The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.

The efficacy of different pegylated interferon (PEG-IFN) treatment strategies for achieving sustained hepatitis B surface antigen (HBsAg) clearance in chronic hepatitis B (CHB) remains controversial. This study assesses the efficacy of different PEG-IFN treatment regimens and factors influencing sustained HBsAg clearance after PEG-IFN discontinuation. PubMed , Embase , Web of Science , and the Cochrane Library databases were searched from inception to June 2023, regarding PEG-IFN therapy in CHB. Methodological quality was assessed using the Cochrane risk of bias tool. We explored sources of heterogeneity through univariate meta-regression. Frequentist network meta-analyses were used to compare the efficacy of different PEG-IFN treatment strategies. We analyzed 53 studies (including 9338 CHB patients). After PEG-IFN withdrawal, the annual rates of HBsAg clearance and seroconversion were 6.9% [95% confidence interval (CI), 5.10-9.31] and 4.7% (95% CI, 2.94-7.42). The pooled 1-, 3-, and 5-year sustained HBsAg clearance rates were 7.4%, 9.9%, and 13.0%, and the sustained HBsAg seroconversion rates were 6.6%, 4.7%, and 7.8%, respectively. HBsAg quantification, hepatitis B e antigen status, and PEG-IFN treatment protocols were major sources of heterogeneity. Baseline HBsAg quantification was significantly lower in patients with sustained HBsAg clearance versus those without ( P  < 0.046). PEG-IFN combined with tenofovir has the highest probability of achieving HBsAg seroconversion (surface under the cumulative ranking of 81.9%). Sustained HBsAg clearance increased approximately linearly from years 1 to 5 after PEG-IFN discontinuation. Low baseline HBsAg quantification has a significant impact on sustained HBsAg clearance. PEG-IFN combined with tenofovir may be optimal in achieving sustained HBsAg seroconversion.

Hepatitis B Virus (HBV) infection can progress to chronic HBV (CHB) disease, thereby increasing the risk of severe forms of liver disease (i.e. liver cirrhosis and hepatocellular carcinoma) and resulting in a high global burden of morbidity, mortality, and health-care utilization.

We discuss how future therapeutic strategies and treatment guidelines may address the large unmet medical needs among patients with CHB.

Complexity and a lack of consensus in current CHB treatment guidelines may limit their effective implementation. To minimize poor outcomes in patients not currently receiving treatment (including immune-tolerant and inactive carriers), a simplified harmonized treatment approach is needed across guidelines. Current treatment recommendations focus on nucleot(s)ide analogs (NAs) and pegylated interferon (Peg-IFN), both of which have limitations. NAs provide clinical benefits, but treatment is prolonged and has little impact on functional cure rates. Peg-IFN offers the potential for functional cure but has notable safety and tolerability issues. A shift toward finite treatments with acceptable safety and tolerability profiles is needed.

The key to achieving World Health Organization targets for the global eradication of HBV involves enhanced diagnosis with new treatments and/or combinations of existing treatments alongside globally aligned and simplified treatment guidelines for untreated/inadequately treated populations.

Nucleos(t)ide analogues (NAs) are the main drug category used in the treatment of chronic hepatitis B (CHB). There is a need to update the economic evaluation of CHB treatment.

This study aimed to determine the cost effectiveness of NAs for CHB in Thailand.

We used a lifetime Markov model undertaken from a societal perspective. Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), entecavir (ETV) with TDF or TAF as rescue medications, and lamivudine (LAM) with TDF or TAF rescue medications were compared with best supportive care (BSC). We performed a network meta-analysis to estimate the treatment effects of each NA on hepatitis B surface antigen (HBsAg) loss in an Asian population and performed an additional literature review to identify inputs. We calculated incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-years (QALYs) and performed sensitivity analyses.

Compared with BSC, all NAs could improve patients' QALYs, with results ranging from 4.04 to 4.25 QALYs gained. TAF, TDF, LAM/TAF, and LAM/TDF yielded lower total lifetime costs than BSC, ranging from - $US1387 to - 814, whereas ETV/TAF and ETV/TDF yielded higher total lifetime costs than BSC, ranging from $US4965 to 4971. The ICER was $US1230/QALY for ETV/TDF and $US1228/QALY for ETV/TAF. Full incremental analysis showed that the ICER for LAM/TAF was $US1720/QALY compared with TAF.

At current prices, TAF, TDF, LAM/TAF, and LAM/TDF are dominant options, and ETV/TAF or ETV/TDF are cost-effective options. LAM/TAF is the most cost-effective option, followed by TAF.