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

Abstract

BACKGROUND

Chronic hepatitis B virus (HBV) infection acquired in childhood frequently presents with mild or nonspecific symptoms, yet a distinct subset of pediatric patients develops rapid progression to liver cirrhosis (LC) before adulthood.

AIM

To identify clinical and pathological characteristics of pediatric HBV-related LC.

METHODS

A total of 1332 pediatric patients with chronic HBV infection from the Fifth Medical Center of PLA General Hospital from January 2010 to January 2023 were included in this study. We identified 62 pediatric HBV-related LC by liver biopsy from the group. Subsequently, we described the clinical and pathological characteristics of pediatric LC. And 64 pediatric chronic hepatitis B (CHB; age and sex were matched with pediatric LC group) and 69 adult HBV-related LC (sex were matched with pediatric LC group) were enrolled to further demonstrate clinical and pathological differences between pediatric LC, pediatric CHB and adult LC.

RESULTS

We enrolled 62 pediatric LC, including 54 (87.1%) males and 8 (12.9%) females. The median age was 11 (4-14) years old. The pediatric LC group showed significantly lower median quantitative HBV DNA loads (log₁₀IU/mL: 6.3 vs 17.4, P < 0.001), reduced HBsAg titers (log₁₀IU/mL: 3.11 vs 8.956, P < 0.0001), and diminished hepatitis B e antigen-positive positive rate (81.4% vs 93.8%, P < 0.05) compared with pediatric CHB. A higher proportion of pediatric patients were asymptomatic (77.4%) compared to adult patients (11.6%) as they first diagnosed as LC, pediatric LC showed milder initial symptoms compared with adult patients such as fatigue (4.8% vs 27.5%), abdominal discomfort (9.7% vs 23.2%), nausea (0% vs 10.1%), and poor appetite (6.5% vs 8.7%; all P < 0.0001). Notably, pediatric LC can achieve a significant percentage of functional cure compared with adult LC as 17.4% and 0%. The incidence of progression of LC in children after antiviral therapy continues to be much lower than that in adult LC (hazard ratio = 6.102, 95% confidence interval: 1.72-21.65, P = 0.00051). While the incidence of LC remission in children after antiviral therapy continues to be much higher than that in adult LC (hazard ratio = 0.055, 95% confidence interval: 0.07128-0.2802, P < 0.0001).

CONCLUSION

Pediatric patients with HBV-related cirrhosis exhibit elevated virological parameters and heightened transaminase levels than adult patients. However, the frequent paucity of overt clinical symptoms contributes to diagnostic challenges. Notably, early initiation of antiviral therapy in this population substantially improved clinical outcomes.

Key Words: Pediatric; Hepatitis B virus; Liver cirrhosis; Clinical; Pathological

Core Tip: Pediatric cirrhosis is mostly detected via physical examination with rare symptoms, whereas adults typically present with jaundice, hematochezia, and fatigue. Pediatric cirrhosis has a better prognosis than adult cases, with higher hepatitis B surface antigen seroclearance rates and potential rapid reversal in some instances, while adult cirrhosis generally carries a poor prognosis. Pediatric cirrhosis progresses more rapidly (even occurring in children < 3 years old), whereas adult cases follow a slower clinical course. Children with cirrhosis often have a history of liver dysfunction and frequently experience disease recurrence due to self-discontinuation of hepatoprotective/antiviral/traditional Chinese medicine treatments.

INTRODUCTION

Liver cirrhosis (LC) is a leading cause of end-stage liver disease in children, with a more complex etiological spectrum than adults, involving multiple mechanisms such as genetic metabolic disorders, congenital developmental defects, infectious factors, and autoimmune conditions[1-3]. LC, typically develops over decades in adults[4], however, a distinct subset of pediatric hepatitis B virus (HBV) patients progresses to cirrhosis much earlier in life, often during childhood, while most others exhibit only mild fibrosis. The mechanisms underlying this accelerated fibrogenesis remain poorly understood and warrant further investigation[5]. Although clinical and biochemical monitoring is routinely performed, liver histopathology remains the gold standard for definitive diagnosis and outcome prediction.

