A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.

This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization.

From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients.

To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.

This study aims to explore the effects of various hepatic steatosis conditions on histological outcomes in patients with significant inflammation and fibrosis in chronic hepatitis B (CHB) and analyze their impact on HBV virological suppression outcomes and biochemical improvement.

This retrospective study included 219 chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogues therapy. Each of these patients underwent two liver biopsies. Patients were categorized into four groups based on hepatic steatosis status: sustained non-hepatic steatosis (n = 118), new-onset hepatic steatosis (n = 33), sustained hepatic steatosis (n = 37), and disappeared hepatic steatosis (n = 31). We compared the liver biochemical parameters and histological changes before and after treatment. Logistic regression analysis was performed to evaluate characteristics associated with the improvement of significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2), and the persistence of hepatic steatosis.

After treatment, the sustained non-steatosis group exhibited the highest rate of improvement in baseline significant inflammation (75.31%), while the sustained steatosis group had the lowest (42.31%, p = 0.008). The sustained steatosis group also had the highest rate of inflammation progression (15.38%, p = 0.020) and was identified as a risk factor for inadequate baseline inflammation improvement (p = 0.006, OR = 0.244, 95% CI 0.090-0.665). In terms of baseline significant liver fibrosis improvement, the sustained non-hepatic steatosis group showed the highest improvement rate (67.14%), while the sustained hepatic steatosis group had the lowest (28.00%, p = 0.006). The new-onset steatosis group had the highest rate of liver fibrosis progression (15.00%, p = 0.027), and sustained hepatic steatosis was a risk factor for poor baseline fibrosis improvement (p = 0.001, OR = 0.180, 95% CI 0.064-0.507). Furthermore, the sustained hepatic steatosis group showed the smallest decrease in liver enzyme markers ALT, GGT, and ALP post-treatment, with reductions of 22.11% (p = 0.023), 13.86% (p = 0.003), and 1.98% (p = 0.025), respectively. Logistic regression analysis revealed that high baseline BMI and LDL-C levels were significantly associated with persistent fatty liver, with high BMI (p = 0.042, OR = 1.109, 95% CI 1.004-1.226) and high LDL-C (p < 0.001, OR = 2.570, 95% CI 1.524-4.332).

In CHB patients with significant inflammation and fibrosis, the persistence of hepatic steatosis during antiviral treatment may impede the improvement of inflammation and fibrosis, leading to disease progression and biochemical abnormalities.

To assess the performance of fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and aspartate aminotransferase to platelet ratio index (APRI) for advanced fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) subgroups categorized by concomitant liver conditions.

We conducted a multicentered study comprising inpatients with type 2 diabetes mellitus and MAFLD. Participants were categorized into 2 groups: MAFLD with pure metabolic etiologies (MAFLD-P) and MAFLD with mixed etiologies (MAFLD-M). Diagnostic performance of FIB-4, NFS, and APRI was assessed by area under the curve (AUC), sensitivity, and specificity.

This study comprised a total of 1475 participants, with a mean (SD) age of 58.4 (13) years and 835 (56.6%) males. FIB-4 and APRI had higher AUCs for advanced fibrosis in the MAFLD-M group than in the MAFLD-P group (MAFLD-M vs MAFLD-P: FIB-4 0.680 vs 0.591, P = .0442; APRI 0.723 vs 0.631, P = .0363). No significant difference was observed in the AUC of NFS between the 2 subgroups (MAFLD-M 0.572 vs MAFLD-P 0.617; P = .3237). Besides, the sensitivity of FIB-4 (69.6% vs 54.0%; P = .019) and APRI (43.5% vs 26.1%; P = .005) was higher in the MAFLD-M group. However, no significant difference in sensitivity of NFS and specificity of FIB-4, NFS, and APRI was observed between subgroups.

In this diagnostic study of the type 2 diabetes mellitus population, FIB-4 and APRI showed better performance for identifying advanced fibrosis in MAFLD with mixed etiologies.

