Clinical features
Fibrosis is the earliest pathological sign of CHB, and cirrhosis represents the last stage of fibrosis, at which point liver transplantation may be required. In our study, patients were divided into three groups. Group 1 was divided by the degree of fibrosis, consisting of group 1a (S1) with non-significant fibrosis, and group 1b (S2-4) with significant fibrosis. Group 1a (S1) consisted of 1082 male patients (72.8%) and 404 female patients (27.2%), with an average age of 40.0±10.5 years. Group 1b (S2-4) contained of 618 male patients (79.2%) and 162 female patients (20.8%), with an average age of 44.8±12.1 years. Group 2 was stratified by the level of cirrhosis. Group 2a (S1-3) was the non-cirrhosis group, with an average age of 41.0±10.9 years and composed of 1540 male patients (74.4%) and 531 female patients (25.6%). Group 2b (S4) was the early cirrhosis group (average age of 48.4±12.8 years), which included 160 male patients (82.1%)and 35 female patients (17.9%). Group 3 was divided into non-fatty liver group (3a) and fatty liver group (3b). The non-fatty liver group had an average age of 42.8±10.9 years and contained 659 male patients (69.2%) and 294 female patients (30.8%). The fatty liver group had 1041 male patients (79.3%) and 272 female patients (20.7%), with an average age of 40.1±11.6 years. In all three groups, the incidence of fatty liver or liver fibrosis was markedly higher in men than in women (p<0.05). Groups 1b, 2b, and 3b suffered from worse or abnormal liver function, fibrosis parameters, and hepatitis B viral load than groups 1a, 2a, and 3a respectively.
In our cohort of 2266 patients, we detected a total of 780 cases with significant liver fibrosis (34.42%). In men, the incidence of fibrosis detection was higher than in women (36.35% of men showed fibrosis [618/1700], as opposed to 28.62% of women [162/566]). This sex difference was statistically significant (p<0.001). All patients were then divided into either a non-significant fibrosis group (further referred to NSF, 1486 patients) or a significant fibrosis group (further referred to as SF, 780 patients). The clinical characteristics of the two groups are shown in Table 1. A comparative analysis of the two groups (Table 1) shows age, glutamic-pyruvic transaminase (ALT), glutamic-oxaloacetic transaminase (AST), gamma-glutamyltransferase (GGT), albumin (Alb), globin, total bilirubin (TB), direct bilirubin (DB), white blood cell (WBC) count, hemoglobin (Hb), platelet (Pl), blood urea nitrogen, creatinine, uric acid, glucose, total cholesterol, triglycerides, high-density and low-density lipoprotein (HDL and LDL respectively), apolipoprotein A and B, hyaluronic acid, laminin, type III and IV procollagen, HBV DNA load, as well as CAP and LSM scores for each patient. Unsurprisingly, most liver function parameters were significantly higher in the SF group than in the NSF group (p<0.001). Blood type III and IV procollagen levels, which represent liver fibrosis severity and HBV DNA load, were furthermore significantly higher in the SF group than in the NSF group (p<0.001). There were no significant differences in age, kidney function, levels of triglycerides, HDL, or apolipoprotein A between the two groups (p>0.05).CAP scores were 251.2±54.3 db/m and 251.4±59.6 db/m for the NSF group and SF group respectively, indicating no significant difference in CAP values between the two groups (p>0.05). However, there was a significant difference in LSM values (p<0.001); the SF group had a significantly increased LSM value (15.8±12.8 kPa) compared to the NSF group (5.0±1.1 kPa).
