HBV-related Cirrhosis Research Articles

Changing spectrum and mortality disparities of etiology of liver cirrhosis in Beijing, China.

Liver cirrhosis remains a major health concern globally, but its epidemiology and etiology evolve with time. However, the changing pattern in etiology and cause of liver-related mortality for patients with cirrhosis are not fully elucidated. Herein, our aim was to characterize the temporal trend of the etiological spectrum and evaluate the impact of etiology on liver-related death among patients with compensated cirrhosis (CC) in Beijing, China. Clinical profiles of patients with CC discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. The mortalities of different etiologies of cirrhosis were calculated. The risks of readmission and liver-related death associated with etiologies were evaluated by the Cox regression model. A total of 23 978 cirrhotic patients were included. The predominant cause was hepatitis B virus (HBV) (58.93%), followed by alcohol (21.35%), autoimmune (14.85%), miscellaneous etiologies (3.55%), and hepatitis C virus (HCV) (1.32%). From 2008 to 2015, the proportion of HBV-related cirrhosis decreased to 28.11%. Meanwhile, the proportions of autoimmune- and miscellaneous-related cirrhosis increased to 28.54% and 13.11%. The risk of liver-related death ranked the highest in patients with miscellaneous cirrhosis, followed by HBV-related cirrhosis, alcohol-related cirrhosis, autoimmune-related cirrhosis, and HCV-related cirrhosis. The 5-year rates of liver-related death were 22.56%, 18.99%, 18.77%, 16.01%, and 10.76%, respectively. HBV-related cirrhosis caused the highest risk of hepatocellular carcinoma (HCC)-related death, whereas alcohol- and miscellaneous-related cirrhosis caused higher risks of decompensation (DC)-related death than HBV-related cirrhosis, with hazard ratios of 1.35 (95% confidence interval [CI]: 1.24-1.48) and 1.20 (95% CI: 1.03-1.40), respectively. HBV remained a common cause of liver cirrhosis but gradually decreased. Mortality disparities existed in etiologies, with higher risks of HCC-related death in HBV-related cirrhosis, and DC-related death in alcohol- and miscellaneous-related cirrhosis.

Predicting Early Post-Transplant Mortality: The Role of ICU Stay in Liver Transplant Recipients with HBV-Related Cirrhosis

Predicting Early Post-Transplant Mortality: The Role of ICU Stay in Liver Transplant Recipients with HBV-Related Cirrhosis

Quantitative PCR-based high-sensitivity detection of HBV-DNA levels reflects liver function deterioration in patients with hepatitis B virus-related cirrhosis.

To investigate the clinical implication of quantitative polymerase chain reaction (PCR)-based high-sensitivity detection of hepatitis B virus (HBV)-DNA levels in patients with HBV-related liver cirrhosis (LC). From January 2020 to December 2022, 100 fasting serum samples were collected and retrospectively analyzed from patients with treated HBV-related LC attending the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine and Suzhou Guangci Cancer Hospital. Patients were divided into a negative group (HBV-DNA < 20 IU/mL) and a positive group (HBV-DNA ≥ 20 IU/mL) according to their high-sensitivity HBV-DNA test results. The clinical characteristics and serological indicators of the two groups were compared, mainly including gender, age, liver function [total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL)], lipids [total cholesterol (TC) and triglycerides (TG)], platelets (PLT), five serum liver fibrosis markers [cholyglycine (CG), hyaluronic acid (HA), laminin (LN), precollagen type III (PCIII), and type IV collagen (IV-C)], serum gastrointestinal tumor markers [α-fetoprotein (AFP) and carcinoembryonic antigen (CEA)], and hepatitis B surface antigen (HBsAg). The differences between the two groups in terms of liver function Child-Pugh grades and the incidence of hepatocellular carcinoma (HCC) were also compared. There were 39 patients in the positive group, including 29 males and 10 females, and 61 patients in the negative group, including 38 males and 23 females, with no statistically significant differences in gender and age distribution between the two groups (P > 0.05). The levels of serological indicators (TP, ALB, AST, GGT, ALP, TBIL, DBIL, IBIL, TC, TG, PLT, CG, HA, LN, PCIII, IV-C, AFP, CEA, and HBsAg) in both groups showed no significant differences (P > 0.05), but the ALT level in the positive group was higher than that in the negative group (P < 0.0001). The positive group had worse Child-Pugh grades and higher HCC incidence compared to the negative group (P < 0.0001, P = 0.028). Patients with HBV-related LC and HBV-DNA ≥ 20 IU/mL have higher serum ALT levels, worse liver function Child-Pugh grades, and higher HCC incidence than those with HBV-DNA < 20 IU/mL. High-sensitivity HBV-DNA quantification can reflect the deterioration of liver function in patients with HBV-related LC to some extent.

Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis.

HBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management. We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases. Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14μg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions. AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B.

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir. Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson's or Spearman's correlation analysis. Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r 2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014). Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.

Comparative effectiveness of tenofovir versus entecavir in patients with hepatitis B virus-related cirrhosis in Taiwan: a retrospective cohort study.

Background: Tenofovir and entecavir demonstrated substantial effectiveness in the reversion of fibrosis and reversed cirrhosis in patients with hepatitis B virus (HBV)-related cirrhosis. However, there has not been a definitive conclusion regarding the association between entecavir and tenofovir on the risk of cirrhosis-related complications. Therefore, this study aimed to investigate the comparative effectiveness between tenofovir and entecavir in HBV-related cirrhosis patients. Methods: This was a retrospective study using Taiwan's Health Insurance Research Database. We enrolled newly diagnosed HBV-related cirrhosis patients who initiated entecavir and tenofovir between 2011 and 2019. Treatment groups were determined by the initial HBV antiviral medication prescribed. The primary composite outcome was the development of hepatocellular carcinoma (HCC), death from any causes, and liver transplantation. The secondary outcomes included all the individual components of the primary outcome. The incidence rate was calculated for each outcome for both treatment groups using the Fine-Gray subdistribution hazard models. Propensity score adjustment was used to balance treatment groups. Results: A total of 7,316 propensity score-matched treatment-naïve patients and 3,524 propensity score-matched treatment-experienced patients were included. Within treatment-naïve patients, those receiving tenofovir showed significantly lower hazards of developing the composite outcome (HR, 0.79; p < 0.0001), hepatocellular carcinoma (HR, 0.86; p = 0.027), mortality (HR, 0.75; p < 0.0001), and liver transplantation (HR, 0.70; p = 0.0189) than those receiving entecavir. As for treatment-experienced patients, tenofovir was associated with a significantly lower risk of the composite outcome (HR, 0.82; p = 0.0033) and hepatocellular carcinoma (HR, 0.60; p < 0.0001), but it did not show a significantly different risk of all-cause mortality (HR, 0.93; p = 0.3374) or liver transplantation (HR, 1.17; p = 0.5112) compared to entecavir. Conclusion: Tenofovir presented a significantly lower incidence of cirrhosis-related complications than entecavir in patients with hepatitis B virus-related cirrhosis. However, no statistically significant difference in death and liver transplantation was seen in treatment-experienced patients.

Interleukin-8 predicts short-term mortality in acute-on-chronic liver failure patients with hepatitis B-related-related cirrhosis background