In recent years, the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, given the substantial global prevalence of chronic hepatitis B (CHB), instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios. Both conditions can lead to liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). However, the intricacies of the dual etiology, consequential outcomes, and associated risks of CHB concurrent with MASLD are still not fully understood.

A literature search was conducted on PubMed for articles published up to March 2024. The search keywords included nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic hepatitis B, liver fibrosis, hepatocellular carcinoma, nuclear factor erythroid 2-related factor 2, and oxidative stress.

This review examined recent studies on the interplay between MASLD and CHB. The coexistence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus (HBV) replication. Conversely, individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD. Nevertheless, these observations do not necessarily indicate universally positive outcomes. Indeed, MASLD and CHB may synergistically act as "co-conspirators" to exacerbate clinical manifestations, particularly liver fibrosis and HCC.

As our understanding of the interaction between steatosis and HBV infection becomes clearer, we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD. These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.

Steatotic liver disease (SLD) is prevalent among individuals with chronic hepatitis B virus (CHB), yet its impact on clinical outcomes remains controversial.

We used electronic health record data from 98 US healthcare-delivery systems to compare adults with (CHB-SLD) and without SLD (CHB-wo-SLD) from 2000 to 2024. We applied 1: 1 propensity score matching to balance cohorts by demographic and clinical characteristics. We further performed sensitivity analyses in the presence or absence of cirrhosis. We compared incidence rates (IR) and hazard ratios (HRs) of all-cause mortality, hepatocellular carcinoma (HCC), end-stage liver disease (ESLD) events, and detectable HBsAg and HBeAg as markers of seroclearance.

Among 124,932 individuals with CHB (12.43% CHB-SLD), there were 470,707 person-years of observations (median follow-up 2.95 years). Compared with CHB, individuals with CHB-SLD had a lower mortality risk (HR 0.44, 95% CI 0.40-0.48). Fibrosis risk was higher among those with CHB-SLD (vs CHB-wo-SLD) (HR 1.93, 95% CI 1.71-2.19); however, cirrhosis risk was comparable (HR 1.06, 95% CI 0.96-1.18) between cohorts, while HCC risk was lower in the CHB-SLD cohort (HR 0.83, 95% CI 0.70-0.96). The CHB-SLD cohort also had significantly reduced risks of ESLD events, including ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome (all p < 0.001). Additionally, detectable HBsAg and HBeAg IRs and HRs were lower among CHB-SLD compared to the CHB-wo-SLD cohort: 26.83 vs. 31.96 per 1,000 person-years (HR 0.80, 95% CI 0.73-0.87) and 8.52 vs. 11.36 per 1,000 person-years (HR 0.74, 95% CI 0.65-0.85), respectively. Sensitivity analyses stratified by cirrhosis status supported these findings.

CHB-SLD status was associated with more favorable outcomes, highlighting the complexity of CHB and SLD interactions.

This study investigated the consistency of the FIB-4, APRI, and GPR indices in assessing significant liver fibrosis and cirrhosis in patients with Coronavirus Disease 2019(COVID-19) who also suffer from various liver diseases, providing references for the clinical selection and application for non-invasive assessment methods.

The study evaluated 744 COVID-19 patients with coexisting liver diseases: 508 cases with non-alcoholic fatty liver disease (NAFLD), 158 cases with chronic hepatitis B (CHB), and 78 cases with a combination of both ailments. FIB-4, APRI, and GPR were employed to assess significant liver fibrosis and cirrhosis. Concordance among the methods was determined using Kappa analysis, and receiver operating characteristic (ROC) curves helped identify the optimal cutoff values for each index.

