Background: Nucleos(t)ide analogues withdrawal may improve HBsAg loss rates. However, conditions to select patients are not well established. Aims: to evaluate the impact of HBsAg kinetics before treatment interruption on post-treatment response. Methods: Longitudinal, ambispective study in non-cirrhotic chronic hepatitis B HBeAg-negative patients, analysing on-treatment and post-treatment HBsAg kinetics. On-treatment HBsAg kinetics diagnostic accuracy (AUROC) to identify HBsAg loss was evaluated. Results: 52 HBeAg-negative patients stopped treatment after 8.2 years, and 6 (11.5%) achieved HBsAg loss one year after withdrawal. Multivariate analysis showed that on-treatment HBsAg kinetics was related to HBsAg loss (OR = 0.10; 95%CI = 0.016-0.632; p = 0.014) with a high diagnostic accuracy (AUROC = 0.935). A significant HBsAg decline ≥1 log10 IU/mL showed a positive and negative predictive value of 50% and of 97.6%, respectively. After treatment interruption, HBsAg decline speed (log10 IU/mL/year) accelerated in patients treated > 6 years (from -0.06 to -0.20, p < 0.05) and remained stable in treated < 6 years (from -0.12 to -0.12 p = ns). Conclusions: On-treatment HBsAg kinetics can predict post-treatment HBsAg loss rate. Half of patients with a significant HBsAg decline can eliminate HBsAg the first year after withdrawal. Post-treatment HB-sAg decline is faster not only in patients who lost the HBsAg but also in those who remain HBsAgpositive.

BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss. AIM To evaluate if the addition of pegylated interferon (Peg-IFN) could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels and increase HBsAg loss rate in patients under NAs therapy. METHODS Prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/week plus NAs during forty-eight weeks vs NAs in monotherapy. Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital, under NAs therapy for at least 2 years and with undetectable viral load, were eligible. Patients with hepatitis C virus, hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded. HBsAg and HBcrAg levels (log10 U/mL) were measured at baseline and during ninety-six weeks. HBsAg loss rate was evaluated in both groups. Adverse events were recorded in both groups. The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline (log10 IU/mL/week) using a linear regression model. RESULTS Sixty-five patients were enrolled, 61% receiving tenofovir and 33% entecavir. Thirty-six (55%) were included in Peg-IFN-NA group and 29 (44%) in NA group. After matching by age and treatment duration, baseline HBsAg levels were comparable between groups (3.1 vs 3.2) ( P = 0.25). HBsAg levels at weeks 24, 48 and 96 declined in Peg-IFN-NA group (-0.26, -0.40 and -0.44) and remained stable in NA group (-0.10, -0.10 and -0.10) ( P < 0.05). The slope of HBsAg decline in Peg-IFN-NA group (-0.02) was higher than in NA group (-0.00) ( P = 0.015). HBcrAg levels did not change. Eight (22%) patients discontinued Peg-IFN due to adverse events. The HBsAg loss was achieved in 3 (8.3%) patients of the Peg-IFN-NA group and 0 (0%) of the NA group. CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy. Side effects of Peg-IFN can limit its use in clinical practice.

Abnormal liver function tests (A‐LFTs) during admission for coronavirus disease‐19 (COVID‐19) are frequent, but its evolution after COVID‐19 resolution remains unexplored. We evaluated factors related to A‐LFTs during COVID‐19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A‐LFTs during COVID‐19; and (2) follow‐up evaluation with blood test, transient elastography and liver biopsy in those with persistent A‐LFTs. A‐LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A‐LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A‐LFTs. Follow‐up evaluation was performed in 153 individuals. Persistent A‐LFTs at follow‐up was similar in patients with/without A‐LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A‐LFTs at follow‐up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A‐LFTs during COVID‐19 were related to infection severity. Abnormalities remitted at follow‐up in >80% of patients, and no correlation between A‐LFTs at admission and at follow‐up was found. Most patients with A‐LFTs at follow‐up had non‐invasive and histologically proven fatty liver disease.

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Background The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration This study is registered on Clinicaltrials.gov (NCT03789825).

Treatment with PTV/r/OBV/DSV in genotype 1b-infected treatment-naive patients with mild-moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT03122132.

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