Background Acute-on-chronic liver failure (ACLF) is a distinctive and severe syndrome, marked by an excessive systemic inflammatory response. In vivo, interleukin 8 (IL-8) is an essential pro-inflammatory cytokine. We aimed to investigate the value of serum IL-8 levels in predicting mortality in ACLF patients in the background of hepatitis B virus-related cirrhosis. Methods In this study, we conducted a retrospective analysis of the clinical baseline characteristics of 276 patients with ACLF in the context of HBV-related cirrhosis. Logistic regression analysis was employed to identify independent risk factors for short-, intermediate-, and long-term mortality. Using these independent risk factors, we developed a nomogram model, which was subsequently validated. To assess the clinical usefulness of the nomogram model, we performed decision curve analysis (DCA). Results Out of the 276 patients with ACLF, 98 (35.5%), 113 (40.9%), and 128 (46.4%) died within 28, 90, and 180 days, respectively. Serum IL-8 levels were only an independent predictor of 28-day mortality and could simply classify ACLF patients. Conversely, mean arterial pressure (MAP), HBV-DNA, and COSHACLF IIs were independent predictors of mortality across all three observation periods. We constructed a nomogram based on IL-8 that was able to visualise and predict 28-day mortality with a C-index of 0.901 (95% CI: 0.862–0.940). Our calibration curves, Predicted Probability of Death & Actual Survival Status plot, and Confusion Matrix demonstrated the nomogram model’s strong predictive power. DCA indicated the nomogram’s promising clinical utility in predicting 28-day mortality in ACLF patients. Conclusion Serum IL-8 levels predict short-term mortality in ACLF patients in the background of HBV-associated cirrhosis, and the developed Nomogram model has strong predictive power and good clinical utility.

Performance of Spleen Stiffness, Liver Stifness, and their Combination for Predicting Esophageal among Patient with HBV-Related Cirrhosis

Background: Liver cirrhosis in Indonesia still become a burden disease, and the etiology is mostly from the hepatitis B virus. Esophageal varices (EV) is the most common complication of portal hypertension in liver cirrhosis. Due to many reasons, esophagogastroduodenoscopy is still not fully suitable for routine surveillance in daily practice. Hence, studies that work in the search for the best non-invasive test are still important for predicting EV.Method: A total of 71 patients with liver cirrhosis due to hepatitis B who had undergone endoscopy, spleen stiffness measurement (SSM), and liver stiffness measurement (LSM), between January–April 2023 were enrolled. Diagnostic applicability was assessed by the area under the receiver-operator curve (AUC) to measure and compare the performance of each measurement and combination for predicting EV and to obtain the corresponding optimal prediction value.Results: This study was participated by 71 subjects with liver cirrhosis. The prevalence of Child-Pugh A was 74.6% (53 patients), Child-Pugh B 22.5% (16 patients), and 2.8% (2 patients) with Child-Pugh C. Among these patients, the proportion of EV was 71.8%. This study showed that SSM with a cut-off of 38.8 kPa had AUC 0.867 (95% CI: 0.774–0.960) (sensitivity 78.4%, specificity 80%) and LSM with a cut-off of 10.55 kPa had AUC 0.822 (95% CI: 0.701–0.943) (sensitivity 88.2%, specificity 65%).Conclusion: Spleen stiffness and liver stiffness measurements have a good performance for predicting EV in patients with liver cirrhosis caused by hepatitis B.

Expression of circulating miRNA-21 and miR-99b in HBV-related liver cirrhosis and hepatocellular carcinoma

Objective: Our primary objective was to assess whether these miRNAs could serve as potential biomarkers for distinguishing hepatocellular carcinoma (HCC), even in its early stages, from other liver diseases, particularly liver cirrhosis (LC). Subject and method: We conducted a study involving two patient groups: 50 LC and 50 HCC patients. We employed a screening approach utilizing open data sources (PubMed, Science Research, Google Scholar…), alongside bioinformatics analysis tools to identify miRNAs exhibiting high expression levels in cirrhosis and liver cancer. The miRNAs we selected for evaluation included miRNA-21, miRNA-34a, miRNA-99b, and miRNA-224. Result: The expression levels of miRNA-21 in plasma were found to be significantly higher in the HCC group compared to the cirrhosis group (p&lt;0.001). The combination of miRNA-21 or miRNA-99b and AFP had improved diagnostic performance in distinguishing between these two groups compared to single markers. The area under the ROC curve was significantly high as expected when combining miRNA-99b and AFP with AUC = 0.85 (single miRNA-99b: AUC = 0.715). Similarly for the combination of miRNA-21 and AFP, this simple panel also had a good performance with the AUC = 0.794 (single miRNA-21: AUC = 0.715). Conclusion: miRNA-21 and miRNA-99b hold promise as potential biomarkers for the diagnosis of HCC.