For COVID-19 patients with NAFLD, Kappa values for significant liver fibrosis were 0.81, 0.90, 0.80, and 0.79, and for cirrhosis, they were 0.88, 0.97,0.88, and 0.88, respectively (all p < 0.05). Among those with CHB, Kappa values were 0.81, 0.81, 0.83, and 0.75 for fibrosis, and0.87, 0.91, 0.88, and 0.92 for cirrhosis (all p < 0.05). In patients with coexisting liver diseases, the values were 0.87, 0.86, 0.86, and 0.78 for fibrosis, and 0.67, 0.69, 0.54, and 0.81for cirrhosis (all p < 0.05). Linear trend analysis revealed significant relationships between FIB-4 values, APRI values, GPR values, and the severity of COVID-19 (χ2 trend: 15.205,35.114, and 13.973, respectively, all p < 0.001), between FIB-4 values and APRI values and the coronavirus negative conversion time (all p < 0.05) in COVID-19 with NAFLD, and between FIB-4 values and GPR values and the coronavirus negative conversion time in patients with COVID-19 with CHB(all p < 0.05).

Using the current cutoff values, the non-invasive assessments demonstrated almost perfect consistency in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with liver diseases, though FIB-4 and GPR showed moderate consistency in cirrhosis evaluation in patients with coexisting liver conditions. Moreover, it also indicated that increased liver fibrosis correlates with more severe COVID-19 and prolonged coronavirus negative conversion time.

Metabolic dysfunction-associated steatotic disease (MASLD) and chronic hepatitis B (CHB) are prevalent liver disorders. Ongoing discussions investigate the impact of MASLD on the therapeutic outcomes of CHB.

A cohort of 320 CHB patients on antiviral therapy (including NAs and PEG IFNα) were included and categorized into CHB + MASLD (n = 125) and CHB group (n = 195). The treatment response rates, Kaplan-Meier survival analysis, and Cox regression were assessed between the two groups to investigate the impact of MASLD on antiviral responses in patients with CHB.

At weeks 24 and 48, the CHB + MASLD group displayed a higher HBsAg response rate than the CHB group (24 weeks: 11.5% vs. 3.8%, p = 0.026; 48 weeks: 24.4% vs. 8.4%, p = 0.001). The pgRNA response was also higher in the CHB + MASLD group at both time points (24 weeks: 30.9% vs. 19.7%, p = 0.163; 48 weeks: 48.8% vs. 28.3%, p = 0.049). Kaplan-Meier survival analysis revealed a shorter median time to HBsAg response at 48 weeks for the CHB + MASLD group (HR = 3.251, 40 weeks vs. 42.5 weeks, p = 0.002). This is particularly evident among individuals who are negative for HBeAg (48w: 24.2% vs 12.2%, p = 0.005). KM survival analysis demonstrated that the CHB + MASLD group was more likely to achieve HBsAg response (HR = 2.428, p = 0.039).COX regression analysis identified age (HR = 0.948, p = 0.005), antiviral regimen (NAs + PEG IFNα: HR = 5.33, p < 0.001; PEG IFNα: HR = 1.099, p = 0.93), baseline HBsAg level (HR = 0.648, p = 0.009), and MASLD presence (HR = 3.321, p = 0.002) as independent predictors for HBsAg response. Time-ROC analysis showed that these factors effectively predicted HBsAg decline (24 weeks: AUC = 0.902; 48 weeks: AUC = 0.890). The model demonstrated strong discriminative power, calibration, and clinical relevance.

In CHB patients without significant liver fibrosis who receive antiviral therapy, concurrent MASLD enhances HBsAg response, particularly in HBeAg-negative patients. Factors like younger age, NAs with PEG IFNα therapy, lower initial HBsAg levels, and MASLD presence predict treatment success. Further investigations are required to elucidate the impact of diverse metabolic disorders on the advancement of liver fibrosis.

Registry and the registration No. Of the study/trial: ChiCTR23000 74064(2023-07-28).

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among the chronic hepatitis B (CHB) population. This study aimed to explore the impact of metabolic dysfunction (MD) on cirrhosis and cirrhotic complication risks in CHB.

