Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients.

BACKGROUND: The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial. METHODS: We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients). RESULTS: During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence. CONCLUSIONS: We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.

Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. METHODS: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. RESULTS: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. DISCUSSION: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

Isolated nonspecific terminal ileitis: prevalence, clinical evolution and correlation with metachronous diagnosis of Crohn's disease: a retrospective study and review of the literature.

Background: The existing literature does not provide adequate guidance on the diagnosis and management of patients with nonspecific terminal ileitis, while data regarding the percentage of patients who ultimately develop Crohn's disease (CD) are scarce. We evaluated the prevalence and natural course of nonspecific terminal ileitis in patients who underwent colonoscopy during a 11-year period. Methods: All patients with endoscopic findings of terminal ileitis and nonspecific histological findings were included. Exclusion criteria were a clinical history of CD or any other disease that can cause terminal ileitis, or a recent history of using drugs implicated in lesions of the terminal ileum. Results: From 5353 colonoscopies, 92 patients with nonspecific terminal ileitis were identified (prevalence: 1.7%). Among these patients, 56 (61%) had available follow up for ≥6 months after the initial endoscopy. Main indications for endoscopy were chronic diarrhea (37.5%), screening endoscopy (23%), and abdominal pain (20%). Sixteen (29%) patients received medical treatment, while recession of symptoms was recorded in 19 of 43 symptomatic patients (44.1%). Twenty-three (41%) of the 56 patients underwent a second endoscopy and 15 (65.2%) cases had persistent endoscopic findings. Eleven (19.6%) of the 56 patients were eventually diagnosed with CD. The probability of CD diagnosis was significantly higher in patients with persistent symptoms (P=0.002) and endoscopic findings at follow up (P=0.038). Conclusions: Nonspecific terminal ileitis generally has a benign clinical course. However, patients with persistent symptoms and endoscopic lesions are at increased risk for subsequent development of CD.

Natural history of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which has been the term for non-alcoholic fatty liver disease (NAFLD) since June 2023, represents the most common liver disease worldwide and is a leading cause of liver-related morbidity and mortality. A thorough knowledge of the disease's natural history is required to promptly stratify patients' risks, since MASLD is a multifaceted disorder with a broad range of clinical phenotypes. The histological disease spectrum ranges from isolated hepatic steatosis, currently named as metabolic dysfunction-associated steatotic liver (MASL), to metabolic dysfunction-associated steatohepatitis (MASH) and eventually may accumulate hepatic fibrosis and develop cirrhosis and/or hepatocellular carcinoma (HCC). Several risk factors for fibrosis progression have been identified, while the disease's progression displays notable dynamism and bidirectionality. When compared to the general population, all MASLD histological stages are substantially related with greater overall mortality, and this association exhibits a disease severity-dependent pattern. Interestingly, the fibrosis stage is the most accurate predictor of mortality among MASLD patients. The mortality attributed to MASLD predominantly stems from issues linked with the liver and cardiovascular system, as well as HCC and extrahepatic cancers. In light of the disease natural course, it is crucial to prioritize the identification of at-risk patients for disease progression in order to effectively address and change modifiable risk factors, hence mitigating disease complications. Further investigation is required to define the phenotype of rapid progressors more precisely as well as to improve risk stratification for HCC in non-cirrhotic individuals.

Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D.

BACKGROUND & AIMS: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown. METHODS: In the HIDIT-II study patients (including 40% with liver cirrhosis) received 180 µg PEG-IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 µg PEG-IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy). RESULTS: Until the end of follow-up, 16 (13%) patients developed liver-related complications (PEG-IFNa + TDF, n = 5 vs PEG-IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long-term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG-IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG-IFNa (16/102, p > .999) but was associated with a higher chance of HDV-RNA suppression (p = .024, odds ratio 3.9 [1.3-12]). CONCLUSIONS: Liver-related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG-IFNa treatment. PEG-IFNa treatment should be recommended to HDV-infected patients until alternative therapies become available. Retreatment with PEG-IFNa should be considered for patients with inadequate response to the first course of treatment. CLINICAL TRIAL REGISTRATION: NCT00932971.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

BACKGROUND: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). METHODS: One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. RESULTS: LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. CONCLUSION: In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Background: Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. Methods: We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). Results: We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). Conclusions: This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial.

BACKGROUND & AIMS: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. METHODS: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. RESULTS: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL. CONCLUSIONS: Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.

An international multidisciplinary consensus statement on MAFLD and the risk of CVD.

BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta-analysis.