Table 1.Clinical features of patients with non-significant fibrosis (S1 group) and significant fibrosis (S2-4 group)
| S1 | S2-4 | p value |
| n=1486 | n=780 | |
Male, n (%) | 1082 (68.4) | 618 (79.2) | <0.001 |
Female, n (%) | 404 (31.6) | 162 (20.8) | <0.001 |
Age in years | 40.0±10.5 | 44.8±12.1 | 0.942 |
Glutamic-pyruvic transaminase in U/L | 32 (22, 49) | 53 (31, 111) | <0.001 |
Glutamic-oxaloacetic transaminase in U/L | 30 (23, 39) | 46 (32, 81) | <0.001 |
Gamma-glutamyltransaminase in U/L | 23 (15, 35) | 45 (26, 83) | <0.001 |
Albumin in G/L | 51.0±33.0 | 45.5±15.4 | <0.001 |
Globin in G/L | 29.6±11.2 | 32.0±20.2 | 0.003 |
Total bilirubin in μmol/L | 13.9 (10.9, 17.2) | 15.7 (12.0, 21.1) | <0.001 |
Direct bilirubin in μmol/L | 3.3 (2.5, 4.4) | 4.2 (3.0, 6.2) | <0.001 |
White blood cells in G/L | 7.0±3.3 | 6.4±2.2 | <0.001 |
Hemoglobin in G/L | 147.5±20.7 | 142.8±20.3 | <0.001 |
Platelets in G/L | 218.4±60.2 | 171.2±69.0 | <0.001 |
Blood urea nitrogen in μmol/L | 5.1±2.8 | 5.2±3.1 | 0.723 |
Creatinine in μmol/L | 81.8±32.6 | 84.5±62.6 | 0.199 |
Uric acid in μmol/L | 397.0±118.9 | 389.2±117.4 | 0.173 |
Glucose in mmol/L | 7.2±25.2 | 7.6±28.7 | 0.727 |
Total cholesterol in mmol/L | 4.9 (4.4, 5.7) | 4.7 (4.1, 5.5) | <0.001 |
Triglycerides in mmol/L | 1.1 (0.8, 1.6) | 1.0 (0.8, 1.5) | 0.054 |
High-density lipoprotein in mmol/L | 1.3±0.4 | 1.3±0.7 | 0.552 |
Low-density lipoprotein in mmol/L | 3.1 (2.5, 3.7) | 2.8 (2.2, 3.5) | <0.001 |
Apolipoprotein A in mmol/L | 1.3±0.3 | 1.3±0.9 | 0.830 |
Apolipoprotein B in mmol/L | 1.1±0.4 | 1.0±0.5 | 0.014 |
Hyaluronic acid | 51.7 (28.7, 79.5) | 88.5 (49.8, 160.4) | <0.001 |
Laminin | 35.1 (21.7, 49.8) | 48.5 (30.5, 78.7) | <0.001 |
Type III procollagen | 9.2 (7.3, 11.9) | 12.1 (9.1, 17.5) | <0.001 |
Type IV procollagen | 30.6 (23.3, 39.7) | 53.7 (34.7, 98.8) | <0.001 |
HBV DNA load as log10 IU/mL | 3.4±2.1 | 4.1±2.2 | <0.001 |
Controlled attenuation parameter | 251.2±54.3 | 251.4±59.6 | 0.942 |
Liver stiffness measurement | 5.0±1.1 | 15.8±12.8 | <0.001 |
In total, 195 cases of early cirrhosis were detected among the 2266 patients, representing a rate of 8.61%. Early cirrhosis was more frequently found in men compared to women (9.41% of men [160/1700] compared to 6.18% of women [35/56]). Similar to fibrosis, this sex-specific difference in incidence was statistically significant (p<0.001). Patients were then divided into the non-cirrhosis group (further referred to as NC group, 2071 patients) and early cirrhosis group (further referred to as EC group, 195 patients), according to presence or absence of cirrhosis. The clinical characteristics and comparative analysis of the two groups can be found in Table 2. Most liver function parameters in the EC group were higher than in the NC group (p<0.001). Blood type III and IV procollagen levels, which represent liver fibrosis severity and HBV DNA load, were higher in the EC group than in the NC group (p<0.001)but no significant differences were found in kidney function, triglycerides, HDL and apolipoprotein B between the two groups (p>0.05). Both CAP and LSM values were significantly different between the two groups (p<0.001; NC: CAP of 237.4±57.9, LSM of 32.7±16.0 kPa; EC: CAP of 252.6±55.9, LSM of 6.5±2.8 kPa).