Globally, LC cases among children and adolescents have risen concerningly, increasing from 724200 in 1990 to 917800 in 2017, with an annual growth rate of 0.13%[6]. Children with LC face significantly higher mortality risks, particularly in early childhood[7,8]. In the study by Hu et al[9], the incidence rates of mild to moderate fibrosis and cirrhosis in children with chronic hepatitis B (CHB) were 80.2% and 8.3%, respectively, indicating that HBV-related cirrhosis in the pediatric population still requires close attention[9].

The transmission routes of HBV include mother-to-child transmission, blood transmission, and sexual transmission, etc. With the implementation of large-scale vaccination programs, the incidence of HBV infection in children has been declining annually. However, China, as a high-endemic region for HBV, still exhibits a high proportion of children with CHB. Due to reasons such as failures in mother-to-child blockade and vaccination inefficacy, vertical transmission remains the primary route of CHB infection among children in China. Therefore mother-to-child transmission is still the primary route of HBV infection in pediatric cases[10-12]. Notably, some of these children rapidly develop advanced fibrosis (F4), exhibiting distinct clinical and pathological features compared to adults with HBV-related cirrhosis.

Despite these critical observations, research on early-onset LC in young children - particularly infants, toddlers, and preschoolers - remains scarce. Existing studies predominantly focus on adult populations, with only limited reports addressing pediatric HBV-associated cirrhosis. To bridge this gap, our study systematically compared cirrhotic and non-cirrhotic pediatric HBV patients, as well as contrast early-onset pediatric cases with adult-onset cirrhosis following vertical transmission. Additionally, potential risk factors for pediatric LC were identified. These findings may provide a theoretical foundation for early intervention strategies and improved prognostic prediction in high-risk pediatric populations.

MATERIALS AND METHODS

Study population

From January 2010 to February 2023, we enrolled 1332 patients aged ≤ 18 years with CHB infection from the Fifth Medical Center of PLA General Hospital. Among them, 150 patients coinfected with hepatitis C virus (HCV) or hepatitis D virus (HDV). The total number of patients being excluded by other etiologies was 232. The number of patients with autoimmune liver disease was 84, drug-induced liver injury was 51 and inherited metabolic liver diseases was 97. The exclusion criteria are based on the corresponding diagnostic and treatment guidelines[13-16], 123 CHB infection children with incomplete clinical data were excluded. The exclusion criteria with autoimmune liver disease are based on American Association for the Study of Liver Diseases 2019 Practice Guidance and Guidelines[13], the exclusion criteria with drug-induced liver disease according to American Association for the Study of Liver Diseases Practice Guidance on Drug, Herbal, and Dietary Supplement-Induced Liver Injury[14], the exclusion criteria with Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome as shown in Strassburg’ study[15], and the exclusion criteria with Wilson’s disease, hereditary hemochromatosis and alpha-1 antitrypsin deficiency are based on Ferreira et al’s study[16]. Among the remaining 827 children, 62 pediatric patients were diagnosed as LC and 765 were diagnosed as CHB by liver biopsy. And we enrolled 64 pediatric CHB patients (age and sex were matched) to further investigate clinical and pathological characteristics of pediatric LC. From a concurrent group of 3358 adult LC patients, exclusions were applied as follows, 953 due to HCV or HDV co-infection, 681 due to autoimmune liver disease, drug-induced liver injury, or metabolic liver diseases, 1158 due to incomplete clinical data, and 350 due to hepatocellular carcinoma (HCC). Subsequently, 69 adult patients with LC without other chronic liver diseases were matched by sex for comparative analysis (Figure 1). The CHB patients and HBV-related pediatric LC patients included in this study were all infected by mother-to-child transmission.

