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.

The incidence of chronic hepatitis B (CHB) combined with metabolism-associated fatty liver disease (MAFLD) is increasing annually, and the presence of MAFLD may influence the clinical assessment of viral activity and transaminase levels. However, it remains unclear whether MAFLD impacts the achievement of clinical cure in CHB patients treated with polyethylene glycol interferon (Peg-IFN).

A prospective cohort study was conducted to enroll patients with dominant CHB (on NA treatment, HBsAg <1,500 IU/mL, HBeAg negative, HBV DNA <10 IU/mL) and patients with dominant CHB combined with MAFLD, all of whom were treated with Peg-IFN. The study aimed to assess the efficacy and safety of Peg-IFN treatment and to elucidate the effect of MAFLD on achieving HBsAg clearance in these patients. Additionally, the study explored the T-lymphocyte characteristics of patients with CHB combined with MAFLD, analyzed the role of T-lymphocytes expressing inhibitory receptors in HBsAg clearance, and investigated the immunological mechanisms of HBsAg clearance through single-cell transcriptome sequencing technology.

Patients will be recruited at four medical centers in Beijing and Hebei, and written informed consent will be obtained to inform participants of the purpose of the study, potential risks, and benefits. Ethical approval has been granted for the study, which will focus on 48-week HBsAg clearance, and a detailed follow-up and adverse event monitoring plan has been developed.

Strengths are that this study fills the gap in treatment strategies for patients with CHB combined with MAFLD and provides important treatment guidance to clinicians; the multicenter design may increase the diversity of the sample size, reduce the bias of single-center studies, and improve the external validity of the results. Limitations are that interferon therapy is often associated with side effects, which may lead to lower patient adherence and affect long-term follow-up and outcome monitoring of the study; the heterogeneity of the MAFLD population may have different effects on the efficacy of interferon therapy.

http://www.chictr.org.cn/bin/project/edit?pid=231498, identifier ChiCTR2400084913.

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 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.

Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased.

To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.

Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.

Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone.

Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

HBsAg clearance represents clinical cure for patients with hepatitis B, but remains difficult to obtain for most HBV-infected patients. Recent studies have shown that inactive HBsAg carriers treated with pegylated interferon can achieve higher clinical cure rates, which may imply that the lower the baseline HBsAg quantification, the higher HBsAg clearance rate. Therefore, this study further investigated the HBsAg clearance rate in inactive HBsAg carriers with low level of HBsAg (<200 IU/ml) treated with pegylated interferon.

This is a prospective cohort study. Inactive HBsAg carriers with HBsAg<200 IU/ml were divided into treatment and control groups. Pegylated interferon was administered to the patients in therapeutic group for 96 weeks. The patients in control group underwent 96 weeks of observation without any anti-viral treatment. All patients were tested for HBsAg, anti-HBs, HBV DNA, liver function, blood count, thyroid function, thyroid antibodies and autoantibodies at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96. Controlled attenuation parameter (CAP) and liver stiffness measure (LSM) were evaluated at baseline and week 96. Patients were classified into no steatosis, mild steatosis, moderate steatosis and severe steatosis according to the value of CAP.

A total of 174 inactive HBsAg carriers with HBsAg<200IU/ml were enrolled, including 84 in the treatment group and 90 in the control group. In the treatment group, HBsAg clearance rate was 30.77% (24/78) at week 48, and increased to 57.69% (45/78) at week 96. HBsAg clearance occurred in 2 patients with a clearance rate of 2.27% (2/88) in control group, The HBsAg clearance rate of the treatment group was significantly higher than that of the control group (P<0.001). HBsAg clearance was significantly higher in patients with moderate steatosis than in those without steatosis (74.07% vs. 48.15%, p=0.008) at week 96.

High HBsAg clearance rate could be obtained for inactive HBsAg carriers with HBsAg< 200 IU/ml treated with peginterferons. Inactive HBsAg carriers with moderate hepatic steatosis are more sensitive for the treatment.

NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial.

Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12-2.26; I²  = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08-2.25), studies with a median follow-up duration of ≥5 years (OR, 2.82; 95% CI, 1.57-5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01-2.91), and biopsy-proven steatosis (OR, 2.86; 95% CI, 1.61-5.06), although no significant association was noted among nucleos(t)ide analogue-treated patients (OR, 1.05; 95% CI, 0.62-1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07-2.16; I²  = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58-3.10; I²  = 49.0%).

Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.

Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.We aimed to explore the efficacy after 1-year TAF treatment.A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000-1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079-0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003-1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m2, P = .004) after 1-year TAF treatment.One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.

Chronic hepatitis B (CHB) and metabolic associated fatty liver disease (MAFLD) are both important public health problems. The effect of concomitant MAFLD on patients with CHB is still unclear. This study aimed to explore the influence of MAFLD on liver fibrosis and inflammation in CHB patients with different hepatitis B e antigen (HBeAg) status.

We retrospectively collected the clinical data of 399 treatment-naïve CHB patients who underwent liver biopsy. All patients were divided into two groups (HBeAg± group). Logistic regression analysis was used to identify factors associated with liver inflammatory activity and significant fibrosis in patients with CHB. Multivariable logistic regressions were repeated in subgroups stratified by HBeAg status.

In patients with CHB, MAFLD was independently associated with a risk of moderate-to-severe liver activity and significant fibrosis (P <0.05). In the HBeAg-negative group, patients with MAFLD had significantly higher levels of alanine aminotransferase (ALT) (P <0.05) and more severe liver inflammatory activity and fibrosis (P <0.05) compared to those without MAFLD. MAFLD was independently associated with a risk of moderate-to-severe liver activity (A ≥3: OR 3.97, 95% CI 1.71-9.22, P =0.001) and significant fibrosis (F ≥2: OR 2.02, 95% CI 1.09-3.73, P =0.026). In the HBeAg-positive group, MAFLD was found to be independently associated with moderate-to-severe liver activity (OR 2.44, 95% CI 1.03-5.79, P =0.044) but not fibrosis (P =0.618).

MAFLD is associated with the risk of liver fibrosis and inflammatory activity in HBeAg-negative CHB patients. Sufficient attention should be paid to the prevention and treatment of MAFLD in patients with CHB, especially in HBeAg-negative patients.

Patients with chronic hepatitis B (CHB) are at an increased risk of disease progression. The influence of hepatic steatosis (HS) to liver fibrosis was controversial. We aim to investigate the association between HS and liver fibrosis and explore the predicting factors for advanced fibrosis.

CHB patients undergoing liver biopsy with complete assessments of HS, necroinflammation grade [histological activity index (HAI) score], and fibrosis stage were retrospectively recruited. Logistic regression analysis was performed to determine the factors associated with advanced liver fibrosis.

In this cohort of 672 patients, 342 (50.9%) had HS and 267 (39.4%) were of advanced liver fibrosis. Age [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.007-1.046, p = 0.008], body mass index (BMI, OR 1.091, 95% CI 1.026-1.159, p = 0.005), genotype (C vs. B) (OR 2.790, 95% CI 1.847-4.214, p < 0.001), platelet (OR 0.986, 95% CI 0.982-0.991, p < 0.001), and HAI score (OR 1.197, 95% CI 1.114-1.285, p < 0.001) were independent factors for advanced liver fibrosis in multivariate logistic regression analysis. HAI score was also a significantly associated factor for significant liver fibrosis in non-cirrhotic subpopulation (OR 1.578, 95% CI 1.375-1.810, p < 0.001). HS was not related to advanced/significant liver fibrosis in overall/non-cirrhotic population (p > 0.05).

Significant or advanced liver fibrosis is associated with grade of necroinflammation but not with HS in CHB patients.