Silent progression and therapeutic reversibility of pediatric hepatitis B virus-related cirrhosis: Needs unmet

Abstract

Hepatitis B virus-related cirrhosis in pediatric patients represents a silent yet rapidly progressive condition. Recent evidence from a study by Zhao et al published in the World Journal of Gastroenterology, highlights distinct clinical and pathological features of this pediatric disease compared to adult cirrhosis and demonstrates remarkable potential for reversal under timely antiviral therapy. This editorial explores the implications of these findings for clinical practice, policy, and research, emphasizing early detection, pediatric-specific management, and future directions to optimize clinical outcomes.

Key Words: Pediatric; Hepatitis B virus; Liver cirrhosis; Antiviral therapy; Prognosis; Fibrosis regression

Core Tip: This editorial emphasizes that pediatric hepatitis B virus-related cirrhosis is a silent yet rapidly progressive condition that is often overlooked, despite its potential reversibility with timely antiviral therapy. Unlike adult cirrhosis, pediatric cases frequently present without symptoms, making early detection through routine screening essential. The manuscript highlights the unique pathophysiology in children: Marked high viral replication, minimal inflammation, and strong regenerative capacity, which creates a critical therapeutic window for fibrosis regression and functional cure. We recommend structured pediatric programs emphasizing periodic virologic and biochemical testing, a low threshold for elastography and other noninvasive fibrosis tools, prompt initiation of antiviral therapy in high-risk children, and sustained adherence support. These measures, coupled with reinforced perinatal prevention, can materially improve long-term outcomes.

This editorial refers to "Clinical, pathological characteristics and long-term outcomes of hepatitis B virus related cirrhosis in pediatric observational study" by Zhao et al, 2025; https://doi.org/10.3748/wjg.v31.i48.114049.

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INTRODUCTION

Hepatitis B virus (HBV) infection remains a major global health challenge, affecting over 250 million individuals worldwide[1,2]. Despite widespread vaccination programs, vertical transmission continues to drive pediatric infections in endemic regions. The World Health Organization estimates that over 1.5 million new HBV infections occur annually, with global hepatitis B surface antigen (HBsAg) prevalence in children under 5 years old at 1.3%[3].

While most HBV-infected children enter a prolonged immune-tolerant phase with high viremia and normal alanine aminotransferase (ALT), the progression of fibrosis in chronic HBV infection is indeed a dynamic, complex process profoundly influenced by the child's immature and changing immune system, leading to a distinct natural history compared to adults. In hepatitis B e antigen (HBeAg)-positive children, chronic viral hepatitis (HBV, hepatitis C virus) poses a risk of 1%-5% cirrhosis[3,4]. Although cirrhosis is traditionally considered a disease of adulthood[5], emerging evidence reveals that HBV-related cirrhosis can occur in children, often progressing rapidly and silently, which can be life-threatening and frequently necessitates liver transplantation[6,7]. These epidemiological trends underscore the urgency of addressing pediatric HBV-related cirrhosis as a public health priority.

The recent observational study by Zhao et al[8] published in the World Journal of Gastroenterology provides one of the most comprehensive analyses of pediatric HBV-related cirrhosis to date. Whereas authors in prior studies estimated the occurrence of HBV-related cirrhosis in children at 1.7%-3%, Zhao et al[8] identified a total of 62 (4.65%) cases of biopsy-confirmed cirrhosis in this large cohort compromising 1332 HBV-infected pediatric patients, with a male/female ratio of 6.75, and the majority (77.4%) being asymptomatic. Although HBV-related cirrhosis in children progressed earlier in the study, antiviral therapy achieved encouraging clinical outcomes.

Historically, cirrhosis was considered irreversible, but recent advances in antiviral therapy and liver regeneration research have challenged this notion. Numerous studies have documented fibrosis reverse in hepatitis B, hepatitis C, and metabolic associated steatohepatitis upon treatment[9-12]. Pediatric cases, in particular, offer a unique opportunity to study fibrosis reversal due to their overall robust regenerative capacity. The study by Zhao et al[8] revealed distinct clinicopathological features of HBV-related cirrhosis in pediatric patients and has significant implications that will be discussed below, combined with current guidelines and mechanistic insights.