Figure 1 Patient study flow diagram. A total of 1332 pediatric patients with chronic hepatitis B (CHB) diagnosed at the Fifth Medical Center of PLA General Hospital between January 2010 and February 2023 were enrolled in this study. According to the exclusion criteria, 150 patients were excluded due to co-infection with hepatitis C virus or hepatitis D virus; 232 were excluded for autoimmune liver disease, drug-induced liver disease, or other inherited metabolic liver diseases; and 123 were excluded due to incomplete clinical data. Ultimately, the study included 62 children with hepatitis B virus-related liver cirrhosis (LC) and 765 children with CHB. From the pediatric CHB group, 64 patients were randomly matched by age and sex for comparative analysis. From a concurrent cohort of 3358 adult LC patients, exclusions were applied as follows: 953 due to hepatitis C virus or hepatitis D virus co-infection, 681 due to autoimmune, drug-induced, or metabolic liver diseases, 1158 due to incomplete clinical data, and 350 due to hepatocellular carcinoma. Subsequently, 69 adult patients with LC without other chronic liver diseases were matched by sex for comparative analysis. By characterizing the clinical and pathological features of pediatric LC, comparing pediatric CHB with pediatric LC, and identifying differences between pediatric and adult LC, this study demonstrated that although chronic hepatitis B can progress to cirrhosis early in childhood, antiviral therapy may lead to the reversal of liver cirrhosis. CHB: Chronic hepatitis B; HCV: Hepatitis C virus; HDV: Hepatitis D virus; LC: Liver cirrhosis; HBV: Hepatitis B virus; pCHB: Pediatric chronic hepatitis B; HCC: Hepatocellular carcinoma.

CHB were diagnosed as hepatitis B surface antigen (HBsAg) positivity lasts more than 6 months accompanied by different degrees of liver inflammation, necrosis, and/or liver fibrosis[17]. The diagnostic criteria for children with LC are based on the 2019 Guidelines for the Diagnosis and Treatment of LC: In the compensated stage of LC, it includes (any one of the following 3 items): (1) Histological evidence of LC; (2) Endoscopy showing esophageal and gastric varices or ectopic varices in the digestive tract, excluding non-LC-related portal hypertension; and (3) Imaging examinations such as B-ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) indicating the characteristics of LC or portal hypertension. The diagnostic criteria for decompensated LC include: On the basis of LC, complications of portal hypertension and/or liver function decline occur[18]. At admission, informed consent was obtained from each child's parents. The study was approved by the ethics committees of the Fifth Medical Center of PLA General Hospital.

Routine tests

The routine preoperative examination included liver and renal function tests, HCV and HDV detection, blood ammonia, serum alpha-fetoprotein (AFP) level, prothrombin time (PT), and blood routine test. HBV DNA quantification was detected with a lower limit of 20 IU/mL (Roche COBAS AmpliPrep, Roche Molecular Systems, Inc., NJ, United States) and HBsAg quantification (anti-HBsAg) was quantified with a lower limit of 0.05 IU/mL (Roche COBAS AmpliPrep, Roche Molecular Systems, Inc., NJ, United States). Abdominal ultrasonography was routinely performed. Other imaging examinations, including X-ray, CT, MRI and liver stiffness measurement, were carried out wherever necessary.

Pathological examination

Liver biopsy specimens were obtained under strict aseptic precautions. All samples were processed through hematoxylin and eosin, Masson’s trichrome and reticulin staining. All slides were independently evaluated by three experienced pathologists without inter-observer consultation. All pathologists performed their evaluations independently initially. Subsequently, they participated in a consensus conference where any discrepant cases were discussed jointly under a multi-head microscope until a unanimous final diagnosis was achieved. Histological features were quantitatively assessed according to the Brunt criteria to determine inflammatory activity (distinct grade) and fibrosis stage. Grading ranges from grade 0 (no inflammation) to grade 3 (severe inflammation with ballooning degeneration and necrosis), while staging progresses from stage 0 (no fibrosis) to stage 4 (cirrhosis), characterized by nodular regeneration, bridging fibrosis, and disrupted liver architecture. Cirrhosis diagnosis required definitive evidence of nodular regeneration surrounded by diffuse fibrosis with loss of normal hepatic architecture, with findings validated through collagen proportionate area quantification in select cases[19,20].