Patients with CHB were consecutively recruited between 2006 and 2021. The presence of MD was based on the 5 cardiometabolic criteria specified in the MASLD definition. Patients were categorized into MD/non-MD groups based on these criteria.

Eleven thousand five hundred two treatment-naive noncirrhotic patients with CHB were included with a median follow-up of 5.3 years. Patients in the MD group (n = 7,314) were older and had lower hepatitis B virus DNA levels than non-MD patients (n = 4,188). After adjustment for clinical and viral factors, MD patients had significantly higher risks of cirrhosis (adjusted hazard ratio [aHR]: 1.82, 95% confidence interval [CI]: 1.40-2.37, P < 0.001) and cirrhotic complications (aHR: 1.30 per MD, 95% CI: 1.03-1.63, P = 0.025) in a dose-dependent manner. Furthermore, new-onset diabetes mellitus during the follow-up aggravated the risk of cirrhotic complications (aHR: 2.87, 95% CI: 1.34-6.11, P = 0.006). Hepatic steatosis was associated with lower risks of cirrhosis (aHR: 0.57 within 5 years, 95% CI: 0.44-0.74, P < 0.001) and cirrhotic complications (aHR: 0.45, 95% CI 0.23-0.88, P = 0.020). Among individuals with hepatic steatosis, patients with MASLD exhibited a higher cirrhosis risk than non-MD patients.

Concurrent and new-onset MDs increase the risks of cirrhosis and cirrhotic complications in patients with CHB, independent of hepatic steatosis. Proactively investigating metabolic comorbidities in CHB is critical to stratify the risk of liver disease progression.

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

This study investigates the influence of metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) on the incidence of hepatocellular carcinoma (HCC) among general population and patients with chronic hepatitis B (CHB). It also explores its implications for the long-term prognosis of HCC patients following hepatic resection.

Relevant studies were selected based on predefined inclusion and exclusion criteria, including adherence to diagnostic criteria for MAFLD/MASLD and reporting hazard ratios (HRs) using Cox proportional hazards models. The meta-analysis utilized R statistical software (version 4.3.0) with random-effects models to calculate pooled HRs. Sensitivity analyses were performed to ensure the robustness of results.

Our analysis included 19 studies, among which 12 studies focused on the cumulative incidence of HCC in the general population (979,213 individuals; 294,984 with MAFLD/MASLD and 684,229 without). MAFLD/MASLD significantly increased the cumulative incidence of HCC in the general population (HR = 1.82; 95% CI, 1.34-2.48). In CHB patients (316,445 participants; 108,183 with MAFLD/MASLD and 208,262 without), the cumulative incidence of HCC was also higher in the MAFLD/MASLD group (HR = 1.36; 95% CI, 1.32-1.40). For 7383 postoperative HCC patients (2192 with MAFLD/MASLD and 5191 without), MAFLD/MASLD did not significantly affect overall survival (OS) (HR = 0.93; 95% CI, 0.69-1.26) or recurrence-free survival (RFS) (HR = 0.98; 95% CI, 0.86-1.13).

In conclusion, MAFLD/MASLD can significantly increase the incidence of HCC in both the general population and CHB patients. However, it does not significantly influence long-term prognosis after hepatic resection, suggesting that other factors may have a greater role in determining postoperative outcomes. This highlights the need for tailored management strategies for MAFLD/MASLD patients undergoing HCC resection.

This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB).

CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses.

Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not.

CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Steatotic liver disease (SLD) is an emerging liver disease that has been associated with an increased risk for hepatocellular carcinoma (HCC). The impact of concurrent SLD on the prognosis of HCC remains unknown. This study investigates how concurrent SLD affects the outcomes of patients with HCC undergoing curative radiofrequency ablation (RFA) therapy.

A retrospective analysis of patients with early-stage HCC receiving curative RFA at a tertiary medical center was conducted. Laboratory data and HCC characteristics were recorded and analyzed by a Cox proportional hazards regression model to predict recurrence and all-cause mortality after RFA.