Table 2.Clinical features of patients with non-cirrhosis (S1-3 group) and early cirrhosis (S4 group)
| S1-3 | S4 | p value |
| n=2071 | n=195 | |
Male, n (%) | 1540 (74.4) | 160 (82.1) | 0.018 |
Female, n (%) | 531 (25.6) | 35 (17.9) | <0.001 |
Age in years | 41.0±10.9 | 48.4±12.8 | <0.001 |
Glutamic-pyruvic transaminase in U/L | 35 (23, 60) | 66 (36, 196) | <0.001 |
Glutamic-oxaloacetic transaminase in U/L | 32 (24, 45) | 66 (45, 158) | <0.001 |
Gamma-glutamyltransaminase in U/L | 26 (17, 43) | 86 (51, 166) | <0.001 |
Albumin in G/L | 49.9±29.3 | 40.0±9.9 | <0.001 |
Globin in G/L | 30.1±13.9 | 34.3±23.2 | 0.015 |
Total bilirubin in μmol/L | 14.1 (11.0, 17.7) | 22.3 (16.4, 30.9) | <0.001 |
Direct bilirubin in μmol/L | 3.5 (2.6, 4.7) | 6.7 (4.6, 12.3) | <0.001 |
White blood cells in G/L | 6.9±3.1 | 5.6±2.0 | <0.001 |
Hemoglobin in G/L | 147.3±19.5 | 131.6±25.7 | <0.001 |
Platelets in G/L | 209.3±36.1 | 127.6±63.1 | <0.001 |
Blood urea nitrogen in μmol/L | 5.2±2.9 | 5.3±3.6 | 0.621 |
Creatinine in μmol/L | 82.2±33.7 | 88.8±110.8 | 0.457 |
Uric acid in μmol/L | 395.6±118.1 | 380.1±122.8 | 0.140 |
Glucose in mmol/L | 5.7 (5.3, 6.1) | 5.6 (5.1, 6.6) | 0.709 |
Total cholesterol in mmol/L | 4.9 (4.3, 5.6) | 4.6 (3.9, 5.2) | <0.001 |
Triglycerides in mmol/L | 1.1 (0.8, 1.6) | 1.0 (0.8, 1.6) | 0.054 |
High-density lipoprotein in mmol/L | 1.3±0.5 | 1.3±0.4 | 0.074 |
Low-density lipoprotein in mmol/L | 3.0 (2.5, 3.6) | 2.5 (1.9, 3.0) | <0.001 |
Apolipoprotein A in mmol/L | 1.4±0.7 | 1.1±0.4 | 0.017 |
Apolipoprotein B in mmol/L | 1.1±0.5 | 1.0±0.3 | 0.184 |
Hyaluronic acid | 56.1 (32.9, 88.8) | 213.0 (114.7, 411.5) | <0.001 |
Laminin | 36.4 (23.7, 53.3) | 80.5 (55.9, 140.4) | <0.001 |
Type III procollagen | 9.6 (7.5, 12.8) | 17.5 (13.4, 24.2) | <0.001 |
Type IV procollagen | 33.3 (25.0, 47.4) | 146.6 (80.3, 244.7) | <0.001 |
HBV DNA load as log10 IU/mL | 3.6±2.1 | 4.5±2.4 | <0.001 |
Controlled attenuation parameter | 252.6±55.9 | 237.4±57.9 | <0.001 |
Liver stiffness measurement | 6.5±2.8 | 32.7±16.0 | <0.001 |
In total, 1313 fatty liver cases were detected among the 2266 patients, marking an overall incidence of 57.94%. Again, incidence was higher in males than in females, with 61.24% (1041/1700) of men showing fatty liver compared to 48.06% of women (272/566). The difference in incidence between the two sexes was statistically significant (p<0.001). Patients were divided into a non-fatty liver group (NFL, 953 patients) and fatty liver group (FL, 1313 patients). The clinical characteristics and comparative analysis of the two groups are shown in Table 3. Blood glucose levels, total cholesterol, triglycerides, LDL, apolipoprotein B, laminin and type III procollagen were significantly higher in NFL patients compared to FL patients (p<0.05). On the other hand, blood HDL, hyaluronic acid and type IV procollagen levels and HBV DNA load were significantly lower in the NFL group than in the FL group (p<0.05). Here, we found significant differences in the CAP score between the groups (p<0.001). NFL CAP scores were 284 (265, 313) db/m, while FL CAP scores were 203(182, 220) db/m. LSM values were 5.9 (4.6, 8.3) kPa and 6.0 (4.6, 9.3) kPa for NFL and FL respectively. There were no significant differences in LSM values between the two groups (p>0.05).