Statistical analysis

Statistical analyses were performed and visualized using SPSS version 26.0 (IBM Corp., Armonk, NY, United States) and GraphPad Prism (GraphPad Software, San Diego, CA, United States). Continuous variables were subjected to normality testing (Shapiro-Wilk) and expressed appropriately: mean ± SD for parametric data (compared via two-tailed t-tests) or median (interquartile range) for non-parametric data (analyzed with Mann-Whitney U test). Categorical variables were reported as frequencies [n (%)] and compared using χ²/Fisher’s exact tests. Cox regression was used to analyze factors influencing the remission/progression of LC in both pediatric and adult patients. Survival analysis was conducted via Kaplan-Meier test, with between-group differences assessed by the log-rank test. All statistical tests were two-sided, and a P < 0.05 defined statistical significance.

RESULTS

Clinical characteristics of pediatric LC

Our study enrolled 62 pediatric patients with cirrhosis, including 54 (87.1%) males and 8 (12.9%) females. The median age was 11 (4-14) years. The median BMI was 16.77 (15.45-20.67) kg/m². There were 4 cases (6.5%) with ascites, and no cases of hepatic encephalopathy or gastrointestinal bleeding were observed when they first diagnosed as LC. A total of 77.4% (n = 48) were asymptomatic, 9.7% (n = 6) had jaundice, 6.5% (n = 4) exhibited aberration, 4.8% (n = 3) presented fatigue, 3.2% (n = 2) showed discomfort in the liver area. Thoracoabdominal bleeding points, recurrent epistaxis, and progressive elevation of AFP were presented in one patient each, respectively. Liver function tests revealed significant abnormalities with median alanine aminotransferase as 107.5 (58.5-207.25) U/L, aspartate aminotransferase as 110.5 (64.25-169.5) U/L, and gamma-glutamyltransferase (GGT) as 70.5 (48-105) U/L. The median value of platelets (PLT), albumin (ALB) and PT levels were within the normal range as 16 (113.5-221) × 10⁹/L, 39 (36-41.25) g/L and 12.3 (11.55-13.35) seconds, respectively. The median Child-Pugh score was 5 (5-6), and the median pediatric end-stage liver disease/model for end-stage liver disease score was 3.5 (0.75-8). Virologically, genotype C predominated (69.4%, n = 43) in all the 62 LC patients. The hepatitis B e antigen-positive (HbeAg) positive rate was 81.4% (n = 48). Median log₁₀HBsAg was 3.11 (0-3.69) and median log₁₀(HBV DNA load) was 6.3 (4.58-7.54) IU/mL. Notably, only 12.9% (n = 8) received antiviral therapy before being diagnosed as LC (Table 1).

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.

A total of 46 children received antiviral therapy after being diagnosed as LC, including 82.6% (n = 38) males and 17.4% (n = 8) females. Among them, 5 patients were treated with nucleos(t)ide analogues monotherapy, among whom 4 achieved HBV DNA seroclearance, with a median seroclearance time as 14.93 (4.99-54.47) months. And 41 patients were treated with interferon combined with nucleos(t)ide analogues. In the combined treatment group, the HBsAg seroclearance rate was 20% (n = 8), with a seroclearance time as 35.17 ± 21.51 months; the HBeAg seroclearance rate was 65% (n = 26), with a median seroclearance time as 10.54 (3.52-37.87) months, and the HBV DNA seroclearance rate was 95% (n = 38), with a median seroclearance time as 7.77 (5.22-14.41) months. At the end of treatment, the HBsAg seroclearance rate was 17.4% (n = 8), with a seroclearance time as 35.17 ± 21.51 months; the HBeAg seroclearance rate was 56.5% (n = 26), with a median seroclearance time as 42.14 (14.07-151.46) months, and the HBV DNA seroclearance rate was 91.3% (n = 42), with a median seroclearance time as 7.77 (4.79-14.46) months (Table 2).

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.

Pathological characteristics of children with different fibrosis stages

The pathological changes of CHB in children are generally similar to those in adults. However, during the inactive phase, hepatocytes with ground-glass appearance due to HBsAg overexpression are frequently observed in the hepatic lobules of pediatric patients, while inflammatory necrosis is typically absent or minimal. In the active phase, children with CHB usually demonstrate mixed inflammatory necrosis and ground-glass hepatocytes. Most pediatric patients exhibit relatively mild hepatic fibrosis that progresses insidiously, though a minority may develop significant or progressive fibrosis or even cirrhosis, as observed in the 62 pediatric cases with confirmed cirrhosis included in this study (Figure 2).

