Clinical, pathological characteristics and long-term outcomes of hepatitis B virus related cirrhosis in pediatric observational study

Table 1 Baseline characteristics of pediatric liver cirrhosis, median (interquartile range)/n (%)/mean ± SD

Variable	Total (N = 62)
Demographics
Age (years)	11 (4-14)
Male	54 (87.1)
Female	8 (12.9)
BMI (kg/m2)	16.76 (15.45-20.67)
Comorbidity
Hepatic encephalopathy	0 (0)
Ascites	4 (6.5)
Gastrointestinal bleeding	0 (0)
No comorbidity	58 (93.5)
Presenting symptoms of cirrhosis
Asymptomatic	48 (77.4)
Fatigue	3 (4.8)
Aberration	4 (6.5)
Jaundice	6 (9.7)
Discomfort in the liver area	2 (3.2)
Bleeding points on the chest and abdomen	1 (1.6)
Repeated epistaxis	1 (1.6)
AFP progressively increases	1 (1.6)
Antiviral therapy before LC	8 (12.9)
Genotype
Unknown	14 (22.6)
B	5 (8.1)
C	43 (69.4)
Biochemistry
ALT (U/L)	107.5 (58.5-207.25)
AST (U/L)	110.5 (64.25-169.5)
GGT (U/L)	70.5 (48-105)
ALP (U/L)	299 (232.25-373)
ALB (g/L)	39 (36-41.25)
TBIL (μmol/L)	11.05 (8.1-19.15)
DBIL (μmol/L)	4.7 (3.08-8.48)
Glucose (mmol/L)	4.5 (4.08-4.89)
HDL-C (mmol/L)	1.15 (0.97-1.4)
LDL-C (mmol/L)	2.27 (2.02-2.85)
TG (mmol/L)	0.94 (0.75-1.28)
Cr (μmol/L)	48.68 ± 14.11
HGB (g/L)	127.84 ± 14.45
PLT (109/L)	165 (113.5-221)
WBC (109/L)	6.19 (4.67-7.63)
Lymphocyte (109/L)	3.15 (2.12-4.26)
Neutrophil (109/L)	3.175 (2.15-4.27)
log10(qHBV DNA)	6.3 (4.58-7.54)
log10(qHBsAg)	3.11 (0-3.69)
HBeAg(+)	48 (81.4)
Child-Pugh score	5 (5-6)
PELD/MELD score	3.5 (0.75-8)
AFP (ng/mL)	51 (13.73-255)
T lymphocyte	2060.62 ± 1121.46
B lymphocyte	599.5 (437-940)
NK	183.5 (113-327.25)
CD8+	718 (502.25-1012)
CD4+	1003.5 (722.25-1422.85)
CD4/CD8	1.44 (1.11-1.81)
PT (seconds)	12.3 (11.55-13.35)
INR	1.06 (0.99-1.14)

BMI: Body mass index; LC: Liver cirrhosis; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; TG: Triglyceride; Cr: Creatinine; HGB: Hemoglobin; PLT: Platelets; WBC: White blood cell; qHBV: Quantification hepatitis B virus; qHBsAg: Quantification hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; PELD: Pediatric end-stage liver disease model; MELD: Model for end-stage liver disease; AFP: Alpha fetoprotein; NK: Natural killer; CD: Cluster of differentiation; PT: Prothrombin time; INR: International normalized ratio.

Table 2 Antiviral response of pediatric liver cirrhosis, median (interquartile range)/n (%)/mean ± SD

Variable	Total (N = 46)
Demographics
Age (years)	8 (3.5-13)
Male	38 (82.6)
Female	8 (17.4)
BMI (kg/m2)	16.38 (15.3-18.15)
Antiviral regimen
NA	5 (10.8)
NA-HBV DNA loss	4 (80)
NA-HBV DNA loss time (months)	14.93 (4.99-54.47)
IFN + NA	41 (89.2)
IFN + NA HBsAg loss	8 (20)
IFN + NA HBeAg loss	26 (65)
IFN + NA HBV DNA loss	38 (95)
IFN + NA HBsAg loss time (months)	35.17 ± 21.51
IFN + NA HBeAg loss time (months)	10.54 (3.52-37.87)
IFN + NA HBV DNA loss time (months)	7.77 (5.22-14.41)
LC resolution at EOT
HBsAg loss	8 (17.4)
HBeAg loss	26 (56.5)
HBV DNA loss	42 (91.3)
HBsAg loss time (months)	35.17 ± 21.51
HBeAg loss time (months)	42.14 (14.07-151.46)
HBV DNA loss time (months)	7.77 (4.79-14.46)

BMI: Body mass index; NA: Nucleoside analogue; HBV: Hepatitis B virus; IFN: Interferon; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; LC: Liver cirrhosis; EOT: End of treatment.

