cases,193 cases(37.8%)with primary liver cancer and 317 cases without liver cancer,the average age was 48.76±9.26 years old.There was no significant difference in gender,age and family history of liver cancer between the two groups(P>0.05).Compared with the non-diabetic group,the incidence of primary liver cancer was significantly higher in the type 2 diabetic group(P<0.05),and type 2 diabetes was associated with anincreased risk of primary liver cancer in patients with chronic hepatitis B(RR:1.847,95%CI:1.543～2.210,P<0.05).2.Comparison of general data of hepatitis B related liver cancer patients with type 2 diabetes and without diabetes:Patients in type 2 diabetic subgroup had a significantly higher proportion of grade C(12.1%)than that in non-diabetic subgroup(3.6%),and the difference between the two groups was statistically significant(P<0.05).Alkaline phosphatase(ALP)and glutamyl transpeptidase(GGT)levels were higher in type 2 diabetic subgroup than those in non-diabetic subgroup.The differences between the two groups were statistically significant(P<0.05).There was no significant difference in and gender between the two groups(P>0.05).3.Comparison of tumor markers of hepatitis B related liver cancer patients with type 2 diabetes and without diabetes:Compared with non-diabetic subgroup,the level of serum alpha-fetoprotein(AFP)was lower[101.60(11.81～1057.30)ng/mL and 12.75(3.58～105.73)ng/mL],the level of serum alpha-fetoprotein-L3(AFP-L3)was lower[10.88(0.50～72.31)ng/mL and 1.25(0.23～4.50)ng/mL],the negative rate of AFP was higher(22.3%and 44.8%),and the level of serum carbohydrate antigen 19-9(CA19-9)was higher[20.75(10.57～50.45)U/mL and 42.47(21.01～71.15)U/mL]in type 2 diabetic subgroup.The difference between the two subgroups was statistically significant(P<0.05).There was no statistical difference in serum Golgi protein(GP73),protein induced by vitamin K absence or antagonist-II(PⅣKA=Ⅱ),α-fucosidase(AFU)and 5’nucleotide enzyme(5’-NT)between the two subgroups(P>0.05).4.Comparison of clinicopathological characteristics of hepatitis B related liver cancer patients with type 2 diabetes and without diabetes:Compared with non-diabetic subgroup,the proportion of non-hepatocellular carcinoma was higher(3.7%and 27.8%),the proportion of poor histological differentiation was higher(5.6%and 33.3%),the proportion of advanced clinical stage was higher(30.8%and 55.6%)in type 2 diabetic subgroup.The difference between the two subgroups was statistically significant(P<0.05).There was no significant difference in tumor size(P>0.05).Conclusions1.Chronic hepatitis B with type 2 diabetes mellitus patients is associated with an increased risk of primary liver cancer.2.Compared with those without diabetes mellitus,hepatitis B related liver cancer patients with type 2 diabetes have lower serum levels of AFP and AFP-L3,higher AFP negative rate and higher serum level of CA19-9.3.Compared with those without diabetes mellitus,hepatitis B related liver cancer patients with type 2 diabetes have the higher proportion of non-hepatocellular carcinoma,lower histological differentiation and later clinical stages. |
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