Long-term evolution of LR-2, LR-3 and LR-4 observations in HBV-related cirrhosis based on LI-RADS v2018 using gadoxetic acid-enhanced MRI.

To investigate the long-term evolution of LR-2, LR-3 and LR-4 observations in patients with hepatitis B virus (HBV)-related cirrhosis based on LI-RADS v2018 and identify predictors of progression to a malignant category on serial gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI). This retrospective study included 179 cirrhosis patients with untreated indeterminate observations who underwent Gd-EOB-MRI exams at baseline and during the follow-up period between June 2016 and December 2021. Two radiologists independently assessed the major features, ancillary features, and LI-RADS category of each observation at baseline and follow-up. In cases of disagreement, a third radiologist was consulted for consensus. Cumulative incidences for progression to a malignant category (LR-5 or LR-M) and to LR-4 or higher were analyzed for each index category using Kaplan‒Meier methods and compared using log-rank tests. The risk factors for malignant progression were evaluated using a Cox proportional hazard model. A total of 213 observations, including 74 (34.7%) LR-2, 95 (44.6%) LR-3, and 44 (20.7%) LR-4, were evaluated. The overall cumulative incidence of progression to a malignant category was significantly higher for LR-4 observations than for LR-3 or LR-2 observations (each P < 0.001), and significantly higher for LR-3 observations than for LR-2 observations (P < 0.001); at 3-, 6-, and 12-month follow-ups, the cumulative incidence of progression to a malignant category was 11.4%, 29.5%, and 39.3% for LR-4 observations, 0.0%, 8.5%, and 19.6% for LR-3 observations, and 0.0%, 0.0%, and 0.0% for LR-2 observations, respectively. The cumulative incidence of progression to LR-4 or higher was higher for LR-3 observations than for LR-2 observations (P < 0.001); at 3-, 6-, and 12-month follow-ups, the cumulative incidence of progression to LR-4 or higher was 0.0%, 8.5%, and 24.6% for LR-3 observations, and 0.0%, 0.0%, and 0.0% for LR-2 observations, respectively. In multivariable analysis, nonrim arterial phase hyperenhancement (APHE) [hazard ratio (HR) = 2.13, 95% CI 1.04-4.36; P = 0.038], threshold growth (HR = 6.50, 95% CI 2.88-14.65; P <0.001), and HBP hypointensity (HR = 16.83, 95% CI 3.97-71.34; P <0.001) were significant independent predictors of malignant progression. The higher LI-RADS v2018 categories had an increasing risk of progression to a malignant category during long-term evolution. Nonrim APHE, threshold growth, and HBP hypointensity were the imaging features that were significantly predictive of malignant progression.

Association of C-type lectin-like receptor 2 and galectin-1 with portal vein system thrombosis in HBV-related liver cirrhosis.

