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ABSTRACT Background and Aims Methods Results Conclusions To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.The annual incidence of HCC was 2.1/100 person‐years after a follow‐up period of over 4840.5 person‐years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55–5.81; p = 0.001), male sex (2.98/1.51–5.90; p = 0.02), body mass index (1.11/1.04–1.18; p = 0.002) and age (1.06/1.04–1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00–4.25; p = 0.04) and NO2 (per one‐unit increment, parts per billion; 1.07/1.01–1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three‐fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34–7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79–19.23; p = 0.004), age (1.12/1.07–1.17; p < 0.001) and platelet count (0.99/0.98–1.00; p = 0.04).Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long‐term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers. Methods: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA. Results: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples. Conclusions: Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA). Impact and Implications: HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes.

Acute-on-chronic liver failure (ACLF) is a complex health problem with a high short-term mortality. It is a form of end-stage liver disease (ESLD) characterized by acute hepatic insult on the background of an underlying chronic liver disease leading to other extrahepatic organ failures. Due to its rapid rate of progression, it is a challenge for both hepatologists and intensivists to treat. Many variations exist regarding its definition, leading to descriptions of various clinical phenotypes. Patients who have chronic hepatitis B (CHB) or Hepatitis B virus (HBV)-related cirrhosis are also prone to develop hepatic or extrahepatic failures when they develop a superadded insult. Different severity criteria and prognostic scores have been proposed and validated among various populations and various etiologies including HBV. The management mainly focusses on support of various organ failures while waiting for the liver to regenerate, for liver transplantation, or, in the case of HBV-related ACLF (HBV-ACLF), for the anti-virals to take effect. Liver transplantation still remains the definitive treatment for HACLV in general and even for HBV- ACLF. Medical therapies, such as nucleos(t)ide analogue (NUCs)and artificial liver support, may improve survival in a subset of patients with HBV-related ACLF. This review updates the understanding of HBV-ACLF from epidemiological and clinical studies and provides new insights into the definition, diagnostic criteria, epidemiology, pathogenesis, treatment, and prognostication of HBV-ACLF.

Using commercial quantitative assays, quantitative hepatitis B surface antigen (qHBsAg) has improved our understanding and management of chronic hepatitis B (CHB). The HBsAg level is highest in the immune tolerance phase, starts to decline during the immune clearance phase, and decreases slowly but progressively after hepatitis B e antigen (HBeAg) seroconversion. The HBsAg level is lowest in individuals with an inactive carrier state but higher in those who develop HBeAg-negative hepatitis. It has been shown that a reduction of HBsAg by 1 log IU/mL or more reflects improved host immune control of HBV infection. A combination of HBsAg <1000 IU/mL and HBV-DNA <2000 IU/mL can identify a 3-year inactive state in a genotype D HBeAg-negative carrier population. In the Asian-Pacific region, where HBV genotypes B and C are dominant, HBsAg levels of ≤10-100 IU/mL predict HBsAg loss over time. As to the prediction of disease progression, low-viremic carriers with HBsAg >1000 IU/mL have been shown to be at higher risks of HBeAg-negative hepatitis, cirrhosis, and hepatocellular carcinoma than those with HBsAg <1000 IU/mL. Although qHBsAg has been widely used in CHB patients receiving pegylated interferon therapy, the HBsAg decline is slow and does not correlate with HBV-DNA levels during nucleos(t)ide analogue (NUC) therapy. However, a rapid HBsAg decline during NUC therapy may identify patients who will finally clear HBsAg. A 6- to 12-monthly assessment of HBsAg level could be considered during NUC therapy. Taking these lines of evidence together, qHBsAg can complement HBV-DNA levels to optimize the management of CHB patients in our daily clinical practice. [ABSTRACT FROM AUTHOR]