THE SILENT PROGRESSION OF HBV-RELATED PEDIATRIC CIRRHOSIS

One of the most striking observations from Zhao et al’s study[8] is the asymptomatic nature of pediatric cirrhosis: At diagnosis, 77.4% of children were asymptomatic, compared to only 11.6% of adults. It is well-known that severe complications common in adult cirrhosis, such as hepatic encephalopathy and gastrointestinal bleeding, were absent in pediatric cases. In contrast, most children were diagnosed incidentally during routine examinations or investigations for unrelated conditions[6,7].

This silent progression poses significant diagnostic challenges. Without overt clinical presentations, pediatric cirrhosis often escapes detection until advanced stages, limiting opportunities for early intervention. The implications are profound: In children, significant fibrosis or cirrhosis may progress for years with minimal biochemical or symptomatic clues. Clinical examples illustrated this silent progression: In Zhao et al’s cohort[8], several children under three years old were diagnosed with advanced fibrosis despite normal physical examinations and only mild biochemical abnormalities. This really challenges the long-standing conviction that most HBV-infected children remain in a harmless “immune tolerant” phase for years with minimal damage. The samples also underscore the need for routine screening protocols in all HBV-infected children, regardless of symptomatology. Such cases not only highlight the inadequacy of symptom-based monitoring and reinforce the need for initiative-taking screening strategies, including elastography and non-invasive fibrosis markers, but also underscore the need for routine screening protocols in all HBV-infected children, regardless of symptomatology. In other words, symptom-based “watchful waiting” strategy, relying on symptoms (fatigue, jaundice, abdominal pain) to trigger further evaluation, is unsafe in children, and must be risk-stratified for the subset of children are at real risk of rapid fibrosis and cirrhosis, even when they appear well and lab abnormalities are modest.

Zhao et al’s findings[8] also displayed the other side of the coin: Pediatric cirrhosis, although progressing silently, appeared more “plastic” and reversible than adult cirrhosis post HBV infection. Essentially, pediatric cirrhosis is not a “point of no return” but a dynamic, modifiable state, which undoubtedly raises the stakes for early identification and aggressive treatment: The window of reversibility is real, and it should be the focus of treatment and actively targeted. Unfortunately, virtually all pediatric cases in this study were vertically infected, and some progressed to cirrhosis before age 3, urging effective and timely follow-up and monitoring strategies to be executed. In addition, the reliance on biopsy in the study to uncover advanced disease further underscores how easily cirrhosis would be missed in usual practice. Undoubtedly, non-invasive fibrosis tests in children should be considered earlier and more routinely, not reserved only for obvious decompensation. Therefore, we propose that a structured hepatitis B program for children should adapt the following 3 measures: (1) Regularly monitor liver biochemistry [ALT, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, bilirubin], virological activities (HBV DNA, HbsAg quantification, HbeAg status), liver synthetic function and portal hypertension markers [platelets, albumin, prothrombin time/international normalized ratio (INR)]; (2) Use lower threshold for non-invasive fibrosis assessment, such as transient elastography or other stiffness measurements, repeated imaging focusing on texture, nodularity, and portal hypertension, and, where feasible and safe, liver biopsy in high-risk children; and (3) Long-term follow-up even after “stabilization”.

PATHOPHYSIOLOGICAL INSIGHTS

Liver fibrosis is a universal reparative process in the liver in response to diverse types of liver injuries, characterized by deposition of excess extracellular matrix in the subendothelial space of Disse. Why pediatric cirrhosis progresses silently yet rapidly reflects the interplay of viral replication, immune maturation, and hepatic development, which together create physiologic and immunologic differences between children and adults[7].

Cirrhosis represents the final common pathway of chronic liver injury, pathologically defined by diffuse architectural remodeling characterized by advanced fibrosis, regenerative nodule formation, and distortion of normal lobular structure. Compared to adult cirrhosis, the pathophysiology of pediatric cirrhosis is less clear, especially in patients with hepatitis B. It is known that children usually exhibit prolonged immune tolerance to HBV, characterized by high viral replication and minimal inflammatory activity. This state, while protective against severe hepatitis, permits ongoing fibrogenesis[13,14]. However, the dynamic of liver fibrosis in children has not been fully elucidated. What we know so far is that, across different cohorts[15-17], cirrhosis rates range from 2.27% to 8.3%, among treatment-naïve children with chronic hepatitis B. In addition, younger children can paradoxically show more advanced fibrosis, suggesting that significant liver damage can occur early in the disease course[17]. In a 10-year cohort study of biopsy-proven cirrhosis in young children, the median age at cirrhosis diagnosis was 2 years (range: 1 month to 6 years), with HBV infection accounting for 33.3% of cases[18].