Table 3 Baseline characteristics of pediatric liver cirrhosis and chronic hepatitis B, median (interquartile range)/n (%)/mean ± SD

Variable	Liver cirrhosis (n = 62)	Chronic hepatitis B (n = 64)	P value
Demographics
Age (years)	11 (4-14)	10.5 (3-15)	0.7237
Sex			0.128
Male	54 (87.1)	49 (76.6)
Female	8 (12.9)	15 (23.4)
BMI (kg/m2)	16.76 (15.45-20.67)	17.28 (15.43-19.87)	0.6623
Biochemistry
ALT (U/L)	107.5 (58.5-207.25)	95 (44-176)	0.9829
AST (U/L)	110.5 (64.25-169.5)	76 (56-147)	0.6596
GGT (U/L)	70.5 (48-105)	23 (14-54)	< 0.0001
ALP (U/L)	299 (232.25-373)	273 (193-349)	0.0852
ALB (g/L)	39 (36-41.25)	40 (38-43)	0.0011
TBIL (μmol/L)	11.05 (8.1-19.15)	8.5 (6.3-11.7)	0.0277
DBIL (μmol/L)	4.7 (3.08-8.48)	3.1 (2-4.7)	0.0008
HDL-C (mmol/L)	1.15 (0.97-1.4)	1.18 (1.02 1.35)	0.7982
LDL-C (mmol/L)	2.27 (2.02-2.85)	2.28 (2.04-2.86)	0.631
TG (mmol/L)	0.94 (0.75-1.28)	0.86 (0.68-1)	0.0461
Cr (μmol/L)	48.68 ± 14.11	51.6 ± 15.41	0.2733
HGB (g/L)	127.84 ± 14.45	131.19 ± 12.05	0.1622
PLT (109/L)	165 (113.5-221)	236 (206.75-284.75)	< 0.0001
WBC (109/L)	6.19 (4.67-7.63)	6.56 (5.04-8.45)	0.0718
Lymphocyte (109/L)	3.15 (2.12-4.26)	2.97 (2.17-4.1)	0.726
Neutrophil (109/L)	3.175 (2.15-4.27)	2.5 (1.94-3.11)	0.002
log10(qHBV DNA)	6.3 (4.58-7.54)	17.4 (15.41-18.62)	0.0003
log10(qHBsAg)	3.11 (0-3.69)	8.956 (7.78-10.28)	< 0.0001
HBeAg(+)	48 (81.4)	60 (93.8)	0.0361
PT (seconds)	12.3 (11.55-13.35)	11.5 (10.98-12.2)	< 0.0001

BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; TG: Triglyceride; Cr: Creatinine; HGB: Hemoglobin; PLT: Platelets; WBC: White blood cell; qHBV: Quantification hepatitis B virus; qHBsAg: Quantification hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; PT: Prothrombin time.

Table 4 Comparisons between pediatric liver cirrhosis and adult liver cirrhosis, median (interquartile range)/n (%)/mean ± SD