A total of 598 patients with HCC were included between 2005 and 2015, with 139 and 459 classified in SLD and non-SLD groups, respectively. The SLD group exhibited a significantly better liver reserve and a lower cumulative incidence of HCC recurrence and liver-related and all-cause mortality after a median follow-up of 51 months. After adjusting for metabolic dysfunction, liver reserve, and HCC characteristics, the presence of SLD reduced all-cause mortality (adjusted hazard ratio [aHR], 0.67; 95% confidence interval [CI], 0.45-0.996; p = .048), which was supported by inverse probability weighting analysis (aHR, 0.65; 95% CI, 0.42-1.00; p = .049). Poor liver functional reserve (high albumin-bilirubin grades) increased all-cause mortality dose dependently. Barcelona Clinic Liver Cancer staging and a higher Fibrosis-4 index were predictors for HCC recurrence, whereas SLD was not.

Among patients with HCC undergoing curative RFA, those with concurrent SLD had a lower risk of all-cause mortality compared to those with poor liver functional reserve.

The present research demonstrated that patients with both liver cancer and steatotic liver disease who received curative radiofrequency ablation for liver cancer survived longer compared to those without steatotic liver disease. Maintaining good liver function is an important prognostic factor for survival.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demonstrating the bidirectional impacts between gut microbiome and host genetics/epigenetics, emphasising the significance of this interconnection in MASLD prevention and treatment.

Cigarette smoking is associated with worse clinical outcomes in patients with chronic hepatitis B (CHB) infection, but the effects on hepatitis B surface antigen (HBsAg) seroclearance are unclear. This study aimed to investigate the effect of active smoking on HBsAg seroclearance (SC) and its impact on peripheral blood lymphocytes in patients with CHB infection. Longitudinal follow-up data was retrieved in 7833 antiviral-treated CHB subjects identified from a centralised electronic patient record database (Part 1). Phenotypic analysis of peripheral blood mononuclear cells (PBMCs) from 27 CHB-infected patients (6 active smokers; 13 with SC) was performed by flow cytometry to assess programmed death-1 (PD-1) expression and proportion of regulatory T cells (CD4+CD25+CD127lo). Effector function of HBV-specific T cells was examined by comparing granzyme B (GZMB) and transforming growth factor beta (TGFβ) production in undepleted PBMCs and Treg-depleted PBMCs after 7 days in vitro stimulation with HBV envelope protein overlapping peptides (Part 2). Over a median follow-up of 5 years, smoking was associated with lower probability of SC (aHR 0.70, 95% CI 0.57-0.87). PD-1 expression was increased in CD4+ T cells, CD8+ T cells and CD20+ B cells among smokers compared to non-smokers and positively correlated with pack years (all p < 0.05). Treg depletion led to partial functional recovery of HBV-specific T cells, with significantly bigger magnitude in smokers (p = 0.0451, mean difference = 4.68%) than non-smokers (p = 0.012, mean difference = 4.2%). Cigarette smoking is associated with lower chance of HBsAg seroclearance, higher PD-1 expression on lymphocytes, and impairment of effector functions of HBV-specific T cells in CHB.

We assessed the effect of hepatitis B surface antigen (HBsAg) seroclearance (HBsAg-loss) on liver fibrosis regression in patients with chronic hepatitis B (CHB) infection.

CHB patients with recent documented HBsAg-loss were age- and gender-matched with treatment-naïve HBeAg-negative CHB infection. Paired assessment with transient elastography and enhanced liver fibrosis (ELF) measurements were performed and repeated at 3 years. Fibrosis regression was arbitrarily defined as decrease in ≥ 1 fibrosis stage by ELF, or combining with reduction > 30% in liver stiffness.