Zhao et al[8] depicted histological details of HBV-related cirrhosis in children: Mild inflammation, delicate septal architecture, strong regenerative potential, and a comparatively reversible disease course. The predominant pattern of well-developed cirrhosis was micronodular cirrhosis with limited vascular remodeling and relatively preserved portal venous architecture. This pattern has two implications: (1) It reflects rapid progression of fibrosis in the pediatric participants, which does not allow for enough time for the micronodular cirrhotic nodules to merge to form larger cirrhotic nodules; and (2) It also likely contributes to the low incidence of portal hypertension complications at diagnosis. The documented mild inflammatory activity reflects the immature adaptive immune response in children and the prolonged immune-tolerant phase of vertically acquired HBV infection. The observed high regenerative capacity of the developing liver, with rare cellular atypia and infrequent dysplastic nodules, could contribute to: (1) The remarkable potential for fibrosis regression as observed after antiviral therapy; and (2) Lower risk of developing hepatocellular carcinoma. Zhao et al’s observation[8] highlighted the biological distinction of pediatric cirrhosis from adults and underscores the importance of early detection and antiviral intervention.

Virologically, pediatric cirrhosis patients in Zhao et al’s cohort[8] had higher HBV DNA loads (median log₁₀ 6.3 IU/mL) and lower HBsAg titers compared to adults, with genotype C predominating (69.4%), a genotype-associated with aggressive disease in Asian populations. These findings suggest that viral replication, rather than immune-mediated injury, drives early fibrogenesis in children, which is supported by the absence of severe necroinflammation in pediatric biopsies.

Emerging research on hepatic stellate cell activation provides mechanistic insights into fibrosis progression. For example, HBV proteins, including HBx, have been implicated in promoting stellate cell activation and extracellular matrix deposition[19]. These effects may be amplified in pediatric livers under ongoing developmental processes, leading accelerated fibrogenesis. Conversely, the robust regenerative capacity of pediatric hepatocytes offers a therapeutic window for reversing fibrosis, particularly when antiviral therapy is initiated early. Together, these features help explain simultaneously silent progression and high potential for reversal in pediatric cirrhosis.

THERAPEUTIC BREAKTHROUGHS AND PROGNOSIS

Functional cure of hepatitis B, defined as sustained undetectable HBsAg and HBV DNA after a definite course of treatment, remains rare with current treatments[20-22].

In adults with hepatitis B, effective antiviral therapy is one of the key factors determining cirrhosis remission[23]. As shown in Zhao et al’s study[8], more than half of the adults had prior treatment, while in sharp contrast, only 12.9% of pediatric patients received antiviral therapy before cirrhosis was diagnosed, even though these children had higher HBV DNA levels and more active biochemistry at the time of diagnosis of cirrhosis, indicating that children are often undertreated or treated too late for cirrhosis. Accordingly, we can conclude that: (1) Persistent high HBV DNA (and/or high HBsAg) with elevated transaminases and/or early fibrosis should trigger treatment early, not after “waiting to see” for years; and (2) Strict adherence to adult-based “immune tolerant” thresholds will miss the window when pediatric livers are still highly regenerable. Indeed, these conclusions are evidenced by the most transformative finding in the study, i.e., the exceptional responsiveness of pediatric cirrhosis to antiviral therapy, which demonstrated that, among children treated with nucleos(t)ide analogue (NA) monotherapy or combinatory therapy with interferon (IFN) combined with NAs, overall 58.49% patients achieved fibrosis regression and 17.4% attained HBsAg clearance - outcomes that were not observed in adults. These results challenge the long-held belief that cirrhosis is irreversible and highlight the regenerative potential of developing livers and the critical importance of early intervention. One clinical vignette from the study illustrated these therapeutic breakthroughs: One child with biopsy-confirmed cirrhosis demonstrated regression to stage 1 fibrosis after 4.6 years of combination therapy, exemplifying the potential for histological reversal.