Table 3.Clinical features of patients with non-fatty liver and fatty liver
| Non-fatty liver | Fatty liver | p value |
| n=953 | n=1313 | |
Male, n (%) | 659 (69.2) | 1041 (79.3) | <0.001 |
Female, n (%) | 294 (30.8) | 272 (20.7) | <0.001 |
Age in years | 42.8±10.9 | 40.1±11.6 | <0.001 |
Glutamic-pyruvic transaminase in U/L | 38 (25, 61) | 34 (22, 68) | 0.033 |
Glutamic-oxaloacetic transaminase in U/L | 31 (23, 44) | 37 (27, 59) | <0.001 |
Gamma-glutamyltransaminase in U/L | 31 (20, 51) | 22 (14, 44) | <0.001 |
Albumin in G/L | 50.6±34.3 | 46.9±16.6 | 0.003 |
Globin in G/L | 29.5±9.3 | 31.7±20.3 | 0.004 |
Total bilirubin in μmol/L | 14.0 (10.8, 17.5) | 15.3 (11.9, 20.0) | <0.001 |
Direct bilirubin in μmol/L | 3.4 (2.5, 4.6) | 3.9 (2.8, 5.4) | <0.001 |
White blood cells in G/L | 7.2±3.6 | 6.2±1.8 | <0.001 |
Hemoglobin in G/L | 148.5±20.4 | 142.1±20.4 | <0.001 |
Platelets in G/L | 212.3±65.9 | 187.8±66.3 | <0.001 |
Blood urea nitrogen in μmol/L | 5.3±3.4 | 5.0±2.2 | 0.032 |
Creatinine in μmol/L | 82.3±26.4 | 83.2±62.5 | 0.617 |
Uric acid in μmol/L | 414.2±119.0 | 365.8±116.7 | <0.001 |
Glucose in mmol/L | 5.8 (5.4, 6.3) | 5.5 (5.2, 5.9) | <0.001 |
Total cholesterol in mmol/L | 5.1 (4.4, 5.8) | 4.7 (4.0, 5.4) | <0.001 |
Triglycerides in mmol/L | 1.3 (0.9, 1.8) | 0.9 (0.7, 1.2) | <0.001 |
High-density lipoprotein in mmol/L | 1.3±0.4 | 1.4±0.7 | <0.001 |
Low-density lipoprotein in mmol/L | 3.2 (2.6, 3.8) | 2.8 (2.3, 3.3) | <0.001 |
Apolipoprotein A in mmol/L | 1.3±0.8 | 1.3±0.4 | 0.791 |
Apolipoprotein B in mmol/L | 1.1±0.5 | 1.0±0.3 | <0.001 |
Hyaluronic acid | 56.1 (32.0, 98.7) | 64.3 (38.9, 101.3) | 0.038 |
Laminin | 65.1 (21.1, 52.0) | 44.1 (28.4, 66.5) | <0.001 |
Type III procollagen | 10.3 (7.8, 14.7) | 9.8 (7.5, 13.5) | 0.046 |
Type IV procollagen | 34.7 (25.0, 51.7) | 35.7 (27.0, 58.3) | 0.032 |
HBV DNA load as log10 IU/mL | 3.3±2.0 | 4.1±2.2 | <0.001 |
Controlled attenuation parameter | 284 (265, 313) | 203 (182, 220) | <0.001 |
Liver stiffness measurement | 5.9 (4.6, 8.3) | 6.0 (4.6, 9.3) | 0.119 |
Statistical analysis results
Spearman’s correlation analyses showed that CAP scores and LSM values correlated with sex (r=0.137), age (r=0.119), ALT (r=0.082), AST (r=–0.172), GGT (r=0.225), Alb (r=0.150), globulin (r=–0.107), TB (r=–0.132), DB (r=–0.145), WBC count (r=0.254), Hb (r=0.205), Pl (r=0.206), total cholesterol (r=0.214), HDL (r=–0.243), LDL (r=0.255), apolipoprotein B (r=0.217), hyaluronic acid (r=–0.069), laminin (r=–0.188), procollagen type IV (r=–0.067), and hepatitis B viral DNA load (r=–0.216).