Hepatitis B virus (HBV) infection is the most common cause of liver cirrhosis. Portal venous system thrombosis (PVST) is a major complication of liver cirrhosis. Recently, it has been shown that C-type lectin-like receptor 2 (CLEC-2) and galectin-1 participate in the activation and aggregation of platelets, thereby promoting the development of thrombosis. This cross-sectional study aims to evaluate the association of serum CLEC-2 and galectin-1 levels with PVST in patients with HBV-related liver cirrhosis. Overall, 65 patients with HBV-related liver cirrhosis were included, of whom 23 had PVST and 42 did not have. Serum CLEC-2 and galectin-1 levels were measured using enzyme-linked immunosorbent assay kits. PVST was assessed by contrast-enhanced computed tomography and/or magnetic resonance imaging scans. Subgroup analyses were conducted according to the degree and location of PVST. Patients with PVST had significantly higher serum CLEC-2 (p = 0.006) and galectin-1 (p = 0.009) levels than those without. Patients with partial/complete PVST or fibrotic cord (p = 0.007; p = 0.002), but not those with mural PVST (p = 0.199; p = 0.797), had significantly higher serum CLEC-2 and galectin-1 levels than those without PVST. Patients with superior mesenteric vein thrombosis had significantly higher serum CLEC-2 (p = 0.013) and galectin-1 (p = 0.025) levels than those without PVST. Patients with main portal vein thrombosis had higher serum CLEC-2 (p = 0.020) and galectin-1 (p = 0.066) levels than those without PVST, but the difference in serum galectin-1 level was not significant between them. Serum CLEC-2 and galectin-1 levels may be associated with the presence of PVST in HBV-related cirrhotic patients, but this association should be dependent upon the degree of PVST.

Prognosis after splenectomy plus pericardial devascularization vs transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding.

Portal hypertension combined with esophagogastric variceal bleeding (EGVB) is a serious complication in patients with hepatitis B virus (HBV)-related cirrhosis in China. Splenectomy plus pericardial devascularization (SPD) and transjugular intrahepatic portosystemic shunt (TIPS) are effective treatments for EGVB. However, a comparison of the effectiveness and safety of those methods is lacking. To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding (VRB) in patients with HBV-related cirrhosis combined with portal hypertension. This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013. Propensity score-matched analysis (PSM), the Kaplan-Meier method, and multivariate Cox regression analysis were used to compare overall survival, VRB rate, liver function abnormality rate, and hepatocellular carcinoma (HCC) incidence between the two patient groups. The median age was 45.0 years (n = 318; 226 (71.1%) males). During a median follow-up duration of 43.0 mo, 18 (11.1%) and 33 (21.2%) patients died in the SPD and TIPS groups, respectively. After PSM, SPD was significantly associated with better overall survival (OS) (P = 0.01), lower rates of abnormal liver function (P < 0.001), and a lower incidence of HCC (P = 0.02) than TIPS. The VRB rate did not differ significantly between the two groups (P = 0.09). Compared with TIPS, SPD is associated with higher postoperative OS rates, lower rates of abnormal liver function and HCC, and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension. There is no significant between-group difference in VRB rates.

Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis.

Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up. From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382). Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.

Hepatitis B and C in Europe: an update from the Global Burden of Disease Study 2019