Figure 2 Liver pathology of children and adult. A: Liver fibrosis F0 in children; B: Liver fibrosis F1 in children; C: Liver fibrosis F2 in children; D: Liver fibrosis F3 in children; E: Liver cirrhosis in children; F: Liver cirrhosis in adult. Scale bar, 100 μm, magnification, 200 ×.

Specifically, due to their immature immune systems, children demonstrate prolonged immune tolerance and slower progression of hepatic fibrosis. Early stages are characterized predominantly by periportal fibrosis with rare bridging fibrosis, often resulting in micronodular cirrhosis. These patients typically show mild inflammatory activity with sparse lymphocyte infiltration. Although hepatocyte regenerative capacity is strong, cellular atypia is uncommon, leading to lower HCC risk.

In contrast, adult patients mount vigorous immune responses that drive rapidly progressive inflammatory necrosis. Bridging fibrosis and extensive pseudolobule formation are common, frequently progressing to macronodular or mixed cirrhosis. Adult cases exhibit marked inflammatory activity featuring prominent interface hepatitis, spotty necrosis, and dense inflammatory cell infiltration. The fibrous septa are broad and densely packed, with significant vascular remodeling. Ground-glass hepatocytes are more prevalent, and these patients carry substantially higher risks of developing dysplastic nodules and hepatocellular carcinoma.

Differences between pediatric LC and pediatric CHB

As delineated in Table 3, a control group of 64 pediatric CHB patients was matched based on age and sex to the pediatric LC group. Cirrhosis patients exhibited substantially elevated GGT (70.5 U/L vs 23 U/L, P < 0.0001) alongside depressed ALB levels [39 (36-41.25) vs 40 (38-43); P < 0.001]. PLT counts were dramatically reduced in cirrhosis (P < 0.0001), correlating with relatively prolonged PT (P < 0.0001). Triglycerides were higher in cirrhosis (P < 0.05) than that in pediatric CHB, but they were all within the normal range. Notably, the cirrhosis group showed significantly lower median quantification HBV DNA loads (log₁₀IU/mL: 6.3 vs 17.4, P < 0.001), reduced HBsAg titers (log₁₀IU/mL: 3.11 vs 8.956, P < 0.0001), and diminished HBeAg positive rate (81.4% vs 93.8%, P < 0.05). These multidimensional disparities underscore distinct pathophysiological trajectories between pediatric CHB and established cirrhosis.

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.

Differences between pediatric LC and adult LC

We analyzed differences in key clinical and demographic characteristics between 62 pediatric LC and 69 adult LC patients. Pediatric patients had no cases of hepatic encephalopathy or gastrointestinal bleeding, whereas 5.8% and 59.4% of adult patients experienced these serious conditions, respectively, and ascites was present in 6.5% of pediatric patients compared to 8.7% of adults (P < 0.0001). We also find that a notably higher proportion of pediatric patients were asymptomatic (77.4%) compared to adult patients (11.6%) as they first diagnosed as LC, pediatric LC showed milder initial symptoms compared with adult patients such as fatigue (4.8% vs 27.5%), abdominal discomfort (9.7% vs 23.2%), nausea (0% vs 10.1%), and poor appetite (6.5% vs 8.7%; all P < 0.0001). Only 12.9% of pediatric patients had received antiviral therapy before LC, which was significantly lower than that of 53.8% in adult LC (P < 0.0001).