The treatment outcomes for pediatric HBV-related cirrhosis represent one of the most compelling aspects of recent research, and recent comparative efficacy data reveal that IFN-based regimens combined with NAs outperform monotherapy approaches[24]. Zhao et al[8] showed that, compared to combinatory therapy, NA monotherapy yielded lower functional cure rates, with only 4 of 5 patients achieving HBV DNA clearance and none achieving HBsAg clearance within similar timelines, indicating the synergistic benefits of combination therapy: While NAs suppress viral replication, reducing hepatic inflammation and fibrogenesis, IFN is needed to enhance immune-mediated viral clearance. Obviously, in children, the potential for true fibrosis reversal is higher and life expectancy is longer than that in adults, amplifying the benefit of preventing progression to end point. While children demonstrated robust rates of fibrosis regression and functional cure, adults in the study achieved neither, even with comparable or longer treatment duration. These age-specific markers may provide a framework for risk stratification and individualized treatment planning. As such, we believe that the risk-benefit balance of aggressive antiviral regimens is more favorable in children than in adults and support a more proactive, “curative-intent” antiviral strategy in pediatric HBV cirrhosis. Age-related differences in treatment response further emphasize the unique therapeutic window in pediatric cirrhosis. Treatment adherence also emerged as a critical determinant of success, with therapy interruptions associated with markedly poorer outcomes.

Timelines for seroclearance in hepatitis B are clinically significant in managing cirrhosis. In Zhao et al’s study[8], HBV DNA clearance within 8 months reduces ongoing viral replication, mitigating further fibrotic progression. HBeAg clearance within 11 months correlates with improved biochemical profiles and reduced inflammatory activity. HBsAg clearance, though slower, represents the ultimate therapeutic milestone, conferring long-term remission and reduced hepatocellular carcinoma risk. Survival analyses from Zhao et al’s cohort[8] reinforced these notions: Pediatric patients demonstrated markedly lower progression rates to liver failure or hepatocellular carcinoma compared to adults [hazard ratio (HR) = 6.102, P = 0.00051]. Conversely, remission rates were substantially higher in children (HR = 0.055, P < 0.0001)[8]. The Kaplan-Meier curves illustrated the prognostic advantage conferred by early, aggressive antiviral therapy in pediatric populations. These findings advocate for pediatric-specific treatment algorithms prioritizing combination therapy, early initiation, and adherence reinforcement. Undoubtedly, functional cure carries meaningful long-term benefits, reducing hepatocellular carcinoma risk, improving quality of life, and lowering healthcare burden. Future research should explore adjunctive strategies, including immune modulators and antifibrotic agents, to further enhance outcomes.

Worldwide, current pediatric hepatitis B guidelines focus on universal infant vaccination at birth, followed by a series, and for infected children, management involves regular monitoring and antiviral therapy for children with active disease. Although IFN combined with NAs offered the highest chance of functional cure in Zhao et al’s study[8], it is worth noting that the American Association for the Study of Liver Diseases (AASLD) and Hepatitis B Foundation guidelines favor IFN as the agent of choice in most cases, reserving NAs as secondary therapies for specific situations such as decompensated liver disease (where IFN is contraindicated), IFN intolerance or treatment failure, and when guardian preference strongly favors oral therapy[25,26]. Despite that, recent real-world evidence suggests potential benefits of combination therapy in specific age groups, and recent Chinese guidelines (2022) expanded indications to include children in the immune-tolerant phase if aged < 7 years or with inflammation grade 1, reflecting evolving understanding of age-dependent immune responses. These findings have not yet been incorporated into formal guidelines[27]. Additional clinical data of combination therapy (entecavir plus peginterferon) in immune-tolerant children showed unsatisfactory efficacy and frequent adverse events[28,29]. A 2025 propensity score-weighted study of 809 children found that de novo IFN and NA combination therapy and IFN monotherapy both outperformed IFN-NA sequential therapy for HBsAg clearance, though no significant difference existed between combination therapy and monotherapy overall (P = 0.5999)[30]. Generally, tolerance and side effects are major limiting factors for IFN combined with NA therapy. IFN is associated with flu-like symptoms, fever, myalgia, fatigue, anorexia, weight loss or growth deceleration, cytopenias, transaminase flares, thyroid dysfunction, mood changes, and, rarely, autoimmune phenomena. NAs add long-term adherence demands and, depending on the agent, potential renal and bone effects. Combination therapy therefore requires a structured monitoring strategy: Regular complete blood count, liver panel, thyroid function, growth and weight tracking, mood/behavior assessment, and, for some NAs, renal function and phosphate levels. Families should be counseled in advance about expected early flu-like symptoms, the importance of maintaining nutrition and hydration, and when to seek urgent care (high fevers, severe abdominal pain, jaundice, bleeding, profound fatigue, mood changes). Management of side effects should also focus on anticipatory guidance, dose timing (e.g., evening injections), antipyretics, nutritional support, and close follow-up. Transient ALT flares may be acceptable if the child remains clinically stable, but significant decompensation signs warrant reassessment or discontinuation. Shared decision-making is crucial: The regimen should be framed as a time-limited, higher-intensity strategy aiming at achieving outcomes (HBsAg loss, fibrosis regression) that are rarely attainable with NAs alone; the family’s capacity to cope with injections, side effects, and frequent monitoring should be explicitly evaluated before initiating therapy.