A total of 142 HBsAg-loss and 142 CHB subjects were recruited (median age 58.1 years, 51.4% male). A total of 1.8% (1.4% HBsAg-loss vs 2.1% CHB) achieved combined endpoint of fibrosis regression at 3 years. When ELF-only definition of fibrosis regression was used, 14.5% HBsAg-loss and 16.9% CHB subjects achieved this endpoint, which was significantly associated with baseline ELF (hazard ratio (HR) 1.827, 95% confidence interval (CI) 1.085-3.075) and time since HBsAg-loss (HR 2.688, 95% CI 1.257-5.748). While increasing time since HBsAg-loss increased the proportion of ELF-defined fibrosis regression, increasing age was also associated with significant fibrosis. Age of achieving HBsAg-loss (ageSC) was independently associated with high baseline ELF values. Up to 52.3% and 63.8% subjects with ageSC > 50 had advanced fibrosis/cirrhosis at baseline and 3 years, respectively, compared with 5.9% and 20.6% in subjects with ageSC < 50.

Fibrosis regression occurred in a minority of subjects achieving HBsAg-loss, which was not significantly different compared with subjects with persistent overt CHB. Subjects after achieving HBsAg-loss, especially among those with ageSC > 50, should receive ongoing surveillance for liver-related complications.

To explore the impact of hepatic steatosis measured by MRI-proton density fat fraction (MRI-PDFF) on liver stiffness measurement (LSM) value and its diagnostic performance for staging liver fibrosis in patients with chronic hepatitis B (CHB).

A total of 914 patients with CHB who underwent liver biopsy and MRI-PDFF were retrospectively reviewed. The influence of MRI-PDFF on LSM value was assessed using univariate and multivariate linear analyses. To assess the influence of liver steatosis on the diagnostic performance of LSM, a series of ROC analyses were performed and compared by stratifying patients into non-steatosis (PDFF < 5%) and steatosis (PDFF ≥ 5%) groups according to MRI-PDFF values. The effects of different LSM cut-off values on the false-positive rate in the steatosis cohort were compared using McNemar's test.

LSM values were significantly affected by MRI-PDFF in the entire cohort (B-coefficient: 0.003, p < 0.001), F1 cohort (B-coefficient: 0.005, p < 0.001), and F2 cohort (B-coefficient: 0.003, p = 0.002). Hepatic steatosis was not observed to have a significant influence on the ROC curve of LSM for staging liver fibrosis. Compared with using the cut-off values for the CHB cohort, using relatively higher cut-off values for hepatic steatosis significantly improved the false-positive rate of LSM in the steatosis cohort.

Steatosis significantly influenced LSM, with a higher value in the early stage of liver fibrosis but did not affect the diagnostic efficiency of LSM for staging liver fibrosis. Moreover, using relatively high cut-off values significantly improved the false-positive rate of LSM in CHB patients with steatosis.

The identified correlation between MRI-PDFF and VCTE-measured LSM is not clinically relevant since the diagnostic performance of LSM in staging liver fibrosis is not affected by steatosis. A higher cut-off should be applied in CHB patients with steatosis to improve the false-positive rate.

Steatosis can affect liver stiff measurement (LSM) values in the early stage of liver fibrosis. The diagnostic performance of LSM in staging liver fibrosis is not affected by steatosis. LSM's cutoffs should be increased in patients with steatosis to improve the false-positive rate.

While previous reports have shown that hepatitis B virus (HBV) infection affects lipid metabolism and vice versa, the impact of dyslipidemia on the functional cure of HBV infection following peginterferon alfa (PegIFNα) therapy remains unknown. Hence, this study aimed to investigate the effect of dyslipidemia on hepatitis B surface antigen (HBsAg) clearance and develop a nomogram model for predicting patients for whom PegIFNα therapy is indicated.

A total of 160 nucleos(t)ide analogues (NAs)- experienced chronic hepatitis B (CHB) patients treated with PegIFNα (180 µg/week) were enrolled in this study. The relationship between serum lipid and HBsAg clearance was analysed. Univariate and multivariate COX analyses were used to construct and plot the nomogram model. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively.