Biochemical analyses revealed that pediatric patients had significantly higher alanine aminotransferase [107.5 (58.5–207.25) U/L vs 29 (18–42) U/L], aspartate aminotransferase [110.5 (64.25–169.5) U/L vs 39 (26–53.5) U/L], ALP [299 (232.25-373) U/L vs 70.5 (58–86) U/L], and GGT [70.5 (48–105) U/L vs 28 (18–46.5) U/L; all P < 0.0001] than adult LC. Pediatric patients also had higher ALB [39 (36–41.25) g/L vs 36 (32-38.5) g/L; P = 0.0003] compared with adult LC. In contrast, total bilirubin in pediatric patients was 11.05 (8.1–19.15) μmol/L, which was lower than that in adult patients as 11.9 (12.65–24.9) μmol/L (P = 0.0002), and direct bilirubin was 4.7 (3.08–8.48) μmol/L in pediatric patient’s vs 8.3 (5.3–11.25) μmol/L in adult patients (P < 0.0001). Metabolic parameters showed that pediatric patients had higher low-density lipoprotein [2.27 (2.02-2.85) mmol/L vs 1.79 (1.56-2.56) mmol/L; P = 0.0018] and lower high-density lipoprotein [1.15 (0.97–1.4) mmol/L vs 1.83 (1.57–2.63) mmol/L; P = 0.008] than those in adult patients. Pediatric patients had lower creatinine (48.68 ± 14.11 μmol/L vs 75.61 ± 15.29 μmol/L; P < 0.0001) and lower glucose [4.5 (4.08–4.89) mmol/L vs 5 (4.26–6.29) mmol/L; P = 0.004) than those in adult patients.

Hematological analyses demonstrated that pediatric patients had elevations in haemoglobin (127.84 ± 14.45 g/L vs 103.38 ± 22.29 g/L, P < 0.0001), PLT [165 (113.5-221) × 10⁹/L vs 91 (53.5-149) × 10⁹/L, P = 0.0072], and lymphocytes [3.15 (2.12-4.26) × 10⁹/L vs 0.79 (0.55-1.49) × 10⁹/L; P < 0.0001], but reduced white blood cell [6.19 (4.67-7.62) × 10⁹/L vs 7.24 (3.31-10.91) × 10⁹/L; P = 0.0062] and neutrophils [2.02 (1.43-2.75) × 10⁹/L vs 5.05 (2.14-9.18) × 10⁹/L; P < 0.0001] than those in adult patients.

Virological profiling revealed that pediatric patients had significantly higher median log₁₀(quantification HBV DNA) [6.3 (4.58-7.54) vs 0 (0–5.43); P < 0.0001] and log₁₀(quantification HBsAg) [3.11 (0-3.69) vs 5.19 (3-9.11); P < 0.0001], with a greater proportion of HBeAg positive patients (81.4% vs 39.1%; P < 0.0001) than those in adult patients. Moreover, AFP levels were higher in pediatric patients [51 (13.73-26) ng/mL vs 3.97 (1.96-12.5) ng/mL; P = 0.0261] than that in adult patients. While pediatric patients had shorter PT [12.3 (11.55-13.35) seconds vs 13.7 (12.9-15) seconds; P < 0.0001] and lower international normalized ratio [1.055 (0.99-1.14) vs 1.18 (1.11-1.28; P < 0.0001] than those in adult patients (Table 4).

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.

Prognosis of pediatric LC and adults LC

We defined LC patients’ progression to HCC or liver failure as end point event, and a reduction in fibrosis by at least one degree in cirrhosis patients was defined as remission (diagnosed by either CT/MRI/Liver stiffness measurement). The number of adults progressing to end point event was 11 (16.41%), and none of the children progressed after regular antiviral therapy. In contrast, none of the adult LC patients get remission after regular antiviral therapy, but 31 (58.49%) of the pediatric LC achieved fibrosis remission of varying degrees. The survival analysis showed that the incidence of progression of cirrhosis in children after antiviral therapy continues to be much lower than that in adults LC (hazard ratio = 6.102, 95% confidence interval: 1.72-21.65, P = 0.00051). While the incidence of remission of LC in children after antiviral therapy continues to be much higher than that in adults LC (hazard ratio = 0.055, 95% confidence interval: 0.07128-0.2802, P < 0.0001; Figure 3).

Figure 3 Comparative survival analysis of liver cirrhosis progression and remission in children vs adults following antiviral therapy. A: Survival analysis of the incidence of progression of cirrhosis in children after antiviral therapy continues to be much lower than that in adults liver cirrhosis (hazard ratio = 6.102, 95% confidence interval: 1.72-21.65, P = 0.00051); B: Survival analysis of the incidence of remission of liver cirrhosis in children after antiviral therapy continues to be much higher than that in adults liver cirrhosis (hazard ratio = 0.055, 95% confidence interval: 0.07128-0.2802, P < 0.0001).