The prognosis of cirrhosis is governed by a range of factors. In adult patients, the post-HBV-infection progression/remission of cirrhosis is determined by viral suppression, baseline disease characteristics, and monitoring; however, the data of pediatric-specific key determinants of cirrhosis/progression and remission are currently very limited[23,27,31,32]. Zhao et al[8] identified a constellation of prognosis-related factors [GGT, HBV DNA, HBsAg, alpha-fetoprotein (AFP), immune cell subsets, glucose], even when fibrosis regressed and viral markers improved. By univariate Cox regression, NK cell number in peripheral blood, serum GGT, glucose, HBV DNA, and HBsAg levels appeared significantly influencing prognosis, while by multivariate Cox regression, serum glucose, HBsAg and AFP levels were big players. In contrast, adult outcomes were linked to INR and viral genotype. The data suggests that the progression/remission of hepatitis B-related cirrhosis in children is framed by both viral and pathophysiological factors. It also necessitates multi-parameter, longitudinal follow-up, continued surveillance for hepatocellular carcinoma (especially in those who had cirrhosis at any point), and monitoring adherence to long-term antiviral regimens, since those who self-discontinue did not achieve functional cure. From standpoint of treatment, this identification implies that therapy thresholds should integrate multiple markers, beyond ALT alone. A practical hint is that a child with high HBV DNA, but “normal ALT”, should not be assumed safe; if other markers or imaging suggest fibrosis, treatment should be considered. Unquestionably, the exact roles of these factors in shaping liver fibrosis need further investigation in large-scale, multicentric randomized clinical trials.

POLICY AND PRACTICE RECOMMENDATIONS

The clinical and public health implications of these findings are clear. First, routine screening of all HBV-infected children is essential, regardless of symptomatology. Reliance on symptoms or ALT patterns alone is insufficient, as pediatric cirrhosis frequently progresses in the absence of clinical or biochemical warning signs. Incorporating non-invasive fibrosis assessments such as elastography and serum fibrosis markers into routine monitoring can facilitate earlier detection and timely initiation of therapy[33]. Second, early and effective antiviral treatment should be prioritized in children with advanced fibrosis or cirrhosis. Combination regimens using IFN and NAs appear to offer the greatest likelihood of functional cure and fibrosis regression, and current evidence supports their use in pediatric patients who stand to derive the most benefit from early intervention. Equally important is the ensuring adherence through counseling, family-centered support, and culturally informed care, given the impact of treatment interruptions on outcomes. Third, strengthening programs aimed at preventing vertical transmission remains a cornerstone of HBV control. Maternal screening, antiviral prophylaxis during pregnancy when indicated, and timely neonatal immunoprophylaxis all reduce the risk of perinatal infection - the primary route of chronic HBV acquisition in children. Enhancing implementation of these measures, especially in high-burden regions, can significantly reduce the future incidence of pediatric cirrhosis.

It is widely accepted that the universal birth dose of HBV vaccination has been very successful, dramatically reducing hepatitis B cases worldwide. Like a stone thrown into a pond, on December 16, 2025, the Centers for Disease Control and Prevent Advisory Committee on Immunization Practices of the United States shifts the universal HBV vaccination policy that was introduced in 1991, and recommends that infants born to mothers who test positive for hepatitis B or whose status is unknown should still receive the vaccine within 12 hours of birth, while recommends shared decision-making for hepatitis B birth doses when mothers test negative (https://www.cdc.gov/media/releases/2025/2025-hepatitis-b-immunization.html). The shift is controversial with undetermined long-term cost-effectiveness: Although this change gives parents more control in this regard, the possibility of missing or delayed HBV vaccination in lower-risk infants with maternal HBsAg negative can create serious health consequences, given the following two important factors: First, 90% of infants acquiring HBV infection develop chronic hepatitis B[32]; and second, pediatric HBV-related cirrhosis is characteristic of progressive and silent nature, as shown by Zhao et al’s data[8].