In 2016, the World Health Assembly adopted the resolution to eliminate viral hepatitis by 2030. This study aims to provide an overview of the burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Europe and their changes from 2010 to 2019 using estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We used GBD 2019 estimates of the burden associated with HBV-related and HCV-related diseases: acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer. We report total numbers and age-standardised rates per 100 000 for mortality, prevalence, incidence, and disability-adjusted life-years (DALYs) from 2010 to 2019. For each HBV-related and HCV-related disease and each measure, we analysed temporal changes and percentage changes for the 2010-19 period. In 2019, across all age groups, there were an estimated 2·08 million (95% uncertainty interval [UI] 1·66 to 2·54) incident cases of acute hepatitis B and 0·49 million (0·42 to 0·57) of hepatitis C in Europe. There were an estimated 8·24 million (7·56 to 8·88) prevalent cases of HBV-related cirrhosis and 11·87 million (9·77 to 14·41) of HCV-related cirrhosis, with 24·92 thousand (19·86 to 31·03) deaths due to HBV-related cirrhosis and 36·89 thousand (29·94 to 45·56) deaths due to HCV-related cirrhosis. Deaths were estimated at 9·00 thousand (6·88 to 11·62) due to HBV-related liver cancer and 23·07 thousand (18·95 to 27·31) due to HCV-related liver cancer. Between 2010 and 2019, the age-standardised incidence rate of acute hepatitis B decreased (-22·14% [95% UI -35·44 to -5·98]) as did its age-standardised mortality rate (-33·27% [-43·03 to -25·49]); the age-standardised prevalence rate (-20·60% [-22·09 to -19·10]) and mortality rate (-33·19% [-37·82 to -28·13]) of HBV-related cirrhosis also decreased in this time period. The age-standardised incidence rate of acute hepatitis C decreased by 3·24% (1·17 to 5·02) and its age-standardised mortality rate decreased by 35·73% (23·48 to 47·75) between 2010 and 2019; the age-standardised prevalence rate (-6·37% [-8·11 to -4·32]), incidence rate (-5·87% [-11·24 to -1·01]), and mortality rate (-11·11% [-16·54 to -5·53]) of HCV-related cirrhosis also decreased. No significant changes were observed in age-standardised rates of HBV-related and HCV-related liver cancer, although we observed a significant increase in numbers of cases of HCV-related liver cancer across all ages between 2010 and 2019 (16·41% [2·81 to 30·91] increase in prevalent cases). Substantial reductions in DALYs since 2010 were estimated for acute hepatitis B (-27·82% [-36·92 to -20·24]), acute hepatitis C (-27·07% [-15·97 to -39·34]), and HBV-related cirrhosis (-30·70% [-35·75 to -25·03]). A moderate reduction in DALYs was estimated for HCV-related cirrhosis (-6·19% [-0·19 to -12·57]). Only HCV-related liver cancer showed a significant increase in DALYs (10·37% [4·81-16·63]). Changes in age-standardised DALY rates closely resembled those observed for overall DALY counts, except for HCV-liver related cancer (-2·84% [-7·75 to 2·63]). Although decreases in some HBV-related and HCV-related diseases were estimated between 2010 and 2019, HBV-related and HCV-related diseases are still associated with a high burden, highlighting the need for more intensive and coordinated interventions within European countries to reach the goal of elimination by 2030. Bill & Melinda Gates Foundation.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitisB virus infection in Caucasians.

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitisB virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitisB envelope antigen (HBeAg) negative chronic hepatitisB (n=255), with HBeAg positive chronic hepatitisB (n=99) and with HBeAg negative HBV infection (n=228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n=195) and in healthy controls (n=160). In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR=1.75, 95% CI 1.04-2.94, p=0.034), with an increased likelihood of HBeAg negative chronic infection (OR=1.93, 95% CI 1.05-3.54, p=0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p=0.029) in male patients. The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Single-cell landscape of immune cells in human livers affected by HBV-related cirrhosis

HBV infection is one of the leading causes of liver cirrhosis. However, the immune microenvironment in patients with HBV cirrhosis remains elusive. Single-cell RNA sequencing was used to analyse the transcriptomes of 76,210 immune cells in the livers of six healthy individuals and in five patients with HBV cirrhosis. Patients with HBV cirrhosis have a unique immune ecosystem characterised by an accumulation of macrophage-CD9/IL18, macrophage-C1QA, NK Cell-JUNB, CD4+ T cell-IL7R, and a loss of B cell-IGLC1 clusters. Furthermore, our analysis predicted enhanced cell communication between myeloid cells and all immune cells in patients with HBV-related cirrhosis. Pseudo-time analysis of myeloid cells, natural killer (NK) cells, and B cells demonstrated a significant accumulation of mature cells and a depletion of naive cells in HBV cirrhosis. In addition, we observed an increase in antigen processing and presentation capacities in myeloid cells in patients with HBV cirrhosis, whereas NK cell-mediated cytotoxicity was substantially reduced. Our results provide valuable insight into the immune landscape of HBV cirrhosis, suggesting that HBV cirrhosis is associated with the accumulation of activated myeloid cells and impaired cytotoxicity in NK cells. The absence of single-cell transcriptome profiling of immune cells in HBV cirrhosis hinders our understanding of the underlying mechanisms driving disease progression. To address this knowledge gap, our study unveils a distinctive immune ecosystem in HBV cirrhosis and represents a crucial advancement in elucidating the impact of the immune milieu on the development of this condition. These findings constitute significant strides towards the identification of more effective therapeutic approaches for HBV cirrhosis and are relevant for healthcare professionals, researchers, and pharmaceutical developers dedicated to combating this disease.