Moreover, correlation analysis revealed distinct prognostic markers between pediatric and adult cirrhosis patients. The remission of pediatric LC was significantly associated with multiple indicators, including glucose, HBV DNA, HBsAg, AFP, and immune cell subsets (T lymphocytes, B lymphocytes, natural killer cells, and cluster of differentiation 4 positive T cells). While in adult cirrhosis patients the progression or remission exhibited differential correlations with international normalized ratio and genotype, as detailed in Tables 5 and 6.

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.

DISCUSSION

LC represents one of the most significant global public health challenges, with its complex pathophysiology and variable clinical manifestations presenting substantial burdens to healthcare systems worldwide[21]. While traditionally considered a disease of adulthood, our study reveals that pediatric cirrhosis exhibits distinct epidemiological, clinical and pathological characteristics that challenge this paradigm. The progression from hepatic fibrosis to end-stage cirrhosis, while often insidious, can sometimes be prevented or delayed through early intervention - particularly relevant for pediatric cases where the disease course appears markedly accelerated compared to adults.

HBV infection emerged as the predominant cause of cirrhosis among young children, which reflects both the endemic nature of HBV in our region and the consequences of vertical transmission. Maternal HBV DNA levels are closely correlated with neonatal infection risk, with higher transmission rates observed in HBeAg-positive mothers or those with elevated HBV viral loads[22]. In our group, children aged younger than 2 years old can progress to LC [13 (20.97%)]. Clinically, pediatric cirrhosis demonstrated a "silent" presentation pattern, with 48 (77.4%) of cases detected incidentally during routine examinations, compared to only 8 (11.6%) of adults. And adult patients predominantly presented with overt symptoms including gastrointestinal bleeding (59.4% vs 3.2%), abdominal discomfort (23.2% vs 9.7%), nausea (10.1% vs 0%), poor appetite (8.7% vs 6.5%) and fatigue (27.5% vs 4.8%; P < 0.001). This discrepancy likely reflects both immunological and developmental factors: (1) Immature immune responses in children may result in less vigorous inflammatory reactions; and (2) Limited symptom reporting capability in pediatric populations. Paradoxically, this asymptomatic progression may contribute to diagnostic delays, therefore, the management plan for pediatric CHB should be clearly distinguished from that in CHB adults.

Pediatric LC had comparable HBsAg levels as adult LC [log₁₀(quantification HBsAg) 3.11 (0-3.69) vs 5.19 (3-9.11), P = 0.465]. But they had higher levels of HBV DNA compared with adult LC [log₁₀(quantification HBV DNA) 6.3 (4.58-7.54) vs 0 (0-5.43); P < 0.0001]. This may be attributed to the fact that most pediatric patients not received antiviral therapy before LC was diagnosed, while most adult patients had received antiviral therapy before LC (12.9% vs 53.8%, P < 0.0001). At the histopathological level, pediatric livers exhibited enhanced vulnerability to fibrogenesis. Risk factors accelerated fibrotic progression may be attributed to developmental factors including: (1) Persistent activation of growth factor pathways (e.g., transforming growth factor-beta) promoting hepatic stellate cell activation; (2) Immature antioxidant defense systems increasing susceptibility to oxidative damage; and (3) Ongoing liver maturation processes that may alter extracellular matrix remodeling[23-25]. Although these mechanisms have also been reported in adults, they may be more pronounced in children due to differences in developmental stages[26].