Variable	Pediatric (n = 62)	Adult (n = 69)	P value
Demographics
Age (years)	11(4-14)	43(34-46.5)	< 0.0001
Sex			0.9812
Male	54 (87.1)	60 (87)
Female	8 (12.9)	9 (13)
Comorbidity			< 0.0001
Hepatic encephalopathy	0 (0)	4 (5.8)
Ascites	4 (6.5)	6 (8.7)
Gastrointestinal bleeding	0 (0)	41 (59.4)
Presenting symptoms of cirrhosis			< 0.0001
Asymptomatic	48 (77.4)	8 (11.6)
Fatigue	3 (4.8)	19 (27.5)
Jaundice	4 (6.5)	3 (4.4)
Abdominal discomfort	6 (9.7)	16 (23.2)
Gastrointestinal bleeding	2 (3.2)	41 (59.4)
Nausea	0 (0)	7 (10.1)
Poor appetite	4 (6.5)	6 (8.7)
Antiviral therapy before LC	8 (12.9)	35 (53.8)	< 0.0001
History of self-discontinuation of antiviral therapy	8 (12.9)	8 (11.6)	0.821
Biochemistry
ALT (U/L)	107.5 (58.5-207.25)	29 (18-42)	< 0.0001
AST (U/L)	110.5 (64.25-169.5)	39 (26-53.5)	< 0.0001
GGT (U/L)	70.5 (48-105)	28 (18-46.5)	< 0.0001
ALP (U/L)	299 (232.25-373)	70.5 (58-86)	< 0.0001
ALB (g/L)	39 (36-41.25)	36 (32-38.5)	0.0003
TBIL (μmol/L)	11.05 (8.1-19.15)	11.9 (12.65-24.9)	0.0002
DBIL (μmol/L)	4.7 (3.08-8.48)	8.3 (5.3-11.25)	< 0.0001
Glucose (mmol/L)	4.5 (4.08-4.89)	5 (4.26-6.29)	0.004
HDL-C (mmol/L)	1.15 (0.97-1.4)	1.83 (1.57-2.63)	0.008
LDL-C (mmol/L)	2.27 (2.02-2.85)	1.79 (1.56-2.56)	0.0018
TG (mmol/L)	0.94 (0.75-1.28)	0.78 (0.57-1.17)	0.06226
Cr (μmol/L)	48.68 ± 14.11	75.61 ± 15.29	< 0.0001
HGB (g/L)	127.84 ± 14.45	103.38 ± 22.29	< 0.0001
PLT (109/L)	165 (113.5-221)	91 (53.5-149)	0.0072
WBC (109/L)	6.19 (4.67-7.62)	7.24 (3.31-10.91)	0.0062
Lymphocyte (109/L)	3.15(2.12-4.26)	0.79 (0.55-1.49)	< 0.0001
Neutrophil (109/L)	3.175 (2.15-4.27)	5.05 (2.14-9.18)	< 0.0001
log10(qHBV DNA)	6.3 (4.58-7.54)	0 (0-5.43)	< 0.0001
log10(qHBsAg)	3.11 (0-3.69)	5.19 (3-9.11)	0.465
HBeAg(+)	48 (81.4)	27 (39.1)	< 0.0001
AFP (ng/mL)	51 (13.73-255)	3.97 (1.96-12.5)	0.0261
PT (seconds)	12.3 (11.55-13.35)	13.7 (12.9-15)	< 0.0001
INR	1.06 (0.99-1.14)	1.18 (1.11-1.28)	< 0.0001

LC: Liver cirrhosis; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; TG: Triglyceride; Cr: Creatinine; HGB: Hemoglobin; PLT: Platelets; WBC: White blood cell; qHBV: Quantification hepatitis B virus; qHBsAg: Quantification hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; AFP: Alpha fetoprotein; PT: Prothrombin time; INR: International normalized ratio.

Table 5 Influencing factors for the remission of pediatric liver cirrhosis, median (interquartile range)

Variable	Univariate Cox [HR (95%CI)]	P value	Multivariate Cox [HR (95%CI)]	P value
Sex	1.743 (0.659-4.607)	0.263
Age	0.955 (0.893-1.021)	0.177
Genotype	1.367 (0.771-2.423)	0.285
Biochemistry
ALT	1.001 (0.999-1.003)	0.284
AST	1.001 (0.998-1.003)	0.587
GGT	1.006 (1.003-1.009)	0.0001	1 (0.992-1.008)	0.939
ALP	1.001 (0.997-1.004)	0.741
ALB	1.007 (0.927-1.093)	0.873
TBIL	1.008 (0.985-1.031)	0.507
DBIL	1.009 (0.976-1.042)	0.608
Glucose	0.356 (0.167-0.756)	0.007	0.159 (0.032-0.788)	0.024
HDL	2.183 (0.638-7.469)	0.213
LDL	1.592 (0.937-2.707)	0.086
TG	0.556 (0.233-1.325)	0.185
HGB	1.005 (0.978-1.033)	0.717
PLT	1.004 (0.999-1.008)	0.121
WBC	1.149 (0.992-1.33)	0.064
Lymphocyte	1.214 (0.974-1.514)	0.085
Neutrophil	1.155 (0.823-1.62)	0.404
HBV DNA	1.296 (1.046-1.605)	0.018	1.133 (0.748-1.718)	0.555
HBsAg	1.428 (1.089-1.873)	0.01	1.951 (0.954-3.993)	0.067
HBeAg	2.109 (0.638-6.973)	0.222
AFP	1.001 (1-1.001)	0.002	1.001 (1-1.002)	0.003
T lymphocyte	1 (1-1.001)	0.043	0.999 (0.998-1.001)	0.33
B lymphocyte	1 (1-1.001)	0.045	0.999 (1.001-1.003)	0.43
NK	1.003 (1.001-1.005)	0.003	1.004 (1-1.008)	0.063
CD8+	1 (1-1.001)	0.137
CD4+	1.001 (1-1.002)	0.014	1 (0.997-1.003)	0.819
CD4/CD8	1.061 (0.512-2.199)	0.874
PT	1.02 (0.801-1.299)	0.873
INR	0.905 (0.027-30.07)	0.956
Cr	0.993 (0.996-1.02)	0.603