After 48 weeks of PegIFNα therapy, a total of 33 patients in the cohort achieved HBsAg clearance. Univariate and multivariate COX analyses indicated that dyslipidemia was significantly associated with HBsAg clearance and was an independent predictor of HBsAg clearance (HR = 0.243, P = 0.001). Kaplan-Meier survival analyses show that cumulative HBsAg clearance was significantly higher in the normolipidemic group than in the dyslipidemia group (log-rank test, P = 0.007). During the treatment, triglyceride showed an increasing trend, while the levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1 and apolipoprotein B decreased. Dyslipidemia and other indicators independently associated with HBsAg clearance were used to construct the nomogram model. The AUC of the model at 36-week and 48-week were 0.879 and 0.856, and the model demonstrated good discrimination and calibration.

Dyslipidemia can affect the antiviral efficacy of PegIFNα in NAs-experienced CHB patients. Our findings suggest that the nomogram model constructed using serum lipid has good predictive power and may help physicians to identify the superior patients for PegIFNα therapy.

Acute-on-chronic liver failure (ACLF) is a syndrome of liver failure due to an acute hepatic insult leading to liver failure with or without extra-hepatic organ failure in a patient of chronic liver disease (CLD) with or without cirrhosis presenting for the first time. The definition is still with controversy; hence, homogeneity and clarity of the case is an unmet need. There is a paradigm shift noted as far as the etiology of CLD is concerned with rise in metabolic dysfunction-associated fatty liver disease (MAFLD) and ethanol as the dominant cause even in developing countries. MAFLD is the change in nomenclature from NAFLD to justify the metabolic derangement in these group of patients. The shift from an exclusion-based criteria to one that has evolved to a diagnosis that requires positive criteria has profound significance. Clearly there is a difference in terms of its prevalence, disease progression, and liver-related events, as well as management of metabolic risk factors and MAFLD itself which requires further understanding. In tandem with the global rise in MAFLD, the incidence of MAFLD-ACLF is increasing. Excessive alcohol consumption causes metabolic and toxic injury to the liver resulting in nearly similar pathway of fatty liver, hepatitis, and cirrhosis. The interaction of MAFLD as an additional underlying chronic liver injury in ACLF patients is complex due to the presence of metabolic risk factors that are unique to MAFLD. There is lack of clarity on how MAFLD affects the clinical course of ACLF due to scarcity of this specific data. This narrative review aims to understand the unique effects, consequences, and management of MAFLD as the chronic liver injury component in ACLF.

Co-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN-γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p < .01), higher HBV S diversity (p = .02) and greater frequency of HBV variants associated with host-anti-viral immune escape. Pro-inflammatory cytokine levels and HBV-specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low-level viraemia.

Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy.

In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance .

By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance.

Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance.

The role of Non-Alcoholic Fatty Liver Disease (NAFLD) on antiviral response in Chronic Hepatitis B (CHB) remains unclear. Previous studies mainly focus on the impact of the Non-Alcoholic Fatty Liver (NAFL) on antiviral efficacy, whereas the role of Non-Alcoholic Steatohepatitis (NASH) has not been highlighted. The authors aimed to investigate the association of NAFLD (NAFL and NASH), viral and histological characteristics with antiviral response.

The authors collected data of treatment-naïve CHB patients who underwent liver biopsy. All these patients received antiviral monotherapy and 48-week follow-up. The antiviral response was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the variables associated with antiviral response.

Overall, 120 treatment-naïve CHB patients were enrolled, with 49.2 % (59/120) of them were complicated by NAFLD. Male (Odd Ratio [OR = 4.222], 95 % Confidence Interval [95 % CI 1.620-11.003]) and overweight (OR = 8.709, 95 % CI 3.355-22.606) were independent predictors for concurrent NAFLD. After 48-week follow-up, the authors found that the overall antiviral response did not differ between CHB patients with and without concomitant NAFL/NASH (p > 0.05). High viral load (Hazard Ratio [HR = 0.522], 95 % CI 0.286-0.952), advanced fibrosis (HR = 2.426, 95 % CI 1.256-4.686), and moderate-to-severe interface hepatitis (HR = 2.541, 95 % CI 1.406-4.592) were significantly correlated with antiviral response after 8-week follow-up.