Therapeutic outcomes revealed important age-related differences. Pediatric patients showed superior responses to antiviral therapy, with 17.4% achieving functional cure compared to 0% of adults (P < 0.0001). This result is also reflected in the study of Wang et al[27] with 3/320 adult patients achieved functional cure. Extensive research has consistently demonstrated that pediatric patients with CHB achieved higher cure rates after receiving antiviral therapy compared to adults’ patients. This study further reveals that even among patients with CHB-related LC, the rate of HBV clearance remains significantly higher in the pediatric population than that in adults. Most remarkably, one child aged 10 years old demonstrated fibrosis stage regression on follow-up biopsy, from LC to stage 1 liver fibrosis after antiviral therapy for 4.66 years using interferon and nucleos(t)ide analogue combination therapy. The number of adults progressing to HCC or liver failure was 11 (16.41%), and none of the children progressed after regular antiviral therapy. In contrast, none of the adult LC patients get remission after regular antiviral therapy, but 31 (58.49%) of the pediatric LC achieved fibrosis remission of varying degrees. This large difference in prognosis can be explained by their cirrhosis status, the ALB levels [39 (36-41.25) g/L vs 36 (32-38.5) g/L; P = 0.0003], haemoglobin levels (127.84 ± 14.45 g/L vs 103.38 ± 22.29 g/L; P < 0.0001) and PLT levels [165 (113.5-221) × 10⁹/L vs 91 (53.5-149) × 10⁹/L; P = 0.0072] in pediatric patients were higher compared to those in adult patients. However, a study indicated that four patients who had cirrhosis at baseline (Ishak fibrosis score ≥ 5) all showed improvement in their Ishak fibrosis scores, with a median decrease of 3 points[28]. These findings challenge traditional concepts about cirrhosis irreversibility and suggest enhanced regenerative capacity in developing livers. However, treatment adherence remains a significant challenge, with 8 (12.9%) of pediatric cases and 8 (11.6%) reporting treatment interruptions - none of them achieved functional cure in our group.

From a public health perspective, our data support several strategic recommendations for HBV-endemic regions: (1) Implementation of early screening protocols (since they were diagnosed with CHB) for vertically infected children; (2) Development of pediatric-specific risk prediction models incorporating viral, genetic and clinical parameters; and (3) Enhanced family education programs to improve treatment adherence.

Our study provides actionable insights for managing pediatric HBV-related cirrhosis. The identified clinical and pathological features enable better risk stratification, helping clinicians identify children at high risk for rapid fibrosis progression who would benefit from closer monitoring and earlier intervention. The characteristically elevated virological markers and transaminase levels occurring without symptoms highlight the need for increased vigilance in at-risk pediatric populations. Our data support early initiation of potent antiviral therapy, particularly interferon and nucleos(t)ide analogue combinations, which achieved high functional cure and fibrosis regression rates. Additionally, pediatric-specific prognostic markers such as GGT, platelet count, and HBsAg titer can guide individualized treatment and long-term follow-up. Integrating these findings into practice will allow clinicians to optimize treatment timing, enhance adherence through family education, and ultimately improve long-term outcomes in children with HBV-related cirrhosis.

Several limitations must be acknowledged: The study’s limitations include: (1) Its limited sample size, which may constrain statistical power. The single-center design and biopsy-confirmed group may overrepresent advanced disease may limit generalizability. Lack of data on antiviral prevention measures for pregnant women, hepatitis B vaccination for newborns, and injection of hepatitis B immune globulin. Future research should require multicenter studies to validate our findings; (2) Long-term outcome data require extended follow-up, future efforts should prioritize the development of non-invasive pediatric fibrosis biomarkers; (3) Mother-to-child transmission was the primary route of pediatric HBV infection, lack of other transmission routes (e.g. horizontal transmission, regional variations, or the impact of large-scale vaccination programs) due to the characteristics in our group; (4) The molecular mechanisms underlying cirrhosis regression remain incompletely understood, and therefore future research should prioritize mechanistic investigations of liver regeneration in developing organisms; and (5) Collect cases that contain data related to antiviral prevention measures for pregnant women, hepatitis B vaccination for newborns, and injection of hepatitis B immune globulin.

CONCLUSION

This study delineates pediatric HBV-related cirrhosis as a distinct clinical entity characterized by rapid progression, subtle presentations but favorable treatment responses. These insights not only advance our understanding of liver disease pathogenesis across developmental stages but also provide evidence-based rationale for optimizing management strategies in this vulnerable population. Through integrated approaches combining early detection, targeted therapies and comprehensive care systems, we can potentially transform outcomes for children with cirrhosis worldwide.

ACKNOWLEDGEMENTS

The authors wish to thank all the patients and family members that participated in the study.