INTRODUCTION: Everolimus, a selective inhibitor of mamalian target of rapamycin (mTORi), is considered to be an alternative immunosuppressive regimen in the liver transplantation (LT) setting. However, most of the transplant centers avoid its early use (i.e., during the first month) after LT mainly due to safety issues. METHODS: We searched for all articles published between 01/2010 and 7/2022 to evaluate the effectiveness and safety of initial/early administration of everolimus after LT. RESULTS: Seven studies (three randomized controlled trials and four prospective cohort studies) were included: initial/early everolimus-including therapy (group 1) was used in 512 (51%) and calcineurin inhibitor (CNI) based therapy (group 2) in 494 (49%) patients. No significant difference was found between group 1 and group 2 patients regarding the rates of biopsy-proven acute rejection episodes (Odds Ratio [OR]: 1.27, 95% CI: .67-2.41, p = .465) and hepatic artery thrombosis (OR: .43, 95% CI: .09-2.02, p = .289). Everolimus was associated with higher rates of dyslipidemia (14.2% vs. 6.8%, p = .005) and incisional hernia (29.2% vs. 10.1%, p < .001). Finally, no difference was found between the two groups regarding recurrence of hepatocellular carcinoma (Risk Rates [RR]: 1.22 95%CI: .66-2.29, p = .524) and mortality (RR: .85 95%CI: .48-1.50, p = .570). CONCLUSION: Use of initial/early everolimus seems to be effective with a satisfactory safety profile, making its administration a reasonable therapeutic option in the LT setting.

Hepatitis B.

Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.

Management of Hepatocellular Carcinoma in Decompensated Cirrhotic Patients: A Comprehensive Overview.

Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for 75% of primary liver cancer cases, mostly on the basis of cirrhosis. However, the data and therapeutic options for the treatment of HCC in patients with decompensated cirrhosis are rather limited. This patient category is often considered to be in a terminal stage without the possibility of a specific treatment except liver transplantation, which is restricted by several criteria and liver donor shortages. Systemic treatments may provide a solution for patients with Child Pugh class B or C since they are less invasive. Although most of the existing trials have excluded patients with decompensated cirrhosis, there are increasing data from real-life settings that show acceptable tolerability and satisfying efficacy in terms of response. The data on the administration of locoregional treatments in such patients are also limited, but the overall survival seems to be potentially prolonged when patients are carefully selected, and close adverse event monitoring is applied. The aim of this review is to analyze the existing data regarding the administration of treatments in decompensated patients with HCC, evaluate the effect of therapy on overall survival and highlight the potential risks in terms of tolerability.

Incidence of Hepatic Decompensation After Nucleos(t)ide Analog Withdrawal: Results From a Large, International, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Despite improvements in the management of chronic hepatitis B (CHB), risk of cirrhosis and hepatocellular carcinoma remains. While hepatitis B surface antigen loss is the optimal end point, safe discontinuation of nucleos(t)ide analog (NA) therapy is controversial because of the possibility of severe or fatal reactivation flares. METHODS: This is a multicenter cohort study of virally suppressed, end-of-therapy (EOT) hepatitis B e antigen (HBeAg)-negative CHB patients who stopped NA therapy (n = 1,557). Survival analysis techniques were used to analyze off-therapy rates of hepatic decompensation and differences by patient characteristics. We also examined a subgroup of noncirrhotic patients with consolidation therapy of ≥12 months before cessation (n = 1,289). Hepatic decompensation was considered related to therapy cessation if diagnosed off therapy or within 6 months of starting retreatment. RESULTS: Among the total cohort (11.8% diagnosed with cirrhosis, 84.2% start-of-therapy HBeAg-negative), 20 developed hepatic decompensation after NA cessation; 10 events were among the subgroup. The cumulative incidence of hepatic decompensation at 60 months off therapy among the total cohort and subgroup was 1.8% and 1.1%, respectively. The hepatic decompensation rate was higher among patients with cirrhosis (hazard ratio [HR] 5.08, P < 0.001) and start-of-therapy HBeAg-positive patients (HR 5.23, P < 0.001). This association between start-of-therapy HBeAg status and hepatic decompensation remained significant even among the subgroup (HR 10.5, P < 0.001). DISCUSSION: Patients with cirrhosis and start-of-therapy HBeAg-positive patients should be carefully assessed before stopping NAs to prevent hepatic decompensation. Frequent monitoring of viral and host kinetics after cessation is crucial to determine patient outcome.

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B.

BACKGROUND AND AIMS: Whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy. METHODS: This study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen-negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods. RESULTS: During a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups. CONCLUSIONS: TDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

State-of-the-art and emerging antivirals for chronic hepatitis B infection.

INTRODUCTION: Current treatment options for chronic hepatitis B virus (HBV) infection cannot achieve functional cure [hepatitis B surface antigen (HBsAg) loss]; therefore, new approaches are under investigation. This review summarizes the most promising approaches in emerging antivirals against HBV, after search in Medline (2016-2022) and European and American liver meetings (2019-2022). AREAS COVERED: Classes of antivirals include entry inhibitors (bulevirtide), capsid assembly modulators (CAMs), translation inhibitors [small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs)], and HBsAg secretion inhibitors [nucleic acid polymers (NAPs)]. Bulevirtide has good efficacy in hepatitis B and D coinfection, but there is limited data in HBV monoinfection. CAMs profoundly reduce serum HBV DNA/RNA levels, but have minimal effects on antigen levels. siRNAs and ASOs mostly reduce HBsAg levels, but small proportions of patients reach HBsAg seroclearance. NAPs reduce serum HBV DNA and especially HBsAg levels offering substantial HBsAg seroconversion rates, but having limited data over a long period. Combinations of agents of different classes are starting to be evaluated. EXPERT OPINION: Continued efforts are required in order to address many unanswered questions about the optimal combined regimens of finite duration which will be safe and well tolerated achieving functional cure in a substantial proportion of chronic HBV patients.