Finally, pediatric-specific management frameworks are required to reflect the unique pathophysiology, treatment responsiveness, and prognostic characteristics of HBV-related cirrhosis in children. National and global policy strategies should incorporate early antiviral initiation, non-invasive fibrosis monitoring, and long-term follow-up models tailored to pediatric needs. Such approaches will be vital in reducing disease progression, improving long-term outcomes, and ultimately narrowing disparities in access to lifesaving therapies.

FUTURE DIRECTIONS AND RESEARCH GAPS

Zhao et al’s discoveries[8] brought to light a unique combination of silent progression and high reversibility of pediatric HBV-related cirrhosis, but it has several limitations that should be carefully weighed when interpreting the findings. As a single-center, biopsy-based, retrospective, observational and non-randomized cohort with predominantly male patients (87.1%), vertically infected patients, mostly genotype C, the generalizability of these findings requires confirmation in more diverse populations or clinical settings. The reliance on biopsy-confirmed cirrhosis, meaning the present sample represents a more advanced or symptomatic subset of pediatric disease, may underestimate earlier disease stages, and overestimate the prevalence of severe fibrosis and thus limit generalizability to the broader population of vertically infected children.

The interpretation of fibrosis reversal in this study also requires caution. Although regression was assessed using imaging, elastography or biopsy, follow-up intervals were not uniform, and the histological confirmation was a snapshot not reflecting the dynamics in the patients. Without standardized timing, consistent methodology or unified histopathological scoring across all follow-up assessments, there is a risk of over-inferring true architectural remodeling. In addition, variability in elastography thresholds, sampling error in biopsy and natural fluctuations in liver stiffness may contribute to apparent improvement that does not fully manifest structural reversal. Therefore, while the observed regression rates in children were encouraging in the study, they should be regarded as preliminary signals that require validation in prospective studies with standardized fibrosis assessment protocols. Although mechanistical understanding of fibrosis progression and reversal in children is currently limited, we can now at least appreciate that developmental differences in immunity, viral-host interactions, and hepatic regeneration contribute to the pediatric phenotype, but the genetic factors and molecular pathways involved remain unclear. Studies examining interactions between host genetics, epigenetic regulation, and HBV-driven stellate cell activation in dynamics of liver fibrosis in children may clarify why children differ so markedly from adults in both disease progression and treatment response.

Non-invasive tools for early fibrosis detection represent another major need. Current imaging-based non-invasive liver disease assessment methods lack sufficient pediatric validation, and current AASLD guidelines cannot yet recommend a single modality for children because of insufficient evidence[34]. Large, prospective studies are needed to establish accurate pediatric thresholds for elastography, serum fibrosis markers, and emerging multiomic assays.

Long-term outcome data are also essential. While fibrosis regression and functional cure appear achievable in pediatric patients, the durability of these responses and their impact on lifetime hepatocellular carcinoma risk remain unknown. Defining the optimal treatment window and duration will require coordinated multicenter follow-up.

Finally, global disparities in access to antiviral therapy and perinatal prevention must be addressed to reduce the burden of pediatric HBV-related liver disease[35]. Ensuring equitable access to diagnosis, treatment, and monitoring will be critical to improving outcomes worldwide. Prospective, multicenter randomized cohorts focusing on pediatric-specific risk prediction models, therapy window, threshold of therapy, and therapy strategy (aggressive vs conservative) will provide clear information on precise management of pediatric cirrhosis.

CONCLUSION

Early-life HBV acquisition carries the highest lifetime risk of cirrhosis and hepatocellular carcinoma. Zhao et al’s study[8] reinforces this urgency and strongly supports proactive screening strategies and prioritization of early antiviral therapy, structured surveillance, and risk-stratified fibrosis assessment. Public health systems should integrate these principles into post-PMTCT (post-prevention of mother-to-child transmission) care by establishing structured follow-up pathways for all HBV-exposed infants, ensuring access to elastography and antiviral therapy, and reducing regional disparities in diagnostic and treatment resources. Together, these strategies shift pediatric HBV management from passive observation to active prevention of cirrhosis and promotion of reversal, leveraging the unique regenerative capacity of the pediatric liver to leverage long-term clinical benefits.