A Validated Composite Score Demonstrates Potential Superiority to MELD-Based Systems in Predicting Short-Term Survival in Patients with Liver Cirrhosis and Spontaneous Bacterial Peritonitis-A Preliminary Study.

Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.

Combined model with acoustic radiation force impulse to rule out high-risk varices in HBV-related cirrhosis with viral suppression.

To prospectively evaluate the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) via acoustic radiation force impulse (ARFI) imaging combined with platelet counts (PLT) in ruling out HRV in HBV-related cirrhotic patients with viral suppression. Patients with cirrhosis enrolled between June 2020-March 2022 were divided into a derivation cohort and validation cohort. LSM and SSM ARFI-based, and esophagogastroduodenoscopy (EGD) were performed at enrollment. In the derivation cohort, overall, 236 HBV-related cirrhotic patients with maintained viral suppression were enrolled, and the prevalence of HRV was 19.5% (46/236). With the aim of identifying HRV, the most accurate LSM and SSM cut-offs were chosen of 1.46m/s and 2.28m/s, respectively. The combined model (LSM<1.46m/s and PLT>150×109/L strategy combined with SSM ≤ 2.28m/s) can spare 38.6% of EGDs and 4.3% of HRV cases were misclassified. In the validation cohort, we analysed 323 HBV-related cirrhotic patients with maintained viral suppression and validated the combined model can spare 33.4% (108/323) of EGD, and the HRV missed rate was 3.4%. A non-invasive prediction model combining LSM<1.46m/s and PLT>150×109/L strategy with SSM ≤ 2.28m/s exhibited excellent performance in ruling out HRV and avoided a significantly large number (38.6% vs 33.4%) of unnecessary EGDs in HBV-related cirrhotic patients with viral suppression.

Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study

Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis. In this prospective cohort study, we followed up adults who were consecutively diagnosed with cirrhosis or hepatocellular carcinoma between 2012 and 2015 in The Gambia, west Africa. Patients with chronic HBV infection and cirrhosis, without hepatocellular carcinoma, were offered TDF. Primary outcome was overall survival. To determine the effect of TDF on survival, we performed a Cox proportional hazard regression model with inverse probability of treatment weighting (IPTW) based on propensity score. Of 529 patients enrolled in this study, 336 patients (252 with hepatocellular carcinoma and 84 with cirrhosis) were analysed. Patients were predominantly male (253 [75%] men and 83 [25%] women), with a median age of 42 years (IQR 33-55). 276 (84%) of 327 of patients with data were positive for HBV biomarkers, 31 (10%) of 311 were positive for hepatitis C virus antibodies, and 22 (10%) of 223 were positive for hepatitis D virus antibodies. 64% of patients with hepatocellular carcinoma had multifocal tumour, with a median size of 7·5 cm (IQR 5·4-10·8). 173 patients with hepatocellular carcinoma and 70 patients with cirrhosis were included in the survival analysis. Median survival was 1·5 months (95% CI 1·1-2·0) in patients with hepatocellular carcinoma and 17·1 months (11·2-24·0) in patients with cirrhosis (log-rank p<0·0001). In patients with hepatocellular carcinoma, ascites (hazard ratio [HR] 1·78, 95% CI 1·21-2·60), partial or complete portal thrombosis (HR 2·61, 1·58-4·30), and platelet count (HR 1·80, 1·19-2·70) were independent predictive factors of mortality at baseline. In HBV-infected patients with cirrhosis, median turnaround time between cirrhosis diagnosis and TDF initiation was 4·9 months (IQR 3·2-7·3). In IPTW analysis, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (adjusted HR 0·14, 0·06-0·34; p<0·0001). These results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa. European Commission and Medical Research Council UK. For the French translation of the abstract see Supplementary Materials section.

Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.