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; HDL: High density lipoprotein; LDL: Low density lipoprotein; TG: Triglyceride; HGB: Hemoglobin; PLT: Platelets; WBC: White blood cell; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; AFP: Alpha fetoprotein; NK: Natural killer; CD: Cluster of differentiation; PT: Prothrombin time; INR: International normalized ratio; Cr: Creatinine; HR: Hazard ratio; CI: Confidence interval.

Table 6 Influencing factors for the progression/remission of adult liver cirrhosis, median (interquartile range)

Variable	Progression univariate Cox [HR (95%CI)]	P value	Remission univariate Cox [HR (95%CI)]	P value
Sex	0.036 (0-77.861)	0.397	0.04 (0-1544639.826)	0.714
Age	1.045 (0.936-1.167)	0.437	0.66 (0.411-1.061)	0.086
Genotype	0.178 (0.001-43.643)	0.539	7.533 (1.388-40.875)	0.019
Biochemistry
ALT	1.011 (0.975-1.049)	0.549	0.994 (0.908-1.088)	0.889
AST	1.01 (0.983-1.038)	0.473	0.967 (0.877-1.066)	0.501
GGT	1.008 (0.995-1.021)	0.236	1.003 (0.976-1.03)	0.847
ALP	1.022 (0.995-1.049)	0.107	1.028 (0.986-1.071)	0.196
ALB	0.997 (0.88-1.128)	0.956	1.345 (0.913-1.983)	0.134
TBIL	1.055 (0.981-1.135)	0.15	1 (0.859-1.164)	0.997
DBIL	1.051 (0.936-1.181)	0.397	1.098 (0.912-1.323)	0.322
Glucose	1.239 (0.973-1.577)	0.083	0.536 (0.097-2.972)	0.476
HDL	0.382 (0.076-1.913)	0.241	1.348 (0.213-8.539)	0.751
LDL	0.483 (0.029-8.003)	0.611	0.232 (0.003-16.995)	0.505
TG	0.836 (0.078-8.926)	0.883	1.111 (0.036-34.669)	0.952
HGB	1.003 (0.977-1.03)	0.826	0.984 (0.922-1.051)	0.636
PLT	0.999 (0.991-1.006)	0.75	0.996 (0.975-1.017)	0.718
WBC	1.012 (0.926-1.107)	0.788	0.857 (0.585-1.254)	0.426
Lymphocyte	0.463 (0.108-1.979)	0.299	1.812 (0.274-11.985)	0.537
Neutrophil	1.018 (0.926-1.12)	0.708	0.789 (0.451-1.383)	0.408
HBV DNA	0.821 (0.637-1.059)	0.129	1.148 (0.916-1.439)	0.231
HBeAg	2.45 (0.585-10.262)	0.22	0.021 (0-2501.23)	0.518
AFP	1.001 (0.999-1.002)	0.534	1.001 (0.998-1.004)	0.528
PT	1.316 (0.978-1.771)	0.069	0.394 (0.079-1.95)	0.254
INR	16.58 (1.057-260.027)	0.046	0.01 (0-2444.004)	0.468
Cr	1 (0.958-1.044)	0.992	1.013 (0.927-1.107)	0.778

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; ALP: Alkaline phosphatase; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; HDL: High density lipoprotein; LDL: Low density lipoprotein; TG: Triglyceride; HGB: Hemoglobin; PLT: Platelets; WBC: White blood cell; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; AFP: Alpha fetoprotein; PT: Prothrombin time; INR: International normalized ratio; Cr: Creatinine; HR: Hazard ratio; CI: Confidence interval.