Neither NAFL nor NASH had an impact on antiviral therapy for CHB. It was low hepatitis B load, advanced fibrosis, and moderate-to-severe interface hepatitis that contributed to the virological response.

Significant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB.

This retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis.

Patients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635-2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF.

MASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term HBsAg seroclearance after entecavir cessation.

This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance.

A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p <0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p <0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed.

The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption.

Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy.

The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD).

A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment.

In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all).

Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.

The correlation between metabolic syndrome (MetS) and hepatitis B surface antigen (HBsAg) loss remains to be further elucidated, particularly in patients receiving pegylated interferon-α (PEG-IFN) treatment.

758 patients with low HBsAg quantification who had received nucleos(t)ide analog (NUC) therapy for at least one year and subsequently switched to or add on PEG-IFN therapy over an unfixed course were enrolled. 412 patients were obtained with baseline data matched. A total of 206 patients achieved HBsAg loss (cured group) within 48 weeks. Demographic and biochemical data associated with MetS were gathered for analysis. HepG2.2.15 cell line was used in vitro experiments to validate the efficacy of interferon-α (IFN-α).

The proportion of patients with diabetes or hypertension in the uncured group was significantly higher than in the cured group. The levels of fasting blood glucose (FBG) and glycated albumin remained elevated in the uncured group over the 48 weeks. In contrast, the levels of blood lipids and uric acid remained higher in the cured group within 48 weeks. Triglycerides levels and liver steatosis of all patients increased after PEG-IFN therapy. Baseline elevated uric acid levels and hepatic steatosis may be beneficial for HBsAg loss. IFN-α could induce hepatic steatosis and indirectly promote HBsAg loss by increasing triglyceride level through upregulation of acyl-CoA synthetase long-chain family member 1(ACSL1).

IFN-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level through upregulation of ACSL1. Comorbid diabetes may be detrimental to obtaining HBsAg loss with PEG-IFN therapy in CHB patients.

The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known.

A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019.

In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively.

These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population.

CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression.

In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245-0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS.

Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Concurrent hepatic steatosis has diverse effects on chronic hepatitis B (CHB), however the combined effects of metabolic dysfunction-associated steatotic liver disease (MASLD) and CHB on liver fibrosis progression remains unclear. The primary aim of this study was to utilize serial fibrosis measurements to compare the dynamic change in fibrosis in CHB patients with/without concurrent MASLD. The secondary aim was to investigate factors associated with steatosis development and regression in CHB patients.

This was a retrospective cohort study of all non-cirrhotic CHB patients identified from 1/1/2011 to 31/12/2016. Hepatic steatosis was diagnosed by ultrasound. Fibrosis markers included liver stiffness (LSM) by transient elastography, APRI and FIB-4. General linear mixed effects modelling was used to fit polynomial and linear estimates.

Of 810 CHB patients (n = 2,373 LSM measurements; median age 44.4y; 48% male; 24% HBeAg positive), 14% had concurrent MASLD. LSM was higher at baseline but decreased in MASLD patients over time, while LSM remained stable in non-MASLD patients, such that all patients had similar LSM beyond 4-5 years. MASLD patients had lower APRI compared to non-MASLD patients, which was predominately due to a higher platelet count and higher ALT over time. There was substantial discordance between LSM, APRI and FIB-4. Baseline BMI was the only factor that predicted steatosis development and regression.

We found no evidence of an association between concurrent MASLD and fibrosis progression amongst CHB patients without baseline advanced liver disease. APRI and FIB-4 may have reduced accuracy in MASLD patients.